Cases That Test Your Skills

History: Suddenly Speechless

Mr. P, age 52, is transferred to our behavioral health unit after 1 month of unsuccessful treatment at a psychiatric hospital. He is mute and disheveled with blunted affect.

Before his hospitalization, Mr. P—who is mildly retarded and has an IQ of 67—lived independently, managed his finances, held two part-time jobs, volunteered as an usher at church, and had a girlfriend. He has been medically stable with diagnoses of indolent stage-zero chronic lymphocytic leukemia (for which he took no medication), moderate obesity, and essential hypertension. For 2 years he has been taking reserpine, 0.25 mg/d, for hypertension, and weighs 200 lb at presentation (body mass index: 29 kg/m²). He has no history of mental illness.

Seven months ago, Mr. P began having trouble dressing and bathing. He also began eating considerably less—about one-third of his normal food intake—and lost 20 lbs over 6 months.

Mr. P also began standing in the street for hours at a time—calling out to passers-by that people were dying and he was causing their deaths—until family members persuaded him to return home. He was not hallucinating, but his brother—who is Mr. P’s legal guardian—said symptoms worsened after a family friend died. After Mr. P became mute, resistant to direction, and immobile, his brother got him admitted to the psychiatric hospital.

The attending physician stopped reserpine—which might cause depression—and started hydrochlorothiazide, 25 mg/d, to maintain normal blood pressure. A psychiatrist diagnosed major depressive disorder and psychosis not otherwise specified, and prescribed mirtazapine, 30 mg nightly, and quetiapine, 25 mg bid. The psychiatrist ruled out lethal catatonia, as vital signs remained stable. When Mr. P’s symptoms did not improve after 1 month, the psychiatrist recommended electroconvulsive therapy (ECT) and transferred him to our facility.

Physical examination and laboratory findings are normal except for lymphocytosis secondary to leukemia:

poll here

The authors’ observations

Mr. P. has major depression with psychotic features. His staring, catalepsy, negativism, selective mutism, and posturing indicate catatonia, and his nihilistic delusions signal Cotard’s syndrome, a delusional depressive disorder.

Catatonia consists of changes in muscle tone and activity and is accompanied by echopraxia and echolalia. Many medical conditions or medications can cause catatonia (Table 1).¹ Resultant immobility and stupor can lead to contractures, pressure ulcers, venous thrombosis, and pulmonary emboli. Refusal to eat or drink can cause malnutrition, dehydration, weight loss, and muscle wasting. Approximately 9% of psychiatric inpatients develop catatonia at some point.²

DSM-IV-TR³ describes catatonia criteria as specifiers in affective illness and requires two or more of the following features for diagnosis:

• catalepsy or stupor
  
• purposeless, excessive motor activity
  
• negativism or mutism
  
• peculiar voluntary behaviors, such as posturing, stereotypy, or mannerisms
  
• echolalia or echopraxia (Table 2).
  

No consensus exists regarding which behaviors are pathognomonic or how long they must persist to meet criteria for catatonia.

Catatonia can occur during an excited or retarded state:

• Excited catatonia—also called delirious mania or an oneiroid state—is marked by a dreamlike sensorium, rapid onset, confabulation, derealization, depersonalization, disorientation, and a mixture of catatonic features.⁴
  
• Retarded catatonia can be diagnosed using DSM-IV-TR criteria for catatonia. In mild cases or early in presentation, symptoms resemble anergy and psychomotor slowing typical of depression.
  

Lethal catatonia—a rare, extreme, potentially life-threatening form—is clinically indistinguishable from neuroleptic malignant syndrome. Its cause is often toxic or iatrogenic.⁵ Hyperthermia, hypertension, tachycardia, fever, tachypnea, leukocytosis, and serum creatine phosphokinase >500 u/L indicate lethal catatonia.

Table 1

Recognized causes of catatonia

Affective disorders and schizophrenia CNS injury or infection (such as encephalitis) Lupus cerebritis Medications (bupropion, disulfiram, fluoroquinolones, neuroleptics, steroids) Metabolic imbalance Porphyria Seizure disorders Substance abuse (cocaine, phencyclidine)

Table 2

Catatonia: Defining clinical characteristics

Term	Definition
Ambitendency	Indecision, hesitance, becoming stuck regarding stimuli
Analgesia to painful stimuli	Failure to feel or withdraw from pain
Catalepsy	Posturing, including facial expressions such as exaggerated lip puckering, with waxy flexibility and automatic obedience
Echolalia	Repeating words and phrases
Echopraxia	Repeating another person’s movements
Excitement	Loquacious confabulation and autonomic instability
Mannerisms	Purposeful eccentric movements, such as saluting
Negativism	Rigidity and resistance to commands
Perseveration	Continuing a response long after it is appropriate
Prosectic speech	Decreased production and volume of speech
Selective mutism	Absence of speech
Stereotypy	Persistently repeating gestures that do not appear goal-directed, such as head-banging, rocking, and twirling objects
Verbigeration	Repeating a word, phrase, or sentence

In Cotard’s syndrome (Table 3), the patient might believe that he and others around him are dead, that his body is putrefying and missing internal organs and blood, or that the world no longer exists.⁶ Some patients also have delusions of negation and damnation.⁷

Cotard’s syndrome, first described in the late 1800s by French neurologist Jules Cotard, can accompany folie à deux⁷ or lycanthropy, the delusional belief that one has been transformed into a werewolf.⁸ In rare cases, patients believe that their bodies are abnormally enlarged.⁷ Cotard’s syndrome can exist alone or as part of a psychiatric illness with nihilistic delusions.⁷

 

poll hereTable 3

Characteristics of Cotard’s syndrome

Delusional belief that one’s body parts, friends, family, money, or the world do not exist Can accompany major depression, schizophrenia, dementia, or a general medical condition Relatively rare, with unknown incidence and prevalence. More common during late middle life and among women Sudden onset with no history of psychiatric disorder Associated with nondominant parietal lobe lesions and catatonia

The authors’ observations

Mr. P.’s episode appears to have been idiopathic.

Reserpine could have caused his decompensation, though precisely how is unclear. The medication is alleged to cause depression by depleting serotonin, dopamine, and norepinephrine, but some researchers believe it exacerbates pre-existing depression.^9,10

When treating any patient with a history of depression, find out if he or she is taking reserpine. Advise the primary care physician to discontinue the drug if the patient is self-deprecating or despondent, or reports early morning insomnia, loss of appetite, or impotence.¹¹

Treatment: False Start

To address Mr. P’s catatonia, we stop quetiapine and mirtazapine and start IM lorazepam, 2 mg qid. After 4 days his condition is stable, but he still believes that he and everyone else is dead.

poll here

The authors’ observations

Parenteral benzodiazepines typically are used to treat patients with catatonia and Cotard’s syndrome while the clinician searches for a toxic or medical cause. Most patients with nonemergent catatonia respond to a benzodiazepine.¹²

Although opinion differs on starting dosages of IM lorazepam in retarded catatonia, we recommend 2 mg IM and repeat doses every 3 hours if the patient does not respond.^4,13 Lack of response after 20 mg (10 doses) warrants ECT.⁴

Consider ECT—which has shown effectiveness for treating both catatonia and Cotard’s syndrome in case reports^6-8,14,15—as first-line treatment in emergent catatonia. Do not try a first- or second-generation neuroleptic, which can worsen clinical outcome.

Treatment: a Three-Week Trial

We receive informed consent from Mr. P’s brother to try 10 ECT treatments over 3 weeks. We choose left anterior right temporal electrode placement to minimize cognitive interference,¹⁶ and give Mr. P glycopyrrolate, 0.2 mg before each treatment, to manage bradycardia resulting from enhanced vagal tone after electrical stimulation. According to ECT protocol, we administer the anesthetic methohexital, 0.75 to 1.0 mg/kg, and the muscle relaxant succinylcholine, 0.5 to 1 mg/kg, to shorten seizure duration during ECT.

Mr. P also receives forced ventilation at each treatment to counteract brief succinylcholine-induced paralysis of the diaphragm and other muscle tissue. Stimulus intensity begins at 35% and is increased to 50% as the patient’s seizure threshold increases. Each morning, Mr. P also receives extended-release venlafaxine, 225 mg, for depressive symptoms, and hydrochlorothiazide, 25 mg.

After the first ECT treatment, Mr. P’s affect starts to brighten. He speaks a few words after the third treatment and begins eating larger portions by the fifth treatment. After the last treatment, he is performing activities of daily living, talking readily and coherently, and playing basketball with peers. He shows no adverse cognitive effects or other complications from ECT.

The authors’ observations

Although little evidence guides treatment of catatonia in the developmentally disabled,¹⁷ we support early use of ECT in those with serious refractory mental illness.¹⁸ Some clinicians hesitate to administer ECT to patients with mental retardation because they might be particularly vulnerable to adverse medication effects.¹⁹ ECT, however, has been found to cause minimal side effects in this population²⁰ and does not cause or exacerbate brain damage.²¹

If the patient is mentally incapable of consenting to ECT, obtain informed consent from his or her legal guardian.

Conclusion: Leaving the Hospital

We discharge Mr. P after 25 days. He shows no evidence of psychosis, suicidality, or intent to harm others. He continues hydrochlorothiazide and venlafaxine at the same dosages. He returns home with his brother, and 6 months later is functioning well.

Related resources

• National Mental Health Association. Electroconvulsive therapy. www.nmha.org/infoctr/factsheets/ect.cfm.
  

Drug brand names

• Bupropion • Wellbutrin
  
• Disulfiram • Antabuse
  
• Glycopyrrolate • Robinul
  
• Hydrochlorothiazide • Various
  
• Lorazepam • Ativan
  
• Methohexital • Brevital
  
• Mirtazapine • Remeron
  
• Quetiapine • Seroquel
  
• Reserpine • Serpasil
  
• Succinylcholine • Anectine
  
• Venlafaxine XR • Effexor XR
  

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: Suddenly Speechless

Mr. P, age 52, is transferred to our behavioral health unit after 1 month of unsuccessful treatment at a psychiatric hospital. He is mute and disheveled with blunted affect.

Before his hospitalization, Mr. P—who is mildly retarded and has an IQ of 67—lived independently, managed his finances, held two part-time jobs, volunteered as an usher at church, and had a girlfriend. He has been medically stable with diagnoses of indolent stage-zero chronic lymphocytic leukemia (for which he took no medication), moderate obesity, and essential hypertension. For 2 years he has been taking reserpine, 0.25 mg/d, for hypertension, and weighs 200 lb at presentation (body mass index: 29 kg/m²). He has no history of mental illness.

Seven months ago, Mr. P began having trouble dressing and bathing. He also began eating considerably less—about one-third of his normal food intake—and lost 20 lbs over 6 months.

Mr. P also began standing in the street for hours at a time—calling out to passers-by that people were dying and he was causing their deaths—until family members persuaded him to return home. He was not hallucinating, but his brother—who is Mr. P’s legal guardian—said symptoms worsened after a family friend died. After Mr. P became mute, resistant to direction, and immobile, his brother got him admitted to the psychiatric hospital.

The attending physician stopped reserpine—which might cause depression—and started hydrochlorothiazide, 25 mg/d, to maintain normal blood pressure. A psychiatrist diagnosed major depressive disorder and psychosis not otherwise specified, and prescribed mirtazapine, 30 mg nightly, and quetiapine, 25 mg bid. The psychiatrist ruled out lethal catatonia, as vital signs remained stable. When Mr. P’s symptoms did not improve after 1 month, the psychiatrist recommended electroconvulsive therapy (ECT) and transferred him to our facility.

Physical examination and laboratory findings are normal except for lymphocytosis secondary to leukemia:

poll here

The authors’ observations

Mr. P. has major depression with psychotic features. His staring, catalepsy, negativism, selective mutism, and posturing indicate catatonia, and his nihilistic delusions signal Cotard’s syndrome, a delusional depressive disorder.

Catatonia consists of changes in muscle tone and activity and is accompanied by echopraxia and echolalia. Many medical conditions or medications can cause catatonia (Table 1).¹ Resultant immobility and stupor can lead to contractures, pressure ulcers, venous thrombosis, and pulmonary emboli. Refusal to eat or drink can cause malnutrition, dehydration, weight loss, and muscle wasting. Approximately 9% of psychiatric inpatients develop catatonia at some point.²

DSM-IV-TR³ describes catatonia criteria as specifiers in affective illness and requires two or more of the following features for diagnosis:

• catalepsy or stupor
  
• purposeless, excessive motor activity
  
• negativism or mutism
  
• peculiar voluntary behaviors, such as posturing, stereotypy, or mannerisms
  
• echolalia or echopraxia (Table 2).
  

No consensus exists regarding which behaviors are pathognomonic or how long they must persist to meet criteria for catatonia.

Catatonia can occur during an excited or retarded state:

• Excited catatonia—also called delirious mania or an oneiroid state—is marked by a dreamlike sensorium, rapid onset, confabulation, derealization, depersonalization, disorientation, and a mixture of catatonic features.⁴
  
• Retarded catatonia can be diagnosed using DSM-IV-TR criteria for catatonia. In mild cases or early in presentation, symptoms resemble anergy and psychomotor slowing typical of depression.
  

Lethal catatonia—a rare, extreme, potentially life-threatening form—is clinically indistinguishable from neuroleptic malignant syndrome. Its cause is often toxic or iatrogenic.⁵ Hyperthermia, hypertension, tachycardia, fever, tachypnea, leukocytosis, and serum creatine phosphokinase >500 u/L indicate lethal catatonia.

Table 1

Recognized causes of catatonia

Affective disorders and schizophrenia CNS injury or infection (such as encephalitis) Lupus cerebritis Medications (bupropion, disulfiram, fluoroquinolones, neuroleptics, steroids) Metabolic imbalance Porphyria Seizure disorders Substance abuse (cocaine, phencyclidine)

Table 2

Catatonia: Defining clinical characteristics

Term	Definition
Ambitendency	Indecision, hesitance, becoming stuck regarding stimuli
Analgesia to painful stimuli	Failure to feel or withdraw from pain
Catalepsy	Posturing, including facial expressions such as exaggerated lip puckering, with waxy flexibility and automatic obedience
Echolalia	Repeating words and phrases
Echopraxia	Repeating another person’s movements
Excitement	Loquacious confabulation and autonomic instability
Mannerisms	Purposeful eccentric movements, such as saluting
Negativism	Rigidity and resistance to commands
Perseveration	Continuing a response long after it is appropriate
Prosectic speech	Decreased production and volume of speech
Selective mutism	Absence of speech
Stereotypy	Persistently repeating gestures that do not appear goal-directed, such as head-banging, rocking, and twirling objects
Verbigeration	Repeating a word, phrase, or sentence

In Cotard’s syndrome (Table 3), the patient might believe that he and others around him are dead, that his body is putrefying and missing internal organs and blood, or that the world no longer exists.⁶ Some patients also have delusions of negation and damnation.⁷

Cotard’s syndrome, first described in the late 1800s by French neurologist Jules Cotard, can accompany folie à deux⁷ or lycanthropy, the delusional belief that one has been transformed into a werewolf.⁸ In rare cases, patients believe that their bodies are abnormally enlarged.⁷ Cotard’s syndrome can exist alone or as part of a psychiatric illness with nihilistic delusions.⁷

 

poll hereTable 3

Characteristics of Cotard’s syndrome

Delusional belief that one’s body parts, friends, family, money, or the world do not exist Can accompany major depression, schizophrenia, dementia, or a general medical condition Relatively rare, with unknown incidence and prevalence. More common during late middle life and among women Sudden onset with no history of psychiatric disorder Associated with nondominant parietal lobe lesions and catatonia

The authors’ observations

Mr. P.’s episode appears to have been idiopathic.

Reserpine could have caused his decompensation, though precisely how is unclear. The medication is alleged to cause depression by depleting serotonin, dopamine, and norepinephrine, but some researchers believe it exacerbates pre-existing depression.^9,10

When treating any patient with a history of depression, find out if he or she is taking reserpine. Advise the primary care physician to discontinue the drug if the patient is self-deprecating or despondent, or reports early morning insomnia, loss of appetite, or impotence.¹¹

Treatment: False Start

To address Mr. P’s catatonia, we stop quetiapine and mirtazapine and start IM lorazepam, 2 mg qid. After 4 days his condition is stable, but he still believes that he and everyone else is dead.

poll here

The authors’ observations

Parenteral benzodiazepines typically are used to treat patients with catatonia and Cotard’s syndrome while the clinician searches for a toxic or medical cause. Most patients with nonemergent catatonia respond to a benzodiazepine.¹²

Although opinion differs on starting dosages of IM lorazepam in retarded catatonia, we recommend 2 mg IM and repeat doses every 3 hours if the patient does not respond.^4,13 Lack of response after 20 mg (10 doses) warrants ECT.⁴

Consider ECT—which has shown effectiveness for treating both catatonia and Cotard’s syndrome in case reports^6-8,14,15—as first-line treatment in emergent catatonia. Do not try a first- or second-generation neuroleptic, which can worsen clinical outcome.

Treatment: a Three-Week Trial

We receive informed consent from Mr. P’s brother to try 10 ECT treatments over 3 weeks. We choose left anterior right temporal electrode placement to minimize cognitive interference,¹⁶ and give Mr. P glycopyrrolate, 0.2 mg before each treatment, to manage bradycardia resulting from enhanced vagal tone after electrical stimulation. According to ECT protocol, we administer the anesthetic methohexital, 0.75 to 1.0 mg/kg, and the muscle relaxant succinylcholine, 0.5 to 1 mg/kg, to shorten seizure duration during ECT.

Mr. P also receives forced ventilation at each treatment to counteract brief succinylcholine-induced paralysis of the diaphragm and other muscle tissue. Stimulus intensity begins at 35% and is increased to 50% as the patient’s seizure threshold increases. Each morning, Mr. P also receives extended-release venlafaxine, 225 mg, for depressive symptoms, and hydrochlorothiazide, 25 mg.

After the first ECT treatment, Mr. P’s affect starts to brighten. He speaks a few words after the third treatment and begins eating larger portions by the fifth treatment. After the last treatment, he is performing activities of daily living, talking readily and coherently, and playing basketball with peers. He shows no adverse cognitive effects or other complications from ECT.

The authors’ observations

Although little evidence guides treatment of catatonia in the developmentally disabled,¹⁷ we support early use of ECT in those with serious refractory mental illness.¹⁸ Some clinicians hesitate to administer ECT to patients with mental retardation because they might be particularly vulnerable to adverse medication effects.¹⁹ ECT, however, has been found to cause minimal side effects in this population²⁰ and does not cause or exacerbate brain damage.²¹

If the patient is mentally incapable of consenting to ECT, obtain informed consent from his or her legal guardian.

Conclusion: Leaving the Hospital

We discharge Mr. P after 25 days. He shows no evidence of psychosis, suicidality, or intent to harm others. He continues hydrochlorothiazide and venlafaxine at the same dosages. He returns home with his brother, and 6 months later is functioning well.

Related resources

• National Mental Health Association. Electroconvulsive therapy. www.nmha.org/infoctr/factsheets/ect.cfm.
  

Drug brand names

• Bupropion • Wellbutrin
  
• Disulfiram • Antabuse
  
• Glycopyrrolate • Robinul
  
• Hydrochlorothiazide • Various
  
• Lorazepam • Ativan
  
• Methohexital • Brevital
  
• Mirtazapine • Remeron
  
• Quetiapine • Seroquel
  
• Reserpine • Serpasil
  
• Succinylcholine • Anectine
  
• Venlafaxine XR • Effexor XR
  

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: Suddenly Speechless

Mr. P, age 52, is transferred to our behavioral health unit after 1 month of unsuccessful treatment at a psychiatric hospital. He is mute and disheveled with blunted affect.

Before his hospitalization, Mr. P—who is mildly retarded and has an IQ of 67—lived independently, managed his finances, held two part-time jobs, volunteered as an usher at church, and had a girlfriend. He has been medically stable with diagnoses of indolent stage-zero chronic lymphocytic leukemia (for which he took no medication), moderate obesity, and essential hypertension. For 2 years he has been taking reserpine, 0.25 mg/d, for hypertension, and weighs 200 lb at presentation (body mass index: 29 kg/m²). He has no history of mental illness.

Seven months ago, Mr. P began having trouble dressing and bathing. He also began eating considerably less—about one-third of his normal food intake—and lost 20 lbs over 6 months.

Mr. P also began standing in the street for hours at a time—calling out to passers-by that people were dying and he was causing their deaths—until family members persuaded him to return home. He was not hallucinating, but his brother—who is Mr. P’s legal guardian—said symptoms worsened after a family friend died. After Mr. P became mute, resistant to direction, and immobile, his brother got him admitted to the psychiatric hospital.

The attending physician stopped reserpine—which might cause depression—and started hydrochlorothiazide, 25 mg/d, to maintain normal blood pressure. A psychiatrist diagnosed major depressive disorder and psychosis not otherwise specified, and prescribed mirtazapine, 30 mg nightly, and quetiapine, 25 mg bid. The psychiatrist ruled out lethal catatonia, as vital signs remained stable. When Mr. P’s symptoms did not improve after 1 month, the psychiatrist recommended electroconvulsive therapy (ECT) and transferred him to our facility.

Physical examination and laboratory findings are normal except for lymphocytosis secondary to leukemia:

poll here

The authors’ observations

Mr. P. has major depression with psychotic features. His staring, catalepsy, negativism, selective mutism, and posturing indicate catatonia, and his nihilistic delusions signal Cotard’s syndrome, a delusional depressive disorder.

Catatonia consists of changes in muscle tone and activity and is accompanied by echopraxia and echolalia. Many medical conditions or medications can cause catatonia (Table 1).¹ Resultant immobility and stupor can lead to contractures, pressure ulcers, venous thrombosis, and pulmonary emboli. Refusal to eat or drink can cause malnutrition, dehydration, weight loss, and muscle wasting. Approximately 9% of psychiatric inpatients develop catatonia at some point.²

DSM-IV-TR³ describes catatonia criteria as specifiers in affective illness and requires two or more of the following features for diagnosis:

• catalepsy or stupor
  
• purposeless, excessive motor activity
  
• negativism or mutism
  
• peculiar voluntary behaviors, such as posturing, stereotypy, or mannerisms
  
• echolalia or echopraxia (Table 2).
  

No consensus exists regarding which behaviors are pathognomonic or how long they must persist to meet criteria for catatonia.

Catatonia can occur during an excited or retarded state:

• Excited catatonia—also called delirious mania or an oneiroid state—is marked by a dreamlike sensorium, rapid onset, confabulation, derealization, depersonalization, disorientation, and a mixture of catatonic features.⁴
  
• Retarded catatonia can be diagnosed using DSM-IV-TR criteria for catatonia. In mild cases or early in presentation, symptoms resemble anergy and psychomotor slowing typical of depression.
  

Lethal catatonia—a rare, extreme, potentially life-threatening form—is clinically indistinguishable from neuroleptic malignant syndrome. Its cause is often toxic or iatrogenic.⁵ Hyperthermia, hypertension, tachycardia, fever, tachypnea, leukocytosis, and serum creatine phosphokinase >500 u/L indicate lethal catatonia.

Table 1

Recognized causes of catatonia

Affective disorders and schizophrenia CNS injury or infection (such as encephalitis) Lupus cerebritis Medications (bupropion, disulfiram, fluoroquinolones, neuroleptics, steroids) Metabolic imbalance Porphyria Seizure disorders Substance abuse (cocaine, phencyclidine)

Table 2

Catatonia: Defining clinical characteristics

Term	Definition
Ambitendency	Indecision, hesitance, becoming stuck regarding stimuli
Analgesia to painful stimuli	Failure to feel or withdraw from pain
Catalepsy	Posturing, including facial expressions such as exaggerated lip puckering, with waxy flexibility and automatic obedience
Echolalia	Repeating words and phrases
Echopraxia	Repeating another person’s movements
Excitement	Loquacious confabulation and autonomic instability
Mannerisms	Purposeful eccentric movements, such as saluting
Negativism	Rigidity and resistance to commands
Perseveration	Continuing a response long after it is appropriate
Prosectic speech	Decreased production and volume of speech
Selective mutism	Absence of speech
Stereotypy	Persistently repeating gestures that do not appear goal-directed, such as head-banging, rocking, and twirling objects
Verbigeration	Repeating a word, phrase, or sentence

In Cotard’s syndrome (Table 3), the patient might believe that he and others around him are dead, that his body is putrefying and missing internal organs and blood, or that the world no longer exists.⁶ Some patients also have delusions of negation and damnation.⁷

Cotard’s syndrome, first described in the late 1800s by French neurologist Jules Cotard, can accompany folie à deux⁷ or lycanthropy, the delusional belief that one has been transformed into a werewolf.⁸ In rare cases, patients believe that their bodies are abnormally enlarged.⁷ Cotard’s syndrome can exist alone or as part of a psychiatric illness with nihilistic delusions.⁷

 

poll hereTable 3

Characteristics of Cotard’s syndrome

Delusional belief that one’s body parts, friends, family, money, or the world do not exist Can accompany major depression, schizophrenia, dementia, or a general medical condition Relatively rare, with unknown incidence and prevalence. More common during late middle life and among women Sudden onset with no history of psychiatric disorder Associated with nondominant parietal lobe lesions and catatonia

The authors’ observations

Mr. P.’s episode appears to have been idiopathic.

Reserpine could have caused his decompensation, though precisely how is unclear. The medication is alleged to cause depression by depleting serotonin, dopamine, and norepinephrine, but some researchers believe it exacerbates pre-existing depression.^9,10

When treating any patient with a history of depression, find out if he or she is taking reserpine. Advise the primary care physician to discontinue the drug if the patient is self-deprecating or despondent, or reports early morning insomnia, loss of appetite, or impotence.¹¹

Treatment: False Start

To address Mr. P’s catatonia, we stop quetiapine and mirtazapine and start IM lorazepam, 2 mg qid. After 4 days his condition is stable, but he still believes that he and everyone else is dead.

poll here

The authors’ observations

Parenteral benzodiazepines typically are used to treat patients with catatonia and Cotard’s syndrome while the clinician searches for a toxic or medical cause. Most patients with nonemergent catatonia respond to a benzodiazepine.¹²

Although opinion differs on starting dosages of IM lorazepam in retarded catatonia, we recommend 2 mg IM and repeat doses every 3 hours if the patient does not respond.^4,13 Lack of response after 20 mg (10 doses) warrants ECT.⁴

Consider ECT—which has shown effectiveness for treating both catatonia and Cotard’s syndrome in case reports^6-8,14,15—as first-line treatment in emergent catatonia. Do not try a first- or second-generation neuroleptic, which can worsen clinical outcome.

Treatment: a Three-Week Trial

We receive informed consent from Mr. P’s brother to try 10 ECT treatments over 3 weeks. We choose left anterior right temporal electrode placement to minimize cognitive interference,¹⁶ and give Mr. P glycopyrrolate, 0.2 mg before each treatment, to manage bradycardia resulting from enhanced vagal tone after electrical stimulation. According to ECT protocol, we administer the anesthetic methohexital, 0.75 to 1.0 mg/kg, and the muscle relaxant succinylcholine, 0.5 to 1 mg/kg, to shorten seizure duration during ECT.

Mr. P also receives forced ventilation at each treatment to counteract brief succinylcholine-induced paralysis of the diaphragm and other muscle tissue. Stimulus intensity begins at 35% and is increased to 50% as the patient’s seizure threshold increases. Each morning, Mr. P also receives extended-release venlafaxine, 225 mg, for depressive symptoms, and hydrochlorothiazide, 25 mg.

After the first ECT treatment, Mr. P’s affect starts to brighten. He speaks a few words after the third treatment and begins eating larger portions by the fifth treatment. After the last treatment, he is performing activities of daily living, talking readily and coherently, and playing basketball with peers. He shows no adverse cognitive effects or other complications from ECT.

The authors’ observations

Although little evidence guides treatment of catatonia in the developmentally disabled,¹⁷ we support early use of ECT in those with serious refractory mental illness.¹⁸ Some clinicians hesitate to administer ECT to patients with mental retardation because they might be particularly vulnerable to adverse medication effects.¹⁹ ECT, however, has been found to cause minimal side effects in this population²⁰ and does not cause or exacerbate brain damage.²¹

If the patient is mentally incapable of consenting to ECT, obtain informed consent from his or her legal guardian.

Conclusion: Leaving the Hospital

We discharge Mr. P after 25 days. He shows no evidence of psychosis, suicidality, or intent to harm others. He continues hydrochlorothiazide and venlafaxine at the same dosages. He returns home with his brother, and 6 months later is functioning well.

Related resources

• National Mental Health Association. Electroconvulsive therapy. www.nmha.org/infoctr/factsheets/ect.cfm.
  

Drug brand names

• Bupropion • Wellbutrin
  
• Disulfiram • Antabuse
  
• Glycopyrrolate • Robinul
  
• Hydrochlorothiazide • Various
  
• Lorazepam • Ativan
  
• Methohexital • Brevital
  
• Mirtazapine • Remeron
  
• Quetiapine • Seroquel
  
• Reserpine • Serpasil
  
• Succinylcholine • Anectine
  
• Venlafaxine XR • Effexor XR
  

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘They’re making me crazy’

Ms. D, age 22, is brought to the emergency room by her older brother for psychiatric evaluation after a family argument. He tells us that his sister is out most nights, hanging out at nightclubs. When she’s home, he says, she locks herself in her room and avoids him and his younger brother, who also lives with them.

Recently, her brother says, Ms. D signed a contract to appear in pornographic videos. When he found out, he went to the studio’s producer and nullified the contract.

Ms. D, frustrated with her brother’s interference, tells us she dreams of becoming a movie star and going to college, but blames him for “holding me back” and keeping her unemployed.

Worse, she says, he and her two sisters are impostors who are “trying to hurt me” and are “making me go crazy.” She fears her “false brother” will take her house if she leaves, yet she feels unsafe at home because strangers—envious of “my beauty and intelligence”—peek into her windows and stalk her. She tells us her father is near and guards her—even though he died 4 years ago.

Ms. D, who lost her mother at age 2, began having psychotic episodes at age 19, a few months after her father’s death. At that time, she was hospitalized after insisting that her father had faked his death because of a conspiracy against him. A hospital psychiatrist diagnosed bipolar disorder and prescribed a mood stabilizer, but she did not take the medication and her psychosis has worsened.

Ms. D’s Mini-Mental State Examination score of 30 indicates that she is neither grossly confused nor has underlying dementia. However, she is emotionally labile with grossly disorganized thought processes and paranoid and grandiose delusions.

We could not locate other family members, so Ms. D’s family psychiatric history is unknown. She has casual relationships with men but does not have a boyfriend. She acknowledges that she frequents local nightclubs but denies using alcohol.

Blood work and other medical examination results are normal. Negative urine toxicology screen suggests she not abusing substances, and electrolytes and thyroid-stimulating hormone levels are normal. Negative rapid plasma reagin rules out tertiary syphilis. We do not order radiologic studies because her presentation does not suggest focal abnormality, and neurologic exam results are benign.

poll here

The authors’ observations

Patients with both paranoid delusions and manic features are challenging. Prognoses and treatment options for each group of symptoms differ substantially.

Ms. D’s grandiosity, pressured speech, tangential flight of ideas, and hypersexuality strongly suggest bipolar disorder. We could not rule out schizophrenia, however, because of her prominent hallucinations and paranoia.

Pharmacologic intoxication was not likely based on laboratory results and the longstanding, progressive course of Ms. D’s disorder. Organic pathology also was unlikely, given her normal neurologic examination and lack of other medical issues.

Treatment: Talk therapy

We tentatively diagnose Ms. D as having bipolar disorder type I with a manic episode and psychotic features. She does not meet DSM-IV-TR criteria for schizophrenia and lacks affective flattening, poverty of speech, avolition, and other negative symptoms typical of the disorder. We admit her to the inpatient psychiatric unit and prescribe lithium, 300 mg tid, and quetiapine, 50 mg bid.

An internal medicine (IM) resident visits Ms. D for 30 to 45 minutes daily during her hospitalization to check her medical status and to allow her to vent her frustration. A resident in psychiatry also interviews Ms. D for about one half-hour each day. The patient rarely interacts with other patients and speaks only with physicians and nurses.

Ms. D appears to trust the IM resident and confides in her about her brother. During their first meeting, she appears most disturbed that a man who “claims” to be her brother is sabotaging her life. She does not fear that this “impostor” will physically harm her but still distrusts him. She repeatedly reports that her late father is nearby or in the room above hers. She adds that she feels much safer in the hospital, where the “stalkers” cannot reach her.

At times, Ms. D tells the IM resident she has a twin. Other times, she believes her family is much larger than it is, and she sometimes laments that she is losing her identity. She often perseverates on Judgment Day, at which time she says her “fake” relatives will answer for their actions against her.

Ms. D’s delusions of grandiosity, tangentiality, circumferential speech, and flight of ideas persist through 4 days in the hospital. Her affect is extremely labile and occasionally inappropriate. She sometimes cries when discussing her father’s death, then stops, thinks a moment, and begins laughing. At this point, we increase lithium to 600 mg tid and quetiapine to 100 mg tid. She is suffering no side effects and infrequently requires haloperidol as a demand dose only.

 

poll here

The authors’ observations

A patient such as Ms. D who lives in a minimally supportive environment and has paranoid delusions could fabricate an explanation for what she perceives as family members’ incongruent behavior. She could create a reality in which these relatives are impostors.

Although this behavior is not unusual, Ms. D’s extreme reaction toward her siblings suggests Capgras syndrome, a rare misidentification disorder (Box). The syndrome is often missed in clinical practice, and its prevalence has not been quantified.

Capgras syndrome is seen most often in patients with paranoid schizophrenia—the highest functioning and most preserved schizophrenia patients. This association may indicate that both neurologic dysfunction and psychological background are necessary to produce the syndrome.

The belief that family members are impostors could point to a conspiracy theory or paranoid delusion. Ms. D’s suspicion and distrust toward her older brother indicate a paranoid state, and her other delusions—such as her belief that others are stalking her—suggest that her Capgras symptoms are another manifestation of paranoia.

Box

Capgras’ causes. Capgras delusions can occur secondary to neurologic lesions and often appear to have an organic cause, such as abnormal focal paroxysmal discharges.¹ These delusions can occur secondary to systemic infections, thyroid dysfunction, seizures, concussion, intoxication dementia, toxic encephalopathy, or head trauma.^1,2 Theories vary as to physiologic, structural, and neurologic causes (Table).

For Ms. D, structural brain deficits probably interacted with her psychosocial milieu to create Capgras delusions, though we did not perform confirmatory brain imaging or functional neurologic testing. Whereas right cortical lesions might impair recognition while preserving familiarity, Capgras syndrome preserves recognition but deadens the emotion that makes faces seem familiar. When focal lesions are found to cause Capgras delusion, however, the right hemisphere—specifically the frontal cortex—usually is affected.^2,3

Table

Proposed causes of Capgras syndrome

Physiologic
Frontal lobe damage may distort visual stimuli monitoring, thus impairing facial recognition.4
Disruption of neuronal connections within the right temporal lobe scrambles memories needed for facial recognition.5
Neurologic
Disconnection between brain hemispheres lead to cognitive but not affective recognition.6
Bifrontal pathology or other organic cause blurs “judgment of individuality or uniqueness,” as in prosopagnosia.3
Dorsal pathway impairment alters affective response to faces.7
Dissociation in the amygdala may distort affective response to faces.8
Psychological*
In depression, misidentification develops secondary to rationalizing feelings of guilt and inferiority.9
“Two-armed recognition”—one automatic and almost instantaneous, the other attentive and mnemonic—begins to falter.10
Suspicion, preoccupation with details leads to “agnosia through too great attention.”11
Avoidance of unconscious desires leads to recognition problems.12
Patient “projects and splits” family member into two persons; directs love toward real person and hate toward imagined impostor.13
In schizophrenia, world is viewed through primitive mechanisms, such as doubles and dualism.14
*Dependent on psychiatric comorbidity

poll here

The authors’ observations

When interviewing a patient with paranoid delusions, get as much detail as possible about his or her close relationships. Try to interview one or two family members or friends. The information can help determine whether Capgras symptoms underlie paranoia.

Brain imaging might uncover pertinent abnormalities, but the cost could outweigh any benefit. No evidence supports use of CT to diagnose Capgras syndrome. Some evidence supports use of brain MRI, but more research is needed.

No specific treatment exists for Capgras delusions apart from using antipsychotics to treat the psychosis based on clinical suspicion and constellation of symptoms.

Studies have shown no difference in response to atypical antipsychotics between patients with schizophrenia and comcomitant Capgras symptoms and those with schizophrenia alone. In clinical practice, we have found that treating Capgras symptoms does improve schizophrenia’s course.

Adjunctive psychotherapy has not been studied in Capgras syndrome, and directed, insight-guided therapy might not resolve deeply rooted delusions for some patients. With Ms. D, however, “talk therapy” helped us build rapport and gave us insight into her strained familial relationships. Establishing a therapeutic alliance with the patient and encouraging healthy relationships with his or her family and friends can mitigate the effects of Capgras paranoia.

 

Continued treatment: Gradual change

Day by day Ms. D’s mania subsides gradually, though she still fears that a stranger posing as her brother is stalking her. She talks about her brother less frequently, though she is clearly holding fast to her delusional beliefs.

We discharge Ms. D after 10 days. Although her symptoms have not resolved, she is markedly less manic and less agitated than at admission. We arrange treatment with outpatient psychiatry. She does not follow up with her original psychiatrist and is lost to follow-up.

Related resources

• PsychNet-UK. Disorder information sheet: Capgras (delusion) syndrome. www.psychnet-uk.com/dsm_iv/capgras_syndrome.htm.
  
• Bourget D, Whitehurst L. Capgras syndrome: a review of the neurophysiological correlates and presenting clinical features in cases involving physical violence. Can J Psychiatry 2004;49:719-25. Available at: www.cpa-apc.org/Publications/Archives/CJP/2004/november/bourget.asp.
  
• Barton JJ. Disorders of face perception and recognition. Neurol Clin 2003;21:521-48.
  
• Lewis S. Brain imaging in a case of Capgras’ syndrome. Br J Psychiatry 1987;150:117-21.
  
• Christodoulou GN. The syndrome of Capgras. Br J Psychiatry 1977;130:556-64.
  

Drug brand names

• Haloperidol • Haldol
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘They’re making me crazy’

Ms. D, age 22, is brought to the emergency room by her older brother for psychiatric evaluation after a family argument. He tells us that his sister is out most nights, hanging out at nightclubs. When she’s home, he says, she locks herself in her room and avoids him and his younger brother, who also lives with them.

Recently, her brother says, Ms. D signed a contract to appear in pornographic videos. When he found out, he went to the studio’s producer and nullified the contract.

Ms. D, frustrated with her brother’s interference, tells us she dreams of becoming a movie star and going to college, but blames him for “holding me back” and keeping her unemployed.

Worse, she says, he and her two sisters are impostors who are “trying to hurt me” and are “making me go crazy.” She fears her “false brother” will take her house if she leaves, yet she feels unsafe at home because strangers—envious of “my beauty and intelligence”—peek into her windows and stalk her. She tells us her father is near and guards her—even though he died 4 years ago.

Ms. D, who lost her mother at age 2, began having psychotic episodes at age 19, a few months after her father’s death. At that time, she was hospitalized after insisting that her father had faked his death because of a conspiracy against him. A hospital psychiatrist diagnosed bipolar disorder and prescribed a mood stabilizer, but she did not take the medication and her psychosis has worsened.

Ms. D’s Mini-Mental State Examination score of 30 indicates that she is neither grossly confused nor has underlying dementia. However, she is emotionally labile with grossly disorganized thought processes and paranoid and grandiose delusions.

We could not locate other family members, so Ms. D’s family psychiatric history is unknown. She has casual relationships with men but does not have a boyfriend. She acknowledges that she frequents local nightclubs but denies using alcohol.

Blood work and other medical examination results are normal. Negative urine toxicology screen suggests she not abusing substances, and electrolytes and thyroid-stimulating hormone levels are normal. Negative rapid plasma reagin rules out tertiary syphilis. We do not order radiologic studies because her presentation does not suggest focal abnormality, and neurologic exam results are benign.

poll here

The authors’ observations

Patients with both paranoid delusions and manic features are challenging. Prognoses and treatment options for each group of symptoms differ substantially.

Ms. D’s grandiosity, pressured speech, tangential flight of ideas, and hypersexuality strongly suggest bipolar disorder. We could not rule out schizophrenia, however, because of her prominent hallucinations and paranoia.

Pharmacologic intoxication was not likely based on laboratory results and the longstanding, progressive course of Ms. D’s disorder. Organic pathology also was unlikely, given her normal neurologic examination and lack of other medical issues.

Treatment: Talk therapy

We tentatively diagnose Ms. D as having bipolar disorder type I with a manic episode and psychotic features. She does not meet DSM-IV-TR criteria for schizophrenia and lacks affective flattening, poverty of speech, avolition, and other negative symptoms typical of the disorder. We admit her to the inpatient psychiatric unit and prescribe lithium, 300 mg tid, and quetiapine, 50 mg bid.

An internal medicine (IM) resident visits Ms. D for 30 to 45 minutes daily during her hospitalization to check her medical status and to allow her to vent her frustration. A resident in psychiatry also interviews Ms. D for about one half-hour each day. The patient rarely interacts with other patients and speaks only with physicians and nurses.

Ms. D appears to trust the IM resident and confides in her about her brother. During their first meeting, she appears most disturbed that a man who “claims” to be her brother is sabotaging her life. She does not fear that this “impostor” will physically harm her but still distrusts him. She repeatedly reports that her late father is nearby or in the room above hers. She adds that she feels much safer in the hospital, where the “stalkers” cannot reach her.

At times, Ms. D tells the IM resident she has a twin. Other times, she believes her family is much larger than it is, and she sometimes laments that she is losing her identity. She often perseverates on Judgment Day, at which time she says her “fake” relatives will answer for their actions against her.

Ms. D’s delusions of grandiosity, tangentiality, circumferential speech, and flight of ideas persist through 4 days in the hospital. Her affect is extremely labile and occasionally inappropriate. She sometimes cries when discussing her father’s death, then stops, thinks a moment, and begins laughing. At this point, we increase lithium to 600 mg tid and quetiapine to 100 mg tid. She is suffering no side effects and infrequently requires haloperidol as a demand dose only.

 

poll here

The authors’ observations

A patient such as Ms. D who lives in a minimally supportive environment and has paranoid delusions could fabricate an explanation for what she perceives as family members’ incongruent behavior. She could create a reality in which these relatives are impostors.

Although this behavior is not unusual, Ms. D’s extreme reaction toward her siblings suggests Capgras syndrome, a rare misidentification disorder (Box). The syndrome is often missed in clinical practice, and its prevalence has not been quantified.

Capgras syndrome is seen most often in patients with paranoid schizophrenia—the highest functioning and most preserved schizophrenia patients. This association may indicate that both neurologic dysfunction and psychological background are necessary to produce the syndrome.

The belief that family members are impostors could point to a conspiracy theory or paranoid delusion. Ms. D’s suspicion and distrust toward her older brother indicate a paranoid state, and her other delusions—such as her belief that others are stalking her—suggest that her Capgras symptoms are another manifestation of paranoia.

Box

Capgras’ causes. Capgras delusions can occur secondary to neurologic lesions and often appear to have an organic cause, such as abnormal focal paroxysmal discharges.¹ These delusions can occur secondary to systemic infections, thyroid dysfunction, seizures, concussion, intoxication dementia, toxic encephalopathy, or head trauma.^1,2 Theories vary as to physiologic, structural, and neurologic causes (Table).

For Ms. D, structural brain deficits probably interacted with her psychosocial milieu to create Capgras delusions, though we did not perform confirmatory brain imaging or functional neurologic testing. Whereas right cortical lesions might impair recognition while preserving familiarity, Capgras syndrome preserves recognition but deadens the emotion that makes faces seem familiar. When focal lesions are found to cause Capgras delusion, however, the right hemisphere—specifically the frontal cortex—usually is affected.^2,3

Table

Proposed causes of Capgras syndrome

Physiologic
Frontal lobe damage may distort visual stimuli monitoring, thus impairing facial recognition.4
Disruption of neuronal connections within the right temporal lobe scrambles memories needed for facial recognition.5
Neurologic
Disconnection between brain hemispheres lead to cognitive but not affective recognition.6
Bifrontal pathology or other organic cause blurs “judgment of individuality or uniqueness,” as in prosopagnosia.3
Dorsal pathway impairment alters affective response to faces.7
Dissociation in the amygdala may distort affective response to faces.8
Psychological*
In depression, misidentification develops secondary to rationalizing feelings of guilt and inferiority.9
“Two-armed recognition”—one automatic and almost instantaneous, the other attentive and mnemonic—begins to falter.10
Suspicion, preoccupation with details leads to “agnosia through too great attention.”11
Avoidance of unconscious desires leads to recognition problems.12
Patient “projects and splits” family member into two persons; directs love toward real person and hate toward imagined impostor.13
In schizophrenia, world is viewed through primitive mechanisms, such as doubles and dualism.14
*Dependent on psychiatric comorbidity

poll here

The authors’ observations

When interviewing a patient with paranoid delusions, get as much detail as possible about his or her close relationships. Try to interview one or two family members or friends. The information can help determine whether Capgras symptoms underlie paranoia.

Brain imaging might uncover pertinent abnormalities, but the cost could outweigh any benefit. No evidence supports use of CT to diagnose Capgras syndrome. Some evidence supports use of brain MRI, but more research is needed.

No specific treatment exists for Capgras delusions apart from using antipsychotics to treat the psychosis based on clinical suspicion and constellation of symptoms.

Studies have shown no difference in response to atypical antipsychotics between patients with schizophrenia and comcomitant Capgras symptoms and those with schizophrenia alone. In clinical practice, we have found that treating Capgras symptoms does improve schizophrenia’s course.

Adjunctive psychotherapy has not been studied in Capgras syndrome, and directed, insight-guided therapy might not resolve deeply rooted delusions for some patients. With Ms. D, however, “talk therapy” helped us build rapport and gave us insight into her strained familial relationships. Establishing a therapeutic alliance with the patient and encouraging healthy relationships with his or her family and friends can mitigate the effects of Capgras paranoia.

 

Continued treatment: Gradual change

Day by day Ms. D’s mania subsides gradually, though she still fears that a stranger posing as her brother is stalking her. She talks about her brother less frequently, though she is clearly holding fast to her delusional beliefs.

We discharge Ms. D after 10 days. Although her symptoms have not resolved, she is markedly less manic and less agitated than at admission. We arrange treatment with outpatient psychiatry. She does not follow up with her original psychiatrist and is lost to follow-up.

Related resources

• PsychNet-UK. Disorder information sheet: Capgras (delusion) syndrome. www.psychnet-uk.com/dsm_iv/capgras_syndrome.htm.
  
• Bourget D, Whitehurst L. Capgras syndrome: a review of the neurophysiological correlates and presenting clinical features in cases involving physical violence. Can J Psychiatry 2004;49:719-25. Available at: www.cpa-apc.org/Publications/Archives/CJP/2004/november/bourget.asp.
  
• Barton JJ. Disorders of face perception and recognition. Neurol Clin 2003;21:521-48.
  
• Lewis S. Brain imaging in a case of Capgras’ syndrome. Br J Psychiatry 1987;150:117-21.
  
• Christodoulou GN. The syndrome of Capgras. Br J Psychiatry 1977;130:556-64.
  

Drug brand names

• Haloperidol • Haldol
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘They’re making me crazy’

Ms. D, age 22, is brought to the emergency room by her older brother for psychiatric evaluation after a family argument. He tells us that his sister is out most nights, hanging out at nightclubs. When she’s home, he says, she locks herself in her room and avoids him and his younger brother, who also lives with them.

Recently, her brother says, Ms. D signed a contract to appear in pornographic videos. When he found out, he went to the studio’s producer and nullified the contract.

Ms. D, frustrated with her brother’s interference, tells us she dreams of becoming a movie star and going to college, but blames him for “holding me back” and keeping her unemployed.

Worse, she says, he and her two sisters are impostors who are “trying to hurt me” and are “making me go crazy.” She fears her “false brother” will take her house if she leaves, yet she feels unsafe at home because strangers—envious of “my beauty and intelligence”—peek into her windows and stalk her. She tells us her father is near and guards her—even though he died 4 years ago.

Ms. D, who lost her mother at age 2, began having psychotic episodes at age 19, a few months after her father’s death. At that time, she was hospitalized after insisting that her father had faked his death because of a conspiracy against him. A hospital psychiatrist diagnosed bipolar disorder and prescribed a mood stabilizer, but she did not take the medication and her psychosis has worsened.

Ms. D’s Mini-Mental State Examination score of 30 indicates that she is neither grossly confused nor has underlying dementia. However, she is emotionally labile with grossly disorganized thought processes and paranoid and grandiose delusions.

We could not locate other family members, so Ms. D’s family psychiatric history is unknown. She has casual relationships with men but does not have a boyfriend. She acknowledges that she frequents local nightclubs but denies using alcohol.

Blood work and other medical examination results are normal. Negative urine toxicology screen suggests she not abusing substances, and electrolytes and thyroid-stimulating hormone levels are normal. Negative rapid plasma reagin rules out tertiary syphilis. We do not order radiologic studies because her presentation does not suggest focal abnormality, and neurologic exam results are benign.

poll here

The authors’ observations

Patients with both paranoid delusions and manic features are challenging. Prognoses and treatment options for each group of symptoms differ substantially.

Ms. D’s grandiosity, pressured speech, tangential flight of ideas, and hypersexuality strongly suggest bipolar disorder. We could not rule out schizophrenia, however, because of her prominent hallucinations and paranoia.

Pharmacologic intoxication was not likely based on laboratory results and the longstanding, progressive course of Ms. D’s disorder. Organic pathology also was unlikely, given her normal neurologic examination and lack of other medical issues.

Treatment: Talk therapy

We tentatively diagnose Ms. D as having bipolar disorder type I with a manic episode and psychotic features. She does not meet DSM-IV-TR criteria for schizophrenia and lacks affective flattening, poverty of speech, avolition, and other negative symptoms typical of the disorder. We admit her to the inpatient psychiatric unit and prescribe lithium, 300 mg tid, and quetiapine, 50 mg bid.

An internal medicine (IM) resident visits Ms. D for 30 to 45 minutes daily during her hospitalization to check her medical status and to allow her to vent her frustration. A resident in psychiatry also interviews Ms. D for about one half-hour each day. The patient rarely interacts with other patients and speaks only with physicians and nurses.

Ms. D appears to trust the IM resident and confides in her about her brother. During their first meeting, she appears most disturbed that a man who “claims” to be her brother is sabotaging her life. She does not fear that this “impostor” will physically harm her but still distrusts him. She repeatedly reports that her late father is nearby or in the room above hers. She adds that she feels much safer in the hospital, where the “stalkers” cannot reach her.

At times, Ms. D tells the IM resident she has a twin. Other times, she believes her family is much larger than it is, and she sometimes laments that she is losing her identity. She often perseverates on Judgment Day, at which time she says her “fake” relatives will answer for their actions against her.

Ms. D’s delusions of grandiosity, tangentiality, circumferential speech, and flight of ideas persist through 4 days in the hospital. Her affect is extremely labile and occasionally inappropriate. She sometimes cries when discussing her father’s death, then stops, thinks a moment, and begins laughing. At this point, we increase lithium to 600 mg tid and quetiapine to 100 mg tid. She is suffering no side effects and infrequently requires haloperidol as a demand dose only.

 

poll here

The authors’ observations

A patient such as Ms. D who lives in a minimally supportive environment and has paranoid delusions could fabricate an explanation for what she perceives as family members’ incongruent behavior. She could create a reality in which these relatives are impostors.

Although this behavior is not unusual, Ms. D’s extreme reaction toward her siblings suggests Capgras syndrome, a rare misidentification disorder (Box). The syndrome is often missed in clinical practice, and its prevalence has not been quantified.

Capgras syndrome is seen most often in patients with paranoid schizophrenia—the highest functioning and most preserved schizophrenia patients. This association may indicate that both neurologic dysfunction and psychological background are necessary to produce the syndrome.

The belief that family members are impostors could point to a conspiracy theory or paranoid delusion. Ms. D’s suspicion and distrust toward her older brother indicate a paranoid state, and her other delusions—such as her belief that others are stalking her—suggest that her Capgras symptoms are another manifestation of paranoia.

Box

Capgras’ causes. Capgras delusions can occur secondary to neurologic lesions and often appear to have an organic cause, such as abnormal focal paroxysmal discharges.¹ These delusions can occur secondary to systemic infections, thyroid dysfunction, seizures, concussion, intoxication dementia, toxic encephalopathy, or head trauma.^1,2 Theories vary as to physiologic, structural, and neurologic causes (Table).

For Ms. D, structural brain deficits probably interacted with her psychosocial milieu to create Capgras delusions, though we did not perform confirmatory brain imaging or functional neurologic testing. Whereas right cortical lesions might impair recognition while preserving familiarity, Capgras syndrome preserves recognition but deadens the emotion that makes faces seem familiar. When focal lesions are found to cause Capgras delusion, however, the right hemisphere—specifically the frontal cortex—usually is affected.^2,3

Table

Proposed causes of Capgras syndrome

Physiologic
Frontal lobe damage may distort visual stimuli monitoring, thus impairing facial recognition.4
Disruption of neuronal connections within the right temporal lobe scrambles memories needed for facial recognition.5
Neurologic
Disconnection between brain hemispheres lead to cognitive but not affective recognition.6
Bifrontal pathology or other organic cause blurs “judgment of individuality or uniqueness,” as in prosopagnosia.3
Dorsal pathway impairment alters affective response to faces.7
Dissociation in the amygdala may distort affective response to faces.8
Psychological*
In depression, misidentification develops secondary to rationalizing feelings of guilt and inferiority.9
“Two-armed recognition”—one automatic and almost instantaneous, the other attentive and mnemonic—begins to falter.10
Suspicion, preoccupation with details leads to “agnosia through too great attention.”11
Avoidance of unconscious desires leads to recognition problems.12
Patient “projects and splits” family member into two persons; directs love toward real person and hate toward imagined impostor.13
In schizophrenia, world is viewed through primitive mechanisms, such as doubles and dualism.14
*Dependent on psychiatric comorbidity

poll here

The authors’ observations

When interviewing a patient with paranoid delusions, get as much detail as possible about his or her close relationships. Try to interview one or two family members or friends. The information can help determine whether Capgras symptoms underlie paranoia.

Brain imaging might uncover pertinent abnormalities, but the cost could outweigh any benefit. No evidence supports use of CT to diagnose Capgras syndrome. Some evidence supports use of brain MRI, but more research is needed.

No specific treatment exists for Capgras delusions apart from using antipsychotics to treat the psychosis based on clinical suspicion and constellation of symptoms.

Studies have shown no difference in response to atypical antipsychotics between patients with schizophrenia and comcomitant Capgras symptoms and those with schizophrenia alone. In clinical practice, we have found that treating Capgras symptoms does improve schizophrenia’s course.

Adjunctive psychotherapy has not been studied in Capgras syndrome, and directed, insight-guided therapy might not resolve deeply rooted delusions for some patients. With Ms. D, however, “talk therapy” helped us build rapport and gave us insight into her strained familial relationships. Establishing a therapeutic alliance with the patient and encouraging healthy relationships with his or her family and friends can mitigate the effects of Capgras paranoia.

 

Continued treatment: Gradual change

Day by day Ms. D’s mania subsides gradually, though she still fears that a stranger posing as her brother is stalking her. She talks about her brother less frequently, though she is clearly holding fast to her delusional beliefs.

We discharge Ms. D after 10 days. Although her symptoms have not resolved, she is markedly less manic and less agitated than at admission. We arrange treatment with outpatient psychiatry. She does not follow up with her original psychiatrist and is lost to follow-up.

Related resources

• PsychNet-UK. Disorder information sheet: Capgras (delusion) syndrome. www.psychnet-uk.com/dsm_iv/capgras_syndrome.htm.
  
• Bourget D, Whitehurst L. Capgras syndrome: a review of the neurophysiological correlates and presenting clinical features in cases involving physical violence. Can J Psychiatry 2004;49:719-25. Available at: www.cpa-apc.org/Publications/Archives/CJP/2004/november/bourget.asp.
  
• Barton JJ. Disorders of face perception and recognition. Neurol Clin 2003;21:521-48.
  
• Lewis S. Brain imaging in a case of Capgras’ syndrome. Br J Psychiatry 1987;150:117-21.
  
• Christodoulou GN. The syndrome of Capgras. Br J Psychiatry 1977;130:556-64.
  

Drug brand names

• Haloperidol • Haldol
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Tiberius Claudius Germanicus, age 64 and the third emperor of Rome’s Julio-Claudian dynasty, presents to you and reports, “I have severe stomach cramps. I think my wife is poisoning me, but no one believes me. I need your help.”

Retrospective diagnoses are difficult and sometimes ill-advised, but pondering the psychiatric diagnoses of historical figures can alert us to possible differential diagnoses in today’s patients. Consider this imaginary interview between Claudius and a psychiatrist, which suggests several possible diagnoses.

History: terrible royal childhood

Though born into royalty, Claudius was such a sickly infant that his family was ashamed of him and kept him out of their home. He was raised by servants. As a child, he limped and was ridiculed.

He tells you he received little formal education but had many tutors. He learned several languages and became a distinguished historian, scholar, and writer. He served in the military, both in Rome and overseas. For 13 years he has ruled the Roman Empire but fears he will soon be overthrown.

Claudius’ reign began well. He treated his freedmen advisors well, diligently attended to court proceedings, built an aqueduct, and reorganized the Roman government. Recently, however, he has ruled more eccentrically and harshly. He has ordered capricious and costly public works, such as the futile attempt to drain the 12-mile-long Fucine Lake so that the land could be farmed. He has become fond of gladiatorial games and enjoys ordering the execution of political foes. He drinks several liters of wine daily and gorges himself at imperial banquets.

This patient’s family history is complex (Box) and fraught with antisocial behavior and mental illness. Three previous marriages failed, and he describes his current wife, Agrippina, as powerful and manipulative. She has a son, Nero, from an earlier marriage. Claudius fears being poisoned by Agrippina after she instigates a relationship between Nero and Claudius’ daughter.

Box

Interview: ‘surrounded by enemies’

Claudius is uncooperative during the interview. He is irritable, tends to bark orders, smells of alcohol, stutters severely, and drools. He admits that he is depressed over myriad family problems.

He also believes that he will become a deity when he dies. He reminds you that he has the power to order executions and wonders if he should have Agrippina and her minions killed. He claims to have written 43 books and numerous historical monographs and to be the last person in the world to speak fluent Etruscan, but laments that no one appreciates his scholarly work. He says he is “surrounded by enemies” and rambles on about family intrigue, cabals, and executions.

He is oriented and shows no florid psychotic symptoms or signs of suicidality. His insight and judgment are severely impaired, and he rejects the idea that he might have a psychiatric disorder.

Claudius refuses a physical exam and abruptly terminates the interview after about 20 minutes, saying he must attend to important affairs of state.

Follow-up: claudius’ ‘last supper’

You want to get more information from family members but wonder if it is safe to do so. It becomes moot: Claudius dies one evening at dinner, days after the interview.

poll here

The authors’ observations

Lead poisoning can cause a range of medical and neuropsychological problems, including attention deficits, antisocial behavior, and irritability.^1-4 Romans—particularly the upper class—were exposed to lead from numerous sources:

• Drinking water was contaminated because lead was used extensively to build ancient Rome’s water transportation systems.
  
• Grape juice fermented to become wine was often preserved in lead vessels, which made it sweeter. The elite drank wine more profusely than did lower-class Romans, who probably could not afford wine. Lead-sweetened grape juice was also used in delicacies eaten by the wealthy.
  
• The rich also favored expensive, lead-lined bronze bowls and plates, whereas commoners used cheap earthenware. Thus, ancient Rome’s ruling class was ingesting lead-contaminated drink and food.
  

 

Some scholars, noting the relative sterility of many Roman emperors, have suggested that lead poisoning, which can decrease sperm count and cause miscarriage, may have contributed to the fall of the Roman Empire.⁵

Jerome Nriagu, a geochemist who has studied lead’s toxic effects, attributed many of Claudius’ symptoms and negative traits to lead poisoning: “He had disturbed speech, weak limbs, an ungainly gait, tremors, fits of excessive and inappropriate laughter, and unseemly anger, and he often slobbered…his contracting of plumbism would not be surprising, since he was an intemperate glutton.”⁶ Nriagu also argued that the neuropsychological sequelae of lead poisoning might have clouded the judgment of many Roman emperors.⁶

Yet some scholars, notably Robert Graves,^7,8 have argued that Claudius was highly intelligent and that his copious writing showcased his scholarly interests, hard work, and sound judgment in young adulthood. Based on Graves’ assessment, Claudius probably did not suffer severe plumbism as a child.

Birth injury or cerebral palsy might have caused Claudius’ poor gait and drooling, which were present from childhood. As his drinking and gluttony worsened later in life, alcoholism and lead poisoning could have shortened Claudius’ temper and blurred his judgment, particularly in marrying Agrippina.

Claudius’ belief that he would become a god does not strongly indicate psychosis, because his contemporaries believed that emperors could be deified after death. Opler et al,⁹ however, found that prenatal lead exposure, as suggested by elevated D-aminolevulinic acid, may be a risk factor for schizophrenia and other psychiatric disorders that manifest in late adolescence or adulthood.

Although we know little about Claudius’ medical problems, abdominal pain has a broad differential diagnosis. Poisoning at Agrippina’s hands or alcohol-induced gastritis, as well as lead-induced abdominal colic, could have caused his intolerable pain.

Bipolar disorder. Claudius’ unrestrained spending, irritability, impulsivity, grandiosity, and mood lability suggest bipolar disorder. Hypomania could have fueled his vast literary output, which has been lost. His belief that he would be deified could also be a manic symptom.

Hypomania was prevalent among Claudius’ family. Two close relatives—his nephew Caligula and great-nephew/adopted son Nero—had marked mood swings. These two emperors were more antisocial than Claudius and showed behavior more consistent with frank mania.

Caligula, who preceded Claudius as emperor, was well known for his excessive behaviors. He was vicious and promiscuous, having sex in public with men, wives of others, and his sisters. Most famously, he considered making his horse, Incitatus, a consul. He gave this horse a “marble stable…a house and a household of slaves and furniture.”¹⁰

Nero, who succeeded Claudius, was an alcoholic who frequently indulged his appetites. He believed he was a great singer and became infamous for playing his fiddle while Rome burned. Some of his last words are supposed to have been, “What an artist dies with me!”¹⁰

Alcoholism. Some historians have estimated that two-thirds of Roman emperors who reigned from 30 BC (Augustus) to 220 AD (Elegabalus) drank heavily.⁶ Claudius was reputedly a heavy drinker, and many features displayed by him and his relatives—bad temper, poor judgment, paranoia, impulsivity, violence, and sexual indiscretions—can result from alcohol abuse.

Psychosocial stressors. Claudius was raised and surrounded by malevolent people, then given almost limitless power. That mix of circumstances, plus fear fostered by persistent intrigue, may explain some of his behavior, particularly his brutality.

poll here

The authors’ observations

Had laboratories been available in ancient Rome, a blood test would have determined whether Claudius suffered lead poisoning. Diagnosing bipolar disorder and/or alcoholism is much more difficult. Differentiating these disorders from each other and from other psychiatric disorders is challenging, as no laboratory tests confirm the diagnosis. Ongoing clinical observation of the illness and response to medication are crucial.

In some cases, having the patient list his or her depressive and manic episodes on a “life chart” might clarify the diagnosis. This exercise can also help the patient recognize bipolar symptoms and accept that he or she has the illness, which is critical to ensuring treatment adherence. Also start medication at this time.

Treatment

Treat bipolar disorder and alcoholism simultaneously, as either disorder could worsen the other’s course.^11,12

Lithium or valproate would be probable first-line treatments for Claudius. Discuss the medication’s risks and benefits with the patient and involved family members/caretakers. Inform them that you might have to change or add medication if the patient does not respond or experiences side effects.

Psychotherapy and/or psychoeducation are integral to treating comorbid bipolar disorder and alcoholism. Claudius also could have benefited from:

• education about healthy dieting
  
• counseling against high-risk behaviors associated with alcoholism, such as domestic violence and gambling
  
• a support group for patients with bipolar disorder or a 12-step program.
  

 

What claudius can teach us

Although Claudius’ symptoms cannot be diagnosed with certainty, the information and perspective available today offer insight into his likely psychiatric problems. His case reminds us that:

• Patients often have multiple diagnoses. Bipolar disorder is strongly associated with substance abuse disorder—particularly alcoholism.
  
• Lead-containing alcoholic beverages are still a public health concern. Morgan et al¹³ tested 115 samples of moonshine from nine southeastern, south central, and north central U.S. states. One-third of samples contained lead >300 μg/dL. The authors estimated that excessive consumption of 25% of the samples could lead to blood lead levels consistent with lead poisoning (≥25 μg/dL).
  

Lead poisoning is pernicious and still occurs in the United States. Persons who work with lead, live in an old house painted with a lead-based paint, or drink water transported in old pipes with lead solder are at high risk for lead exposure. Children are particularly vulnerable. Some herbal medications also contain lead.¹⁴

Related resources

• Schwartz BS, Stewart WF, Bolla KO, et al. Past adult lead exposure is associated with longitudinal decline in cognitive function. Neurology 2000;55:1144-50.
  
• Canfield RL, Henderson CR Jr, Cory-Slechta DA, et al. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med 2003;348:1517-26.
  
• Salloum IM, Thase ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disord 2000;2:269-80.
  
• Nriagu JO. Lead and lead poisoning in antiquity. New York: John Wiley and Sons; 1983.
  

Drug brand names

• Lithium • Eskalith, others
  
• Valproate • Depakene
  

Disclosure

Dr. Frankenburg reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Tiberius Claudius Germanicus, age 64 and the third emperor of Rome’s Julio-Claudian dynasty, presents to you and reports, “I have severe stomach cramps. I think my wife is poisoning me, but no one believes me. I need your help.”

Retrospective diagnoses are difficult and sometimes ill-advised, but pondering the psychiatric diagnoses of historical figures can alert us to possible differential diagnoses in today’s patients. Consider this imaginary interview between Claudius and a psychiatrist, which suggests several possible diagnoses.

History: terrible royal childhood

Though born into royalty, Claudius was such a sickly infant that his family was ashamed of him and kept him out of their home. He was raised by servants. As a child, he limped and was ridiculed.

He tells you he received little formal education but had many tutors. He learned several languages and became a distinguished historian, scholar, and writer. He served in the military, both in Rome and overseas. For 13 years he has ruled the Roman Empire but fears he will soon be overthrown.

Claudius’ reign began well. He treated his freedmen advisors well, diligently attended to court proceedings, built an aqueduct, and reorganized the Roman government. Recently, however, he has ruled more eccentrically and harshly. He has ordered capricious and costly public works, such as the futile attempt to drain the 12-mile-long Fucine Lake so that the land could be farmed. He has become fond of gladiatorial games and enjoys ordering the execution of political foes. He drinks several liters of wine daily and gorges himself at imperial banquets.

This patient’s family history is complex (Box) and fraught with antisocial behavior and mental illness. Three previous marriages failed, and he describes his current wife, Agrippina, as powerful and manipulative. She has a son, Nero, from an earlier marriage. Claudius fears being poisoned by Agrippina after she instigates a relationship between Nero and Claudius’ daughter.

Box

Interview: ‘surrounded by enemies’

Claudius is uncooperative during the interview. He is irritable, tends to bark orders, smells of alcohol, stutters severely, and drools. He admits that he is depressed over myriad family problems.

He also believes that he will become a deity when he dies. He reminds you that he has the power to order executions and wonders if he should have Agrippina and her minions killed. He claims to have written 43 books and numerous historical monographs and to be the last person in the world to speak fluent Etruscan, but laments that no one appreciates his scholarly work. He says he is “surrounded by enemies” and rambles on about family intrigue, cabals, and executions.

He is oriented and shows no florid psychotic symptoms or signs of suicidality. His insight and judgment are severely impaired, and he rejects the idea that he might have a psychiatric disorder.

Claudius refuses a physical exam and abruptly terminates the interview after about 20 minutes, saying he must attend to important affairs of state.

Follow-up: claudius’ ‘last supper’

You want to get more information from family members but wonder if it is safe to do so. It becomes moot: Claudius dies one evening at dinner, days after the interview.

poll here

The authors’ observations

Lead poisoning can cause a range of medical and neuropsychological problems, including attention deficits, antisocial behavior, and irritability.^1-4 Romans—particularly the upper class—were exposed to lead from numerous sources:

• Drinking water was contaminated because lead was used extensively to build ancient Rome’s water transportation systems.
  
• Grape juice fermented to become wine was often preserved in lead vessels, which made it sweeter. The elite drank wine more profusely than did lower-class Romans, who probably could not afford wine. Lead-sweetened grape juice was also used in delicacies eaten by the wealthy.
  
• The rich also favored expensive, lead-lined bronze bowls and plates, whereas commoners used cheap earthenware. Thus, ancient Rome’s ruling class was ingesting lead-contaminated drink and food.
  

 

Some scholars, noting the relative sterility of many Roman emperors, have suggested that lead poisoning, which can decrease sperm count and cause miscarriage, may have contributed to the fall of the Roman Empire.⁵

Jerome Nriagu, a geochemist who has studied lead’s toxic effects, attributed many of Claudius’ symptoms and negative traits to lead poisoning: “He had disturbed speech, weak limbs, an ungainly gait, tremors, fits of excessive and inappropriate laughter, and unseemly anger, and he often slobbered…his contracting of plumbism would not be surprising, since he was an intemperate glutton.”⁶ Nriagu also argued that the neuropsychological sequelae of lead poisoning might have clouded the judgment of many Roman emperors.⁶

Yet some scholars, notably Robert Graves,^7,8 have argued that Claudius was highly intelligent and that his copious writing showcased his scholarly interests, hard work, and sound judgment in young adulthood. Based on Graves’ assessment, Claudius probably did not suffer severe plumbism as a child.

Birth injury or cerebral palsy might have caused Claudius’ poor gait and drooling, which were present from childhood. As his drinking and gluttony worsened later in life, alcoholism and lead poisoning could have shortened Claudius’ temper and blurred his judgment, particularly in marrying Agrippina.

Claudius’ belief that he would become a god does not strongly indicate psychosis, because his contemporaries believed that emperors could be deified after death. Opler et al,⁹ however, found that prenatal lead exposure, as suggested by elevated D-aminolevulinic acid, may be a risk factor for schizophrenia and other psychiatric disorders that manifest in late adolescence or adulthood.

Although we know little about Claudius’ medical problems, abdominal pain has a broad differential diagnosis. Poisoning at Agrippina’s hands or alcohol-induced gastritis, as well as lead-induced abdominal colic, could have caused his intolerable pain.

Bipolar disorder. Claudius’ unrestrained spending, irritability, impulsivity, grandiosity, and mood lability suggest bipolar disorder. Hypomania could have fueled his vast literary output, which has been lost. His belief that he would be deified could also be a manic symptom.

Hypomania was prevalent among Claudius’ family. Two close relatives—his nephew Caligula and great-nephew/adopted son Nero—had marked mood swings. These two emperors were more antisocial than Claudius and showed behavior more consistent with frank mania.

Caligula, who preceded Claudius as emperor, was well known for his excessive behaviors. He was vicious and promiscuous, having sex in public with men, wives of others, and his sisters. Most famously, he considered making his horse, Incitatus, a consul. He gave this horse a “marble stable…a house and a household of slaves and furniture.”¹⁰

Nero, who succeeded Claudius, was an alcoholic who frequently indulged his appetites. He believed he was a great singer and became infamous for playing his fiddle while Rome burned. Some of his last words are supposed to have been, “What an artist dies with me!”¹⁰

Alcoholism. Some historians have estimated that two-thirds of Roman emperors who reigned from 30 BC (Augustus) to 220 AD (Elegabalus) drank heavily.⁶ Claudius was reputedly a heavy drinker, and many features displayed by him and his relatives—bad temper, poor judgment, paranoia, impulsivity, violence, and sexual indiscretions—can result from alcohol abuse.

Psychosocial stressors. Claudius was raised and surrounded by malevolent people, then given almost limitless power. That mix of circumstances, plus fear fostered by persistent intrigue, may explain some of his behavior, particularly his brutality.

poll here

The authors’ observations

Had laboratories been available in ancient Rome, a blood test would have determined whether Claudius suffered lead poisoning. Diagnosing bipolar disorder and/or alcoholism is much more difficult. Differentiating these disorders from each other and from other psychiatric disorders is challenging, as no laboratory tests confirm the diagnosis. Ongoing clinical observation of the illness and response to medication are crucial.

In some cases, having the patient list his or her depressive and manic episodes on a “life chart” might clarify the diagnosis. This exercise can also help the patient recognize bipolar symptoms and accept that he or she has the illness, which is critical to ensuring treatment adherence. Also start medication at this time.

Treatment

Treat bipolar disorder and alcoholism simultaneously, as either disorder could worsen the other’s course.^11,12

Lithium or valproate would be probable first-line treatments for Claudius. Discuss the medication’s risks and benefits with the patient and involved family members/caretakers. Inform them that you might have to change or add medication if the patient does not respond or experiences side effects.

Psychotherapy and/or psychoeducation are integral to treating comorbid bipolar disorder and alcoholism. Claudius also could have benefited from:

• education about healthy dieting
  
• counseling against high-risk behaviors associated with alcoholism, such as domestic violence and gambling
  
• a support group for patients with bipolar disorder or a 12-step program.
  

 

What claudius can teach us

Although Claudius’ symptoms cannot be diagnosed with certainty, the information and perspective available today offer insight into his likely psychiatric problems. His case reminds us that:

• Patients often have multiple diagnoses. Bipolar disorder is strongly associated with substance abuse disorder—particularly alcoholism.
  
• Lead-containing alcoholic beverages are still a public health concern. Morgan et al¹³ tested 115 samples of moonshine from nine southeastern, south central, and north central U.S. states. One-third of samples contained lead >300 μg/dL. The authors estimated that excessive consumption of 25% of the samples could lead to blood lead levels consistent with lead poisoning (≥25 μg/dL).
  

Lead poisoning is pernicious and still occurs in the United States. Persons who work with lead, live in an old house painted with a lead-based paint, or drink water transported in old pipes with lead solder are at high risk for lead exposure. Children are particularly vulnerable. Some herbal medications also contain lead.¹⁴

Related resources

• Schwartz BS, Stewart WF, Bolla KO, et al. Past adult lead exposure is associated with longitudinal decline in cognitive function. Neurology 2000;55:1144-50.
  
• Canfield RL, Henderson CR Jr, Cory-Slechta DA, et al. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med 2003;348:1517-26.
  
• Salloum IM, Thase ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disord 2000;2:269-80.
  
• Nriagu JO. Lead and lead poisoning in antiquity. New York: John Wiley and Sons; 1983.
  

Drug brand names

• Lithium • Eskalith, others
  
• Valproate • Depakene
  

Disclosure

Dr. Frankenburg reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Tiberius Claudius Germanicus, age 64 and the third emperor of Rome’s Julio-Claudian dynasty, presents to you and reports, “I have severe stomach cramps. I think my wife is poisoning me, but no one believes me. I need your help.”

Retrospective diagnoses are difficult and sometimes ill-advised, but pondering the psychiatric diagnoses of historical figures can alert us to possible differential diagnoses in today’s patients. Consider this imaginary interview between Claudius and a psychiatrist, which suggests several possible diagnoses.

History: terrible royal childhood

Though born into royalty, Claudius was such a sickly infant that his family was ashamed of him and kept him out of their home. He was raised by servants. As a child, he limped and was ridiculed.

He tells you he received little formal education but had many tutors. He learned several languages and became a distinguished historian, scholar, and writer. He served in the military, both in Rome and overseas. For 13 years he has ruled the Roman Empire but fears he will soon be overthrown.

Claudius’ reign began well. He treated his freedmen advisors well, diligently attended to court proceedings, built an aqueduct, and reorganized the Roman government. Recently, however, he has ruled more eccentrically and harshly. He has ordered capricious and costly public works, such as the futile attempt to drain the 12-mile-long Fucine Lake so that the land could be farmed. He has become fond of gladiatorial games and enjoys ordering the execution of political foes. He drinks several liters of wine daily and gorges himself at imperial banquets.

This patient’s family history is complex (Box) and fraught with antisocial behavior and mental illness. Three previous marriages failed, and he describes his current wife, Agrippina, as powerful and manipulative. She has a son, Nero, from an earlier marriage. Claudius fears being poisoned by Agrippina after she instigates a relationship between Nero and Claudius’ daughter.

Box

Interview: ‘surrounded by enemies’

Claudius is uncooperative during the interview. He is irritable, tends to bark orders, smells of alcohol, stutters severely, and drools. He admits that he is depressed over myriad family problems.

He also believes that he will become a deity when he dies. He reminds you that he has the power to order executions and wonders if he should have Agrippina and her minions killed. He claims to have written 43 books and numerous historical monographs and to be the last person in the world to speak fluent Etruscan, but laments that no one appreciates his scholarly work. He says he is “surrounded by enemies” and rambles on about family intrigue, cabals, and executions.

He is oriented and shows no florid psychotic symptoms or signs of suicidality. His insight and judgment are severely impaired, and he rejects the idea that he might have a psychiatric disorder.

Claudius refuses a physical exam and abruptly terminates the interview after about 20 minutes, saying he must attend to important affairs of state.

Follow-up: claudius’ ‘last supper’

You want to get more information from family members but wonder if it is safe to do so. It becomes moot: Claudius dies one evening at dinner, days after the interview.

poll here

The authors’ observations

Lead poisoning can cause a range of medical and neuropsychological problems, including attention deficits, antisocial behavior, and irritability.^1-4 Romans—particularly the upper class—were exposed to lead from numerous sources:

• Drinking water was contaminated because lead was used extensively to build ancient Rome’s water transportation systems.
  
• Grape juice fermented to become wine was often preserved in lead vessels, which made it sweeter. The elite drank wine more profusely than did lower-class Romans, who probably could not afford wine. Lead-sweetened grape juice was also used in delicacies eaten by the wealthy.
  
• The rich also favored expensive, lead-lined bronze bowls and plates, whereas commoners used cheap earthenware. Thus, ancient Rome’s ruling class was ingesting lead-contaminated drink and food.
  

 

Some scholars, noting the relative sterility of many Roman emperors, have suggested that lead poisoning, which can decrease sperm count and cause miscarriage, may have contributed to the fall of the Roman Empire.⁵

Jerome Nriagu, a geochemist who has studied lead’s toxic effects, attributed many of Claudius’ symptoms and negative traits to lead poisoning: “He had disturbed speech, weak limbs, an ungainly gait, tremors, fits of excessive and inappropriate laughter, and unseemly anger, and he often slobbered…his contracting of plumbism would not be surprising, since he was an intemperate glutton.”⁶ Nriagu also argued that the neuropsychological sequelae of lead poisoning might have clouded the judgment of many Roman emperors.⁶

Yet some scholars, notably Robert Graves,^7,8 have argued that Claudius was highly intelligent and that his copious writing showcased his scholarly interests, hard work, and sound judgment in young adulthood. Based on Graves’ assessment, Claudius probably did not suffer severe plumbism as a child.

Birth injury or cerebral palsy might have caused Claudius’ poor gait and drooling, which were present from childhood. As his drinking and gluttony worsened later in life, alcoholism and lead poisoning could have shortened Claudius’ temper and blurred his judgment, particularly in marrying Agrippina.

Claudius’ belief that he would become a god does not strongly indicate psychosis, because his contemporaries believed that emperors could be deified after death. Opler et al,⁹ however, found that prenatal lead exposure, as suggested by elevated D-aminolevulinic acid, may be a risk factor for schizophrenia and other psychiatric disorders that manifest in late adolescence or adulthood.

Although we know little about Claudius’ medical problems, abdominal pain has a broad differential diagnosis. Poisoning at Agrippina’s hands or alcohol-induced gastritis, as well as lead-induced abdominal colic, could have caused his intolerable pain.

Bipolar disorder. Claudius’ unrestrained spending, irritability, impulsivity, grandiosity, and mood lability suggest bipolar disorder. Hypomania could have fueled his vast literary output, which has been lost. His belief that he would be deified could also be a manic symptom.

Hypomania was prevalent among Claudius’ family. Two close relatives—his nephew Caligula and great-nephew/adopted son Nero—had marked mood swings. These two emperors were more antisocial than Claudius and showed behavior more consistent with frank mania.

Caligula, who preceded Claudius as emperor, was well known for his excessive behaviors. He was vicious and promiscuous, having sex in public with men, wives of others, and his sisters. Most famously, he considered making his horse, Incitatus, a consul. He gave this horse a “marble stable…a house and a household of slaves and furniture.”¹⁰

Nero, who succeeded Claudius, was an alcoholic who frequently indulged his appetites. He believed he was a great singer and became infamous for playing his fiddle while Rome burned. Some of his last words are supposed to have been, “What an artist dies with me!”¹⁰

Alcoholism. Some historians have estimated that two-thirds of Roman emperors who reigned from 30 BC (Augustus) to 220 AD (Elegabalus) drank heavily.⁶ Claudius was reputedly a heavy drinker, and many features displayed by him and his relatives—bad temper, poor judgment, paranoia, impulsivity, violence, and sexual indiscretions—can result from alcohol abuse.

Psychosocial stressors. Claudius was raised and surrounded by malevolent people, then given almost limitless power. That mix of circumstances, plus fear fostered by persistent intrigue, may explain some of his behavior, particularly his brutality.

poll here

The authors’ observations

Had laboratories been available in ancient Rome, a blood test would have determined whether Claudius suffered lead poisoning. Diagnosing bipolar disorder and/or alcoholism is much more difficult. Differentiating these disorders from each other and from other psychiatric disorders is challenging, as no laboratory tests confirm the diagnosis. Ongoing clinical observation of the illness and response to medication are crucial.

In some cases, having the patient list his or her depressive and manic episodes on a “life chart” might clarify the diagnosis. This exercise can also help the patient recognize bipolar symptoms and accept that he or she has the illness, which is critical to ensuring treatment adherence. Also start medication at this time.

Treatment

Treat bipolar disorder and alcoholism simultaneously, as either disorder could worsen the other’s course.^11,12

Lithium or valproate would be probable first-line treatments for Claudius. Discuss the medication’s risks and benefits with the patient and involved family members/caretakers. Inform them that you might have to change or add medication if the patient does not respond or experiences side effects.

Psychotherapy and/or psychoeducation are integral to treating comorbid bipolar disorder and alcoholism. Claudius also could have benefited from:

• education about healthy dieting
  
• counseling against high-risk behaviors associated with alcoholism, such as domestic violence and gambling
  
• a support group for patients with bipolar disorder or a 12-step program.
  

 

What claudius can teach us

Although Claudius’ symptoms cannot be diagnosed with certainty, the information and perspective available today offer insight into his likely psychiatric problems. His case reminds us that:

• Patients often have multiple diagnoses. Bipolar disorder is strongly associated with substance abuse disorder—particularly alcoholism.
  
• Lead-containing alcoholic beverages are still a public health concern. Morgan et al¹³ tested 115 samples of moonshine from nine southeastern, south central, and north central U.S. states. One-third of samples contained lead >300 μg/dL. The authors estimated that excessive consumption of 25% of the samples could lead to blood lead levels consistent with lead poisoning (≥25 μg/dL).
  

Lead poisoning is pernicious and still occurs in the United States. Persons who work with lead, live in an old house painted with a lead-based paint, or drink water transported in old pipes with lead solder are at high risk for lead exposure. Children are particularly vulnerable. Some herbal medications also contain lead.¹⁴

Related resources

• Schwartz BS, Stewart WF, Bolla KO, et al. Past adult lead exposure is associated with longitudinal decline in cognitive function. Neurology 2000;55:1144-50.
  
• Canfield RL, Henderson CR Jr, Cory-Slechta DA, et al. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med 2003;348:1517-26.
  
• Salloum IM, Thase ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disord 2000;2:269-80.
  
• Nriagu JO. Lead and lead poisoning in antiquity. New York: John Wiley and Sons; 1983.
  

Drug brand names

• Lithium • Eskalith, others
  
• Valproate • Depakene
  

Disclosure

Dr. Frankenburg reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘I can’t face myself’

Jimmy, age 12, is referred to us by his pediatrician, who is concerned about his “frequent nighttime accidents.” His parents report that he wets his bed 5 to 6 times weekly and has never stayed consistently dry for more than a few days.

The accidents occur only at night, his parents say. Numerous interventions have failed, including restricting fluids after dinner and awakening the boy overnight to make him go to the bathroom.

Jimmy, a sixth-grader, wonders if he will ever stop wetting his bed. He refuses to go to summer camp or stay overnight at a friend’s house, fearful that other kids will make fun of him after an accident. Asked how “wet nights” are affecting his life, he says, “I can’t face myself in the mirror.”

The authors’ observations

Primary nocturnal enuresis is diagnosed in children age ≥5 who have never gone 6 consecutive months without an overnight accident. Pediatricians generally discover enuresis incidentally during regular checkups and refer to a psychiatrist only if the child has an emotional problem secondary to enuresis or a comorbid psychiatric disorder.

Once identified, enuresis requires a thorough assessment—including its emotional consequences, which for Jimmy are significant. In its practice parameter for treating enuresis, the American Academy of Child and Adolescent Psychiatry (AACAP)¹ suggests that you:

Take an extensive developmental and family history. Find out if the child was toilet trained and started walking, talking, or running at an appropriate age. Delays in reaching developmental milestones can predict enuresis.¹

Also find out if either parent had enuresis during childhood. Enuresis is heritable,² and children often outgrow the problem at the same age as did the parent(s).

Focus on the bedwetting and the child’s reaction to it. Treat enuresis aggressively if it is hurting the child’s performance at school, social or emotional development, or self-esteem, or if the youth appears emotionally withdrawn or distressed.

Interview the child and parents separately, as each often reacts differently to the problem. In some cases, for example, the child’s bedwetting upsets the parents but the child hardly seems to care. Also, children often feel more at ease talking to a doctor alone, and parents can vent frustration without upsetting their child.

While interviewing the child, listen for psychosocial stressors that can lead to enuresis, such as parents’ marital problems, problems at school, recent hospitalization, physical or sexual abuse, or the recent birth of a sibling.

We spend about one half-hour with the child and another half-hour with the parents to thoroughly gauge enuresis’ emotional impact. To engage the child and hold his attention during that half-hour, we offer toys or play a game.

Check for physical causes. According to the AACAP practice parameter for enuresis treatment, you should:

• assess nare patency and voice quality to rule out enlarged adenoids
  
• check the nasal pharynx for enlarged tonsils
  
• palpate the abdomen to check for bladder distention or fecal impaction
  
• examine genitalia for abnormalities
  
• view the back for a sacral dimple or other sign of a vertebral or spinal cord anomaly.
  

Also order a thorough neurologic examination to rule out subtle dysfunction associated with enuresis.¹

Perform a urinalysis and urine culture to rule out urinary tract infection (UTI).

Order urodynamic studies or renal ultrasound if enuresis persists after two unsuccessful treatment trials, the physical examination uncovers positive findings, or the child has had a UTI.

Psychotherapy has a limited role in treating primary enuresis unless you suspect a psychological cause.¹ We offered Jimmy supportive counseling to help alleviate emotional problems caused by bedwetting. He and his parents declined but agreed to reconsider later.

Further history: Toilet trained At 2

Jimmy was toilet trained at age 2 and reached all other age-appropriate developmental milestones, his mother says. Results of urine culture, repeated urinalyses, and neurologic and physical examinations are normal. Neither Jimmy nor his family have a history of UTI, dysuria, urgency, or increased urination frequency.

When Jimmy was age 9, his pediatrician prescribed imipramine, 25 mg/d, to try to stop his bedwetting. He did not respond after 6 months, so his parents stopped giving the drug to him.

A few months later, Jimmy’s parents heard about a “bedwetting alarm” designed to condition children not to urinate while asleep, but the boy and his parents viewed this treatment as “humiliating” and refused to try it. They have not attempted another intervention for 2 years.

poll here

The authors’ observations

Having found no medical or psychological basis for Jimmy’s enuresis (Box), we pondered our next clinical move.

Box

 

Behavioral interventions. Parents commonly try to stop their child’s bedwetting by restricting his or her fluid or caffeine intake, enforcing a reward system, bladder control training, and/or awakening the child overnight to go to the bathroom.

Among behavioral treatments, only the bedwetting alarm has shown effectiveness in clinical trials,^1,3 and it carries the lowest risk of post-treatment relapse.³ Urine moistens a sensor in the bed pad or inside cloth, triggering an alarm that awakens the child when wetting starts. The child gradually awakens earlier in an enuretic episode until the sensation of bladder fullness awakens him.

Many parents/guardians and their children—particularly older youths—consider alarm systems demeaning. We again suggested this treatment to Jimmy and his parents, but they refused.

Medication. Six months of low-dose imipramine, a tricyclic antidepressant often prescribed for enuresis, produced no response. We did not restart imipramine at a higher dosage because of its association with increased arrhythmia risk.

We instead considered desmopressin acetate, a synthetic analog of ADH vasopressin that regulates diurnal variation, which is usually abnormal in children with enuresis. Desmopressin, often used to treat clozapine-induced enuresis in adults, has been associated with successful outcomes in as many as 65% of children in clinical trials.^1,4

Desmopressin, however, can reduce urine production. Water intoxication or hyponatremia is rare but can lead to seizures or coma, and the risk increases with the dosage. Obtain informed consent from the parents before starting this drug. Check electrolytes 2 or 3 days after the first dose, 1 month later, then again every 2 to 3 months. Discontinue at once if serum sodium decreases significantly from baseline or is

Treatment: Meaningless response

We start Jimmy on oral desmopressin, 0.2 mg at bedtime, after discussing its benefits and risks with his parents. We increase the dosage to 0.4 mg after 3 days and to 0.6 mg the following week, as the lower dosages have not worked. Serum electrolytes, gauged before starting desmopressin and again 2 weeks later, are normal. We see Jimmy every 2 weeks to check progress and monitor for side effects.

Soon after the second dosage increase, Jimmy’s accidents gradually decrease to 2 to 3 per week, but no improvement is seen after that.

Two months later, Jimmy is still avoiding sleepovers and has trouble making friends. His parents worry about his increasing frustration, hopelessness, and low self-esteem. We again offer supportive counseling, but the boy refuses.

poll here

The authors’ observations

We were running out of treatment options. Two medication trials failed, and the family still would not try a bedwetting alarm.

Urodynamic testing usually is not ordered unless the child has a history of urge incontinence or UTI. For some treatment-resistant patients, the test can reveal detruser muscle or bladder capacity deficits that might be causing enuresis.

Testing: Below the norm

We refer Jimmy to a urologist for a urodynamic test. Results showed mild detruser muscle instability and slightly low maximum bladder capacity compared with age-predicted norms.

The authors’ observations

Based on this finding, we considered oxybutynin, an anticholinergic agent that increases bladder control by relaxing the smooth muscles. Patients with detruser instability and inadequate bladder capacity have responded well to oxybutynin in clinical trials,^5,6 and combination oxybutynin/desmopressin therapy has been shown effective in treatment-resistant patients.^7-9

Oxybutynin and desmopressin complement each other; reduced urinary output and bladder filling associated with desmopressin can reduce uninhibited bladder contractions, thus enhancing oxybutynin’s action.

Treatment: Happy summer

We continue desmopressin, 0.6 mg nightly, and add extended-release oxybutynin, 2.5 mg/d. We increase oxybutynin to 5 mg/d after 3 days and to 10 mg/d the following week, as Jimmy reported no side effects from the lower dosages.

We see Jimmy 1 week after adding oxybutynin, then again 3 weeks later. He reports no wet nights after 1 month of combination therapy, then wets his bed once over the next 2 months. We continue to see him every 3 to 4 weeks and check his electrolytes every 2 to 3 months. He reports no side effects

 

Five months after starting combination therapy, Jimmy seems much more confident. He has gone 2 months without a bedwetting accident, and his face lights up while discussing the fun he had last week in summer camp. He remains free of side effects, and his parents are thrilled with his progress.

We see Jimmy three more times, once every 2 months. He is staying “dry” but says he wishes to stop his medication because he wants to control his bladder without it.

poll here

The authors’ observations

Medications and behavioral treatments can preserve the child’s self-esteem until he or she outgrows enuresis (Table).

No guidelines address drug regimen duration. Tapering Jimmy’s medications after 7 to 8 months seemed reasonable, but children with enuresis often relapse after stopping treatment. Researchers have recorded relapse rates as high as 60% after stopping imipramine and 80% after stopping desmopressin.^1,4

Taper medications slowly to avoid withdrawal, immediate relapse, and anticholinergic effects. If the child relapses, restart medication at the previous therapeutic dosage(s), then start tapering after the child has been accident-free for 3 months.

Table

Medication strategies for treating enuresis

Medication	Dosage	Risks
Desmopressin acetate (first-line)	Start with 0.2-mg tablet or 1 to 2 10-μg puffs of nasal spray (half in each nostril) in children age >6; increase to 0.6 mg/d or 4 puffs daily after 1 week if necessary Stop after approximately 6 months without an accident	High relapse rate Reduced urine production Water intoxication, hyponatremia are rare but can result in seizures, coma
Oxybutynin (second-line)	2.5 to 5 mg tid (immediate-release) or 15 mg/d (extended-release) Start at 5 mg at bedtime for children age >5; increase to 15 mg/d after 1 to 2 weeks if needed Stop after approximately 6 months without an accident	High relapse rate Anticholinergic effects (dry mouth, facial flushing, drowsiness, decreased GI motility) Few efficacy studies done Mostly used with other medication
Desmopressin with oxybutynin or imipramine; medication plus alarm method (third-line)	Dosages of individual medications as listed	Limited data available Positive results seen in resistant cases, particularly in older children
Imipramine (last option)	1 to 2.5 mg/kg/d Start with 25 mg/d at bedtime; if no response, increase in weekly 25-mg increments to 50 mg/d for children ages 7 to 12 or up to 75 mg/d for children age >12 Stop after approximately 6 months without an accident	High relapse rate after stopping medication Risk of arrhythmias (order ECG when starting medication, 1 month later, then every 6 months) Fatal in overdose (do not prescribe >75 mg/d in enuresis) Associated with suicidal behavior in youths (carries FDA “black box” warning)

Follow-up: Still dry

After discussing the relapse risk with Jimmy’s parents, we withdraw both oxybutynin and desmopressin over 2 months, reducing each dosage 25% every 2 weeks. We see Jimmy every 4 to 6 weeks during the taper period, then for two bimonthly follow-up visits. He reports no adverse effects and has been accident-free for 8 months.

After consulting with his pediatrician and family, we refer Jimmy, now age 13, back to the pediatrician. We have not seen him for more than 1 year.

Related resources

• National Association For Continence. www.nafc.org.
  
• Mayo ME, Burns MW. Urodynamic studies in children who wet. Br J Urol 1990 65;641-5.
  

Drug brand names

• Desmopressin • DDAVP
  
• Imipramine • Tofranil
  
• Oxybutynin • Ditropan
  

Disclosure

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘I can’t face myself’

Jimmy, age 12, is referred to us by his pediatrician, who is concerned about his “frequent nighttime accidents.” His parents report that he wets his bed 5 to 6 times weekly and has never stayed consistently dry for more than a few days.

The accidents occur only at night, his parents say. Numerous interventions have failed, including restricting fluids after dinner and awakening the boy overnight to make him go to the bathroom.

Jimmy, a sixth-grader, wonders if he will ever stop wetting his bed. He refuses to go to summer camp or stay overnight at a friend’s house, fearful that other kids will make fun of him after an accident. Asked how “wet nights” are affecting his life, he says, “I can’t face myself in the mirror.”

The authors’ observations

Primary nocturnal enuresis is diagnosed in children age ≥5 who have never gone 6 consecutive months without an overnight accident. Pediatricians generally discover enuresis incidentally during regular checkups and refer to a psychiatrist only if the child has an emotional problem secondary to enuresis or a comorbid psychiatric disorder.

Once identified, enuresis requires a thorough assessment—including its emotional consequences, which for Jimmy are significant. In its practice parameter for treating enuresis, the American Academy of Child and Adolescent Psychiatry (AACAP)¹ suggests that you:

Take an extensive developmental and family history. Find out if the child was toilet trained and started walking, talking, or running at an appropriate age. Delays in reaching developmental milestones can predict enuresis.¹

Also find out if either parent had enuresis during childhood. Enuresis is heritable,² and children often outgrow the problem at the same age as did the parent(s).

Focus on the bedwetting and the child’s reaction to it. Treat enuresis aggressively if it is hurting the child’s performance at school, social or emotional development, or self-esteem, or if the youth appears emotionally withdrawn or distressed.

Interview the child and parents separately, as each often reacts differently to the problem. In some cases, for example, the child’s bedwetting upsets the parents but the child hardly seems to care. Also, children often feel more at ease talking to a doctor alone, and parents can vent frustration without upsetting their child.

While interviewing the child, listen for psychosocial stressors that can lead to enuresis, such as parents’ marital problems, problems at school, recent hospitalization, physical or sexual abuse, or the recent birth of a sibling.

We spend about one half-hour with the child and another half-hour with the parents to thoroughly gauge enuresis’ emotional impact. To engage the child and hold his attention during that half-hour, we offer toys or play a game.

Check for physical causes. According to the AACAP practice parameter for enuresis treatment, you should:

• assess nare patency and voice quality to rule out enlarged adenoids
  
• check the nasal pharynx for enlarged tonsils
  
• palpate the abdomen to check for bladder distention or fecal impaction
  
• examine genitalia for abnormalities
  
• view the back for a sacral dimple or other sign of a vertebral or spinal cord anomaly.
  

Also order a thorough neurologic examination to rule out subtle dysfunction associated with enuresis.¹

Perform a urinalysis and urine culture to rule out urinary tract infection (UTI).

Order urodynamic studies or renal ultrasound if enuresis persists after two unsuccessful treatment trials, the physical examination uncovers positive findings, or the child has had a UTI.

Psychotherapy has a limited role in treating primary enuresis unless you suspect a psychological cause.¹ We offered Jimmy supportive counseling to help alleviate emotional problems caused by bedwetting. He and his parents declined but agreed to reconsider later.

Further history: Toilet trained At 2

Jimmy was toilet trained at age 2 and reached all other age-appropriate developmental milestones, his mother says. Results of urine culture, repeated urinalyses, and neurologic and physical examinations are normal. Neither Jimmy nor his family have a history of UTI, dysuria, urgency, or increased urination frequency.

When Jimmy was age 9, his pediatrician prescribed imipramine, 25 mg/d, to try to stop his bedwetting. He did not respond after 6 months, so his parents stopped giving the drug to him.

A few months later, Jimmy’s parents heard about a “bedwetting alarm” designed to condition children not to urinate while asleep, but the boy and his parents viewed this treatment as “humiliating” and refused to try it. They have not attempted another intervention for 2 years.

poll here

The authors’ observations

Having found no medical or psychological basis for Jimmy’s enuresis (Box), we pondered our next clinical move.

Box

 

Behavioral interventions. Parents commonly try to stop their child’s bedwetting by restricting his or her fluid or caffeine intake, enforcing a reward system, bladder control training, and/or awakening the child overnight to go to the bathroom.

Among behavioral treatments, only the bedwetting alarm has shown effectiveness in clinical trials,^1,3 and it carries the lowest risk of post-treatment relapse.³ Urine moistens a sensor in the bed pad or inside cloth, triggering an alarm that awakens the child when wetting starts. The child gradually awakens earlier in an enuretic episode until the sensation of bladder fullness awakens him.

Many parents/guardians and their children—particularly older youths—consider alarm systems demeaning. We again suggested this treatment to Jimmy and his parents, but they refused.

Medication. Six months of low-dose imipramine, a tricyclic antidepressant often prescribed for enuresis, produced no response. We did not restart imipramine at a higher dosage because of its association with increased arrhythmia risk.

We instead considered desmopressin acetate, a synthetic analog of ADH vasopressin that regulates diurnal variation, which is usually abnormal in children with enuresis. Desmopressin, often used to treat clozapine-induced enuresis in adults, has been associated with successful outcomes in as many as 65% of children in clinical trials.^1,4

Desmopressin, however, can reduce urine production. Water intoxication or hyponatremia is rare but can lead to seizures or coma, and the risk increases with the dosage. Obtain informed consent from the parents before starting this drug. Check electrolytes 2 or 3 days after the first dose, 1 month later, then again every 2 to 3 months. Discontinue at once if serum sodium decreases significantly from baseline or is

Treatment: Meaningless response

We start Jimmy on oral desmopressin, 0.2 mg at bedtime, after discussing its benefits and risks with his parents. We increase the dosage to 0.4 mg after 3 days and to 0.6 mg the following week, as the lower dosages have not worked. Serum electrolytes, gauged before starting desmopressin and again 2 weeks later, are normal. We see Jimmy every 2 weeks to check progress and monitor for side effects.

Soon after the second dosage increase, Jimmy’s accidents gradually decrease to 2 to 3 per week, but no improvement is seen after that.

Two months later, Jimmy is still avoiding sleepovers and has trouble making friends. His parents worry about his increasing frustration, hopelessness, and low self-esteem. We again offer supportive counseling, but the boy refuses.

poll here

The authors’ observations

We were running out of treatment options. Two medication trials failed, and the family still would not try a bedwetting alarm.

Urodynamic testing usually is not ordered unless the child has a history of urge incontinence or UTI. For some treatment-resistant patients, the test can reveal detruser muscle or bladder capacity deficits that might be causing enuresis.

Testing: Below the norm

We refer Jimmy to a urologist for a urodynamic test. Results showed mild detruser muscle instability and slightly low maximum bladder capacity compared with age-predicted norms.

The authors’ observations

Based on this finding, we considered oxybutynin, an anticholinergic agent that increases bladder control by relaxing the smooth muscles. Patients with detruser instability and inadequate bladder capacity have responded well to oxybutynin in clinical trials,^5,6 and combination oxybutynin/desmopressin therapy has been shown effective in treatment-resistant patients.^7-9

Oxybutynin and desmopressin complement each other; reduced urinary output and bladder filling associated with desmopressin can reduce uninhibited bladder contractions, thus enhancing oxybutynin’s action.

Treatment: Happy summer

We continue desmopressin, 0.6 mg nightly, and add extended-release oxybutynin, 2.5 mg/d. We increase oxybutynin to 5 mg/d after 3 days and to 10 mg/d the following week, as Jimmy reported no side effects from the lower dosages.

We see Jimmy 1 week after adding oxybutynin, then again 3 weeks later. He reports no wet nights after 1 month of combination therapy, then wets his bed once over the next 2 months. We continue to see him every 3 to 4 weeks and check his electrolytes every 2 to 3 months. He reports no side effects

 

Five months after starting combination therapy, Jimmy seems much more confident. He has gone 2 months without a bedwetting accident, and his face lights up while discussing the fun he had last week in summer camp. He remains free of side effects, and his parents are thrilled with his progress.

We see Jimmy three more times, once every 2 months. He is staying “dry” but says he wishes to stop his medication because he wants to control his bladder without it.

poll here

The authors’ observations

Medications and behavioral treatments can preserve the child’s self-esteem until he or she outgrows enuresis (Table).

No guidelines address drug regimen duration. Tapering Jimmy’s medications after 7 to 8 months seemed reasonable, but children with enuresis often relapse after stopping treatment. Researchers have recorded relapse rates as high as 60% after stopping imipramine and 80% after stopping desmopressin.^1,4

Taper medications slowly to avoid withdrawal, immediate relapse, and anticholinergic effects. If the child relapses, restart medication at the previous therapeutic dosage(s), then start tapering after the child has been accident-free for 3 months.

Table

Medication strategies for treating enuresis

Medication	Dosage	Risks
Desmopressin acetate (first-line)	Start with 0.2-mg tablet or 1 to 2 10-μg puffs of nasal spray (half in each nostril) in children age >6; increase to 0.6 mg/d or 4 puffs daily after 1 week if necessary Stop after approximately 6 months without an accident	High relapse rate Reduced urine production Water intoxication, hyponatremia are rare but can result in seizures, coma
Oxybutynin (second-line)	2.5 to 5 mg tid (immediate-release) or 15 mg/d (extended-release) Start at 5 mg at bedtime for children age >5; increase to 15 mg/d after 1 to 2 weeks if needed Stop after approximately 6 months without an accident	High relapse rate Anticholinergic effects (dry mouth, facial flushing, drowsiness, decreased GI motility) Few efficacy studies done Mostly used with other medication
Desmopressin with oxybutynin or imipramine; medication plus alarm method (third-line)	Dosages of individual medications as listed	Limited data available Positive results seen in resistant cases, particularly in older children
Imipramine (last option)	1 to 2.5 mg/kg/d Start with 25 mg/d at bedtime; if no response, increase in weekly 25-mg increments to 50 mg/d for children ages 7 to 12 or up to 75 mg/d for children age >12 Stop after approximately 6 months without an accident	High relapse rate after stopping medication Risk of arrhythmias (order ECG when starting medication, 1 month later, then every 6 months) Fatal in overdose (do not prescribe >75 mg/d in enuresis) Associated with suicidal behavior in youths (carries FDA “black box” warning)

Follow-up: Still dry

After discussing the relapse risk with Jimmy’s parents, we withdraw both oxybutynin and desmopressin over 2 months, reducing each dosage 25% every 2 weeks. We see Jimmy every 4 to 6 weeks during the taper period, then for two bimonthly follow-up visits. He reports no adverse effects and has been accident-free for 8 months.

After consulting with his pediatrician and family, we refer Jimmy, now age 13, back to the pediatrician. We have not seen him for more than 1 year.

Related resources

• National Association For Continence. www.nafc.org.
  
• Mayo ME, Burns MW. Urodynamic studies in children who wet. Br J Urol 1990 65;641-5.
  

Drug brand names

• Desmopressin • DDAVP
  
• Imipramine • Tofranil
  
• Oxybutynin • Ditropan
  

Disclosure

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘I can’t face myself’

Jimmy, age 12, is referred to us by his pediatrician, who is concerned about his “frequent nighttime accidents.” His parents report that he wets his bed 5 to 6 times weekly and has never stayed consistently dry for more than a few days.

The accidents occur only at night, his parents say. Numerous interventions have failed, including restricting fluids after dinner and awakening the boy overnight to make him go to the bathroom.

Jimmy, a sixth-grader, wonders if he will ever stop wetting his bed. He refuses to go to summer camp or stay overnight at a friend’s house, fearful that other kids will make fun of him after an accident. Asked how “wet nights” are affecting his life, he says, “I can’t face myself in the mirror.”

The authors’ observations

Primary nocturnal enuresis is diagnosed in children age ≥5 who have never gone 6 consecutive months without an overnight accident. Pediatricians generally discover enuresis incidentally during regular checkups and refer to a psychiatrist only if the child has an emotional problem secondary to enuresis or a comorbid psychiatric disorder.

Once identified, enuresis requires a thorough assessment—including its emotional consequences, which for Jimmy are significant. In its practice parameter for treating enuresis, the American Academy of Child and Adolescent Psychiatry (AACAP)¹ suggests that you:

Take an extensive developmental and family history. Find out if the child was toilet trained and started walking, talking, or running at an appropriate age. Delays in reaching developmental milestones can predict enuresis.¹

Also find out if either parent had enuresis during childhood. Enuresis is heritable,² and children often outgrow the problem at the same age as did the parent(s).

Focus on the bedwetting and the child’s reaction to it. Treat enuresis aggressively if it is hurting the child’s performance at school, social or emotional development, or self-esteem, or if the youth appears emotionally withdrawn or distressed.

Interview the child and parents separately, as each often reacts differently to the problem. In some cases, for example, the child’s bedwetting upsets the parents but the child hardly seems to care. Also, children often feel more at ease talking to a doctor alone, and parents can vent frustration without upsetting their child.

While interviewing the child, listen for psychosocial stressors that can lead to enuresis, such as parents’ marital problems, problems at school, recent hospitalization, physical or sexual abuse, or the recent birth of a sibling.

We spend about one half-hour with the child and another half-hour with the parents to thoroughly gauge enuresis’ emotional impact. To engage the child and hold his attention during that half-hour, we offer toys or play a game.

Check for physical causes. According to the AACAP practice parameter for enuresis treatment, you should:

• assess nare patency and voice quality to rule out enlarged adenoids
  
• check the nasal pharynx for enlarged tonsils
  
• palpate the abdomen to check for bladder distention or fecal impaction
  
• examine genitalia for abnormalities
  
• view the back for a sacral dimple or other sign of a vertebral or spinal cord anomaly.
  

Also order a thorough neurologic examination to rule out subtle dysfunction associated with enuresis.¹

Perform a urinalysis and urine culture to rule out urinary tract infection (UTI).

Order urodynamic studies or renal ultrasound if enuresis persists after two unsuccessful treatment trials, the physical examination uncovers positive findings, or the child has had a UTI.

Psychotherapy has a limited role in treating primary enuresis unless you suspect a psychological cause.¹ We offered Jimmy supportive counseling to help alleviate emotional problems caused by bedwetting. He and his parents declined but agreed to reconsider later.

Further history: Toilet trained At 2

Jimmy was toilet trained at age 2 and reached all other age-appropriate developmental milestones, his mother says. Results of urine culture, repeated urinalyses, and neurologic and physical examinations are normal. Neither Jimmy nor his family have a history of UTI, dysuria, urgency, or increased urination frequency.

When Jimmy was age 9, his pediatrician prescribed imipramine, 25 mg/d, to try to stop his bedwetting. He did not respond after 6 months, so his parents stopped giving the drug to him.

A few months later, Jimmy’s parents heard about a “bedwetting alarm” designed to condition children not to urinate while asleep, but the boy and his parents viewed this treatment as “humiliating” and refused to try it. They have not attempted another intervention for 2 years.

poll here

The authors’ observations

Having found no medical or psychological basis for Jimmy’s enuresis (Box), we pondered our next clinical move.

Box

 

Behavioral interventions. Parents commonly try to stop their child’s bedwetting by restricting his or her fluid or caffeine intake, enforcing a reward system, bladder control training, and/or awakening the child overnight to go to the bathroom.

Among behavioral treatments, only the bedwetting alarm has shown effectiveness in clinical trials,^1,3 and it carries the lowest risk of post-treatment relapse.³ Urine moistens a sensor in the bed pad or inside cloth, triggering an alarm that awakens the child when wetting starts. The child gradually awakens earlier in an enuretic episode until the sensation of bladder fullness awakens him.

Many parents/guardians and their children—particularly older youths—consider alarm systems demeaning. We again suggested this treatment to Jimmy and his parents, but they refused.

Medication. Six months of low-dose imipramine, a tricyclic antidepressant often prescribed for enuresis, produced no response. We did not restart imipramine at a higher dosage because of its association with increased arrhythmia risk.

We instead considered desmopressin acetate, a synthetic analog of ADH vasopressin that regulates diurnal variation, which is usually abnormal in children with enuresis. Desmopressin, often used to treat clozapine-induced enuresis in adults, has been associated with successful outcomes in as many as 65% of children in clinical trials.^1,4

Desmopressin, however, can reduce urine production. Water intoxication or hyponatremia is rare but can lead to seizures or coma, and the risk increases with the dosage. Obtain informed consent from the parents before starting this drug. Check electrolytes 2 or 3 days after the first dose, 1 month later, then again every 2 to 3 months. Discontinue at once if serum sodium decreases significantly from baseline or is

Treatment: Meaningless response

We start Jimmy on oral desmopressin, 0.2 mg at bedtime, after discussing its benefits and risks with his parents. We increase the dosage to 0.4 mg after 3 days and to 0.6 mg the following week, as the lower dosages have not worked. Serum electrolytes, gauged before starting desmopressin and again 2 weeks later, are normal. We see Jimmy every 2 weeks to check progress and monitor for side effects.

Soon after the second dosage increase, Jimmy’s accidents gradually decrease to 2 to 3 per week, but no improvement is seen after that.

Two months later, Jimmy is still avoiding sleepovers and has trouble making friends. His parents worry about his increasing frustration, hopelessness, and low self-esteem. We again offer supportive counseling, but the boy refuses.

poll here

The authors’ observations

We were running out of treatment options. Two medication trials failed, and the family still would not try a bedwetting alarm.

Urodynamic testing usually is not ordered unless the child has a history of urge incontinence or UTI. For some treatment-resistant patients, the test can reveal detruser muscle or bladder capacity deficits that might be causing enuresis.

Testing: Below the norm

We refer Jimmy to a urologist for a urodynamic test. Results showed mild detruser muscle instability and slightly low maximum bladder capacity compared with age-predicted norms.

The authors’ observations

Based on this finding, we considered oxybutynin, an anticholinergic agent that increases bladder control by relaxing the smooth muscles. Patients with detruser instability and inadequate bladder capacity have responded well to oxybutynin in clinical trials,^5,6 and combination oxybutynin/desmopressin therapy has been shown effective in treatment-resistant patients.^7-9

Oxybutynin and desmopressin complement each other; reduced urinary output and bladder filling associated with desmopressin can reduce uninhibited bladder contractions, thus enhancing oxybutynin’s action.

Treatment: Happy summer

We continue desmopressin, 0.6 mg nightly, and add extended-release oxybutynin, 2.5 mg/d. We increase oxybutynin to 5 mg/d after 3 days and to 10 mg/d the following week, as Jimmy reported no side effects from the lower dosages.

We see Jimmy 1 week after adding oxybutynin, then again 3 weeks later. He reports no wet nights after 1 month of combination therapy, then wets his bed once over the next 2 months. We continue to see him every 3 to 4 weeks and check his electrolytes every 2 to 3 months. He reports no side effects

 

Five months after starting combination therapy, Jimmy seems much more confident. He has gone 2 months without a bedwetting accident, and his face lights up while discussing the fun he had last week in summer camp. He remains free of side effects, and his parents are thrilled with his progress.

We see Jimmy three more times, once every 2 months. He is staying “dry” but says he wishes to stop his medication because he wants to control his bladder without it.

poll here

The authors’ observations

Medications and behavioral treatments can preserve the child’s self-esteem until he or she outgrows enuresis (Table).

No guidelines address drug regimen duration. Tapering Jimmy’s medications after 7 to 8 months seemed reasonable, but children with enuresis often relapse after stopping treatment. Researchers have recorded relapse rates as high as 60% after stopping imipramine and 80% after stopping desmopressin.^1,4

Taper medications slowly to avoid withdrawal, immediate relapse, and anticholinergic effects. If the child relapses, restart medication at the previous therapeutic dosage(s), then start tapering after the child has been accident-free for 3 months.

Table

Medication strategies for treating enuresis

Medication	Dosage	Risks
Desmopressin acetate (first-line)	Start with 0.2-mg tablet or 1 to 2 10-μg puffs of nasal spray (half in each nostril) in children age >6; increase to 0.6 mg/d or 4 puffs daily after 1 week if necessary Stop after approximately 6 months without an accident	High relapse rate Reduced urine production Water intoxication, hyponatremia are rare but can result in seizures, coma
Oxybutynin (second-line)	2.5 to 5 mg tid (immediate-release) or 15 mg/d (extended-release) Start at 5 mg at bedtime for children age >5; increase to 15 mg/d after 1 to 2 weeks if needed Stop after approximately 6 months without an accident	High relapse rate Anticholinergic effects (dry mouth, facial flushing, drowsiness, decreased GI motility) Few efficacy studies done Mostly used with other medication
Desmopressin with oxybutynin or imipramine; medication plus alarm method (third-line)	Dosages of individual medications as listed	Limited data available Positive results seen in resistant cases, particularly in older children
Imipramine (last option)	1 to 2.5 mg/kg/d Start with 25 mg/d at bedtime; if no response, increase in weekly 25-mg increments to 50 mg/d for children ages 7 to 12 or up to 75 mg/d for children age >12 Stop after approximately 6 months without an accident	High relapse rate after stopping medication Risk of arrhythmias (order ECG when starting medication, 1 month later, then every 6 months) Fatal in overdose (do not prescribe >75 mg/d in enuresis) Associated with suicidal behavior in youths (carries FDA “black box” warning)

Follow-up: Still dry

After discussing the relapse risk with Jimmy’s parents, we withdraw both oxybutynin and desmopressin over 2 months, reducing each dosage 25% every 2 weeks. We see Jimmy every 4 to 6 weeks during the taper period, then for two bimonthly follow-up visits. He reports no adverse effects and has been accident-free for 8 months.

After consulting with his pediatrician and family, we refer Jimmy, now age 13, back to the pediatrician. We have not seen him for more than 1 year.

Related resources

• National Association For Continence. www.nafc.org.
  
• Mayo ME, Burns MW. Urodynamic studies in children who wet. Br J Urol 1990 65;641-5.
  

Drug brand names

• Desmopressin • DDAVP
  
• Imipramine • Tofranil
  
• Oxybutynin • Ditropan
  

Disclosure

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: 3 ‘Uncontrollable’ months

Ms. M, age 57, presents to the ER complaining of coordination problems and involuntary limb movements that have gradually worsened over 3 months.

Two months ago, Ms. M’s primary care physician and neurologist diagnosed her with conversion disorder. Brain MRI at the time showed mild chronic ischemic changes; cervical spinal cord MRI was normal. The neurologist referred Ms. M to a psychiatrist, who prescribed duloxetine, dosage unknown. She started having suicidal thoughts and trembling after starting the medication, so she stopped taking it after 1 week.

Physical exam shows upbeat nystagmus, inconsistent sensory findings, limb ataxia that is more pronounced on the right side, and uncontrollable limb movements, particularly of the right arm.

Ms. M is divorced, lives alone, and works as a medical secretary. Four months ago, she marked the fifth anniversary of her daughter’s death from a drug overdose at age 20. Her parents, whom she cared for, died within the last 3 years. Her son recently left home to attend graduate school, and she is estranged from the rest of her family. She endorses depressed mood and grief over her daughter’s death but says she has no one with whom to talk. She also feels persistent guilt, as she was out on a date when her daughter tried to call home shortly before her death.

The limb movements and lack of coordination are increasingly interfering with Ms. M’s life. She often uses her left hand to stop the right from moving and to guide it in simple tasks, such as opening doors. She can no longer hold a cup of coffee in her right hand or stand on stools at work to reach overhead shelves. At presentation, Ms. M’s imbalance and involuntary movements are so severe that she cannot walk. A coworker drove her to the ER.

poll here

The authors’ observations

A neurologist who evaluates Ms. M in the ER is concerned about her vertical nystagmus, which, unlike horizontal nystagmus, is almost always pathologic. The neurology service admits her for further evaluation.

Ms. M’s age, recent normal MRIs, physical presentation, and lack of other findings suggest a paraneoplastic syndrome. Ataxia associated with subacute cerebellar degeneration can indicate an occult malignancy and is closely linked to gynecologic and breast cancers. Cerebellar degeneration often begins with loss of coordination, can be unilateral, and can appear as intention myoclonus.¹

Also considered are:

• opsoclonus-myoclonus, which presents with ataxia, myoclonus, and random chaotic eye movements. This paraneoplastic disorder is less common in adults than in children, however.¹
  
• alien hand/limb syndrome, in which the limb unintentionally performs seemingly purposeful movements, often prompting the patient to restrain the limb with the other hand. This syndrome, however, usually localizes to a lesion in the medial frontal lobe or corpus callosum. Ms. M’s brain MRIs show no such lesion.
  

The psychiatry consult/liaison (C/L) service is asked to assist with Ms. M’s care because of her prior conversion disorder diagnosis and her ongoing grief, depression, and anxiety.

poll here

Treatment: Searching for answers

We order an extensive neurologic workup for Ms. M, focusing on causes of inherited and acquired ataxias. The evaluation includes:

• brain and cervical spine MRIs to check for focal cerebral and spinal lesions
  
• EEG to search for seizure activity and slowing characteristic of encephalopathies
  
• urine heavy metal testing for toxic processes
  
• thyroid-stimulating hormone testing for hypothyroid-associated ataxia.
  

We also measure serum copper and ceruloplasmin to rule out Wilson’s disease, pyruvic acid and lactic acid to check for a mitochondrial disorder, vitamin E and gamma tocopherol to rule out ataxia with vitamin E deficiency and Bassen-Kornzweig syndrome (abetalipoproteinemia), and endomysial/gliadin antibodies to evaluate for gluten ataxia.

Paraneoplastic workup includes chest, pelvic, and abdominal CT; a gynecologic exam; and a mammogram. All results are negative or equivocal.

We also order blood tests for paraneoplastic antibodies, evidence of opsoclonus/myoclonus, and spinocerebellar ataxia genetic testing; and a CSF check for protein 14-3-3 levels suggestive of prion disease. These tests, run at specialized laboratories, take 4 to 6 weeks.

Ms. M remains hospitalized for 7 days for evaluation. Her movement problems persist, though they often abate when she is distracted. Her upbeat nystagmus appears intermittent. Her affect is diverse, often shifting between tearfulness and inappropriate laughter.

Based on interviews with Ms. M, the C/L team sees prominent depressive symptoms including marked difficulty sleeping, appetite loss, and excessive guilt over her daughter’s death. She also seems indifferent towards her disabling motor symptoms.

The C/L team diagnoses Ms. M with chronic and acute adjustment disorder and major depressive disorder. She is initially hesitant to take another antidepressant but agrees to try mirtazapine, 15 mg nightly, to treat her depression, decreased appetite, and sleep problems. After 2 days, mirtazapine is increased to 30 mg nightly as she is tolerating it and is willing to try a higher dosage.

 

poll here

The authors’ observations

No neurologic or pathologic explanation is found for Ms. M’s symptoms. Imaging reveals no lesions to explain her intermittent upbeat nystagmus, which localizes to the pons and caudal medulla.²

Conversion disorder. Ms. M, however, appears to meet DSM-IV-TR criteria for conversion disorder (Box), which is thought to result from intense psychological distress in persons who can only express such emotions somatically. Her complaints had specific precursors: she was newly separated from her son and had marked the anniversary of her daughter’s death, which intensified her persistent mourning. We link both circumstances temporally to symptom onset. Also, lack of interest in her serious motor symptoms could be the “la belle indifference” typical of conversion disorder.

Ms. M, however, appears highly suggestible. Her physical symptoms improve soon after her attending psychiatrist suggests that treating her depression will decrease her movements. The neurologists also notice day-to-day fluctuations in her gait disturbance and jerking movements. Distraction techniques produce objective improvement in both symptoms.

Box

Is Ms. M faking her symptoms? Mental disorders and medical field employment both increase the risk of factitious disorder.³ In caring for her parents, Ms. M often felt unappreciated and may be trying to enter the sick role that they had filled.

In malingering, the patient seeks external incentives for feigned behavior. The role of secondary gain must be considered, as Ms. M’s illness has reunited her with her son, who visits her regularly at the hospital.

Ms. M’s evaluation, however, uncovers no evidence that she is intentionally producing symptoms.

Follow-up: The answer becomes clear

One month after discharge to inpatient rehabilitation, Ms. M is readmitted to the neurology unit. Her uncontrollable limb jerks and ataxia are worse, and she appears demented and near mute. At that time, we learn that the CSF sample sent during her first admission is positive for protein 14-3-3.

Ms. M is diagnosed with Creutzfeldt-Jakob disease (CJD), a spongiform encephalopathy secondary to prion disease. She dies 6 days later. Sporadic CJD is confirmed at autopsy.

The authors’ observations

The literature lists no comprehensive differential diagnosis for conversion disorder, probably because presentations are diverse and the symptoms overlap with innumerable neurologic and medical conditions. This is underscored by the broad differential diagnosis for Ms. M’s ataxia.

In a study to identify organic syndromes initially diagnosed as conversion disorder,⁴ 10 of 85 patients (11.8%) were initially misdiagnosed and later found to have dyskinesia, amyotrophic lateral sclerosis, multiple system atrophy, extrapyramidal syndrome, multiple sclerosis, dementia, Parkinson’s disease with psychogenic aggravation, lung cancer with cerebral metastases, and radicular syndrome. CJD and conversion disorder also share many symptoms (Table).

Correct diagnosis of conversion disorder calls for ruling out neurologic and medical conditions. Ms. M’s upbeat nystagmus prompted aggressive neurologic evaluation. Although horizontal nystagmus has been reported rarely in conversion disorder,⁵ vertical nystagmus has not. One case report⁶ describes vertical nystagmus as the first clinical sign of CJD.

Leading clinical symptoms of CJD include progressive dementia, myoclonus, cerebellar ataxia, visual problems, and extrapyramidal signs.⁷ Ms. M’s uncontrollable movements and jerks, although not classically myoclonic, were similar to this common finding. She did not present with dementia, but her rapidly progressive end-stage mental status changes were characteristic of CJD.

Sporadic CJD accounts for 84% of transmissible spongiform encephalopathies. Genetic, iatrogenic, and variant CJD forms (linked to bovine spongiform encephalopathy, or “mad-cow disease”) account for other cases.⁸ Psychiatric symptoms are a more-common manifestation of variant CJD⁹ but have been reported in sporadic CJD.¹⁰

 

Eventually, Ms. M’s upbeat nystagmus, persistent abnormal movements, rapidly progressive dementia, and elevated CSF protein 14-3-3 made the CJD diagnosis. Protein 14-3-3 is 94% sensitive and 84% specific for diagnosing CJD.¹¹ Ms. M’s EEG findings did not suggest CJD, but these findings are less sensitive and occur later than the CSF findings.¹¹

Finally, conversion disorder is almost always acute, not slowly progressive as with Ms. M.

Table

Conversion disorder, sporadic Creutzfeldt-Jakob disease share many symptoms

Complaint	Conversion disorder	Sporadic CJD
Paralysis	May not follow motor pathways	No
Myoclonus	Yes	Cardinal manifestation
Ataxia	May be bizarre in character	Present in 25% to 30% of patients, reflecting multiple disease subtypes
Hyperreflexia	No	Yes (40% to 80% of patients)
Dysphagia	Yes	No
Vomiting	Yes	No
Aphonia	Yes	No
Diplopia	Yes	Rare
Nystagmus	Rare	Yes
Blindness	Hysterical blindness detectable by ophthalmologic examination	Rare
Deafness	Yes	Rare
Anesthesia	Yes	No
Paresthesia	Yes	No
Depression	Yes	Yes
Other psychiatry diagnoses	Yes	More common in variant CJD
Progressive dementia	No	Cardinal manifestation
Temporal relationship with stress	Yes	No
Left-side symptoms more common	Yes	No

Getting the diagnosis right

DSM-IV-TR criteria state that conversion disorder symptoms cannot be otherwise explained “after appropriate investigation,” but what constitutes “appropriate” is unclear. Extensive inpatient evaluation eventually produced the correct diagnosis for Ms. M, but such a detailed evaluation may be too expensive and expansive for every patient with conversion disorder symptoms.

In the conversion disorder study,⁴ the 10 misdiagnosed patients received one to eight supplemental diagnostic techniques before being correctly diagnosed. In five of the patients, however, the general neurologic examination was identified as the diagnostic technique responsible for final diagnosis.

These findings suggest that a neurologic examination is key to evaluating complaints that suggest conversion disorder and to identify neurologic conditions. The results can also suggest somatic disorders, as exam findings will reflect patients’ perceptions of neurologic processes. For example:

• patients with conversion motor symptoms may have tonic contractures of antagonistic muscles to “paralyze” certain joints
  
• those with conversion sensory symptoms rarely have sensory impairments that follow known innervation patterns.
  

When exam results suggest a neurologic process rather than conversion disorder, the workup must target the abnormal findings. Determine the need for evaluation on a case-by-case basis.

Motor complaints, such as localized paralysis or abnormal movements, should be evaluated with a brain MRI to look for lesions along the motor or cerebellar tracts. Sensory pathways can be further investigated with brain MRI and the relevant evoked potential(s) (visual, brainstem, or somatosensory).

Order EEG for patients with convulsions, particularly prolonged EEG monitoring with a video component, and measure serum prolactin immediately after an episode. In some cases, the neurologic exam alone or in conjunction with these initial studies can make the diagnosis. If the clinical situation warrants, more-detailed evaluations may be necessary.

Related resources

• Wise MG, Rundell JR. Clinical manual of psychosomatic medicine: a guide to consultation-liaison psychiatry. Arlington, VA: American Psychiatric Publishing; 2005.
  
• National Institute of Neurological Disorders and Stroke. Creutzfeldt-Jakob disease fact sheet. www.ninds.nih.gov/disorders/cjd/detail_cjd.htm.
  

Drug brand names

• Duloxetine • Cymbalta
  
• Mirtazapine • Remeron
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: 3 ‘Uncontrollable’ months

Ms. M, age 57, presents to the ER complaining of coordination problems and involuntary limb movements that have gradually worsened over 3 months.

Two months ago, Ms. M’s primary care physician and neurologist diagnosed her with conversion disorder. Brain MRI at the time showed mild chronic ischemic changes; cervical spinal cord MRI was normal. The neurologist referred Ms. M to a psychiatrist, who prescribed duloxetine, dosage unknown. She started having suicidal thoughts and trembling after starting the medication, so she stopped taking it after 1 week.

Physical exam shows upbeat nystagmus, inconsistent sensory findings, limb ataxia that is more pronounced on the right side, and uncontrollable limb movements, particularly of the right arm.

Ms. M is divorced, lives alone, and works as a medical secretary. Four months ago, she marked the fifth anniversary of her daughter’s death from a drug overdose at age 20. Her parents, whom she cared for, died within the last 3 years. Her son recently left home to attend graduate school, and she is estranged from the rest of her family. She endorses depressed mood and grief over her daughter’s death but says she has no one with whom to talk. She also feels persistent guilt, as she was out on a date when her daughter tried to call home shortly before her death.

The limb movements and lack of coordination are increasingly interfering with Ms. M’s life. She often uses her left hand to stop the right from moving and to guide it in simple tasks, such as opening doors. She can no longer hold a cup of coffee in her right hand or stand on stools at work to reach overhead shelves. At presentation, Ms. M’s imbalance and involuntary movements are so severe that she cannot walk. A coworker drove her to the ER.

poll here

The authors’ observations

A neurologist who evaluates Ms. M in the ER is concerned about her vertical nystagmus, which, unlike horizontal nystagmus, is almost always pathologic. The neurology service admits her for further evaluation.

Ms. M’s age, recent normal MRIs, physical presentation, and lack of other findings suggest a paraneoplastic syndrome. Ataxia associated with subacute cerebellar degeneration can indicate an occult malignancy and is closely linked to gynecologic and breast cancers. Cerebellar degeneration often begins with loss of coordination, can be unilateral, and can appear as intention myoclonus.¹

Also considered are:

• opsoclonus-myoclonus, which presents with ataxia, myoclonus, and random chaotic eye movements. This paraneoplastic disorder is less common in adults than in children, however.¹
  
• alien hand/limb syndrome, in which the limb unintentionally performs seemingly purposeful movements, often prompting the patient to restrain the limb with the other hand. This syndrome, however, usually localizes to a lesion in the medial frontal lobe or corpus callosum. Ms. M’s brain MRIs show no such lesion.
  

The psychiatry consult/liaison (C/L) service is asked to assist with Ms. M’s care because of her prior conversion disorder diagnosis and her ongoing grief, depression, and anxiety.

poll here

Treatment: Searching for answers

We order an extensive neurologic workup for Ms. M, focusing on causes of inherited and acquired ataxias. The evaluation includes:

• brain and cervical spine MRIs to check for focal cerebral and spinal lesions
  
• EEG to search for seizure activity and slowing characteristic of encephalopathies
  
• urine heavy metal testing for toxic processes
  
• thyroid-stimulating hormone testing for hypothyroid-associated ataxia.
  

We also measure serum copper and ceruloplasmin to rule out Wilson’s disease, pyruvic acid and lactic acid to check for a mitochondrial disorder, vitamin E and gamma tocopherol to rule out ataxia with vitamin E deficiency and Bassen-Kornzweig syndrome (abetalipoproteinemia), and endomysial/gliadin antibodies to evaluate for gluten ataxia.

Paraneoplastic workup includes chest, pelvic, and abdominal CT; a gynecologic exam; and a mammogram. All results are negative or equivocal.

We also order blood tests for paraneoplastic antibodies, evidence of opsoclonus/myoclonus, and spinocerebellar ataxia genetic testing; and a CSF check for protein 14-3-3 levels suggestive of prion disease. These tests, run at specialized laboratories, take 4 to 6 weeks.

Ms. M remains hospitalized for 7 days for evaluation. Her movement problems persist, though they often abate when she is distracted. Her upbeat nystagmus appears intermittent. Her affect is diverse, often shifting between tearfulness and inappropriate laughter.

Based on interviews with Ms. M, the C/L team sees prominent depressive symptoms including marked difficulty sleeping, appetite loss, and excessive guilt over her daughter’s death. She also seems indifferent towards her disabling motor symptoms.

The C/L team diagnoses Ms. M with chronic and acute adjustment disorder and major depressive disorder. She is initially hesitant to take another antidepressant but agrees to try mirtazapine, 15 mg nightly, to treat her depression, decreased appetite, and sleep problems. After 2 days, mirtazapine is increased to 30 mg nightly as she is tolerating it and is willing to try a higher dosage.

 

poll here

The authors’ observations

No neurologic or pathologic explanation is found for Ms. M’s symptoms. Imaging reveals no lesions to explain her intermittent upbeat nystagmus, which localizes to the pons and caudal medulla.²

Conversion disorder. Ms. M, however, appears to meet DSM-IV-TR criteria for conversion disorder (Box), which is thought to result from intense psychological distress in persons who can only express such emotions somatically. Her complaints had specific precursors: she was newly separated from her son and had marked the anniversary of her daughter’s death, which intensified her persistent mourning. We link both circumstances temporally to symptom onset. Also, lack of interest in her serious motor symptoms could be the “la belle indifference” typical of conversion disorder.

Ms. M, however, appears highly suggestible. Her physical symptoms improve soon after her attending psychiatrist suggests that treating her depression will decrease her movements. The neurologists also notice day-to-day fluctuations in her gait disturbance and jerking movements. Distraction techniques produce objective improvement in both symptoms.

Box

Is Ms. M faking her symptoms? Mental disorders and medical field employment both increase the risk of factitious disorder.³ In caring for her parents, Ms. M often felt unappreciated and may be trying to enter the sick role that they had filled.

In malingering, the patient seeks external incentives for feigned behavior. The role of secondary gain must be considered, as Ms. M’s illness has reunited her with her son, who visits her regularly at the hospital.

Ms. M’s evaluation, however, uncovers no evidence that she is intentionally producing symptoms.

Follow-up: The answer becomes clear

One month after discharge to inpatient rehabilitation, Ms. M is readmitted to the neurology unit. Her uncontrollable limb jerks and ataxia are worse, and she appears demented and near mute. At that time, we learn that the CSF sample sent during her first admission is positive for protein 14-3-3.

Ms. M is diagnosed with Creutzfeldt-Jakob disease (CJD), a spongiform encephalopathy secondary to prion disease. She dies 6 days later. Sporadic CJD is confirmed at autopsy.

The authors’ observations

The literature lists no comprehensive differential diagnosis for conversion disorder, probably because presentations are diverse and the symptoms overlap with innumerable neurologic and medical conditions. This is underscored by the broad differential diagnosis for Ms. M’s ataxia.

In a study to identify organic syndromes initially diagnosed as conversion disorder,⁴ 10 of 85 patients (11.8%) were initially misdiagnosed and later found to have dyskinesia, amyotrophic lateral sclerosis, multiple system atrophy, extrapyramidal syndrome, multiple sclerosis, dementia, Parkinson’s disease with psychogenic aggravation, lung cancer with cerebral metastases, and radicular syndrome. CJD and conversion disorder also share many symptoms (Table).

Correct diagnosis of conversion disorder calls for ruling out neurologic and medical conditions. Ms. M’s upbeat nystagmus prompted aggressive neurologic evaluation. Although horizontal nystagmus has been reported rarely in conversion disorder,⁵ vertical nystagmus has not. One case report⁶ describes vertical nystagmus as the first clinical sign of CJD.

Leading clinical symptoms of CJD include progressive dementia, myoclonus, cerebellar ataxia, visual problems, and extrapyramidal signs.⁷ Ms. M’s uncontrollable movements and jerks, although not classically myoclonic, were similar to this common finding. She did not present with dementia, but her rapidly progressive end-stage mental status changes were characteristic of CJD.

Sporadic CJD accounts for 84% of transmissible spongiform encephalopathies. Genetic, iatrogenic, and variant CJD forms (linked to bovine spongiform encephalopathy, or “mad-cow disease”) account for other cases.⁸ Psychiatric symptoms are a more-common manifestation of variant CJD⁹ but have been reported in sporadic CJD.¹⁰

 

Eventually, Ms. M’s upbeat nystagmus, persistent abnormal movements, rapidly progressive dementia, and elevated CSF protein 14-3-3 made the CJD diagnosis. Protein 14-3-3 is 94% sensitive and 84% specific for diagnosing CJD.¹¹ Ms. M’s EEG findings did not suggest CJD, but these findings are less sensitive and occur later than the CSF findings.¹¹

Finally, conversion disorder is almost always acute, not slowly progressive as with Ms. M.

Table

Conversion disorder, sporadic Creutzfeldt-Jakob disease share many symptoms

Complaint	Conversion disorder	Sporadic CJD
Paralysis	May not follow motor pathways	No
Myoclonus	Yes	Cardinal manifestation
Ataxia	May be bizarre in character	Present in 25% to 30% of patients, reflecting multiple disease subtypes
Hyperreflexia	No	Yes (40% to 80% of patients)
Dysphagia	Yes	No
Vomiting	Yes	No
Aphonia	Yes	No
Diplopia	Yes	Rare
Nystagmus	Rare	Yes
Blindness	Hysterical blindness detectable by ophthalmologic examination	Rare
Deafness	Yes	Rare
Anesthesia	Yes	No
Paresthesia	Yes	No
Depression	Yes	Yes
Other psychiatry diagnoses	Yes	More common in variant CJD
Progressive dementia	No	Cardinal manifestation
Temporal relationship with stress	Yes	No
Left-side symptoms more common	Yes	No

Getting the diagnosis right

DSM-IV-TR criteria state that conversion disorder symptoms cannot be otherwise explained “after appropriate investigation,” but what constitutes “appropriate” is unclear. Extensive inpatient evaluation eventually produced the correct diagnosis for Ms. M, but such a detailed evaluation may be too expensive and expansive for every patient with conversion disorder symptoms.

In the conversion disorder study,⁴ the 10 misdiagnosed patients received one to eight supplemental diagnostic techniques before being correctly diagnosed. In five of the patients, however, the general neurologic examination was identified as the diagnostic technique responsible for final diagnosis.

These findings suggest that a neurologic examination is key to evaluating complaints that suggest conversion disorder and to identify neurologic conditions. The results can also suggest somatic disorders, as exam findings will reflect patients’ perceptions of neurologic processes. For example:

• patients with conversion motor symptoms may have tonic contractures of antagonistic muscles to “paralyze” certain joints
  
• those with conversion sensory symptoms rarely have sensory impairments that follow known innervation patterns.
  

When exam results suggest a neurologic process rather than conversion disorder, the workup must target the abnormal findings. Determine the need for evaluation on a case-by-case basis.

Motor complaints, such as localized paralysis or abnormal movements, should be evaluated with a brain MRI to look for lesions along the motor or cerebellar tracts. Sensory pathways can be further investigated with brain MRI and the relevant evoked potential(s) (visual, brainstem, or somatosensory).

Order EEG for patients with convulsions, particularly prolonged EEG monitoring with a video component, and measure serum prolactin immediately after an episode. In some cases, the neurologic exam alone or in conjunction with these initial studies can make the diagnosis. If the clinical situation warrants, more-detailed evaluations may be necessary.

Related resources

• Wise MG, Rundell JR. Clinical manual of psychosomatic medicine: a guide to consultation-liaison psychiatry. Arlington, VA: American Psychiatric Publishing; 2005.
  
• National Institute of Neurological Disorders and Stroke. Creutzfeldt-Jakob disease fact sheet. www.ninds.nih.gov/disorders/cjd/detail_cjd.htm.
  

Drug brand names

• Duloxetine • Cymbalta
  
• Mirtazapine • Remeron
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: 3 ‘Uncontrollable’ months

Ms. M, age 57, presents to the ER complaining of coordination problems and involuntary limb movements that have gradually worsened over 3 months.

Two months ago, Ms. M’s primary care physician and neurologist diagnosed her with conversion disorder. Brain MRI at the time showed mild chronic ischemic changes; cervical spinal cord MRI was normal. The neurologist referred Ms. M to a psychiatrist, who prescribed duloxetine, dosage unknown. She started having suicidal thoughts and trembling after starting the medication, so she stopped taking it after 1 week.

Physical exam shows upbeat nystagmus, inconsistent sensory findings, limb ataxia that is more pronounced on the right side, and uncontrollable limb movements, particularly of the right arm.

Ms. M is divorced, lives alone, and works as a medical secretary. Four months ago, she marked the fifth anniversary of her daughter’s death from a drug overdose at age 20. Her parents, whom she cared for, died within the last 3 years. Her son recently left home to attend graduate school, and she is estranged from the rest of her family. She endorses depressed mood and grief over her daughter’s death but says she has no one with whom to talk. She also feels persistent guilt, as she was out on a date when her daughter tried to call home shortly before her death.

The limb movements and lack of coordination are increasingly interfering with Ms. M’s life. She often uses her left hand to stop the right from moving and to guide it in simple tasks, such as opening doors. She can no longer hold a cup of coffee in her right hand or stand on stools at work to reach overhead shelves. At presentation, Ms. M’s imbalance and involuntary movements are so severe that she cannot walk. A coworker drove her to the ER.

poll here

The authors’ observations

A neurologist who evaluates Ms. M in the ER is concerned about her vertical nystagmus, which, unlike horizontal nystagmus, is almost always pathologic. The neurology service admits her for further evaluation.

Ms. M’s age, recent normal MRIs, physical presentation, and lack of other findings suggest a paraneoplastic syndrome. Ataxia associated with subacute cerebellar degeneration can indicate an occult malignancy and is closely linked to gynecologic and breast cancers. Cerebellar degeneration often begins with loss of coordination, can be unilateral, and can appear as intention myoclonus.¹

Also considered are:

• opsoclonus-myoclonus, which presents with ataxia, myoclonus, and random chaotic eye movements. This paraneoplastic disorder is less common in adults than in children, however.¹
  
• alien hand/limb syndrome, in which the limb unintentionally performs seemingly purposeful movements, often prompting the patient to restrain the limb with the other hand. This syndrome, however, usually localizes to a lesion in the medial frontal lobe or corpus callosum. Ms. M’s brain MRIs show no such lesion.
  

The psychiatry consult/liaison (C/L) service is asked to assist with Ms. M’s care because of her prior conversion disorder diagnosis and her ongoing grief, depression, and anxiety.

poll here

Treatment: Searching for answers

We order an extensive neurologic workup for Ms. M, focusing on causes of inherited and acquired ataxias. The evaluation includes:

• brain and cervical spine MRIs to check for focal cerebral and spinal lesions
  
• EEG to search for seizure activity and slowing characteristic of encephalopathies
  
• urine heavy metal testing for toxic processes
  
• thyroid-stimulating hormone testing for hypothyroid-associated ataxia.
  

We also measure serum copper and ceruloplasmin to rule out Wilson’s disease, pyruvic acid and lactic acid to check for a mitochondrial disorder, vitamin E and gamma tocopherol to rule out ataxia with vitamin E deficiency and Bassen-Kornzweig syndrome (abetalipoproteinemia), and endomysial/gliadin antibodies to evaluate for gluten ataxia.

Paraneoplastic workup includes chest, pelvic, and abdominal CT; a gynecologic exam; and a mammogram. All results are negative or equivocal.

We also order blood tests for paraneoplastic antibodies, evidence of opsoclonus/myoclonus, and spinocerebellar ataxia genetic testing; and a CSF check for protein 14-3-3 levels suggestive of prion disease. These tests, run at specialized laboratories, take 4 to 6 weeks.

Ms. M remains hospitalized for 7 days for evaluation. Her movement problems persist, though they often abate when she is distracted. Her upbeat nystagmus appears intermittent. Her affect is diverse, often shifting between tearfulness and inappropriate laughter.

Based on interviews with Ms. M, the C/L team sees prominent depressive symptoms including marked difficulty sleeping, appetite loss, and excessive guilt over her daughter’s death. She also seems indifferent towards her disabling motor symptoms.

The C/L team diagnoses Ms. M with chronic and acute adjustment disorder and major depressive disorder. She is initially hesitant to take another antidepressant but agrees to try mirtazapine, 15 mg nightly, to treat her depression, decreased appetite, and sleep problems. After 2 days, mirtazapine is increased to 30 mg nightly as she is tolerating it and is willing to try a higher dosage.

 

poll here

The authors’ observations

No neurologic or pathologic explanation is found for Ms. M’s symptoms. Imaging reveals no lesions to explain her intermittent upbeat nystagmus, which localizes to the pons and caudal medulla.²

Conversion disorder. Ms. M, however, appears to meet DSM-IV-TR criteria for conversion disorder (Box), which is thought to result from intense psychological distress in persons who can only express such emotions somatically. Her complaints had specific precursors: she was newly separated from her son and had marked the anniversary of her daughter’s death, which intensified her persistent mourning. We link both circumstances temporally to symptom onset. Also, lack of interest in her serious motor symptoms could be the “la belle indifference” typical of conversion disorder.

Ms. M, however, appears highly suggestible. Her physical symptoms improve soon after her attending psychiatrist suggests that treating her depression will decrease her movements. The neurologists also notice day-to-day fluctuations in her gait disturbance and jerking movements. Distraction techniques produce objective improvement in both symptoms.

Box

Is Ms. M faking her symptoms? Mental disorders and medical field employment both increase the risk of factitious disorder.³ In caring for her parents, Ms. M often felt unappreciated and may be trying to enter the sick role that they had filled.

In malingering, the patient seeks external incentives for feigned behavior. The role of secondary gain must be considered, as Ms. M’s illness has reunited her with her son, who visits her regularly at the hospital.

Ms. M’s evaluation, however, uncovers no evidence that she is intentionally producing symptoms.

Follow-up: The answer becomes clear

One month after discharge to inpatient rehabilitation, Ms. M is readmitted to the neurology unit. Her uncontrollable limb jerks and ataxia are worse, and she appears demented and near mute. At that time, we learn that the CSF sample sent during her first admission is positive for protein 14-3-3.

Ms. M is diagnosed with Creutzfeldt-Jakob disease (CJD), a spongiform encephalopathy secondary to prion disease. She dies 6 days later. Sporadic CJD is confirmed at autopsy.

The authors’ observations

The literature lists no comprehensive differential diagnosis for conversion disorder, probably because presentations are diverse and the symptoms overlap with innumerable neurologic and medical conditions. This is underscored by the broad differential diagnosis for Ms. M’s ataxia.

In a study to identify organic syndromes initially diagnosed as conversion disorder,⁴ 10 of 85 patients (11.8%) were initially misdiagnosed and later found to have dyskinesia, amyotrophic lateral sclerosis, multiple system atrophy, extrapyramidal syndrome, multiple sclerosis, dementia, Parkinson’s disease with psychogenic aggravation, lung cancer with cerebral metastases, and radicular syndrome. CJD and conversion disorder also share many symptoms (Table).

Correct diagnosis of conversion disorder calls for ruling out neurologic and medical conditions. Ms. M’s upbeat nystagmus prompted aggressive neurologic evaluation. Although horizontal nystagmus has been reported rarely in conversion disorder,⁵ vertical nystagmus has not. One case report⁶ describes vertical nystagmus as the first clinical sign of CJD.

Leading clinical symptoms of CJD include progressive dementia, myoclonus, cerebellar ataxia, visual problems, and extrapyramidal signs.⁷ Ms. M’s uncontrollable movements and jerks, although not classically myoclonic, were similar to this common finding. She did not present with dementia, but her rapidly progressive end-stage mental status changes were characteristic of CJD.

Sporadic CJD accounts for 84% of transmissible spongiform encephalopathies. Genetic, iatrogenic, and variant CJD forms (linked to bovine spongiform encephalopathy, or “mad-cow disease”) account for other cases.⁸ Psychiatric symptoms are a more-common manifestation of variant CJD⁹ but have been reported in sporadic CJD.¹⁰

 

Eventually, Ms. M’s upbeat nystagmus, persistent abnormal movements, rapidly progressive dementia, and elevated CSF protein 14-3-3 made the CJD diagnosis. Protein 14-3-3 is 94% sensitive and 84% specific for diagnosing CJD.¹¹ Ms. M’s EEG findings did not suggest CJD, but these findings are less sensitive and occur later than the CSF findings.¹¹

Finally, conversion disorder is almost always acute, not slowly progressive as with Ms. M.

Table

Conversion disorder, sporadic Creutzfeldt-Jakob disease share many symptoms

Complaint	Conversion disorder	Sporadic CJD
Paralysis	May not follow motor pathways	No
Myoclonus	Yes	Cardinal manifestation
Ataxia	May be bizarre in character	Present in 25% to 30% of patients, reflecting multiple disease subtypes
Hyperreflexia	No	Yes (40% to 80% of patients)
Dysphagia	Yes	No
Vomiting	Yes	No
Aphonia	Yes	No
Diplopia	Yes	Rare
Nystagmus	Rare	Yes
Blindness	Hysterical blindness detectable by ophthalmologic examination	Rare
Deafness	Yes	Rare
Anesthesia	Yes	No
Paresthesia	Yes	No
Depression	Yes	Yes
Other psychiatry diagnoses	Yes	More common in variant CJD
Progressive dementia	No	Cardinal manifestation
Temporal relationship with stress	Yes	No
Left-side symptoms more common	Yes	No

Getting the diagnosis right

DSM-IV-TR criteria state that conversion disorder symptoms cannot be otherwise explained “after appropriate investigation,” but what constitutes “appropriate” is unclear. Extensive inpatient evaluation eventually produced the correct diagnosis for Ms. M, but such a detailed evaluation may be too expensive and expansive for every patient with conversion disorder symptoms.

In the conversion disorder study,⁴ the 10 misdiagnosed patients received one to eight supplemental diagnostic techniques before being correctly diagnosed. In five of the patients, however, the general neurologic examination was identified as the diagnostic technique responsible for final diagnosis.

These findings suggest that a neurologic examination is key to evaluating complaints that suggest conversion disorder and to identify neurologic conditions. The results can also suggest somatic disorders, as exam findings will reflect patients’ perceptions of neurologic processes. For example:

• patients with conversion motor symptoms may have tonic contractures of antagonistic muscles to “paralyze” certain joints
  
• those with conversion sensory symptoms rarely have sensory impairments that follow known innervation patterns.
  

When exam results suggest a neurologic process rather than conversion disorder, the workup must target the abnormal findings. Determine the need for evaluation on a case-by-case basis.

Motor complaints, such as localized paralysis or abnormal movements, should be evaluated with a brain MRI to look for lesions along the motor or cerebellar tracts. Sensory pathways can be further investigated with brain MRI and the relevant evoked potential(s) (visual, brainstem, or somatosensory).

Order EEG for patients with convulsions, particularly prolonged EEG monitoring with a video component, and measure serum prolactin immediately after an episode. In some cases, the neurologic exam alone or in conjunction with these initial studies can make the diagnosis. If the clinical situation warrants, more-detailed evaluations may be necessary.

Related resources

• Wise MG, Rundell JR. Clinical manual of psychosomatic medicine: a guide to consultation-liaison psychiatry. Arlington, VA: American Psychiatric Publishing; 2005.
  
• National Institute of Neurological Disorders and Stroke. Creutzfeldt-Jakob disease fact sheet. www.ninds.nih.gov/disorders/cjd/detail_cjd.htm.
  

Drug brand names

• Duloxetine • Cymbalta
  
• Mirtazapine • Remeron
  

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: From sociable to sullen

Julie, a Hispanic/Native American, was adopted by a Caucasian couple when she was 6 weeks old. Before age 12, she had no psychiatric problems and was medically healthy though slightly overweight.

At age 12, Julie started having episodes of brooding depression, verbal and physical aggression, and impulsive suicidal behavior. She also began suffering intermittent migraines and having trouble falling asleep. She insisted on sleeping with her parents or with a nightlight in her room.

Once a sociable girl who enjoyed being in the middle school chorus and band, Julie suddenly became sullen and defiant. She dropped out of afterschool activities and stopped socializing with peers except for her best friend, Sheila, age 12, and Mark, age 13, an “almost boyfriend” who lived next door.

Julie also started arguing with her mother, often yelling and screaming when approached with minor requests. Sometimes, Julie hit and pushed her. A psychiatrist diagnosed the 12-year-old with major depressive disorder and prescribed fluoxetine, dosage unknown.

Soon after Julie’s symptoms surfaced, her adoptive father, a sales representative, was laid off. He found work in another state; the family left an ethnically diverse city for a predominantly Caucasian rural area. There, Julie completed middle school and her freshman year of high school, and lost contact with Sheila and Mark.

Midway through her freshman year, Julie tried to induce vomiting after eating so that she would lose weight and “fit in better with the other girls.” She stopped this at the end of the school year.

The following fall, 5 weeks into her sophomore year, she dropped out of high school and was ultimately enrolled in home school.

Treatment: 4 hospitalizations in 3 years

Between ages 12 and 15, Julie was hospitalized four times for outbursts of violence with impulsive self-harm. She “overdosed” on eight aceta-minophen/diphenhydramine tablets on one occasion and superficially cut her forearm on another. During these episodes, she said, she heard voices telling her to harm her mother and herself.

During this period, Julie was diagnosed as having schizophrenia, major depressive disorder, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). Numerous antidepressant and mood stabilizer regimens produced no lasting improvement, though her angry and violent episodes became less frequent.

poll here

The authors’ observations

Although Julie’s psychotic symptoms might suggest an evolving disorder such as schizophrenia, no clear pattern supports this diagnosis. Also:

• Onset at age 12 is unusual. Schizophrenia typically begins in late teens to early adulthood.
  
• Julie showed no premorbid personality problems—found in up to one-third of patients with chronic schizophrenia—and no premorbid adjustment difficulties resulting from negative symptoms, cognitive deficits, or poor social function.¹
  

Julie’s angry behaviors and refusal to stay in school suggest ODD, but this disorder generally presents without self-harm or other impulsive behaviors and occurs apart from psychosis or mood disorder episodes.¹ Her low mood, withdrawal from activities, and suicidal actions may suggest major depressive disorder with psychotic features, but this diagnosis does not explain the sudden dramatic transformation in her baseline personality.

Julie’s birth parents’ mental health history would offer crucial information, but this was not available.

Continued history: ‘I left my body’

Shortly after her 15th birthday, Julie broke down and told her parents that 3 years earlier, four boys had gang-raped her while she was “on a first date” with one of them at a school football game. She said one attacker held a knife to her throat, and they threatened to kill her friend Sheila if anyone was told. Julie said she felt so terrorized that “I left my body and watched what was happening.”

After the rape, Julie went home, showered, and went to bed. She said she felt “emotionally numb” for 2 months, during which she threw herself into schoolwork, stopped attending after-school events, and began arguing with her parents. She developed nightmares of the trauma and, eventually, auditory command hallucinations. When stressed, she has “out of body” feelings lasting several minutes.

The parents, though angry at Julie‘s attackers, did not seek legal counsel or report the rape to authorities because they felt too much time had passed. They sought support from a counselor, who referred their daughter to a male psychiatrist for medication management. Julie, now age 16, preferred to be treated by a woman, so her care was transferred to our clinic.

Based on clinical observations, Julie gets along well with her father. She complains that her mother is overprotective yet Julie cannot bear to be separated from her for even a couple hours. She resents her mother’s overinvolvement but relies on it for emotional regulation. Her mother has been treated for major depressive disorder, generalized anxiety disorder, and alcohol dependence. These were in sustained remission when Julie presented to us.

 

At presentation, we diagnosed Julie as having chronic posttraumatic stress disorder (PTSD), recurrent major depressive disorder, and eating disorder not otherwise specified. At 5 feet, 7 inches and 190 pounds, her body mass index is 30 kg/m², indicating clinical obesity. She has been taking duloxetine, 60 mg/d, extended release dextroamphetamine, 20 mg/d, aripiprazole, 20 mg/d, and amitriptyline, 10 mg/d nightly. She also has been taking sumatriptan, 100 mg as needed, for migraines.

poll here

The authors’ observations

After a life-threatening sexual assault, Julie suddenly became irritable and hostile. She could not keep relationships, yet she feared being alone. She impulsively hurt herself, experienced nightmares, and systematically avoided school activities. These behaviors suggest PTSD,¹ which is prevalent among sexual assault victims (Box 1). For 3 years, however, psychiatrists kept missing the diagnosis as Julie kept her shame a secret.

Julie tells us that she re-experiences trauma-related dysphoria when exposed to cues, such as the anniversary of the rape. She endorses avoidance symptoms, including feelings of estrangement from her family and friends. She shuns thoughts, feelings, places, and conversations associated with the trauma, which partly explains her refusal to stay in school. She reports arousal symptoms, including difficulty falling and staying asleep and fears of harm if left alone, even during the day. At night she has rituals for checking windows and doors to ensure they are locked.

Julie’s decision to hide her trauma was understandable given her age and developmental phase. For a teenager trying to separate from her parents and fit in at school, the humiliation was overwhelming. She lacked the cognitive tools to process and describe her experience. She was assaulted while on a date, normally a positive rite of passage. Further, as a young Hispanic/Native American, Julie feared disappointing her Caucasian parents by not fitting in at school.

When a previously well-adjusted teenager presents with sudden-onset behavioral problems, ask about past or recent trauma. Watch for contextual, developmental, and sociocultural factors that may prevent the youth from disclosing embarrassing events.

Also question the diagnosis if several adequate medication trials have failed. Check for comorbidities, lack of adherence, or other circumstances that can hamper response to treatment.

Box 1

Factors that may signal ptsd

American Psychiatric Association (APA) practice guidelines for treating PTSD list several factors to consider if you suspect this diagnosis:⁵

Impulsive and episodic aggression can result from an anticipatory bias that increases readiness for “fight, flight, or freeze.” For Julie, this turned previously comfortable interactions into dissonance and conflict.

Self-injurious and suicidal behaviors often occur when trauma creates stigma, shame, or guilt. Julie felt these emotions while trying to establish herself in a new community and school. Her obesity and ethnic background further set her apart from peers. She also left behind friends who provided emotional support outside the home and helped her differentiate from her mother.

Trauma during early adolescence can impair age-appropriate development, making it difficult to develop a stable self-image, consolidate and integrate the personality, and form relationships. At age 16, poor self-image and maladaptive coping strategies were an enduring pattern in Julie’s life.

Psychiatric comorbidities. Many patients with PTSD develop psychiatric comorbidities that exaggerate symptoms, making the disorder more difficult to detect and treat. Julie’s depression increased her avoidance tendencies and rein-forced her isolation. Difficulty concentrating—misdiagnosed as ADHD—deterred her from engaging in school. Dissociative symptoms related to PTSD impaired her reality testing, diminishing her ability to interact with others.

Treatment: Medication change

We continued extended-release dextroamphetamine, 20 mg/d, as Julie felt the medication helped her focus on her schoolwork. We also:

• weaned her off aripiprazole, which was not helping her symptoms
  
• stopped amitriptyline and duloxetine because of her history of impulsive overdose and to reduce side-effect risk from polypharmacy
  
• titrated fluoxetine to 40 mg/d to treat her ongoing chronic depression and added trazodone, 50 mg/d as needed, to help her sleep
  
• stopped sumatriptan, as the headaches remitted after Julie’s eyes were tested and eyeglasses prescribed.
  

Initially, we managed Julie’s medications while she received psychotherapy from her counselor, but she eventually shifted her entire care to us. We then began seeing her weekly for psychoeducation and supportive therapy.

 

poll here

The authors’ observations

Medication. APA treatment guidelines support using SSRIs to treat all three PTSD symptom clusters—re-experiencing, avoidance, and hyperarousal—as well as coexisting depression. Evidence also supports use of the tricyclics amitriptyline and imipramine and some monoamine oxidase inhibitors (MAOIs).^6-10 Dietary restrictions associated with MAOIs, however, can pose a problem for teenagers.

Benzodiazepines can decrease anxiety and improve sleep, but they can be addictive and their efficacy in treating PTSD has not been established. Alpha-2-adrenergic agonists such as prazosin and clonidine may decrease hyperarousal and trauma-related nightmares.^11,12

Obtain informed parental consent before starting a child or adolescent on an antidepressant. These medications contain a black-box warning that the drug may increase suicide risk in youths.

Psychotherapy. Varying levels of evidence support psychotherapy models in PTSD (Box 2). Julie can benefit from psychoeducation, supportive therapy, psychodynamic psychotherapy, and cautious re-exposure to trauma where possible.

Psychoeducation provided a safe starting point for Julie’s therapy, engaged her parents and select school counselors and teachers, and helped her understand PTSD’s effects. This allowed us to teach stress reduction and coping strategies.

Supportive techniques helped Julie contain painful affects. She could then network with community resources such as AlaTeen and a peer support group via a local Native American mental health program. This approach helped us gain Julie’s trust, and we anticipate more in-depth work with time.

Trauma re-exposure helps some patients but worsens others’ symptoms. For Julie, trauma re-exposure has been minimal because of the many other issues she was facing.

Developing a trusting relationship over time is crucial to successful trauma re-exposure. Re-exposure should be gradual to keep affective arousal moderate. This will minimize dissociation and affective flooding, which can frustrate treatment.

Cognitive-behavioral therapy (CBT) might help Julie understand the automatic thoughts of failure and defeat that flood her when she is stressed. CBT could help her master her feelings and lay a foundation for improved coping.

Psychodynamic psychotherapy may be started later to help Julie verbalize feelings and modulate how she expresses affect. This model could promote her development, improve her self-image, and treat her depression.

Box 2

Follow-up: Back to school

After 2 months under our care, Julie begins to show improvement. Because of her progress and the fact that her parents drive 45 minutes each way to get to our clinic, we reduce visit frequency from weekly to biweekly.

Julie now attends school 2 hours daily, is earning additional credits through home study, and plans to graduate early and attend community college. Her depression has lifted, and she continues to take fluoxetine, 40 mg/d and extended-release dextroamphetamine, 20 mg/d. She still struggles with social isolation, failure to reach age-appropriate developmental milestones, and a poor body image.

Related resources

• American Psychiatric Association. Practice guideline for treating acute stress disorder and posttraumatic stress disorder. www.psych.org/psych_pract/treatg/pg/PTSD-PG-PartsA-B-C-New.pdf
  
• National Center for Post-Traumatic Stress Disorder. Information on obtaining Impact of Events Scale and Davidson Trauma Scale. www.ncptsd.va.gov/publications/assessment/adult_self_report.html
  

Drug brand names

• Amitriptyline • Elavil
  
• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine (extended-release) • Adderall XR
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Imipramine • Tofranil
  
• Phenelzine • Nardil
  
• Prazosin • Minipress
  
• Sumatriptan • Imitrex
  
• Trazodone • Desyrel
  

Disclosure

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Mossefin reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Acknowledgements

The authors thank Larry Schwartz, MD, for his help in preparing this article for publication.

History: From sociable to sullen

Julie, a Hispanic/Native American, was adopted by a Caucasian couple when she was 6 weeks old. Before age 12, she had no psychiatric problems and was medically healthy though slightly overweight.

At age 12, Julie started having episodes of brooding depression, verbal and physical aggression, and impulsive suicidal behavior. She also began suffering intermittent migraines and having trouble falling asleep. She insisted on sleeping with her parents or with a nightlight in her room.

Once a sociable girl who enjoyed being in the middle school chorus and band, Julie suddenly became sullen and defiant. She dropped out of afterschool activities and stopped socializing with peers except for her best friend, Sheila, age 12, and Mark, age 13, an “almost boyfriend” who lived next door.

Julie also started arguing with her mother, often yelling and screaming when approached with minor requests. Sometimes, Julie hit and pushed her. A psychiatrist diagnosed the 12-year-old with major depressive disorder and prescribed fluoxetine, dosage unknown.

Soon after Julie’s symptoms surfaced, her adoptive father, a sales representative, was laid off. He found work in another state; the family left an ethnically diverse city for a predominantly Caucasian rural area. There, Julie completed middle school and her freshman year of high school, and lost contact with Sheila and Mark.

Midway through her freshman year, Julie tried to induce vomiting after eating so that she would lose weight and “fit in better with the other girls.” She stopped this at the end of the school year.

The following fall, 5 weeks into her sophomore year, she dropped out of high school and was ultimately enrolled in home school.

Treatment: 4 hospitalizations in 3 years

Between ages 12 and 15, Julie was hospitalized four times for outbursts of violence with impulsive self-harm. She “overdosed” on eight aceta-minophen/diphenhydramine tablets on one occasion and superficially cut her forearm on another. During these episodes, she said, she heard voices telling her to harm her mother and herself.

During this period, Julie was diagnosed as having schizophrenia, major depressive disorder, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). Numerous antidepressant and mood stabilizer regimens produced no lasting improvement, though her angry and violent episodes became less frequent.

poll here

The authors’ observations

Although Julie’s psychotic symptoms might suggest an evolving disorder such as schizophrenia, no clear pattern supports this diagnosis. Also:

• Onset at age 12 is unusual. Schizophrenia typically begins in late teens to early adulthood.
  
• Julie showed no premorbid personality problems—found in up to one-third of patients with chronic schizophrenia—and no premorbid adjustment difficulties resulting from negative symptoms, cognitive deficits, or poor social function.¹
  

Julie’s angry behaviors and refusal to stay in school suggest ODD, but this disorder generally presents without self-harm or other impulsive behaviors and occurs apart from psychosis or mood disorder episodes.¹ Her low mood, withdrawal from activities, and suicidal actions may suggest major depressive disorder with psychotic features, but this diagnosis does not explain the sudden dramatic transformation in her baseline personality.

Julie’s birth parents’ mental health history would offer crucial information, but this was not available.

Continued history: ‘I left my body’

Shortly after her 15th birthday, Julie broke down and told her parents that 3 years earlier, four boys had gang-raped her while she was “on a first date” with one of them at a school football game. She said one attacker held a knife to her throat, and they threatened to kill her friend Sheila if anyone was told. Julie said she felt so terrorized that “I left my body and watched what was happening.”

After the rape, Julie went home, showered, and went to bed. She said she felt “emotionally numb” for 2 months, during which she threw herself into schoolwork, stopped attending after-school events, and began arguing with her parents. She developed nightmares of the trauma and, eventually, auditory command hallucinations. When stressed, she has “out of body” feelings lasting several minutes.

The parents, though angry at Julie‘s attackers, did not seek legal counsel or report the rape to authorities because they felt too much time had passed. They sought support from a counselor, who referred their daughter to a male psychiatrist for medication management. Julie, now age 16, preferred to be treated by a woman, so her care was transferred to our clinic.

Based on clinical observations, Julie gets along well with her father. She complains that her mother is overprotective yet Julie cannot bear to be separated from her for even a couple hours. She resents her mother’s overinvolvement but relies on it for emotional regulation. Her mother has been treated for major depressive disorder, generalized anxiety disorder, and alcohol dependence. These were in sustained remission when Julie presented to us.

 

At presentation, we diagnosed Julie as having chronic posttraumatic stress disorder (PTSD), recurrent major depressive disorder, and eating disorder not otherwise specified. At 5 feet, 7 inches and 190 pounds, her body mass index is 30 kg/m², indicating clinical obesity. She has been taking duloxetine, 60 mg/d, extended release dextroamphetamine, 20 mg/d, aripiprazole, 20 mg/d, and amitriptyline, 10 mg/d nightly. She also has been taking sumatriptan, 100 mg as needed, for migraines.

poll here

The authors’ observations

After a life-threatening sexual assault, Julie suddenly became irritable and hostile. She could not keep relationships, yet she feared being alone. She impulsively hurt herself, experienced nightmares, and systematically avoided school activities. These behaviors suggest PTSD,¹ which is prevalent among sexual assault victims (Box 1). For 3 years, however, psychiatrists kept missing the diagnosis as Julie kept her shame a secret.

Julie tells us that she re-experiences trauma-related dysphoria when exposed to cues, such as the anniversary of the rape. She endorses avoidance symptoms, including feelings of estrangement from her family and friends. She shuns thoughts, feelings, places, and conversations associated with the trauma, which partly explains her refusal to stay in school. She reports arousal symptoms, including difficulty falling and staying asleep and fears of harm if left alone, even during the day. At night she has rituals for checking windows and doors to ensure they are locked.

Julie’s decision to hide her trauma was understandable given her age and developmental phase. For a teenager trying to separate from her parents and fit in at school, the humiliation was overwhelming. She lacked the cognitive tools to process and describe her experience. She was assaulted while on a date, normally a positive rite of passage. Further, as a young Hispanic/Native American, Julie feared disappointing her Caucasian parents by not fitting in at school.

When a previously well-adjusted teenager presents with sudden-onset behavioral problems, ask about past or recent trauma. Watch for contextual, developmental, and sociocultural factors that may prevent the youth from disclosing embarrassing events.

Also question the diagnosis if several adequate medication trials have failed. Check for comorbidities, lack of adherence, or other circumstances that can hamper response to treatment.

Box 1

Factors that may signal ptsd

American Psychiatric Association (APA) practice guidelines for treating PTSD list several factors to consider if you suspect this diagnosis:⁵

Impulsive and episodic aggression can result from an anticipatory bias that increases readiness for “fight, flight, or freeze.” For Julie, this turned previously comfortable interactions into dissonance and conflict.

Self-injurious and suicidal behaviors often occur when trauma creates stigma, shame, or guilt. Julie felt these emotions while trying to establish herself in a new community and school. Her obesity and ethnic background further set her apart from peers. She also left behind friends who provided emotional support outside the home and helped her differentiate from her mother.

Trauma during early adolescence can impair age-appropriate development, making it difficult to develop a stable self-image, consolidate and integrate the personality, and form relationships. At age 16, poor self-image and maladaptive coping strategies were an enduring pattern in Julie’s life.

Psychiatric comorbidities. Many patients with PTSD develop psychiatric comorbidities that exaggerate symptoms, making the disorder more difficult to detect and treat. Julie’s depression increased her avoidance tendencies and rein-forced her isolation. Difficulty concentrating—misdiagnosed as ADHD—deterred her from engaging in school. Dissociative symptoms related to PTSD impaired her reality testing, diminishing her ability to interact with others.

Treatment: Medication change

We continued extended-release dextroamphetamine, 20 mg/d, as Julie felt the medication helped her focus on her schoolwork. We also:

• weaned her off aripiprazole, which was not helping her symptoms
  
• stopped amitriptyline and duloxetine because of her history of impulsive overdose and to reduce side-effect risk from polypharmacy
  
• titrated fluoxetine to 40 mg/d to treat her ongoing chronic depression and added trazodone, 50 mg/d as needed, to help her sleep
  
• stopped sumatriptan, as the headaches remitted after Julie’s eyes were tested and eyeglasses prescribed.
  

Initially, we managed Julie’s medications while she received psychotherapy from her counselor, but she eventually shifted her entire care to us. We then began seeing her weekly for psychoeducation and supportive therapy.

 

poll here

The authors’ observations

Medication. APA treatment guidelines support using SSRIs to treat all three PTSD symptom clusters—re-experiencing, avoidance, and hyperarousal—as well as coexisting depression. Evidence also supports use of the tricyclics amitriptyline and imipramine and some monoamine oxidase inhibitors (MAOIs).^6-10 Dietary restrictions associated with MAOIs, however, can pose a problem for teenagers.

Benzodiazepines can decrease anxiety and improve sleep, but they can be addictive and their efficacy in treating PTSD has not been established. Alpha-2-adrenergic agonists such as prazosin and clonidine may decrease hyperarousal and trauma-related nightmares.^11,12

Obtain informed parental consent before starting a child or adolescent on an antidepressant. These medications contain a black-box warning that the drug may increase suicide risk in youths.

Psychotherapy. Varying levels of evidence support psychotherapy models in PTSD (Box 2). Julie can benefit from psychoeducation, supportive therapy, psychodynamic psychotherapy, and cautious re-exposure to trauma where possible.

Psychoeducation provided a safe starting point for Julie’s therapy, engaged her parents and select school counselors and teachers, and helped her understand PTSD’s effects. This allowed us to teach stress reduction and coping strategies.

Supportive techniques helped Julie contain painful affects. She could then network with community resources such as AlaTeen and a peer support group via a local Native American mental health program. This approach helped us gain Julie’s trust, and we anticipate more in-depth work with time.

Trauma re-exposure helps some patients but worsens others’ symptoms. For Julie, trauma re-exposure has been minimal because of the many other issues she was facing.

Developing a trusting relationship over time is crucial to successful trauma re-exposure. Re-exposure should be gradual to keep affective arousal moderate. This will minimize dissociation and affective flooding, which can frustrate treatment.

Cognitive-behavioral therapy (CBT) might help Julie understand the automatic thoughts of failure and defeat that flood her when she is stressed. CBT could help her master her feelings and lay a foundation for improved coping.

Psychodynamic psychotherapy may be started later to help Julie verbalize feelings and modulate how she expresses affect. This model could promote her development, improve her self-image, and treat her depression.

Box 2

Follow-up: Back to school

After 2 months under our care, Julie begins to show improvement. Because of her progress and the fact that her parents drive 45 minutes each way to get to our clinic, we reduce visit frequency from weekly to biweekly.

Julie now attends school 2 hours daily, is earning additional credits through home study, and plans to graduate early and attend community college. Her depression has lifted, and she continues to take fluoxetine, 40 mg/d and extended-release dextroamphetamine, 20 mg/d. She still struggles with social isolation, failure to reach age-appropriate developmental milestones, and a poor body image.

Related resources

• American Psychiatric Association. Practice guideline for treating acute stress disorder and posttraumatic stress disorder. www.psych.org/psych_pract/treatg/pg/PTSD-PG-PartsA-B-C-New.pdf
  
• National Center for Post-Traumatic Stress Disorder. Information on obtaining Impact of Events Scale and Davidson Trauma Scale. www.ncptsd.va.gov/publications/assessment/adult_self_report.html
  

Drug brand names

• Amitriptyline • Elavil
  
• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine (extended-release) • Adderall XR
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Imipramine • Tofranil
  
• Phenelzine • Nardil
  
• Prazosin • Minipress
  
• Sumatriptan • Imitrex
  
• Trazodone • Desyrel
  

Disclosure

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Mossefin reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Acknowledgements

The authors thank Larry Schwartz, MD, for his help in preparing this article for publication.

History: From sociable to sullen

Julie, a Hispanic/Native American, was adopted by a Caucasian couple when she was 6 weeks old. Before age 12, she had no psychiatric problems and was medically healthy though slightly overweight.

At age 12, Julie started having episodes of brooding depression, verbal and physical aggression, and impulsive suicidal behavior. She also began suffering intermittent migraines and having trouble falling asleep. She insisted on sleeping with her parents or with a nightlight in her room.

Once a sociable girl who enjoyed being in the middle school chorus and band, Julie suddenly became sullen and defiant. She dropped out of afterschool activities and stopped socializing with peers except for her best friend, Sheila, age 12, and Mark, age 13, an “almost boyfriend” who lived next door.

Julie also started arguing with her mother, often yelling and screaming when approached with minor requests. Sometimes, Julie hit and pushed her. A psychiatrist diagnosed the 12-year-old with major depressive disorder and prescribed fluoxetine, dosage unknown.

Soon after Julie’s symptoms surfaced, her adoptive father, a sales representative, was laid off. He found work in another state; the family left an ethnically diverse city for a predominantly Caucasian rural area. There, Julie completed middle school and her freshman year of high school, and lost contact with Sheila and Mark.

Midway through her freshman year, Julie tried to induce vomiting after eating so that she would lose weight and “fit in better with the other girls.” She stopped this at the end of the school year.

The following fall, 5 weeks into her sophomore year, she dropped out of high school and was ultimately enrolled in home school.

Treatment: 4 hospitalizations in 3 years

Between ages 12 and 15, Julie was hospitalized four times for outbursts of violence with impulsive self-harm. She “overdosed” on eight aceta-minophen/diphenhydramine tablets on one occasion and superficially cut her forearm on another. During these episodes, she said, she heard voices telling her to harm her mother and herself.

During this period, Julie was diagnosed as having schizophrenia, major depressive disorder, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). Numerous antidepressant and mood stabilizer regimens produced no lasting improvement, though her angry and violent episodes became less frequent.

poll here

The authors’ observations

Although Julie’s psychotic symptoms might suggest an evolving disorder such as schizophrenia, no clear pattern supports this diagnosis. Also:

• Onset at age 12 is unusual. Schizophrenia typically begins in late teens to early adulthood.
  
• Julie showed no premorbid personality problems—found in up to one-third of patients with chronic schizophrenia—and no premorbid adjustment difficulties resulting from negative symptoms, cognitive deficits, or poor social function.¹
  

Julie’s angry behaviors and refusal to stay in school suggest ODD, but this disorder generally presents without self-harm or other impulsive behaviors and occurs apart from psychosis or mood disorder episodes.¹ Her low mood, withdrawal from activities, and suicidal actions may suggest major depressive disorder with psychotic features, but this diagnosis does not explain the sudden dramatic transformation in her baseline personality.

Julie’s birth parents’ mental health history would offer crucial information, but this was not available.

Continued history: ‘I left my body’

Shortly after her 15th birthday, Julie broke down and told her parents that 3 years earlier, four boys had gang-raped her while she was “on a first date” with one of them at a school football game. She said one attacker held a knife to her throat, and they threatened to kill her friend Sheila if anyone was told. Julie said she felt so terrorized that “I left my body and watched what was happening.”

After the rape, Julie went home, showered, and went to bed. She said she felt “emotionally numb” for 2 months, during which she threw herself into schoolwork, stopped attending after-school events, and began arguing with her parents. She developed nightmares of the trauma and, eventually, auditory command hallucinations. When stressed, she has “out of body” feelings lasting several minutes.

The parents, though angry at Julie‘s attackers, did not seek legal counsel or report the rape to authorities because they felt too much time had passed. They sought support from a counselor, who referred their daughter to a male psychiatrist for medication management. Julie, now age 16, preferred to be treated by a woman, so her care was transferred to our clinic.

Based on clinical observations, Julie gets along well with her father. She complains that her mother is overprotective yet Julie cannot bear to be separated from her for even a couple hours. She resents her mother’s overinvolvement but relies on it for emotional regulation. Her mother has been treated for major depressive disorder, generalized anxiety disorder, and alcohol dependence. These were in sustained remission when Julie presented to us.

 

At presentation, we diagnosed Julie as having chronic posttraumatic stress disorder (PTSD), recurrent major depressive disorder, and eating disorder not otherwise specified. At 5 feet, 7 inches and 190 pounds, her body mass index is 30 kg/m², indicating clinical obesity. She has been taking duloxetine, 60 mg/d, extended release dextroamphetamine, 20 mg/d, aripiprazole, 20 mg/d, and amitriptyline, 10 mg/d nightly. She also has been taking sumatriptan, 100 mg as needed, for migraines.

poll here

The authors’ observations

After a life-threatening sexual assault, Julie suddenly became irritable and hostile. She could not keep relationships, yet she feared being alone. She impulsively hurt herself, experienced nightmares, and systematically avoided school activities. These behaviors suggest PTSD,¹ which is prevalent among sexual assault victims (Box 1). For 3 years, however, psychiatrists kept missing the diagnosis as Julie kept her shame a secret.

Julie tells us that she re-experiences trauma-related dysphoria when exposed to cues, such as the anniversary of the rape. She endorses avoidance symptoms, including feelings of estrangement from her family and friends. She shuns thoughts, feelings, places, and conversations associated with the trauma, which partly explains her refusal to stay in school. She reports arousal symptoms, including difficulty falling and staying asleep and fears of harm if left alone, even during the day. At night she has rituals for checking windows and doors to ensure they are locked.

Julie’s decision to hide her trauma was understandable given her age and developmental phase. For a teenager trying to separate from her parents and fit in at school, the humiliation was overwhelming. She lacked the cognitive tools to process and describe her experience. She was assaulted while on a date, normally a positive rite of passage. Further, as a young Hispanic/Native American, Julie feared disappointing her Caucasian parents by not fitting in at school.

When a previously well-adjusted teenager presents with sudden-onset behavioral problems, ask about past or recent trauma. Watch for contextual, developmental, and sociocultural factors that may prevent the youth from disclosing embarrassing events.

Also question the diagnosis if several adequate medication trials have failed. Check for comorbidities, lack of adherence, or other circumstances that can hamper response to treatment.

Box 1

Factors that may signal ptsd

American Psychiatric Association (APA) practice guidelines for treating PTSD list several factors to consider if you suspect this diagnosis:⁵

Impulsive and episodic aggression can result from an anticipatory bias that increases readiness for “fight, flight, or freeze.” For Julie, this turned previously comfortable interactions into dissonance and conflict.

Self-injurious and suicidal behaviors often occur when trauma creates stigma, shame, or guilt. Julie felt these emotions while trying to establish herself in a new community and school. Her obesity and ethnic background further set her apart from peers. She also left behind friends who provided emotional support outside the home and helped her differentiate from her mother.

Trauma during early adolescence can impair age-appropriate development, making it difficult to develop a stable self-image, consolidate and integrate the personality, and form relationships. At age 16, poor self-image and maladaptive coping strategies were an enduring pattern in Julie’s life.

Psychiatric comorbidities. Many patients with PTSD develop psychiatric comorbidities that exaggerate symptoms, making the disorder more difficult to detect and treat. Julie’s depression increased her avoidance tendencies and rein-forced her isolation. Difficulty concentrating—misdiagnosed as ADHD—deterred her from engaging in school. Dissociative symptoms related to PTSD impaired her reality testing, diminishing her ability to interact with others.

Treatment: Medication change

We continued extended-release dextroamphetamine, 20 mg/d, as Julie felt the medication helped her focus on her schoolwork. We also:

• weaned her off aripiprazole, which was not helping her symptoms
  
• stopped amitriptyline and duloxetine because of her history of impulsive overdose and to reduce side-effect risk from polypharmacy
  
• titrated fluoxetine to 40 mg/d to treat her ongoing chronic depression and added trazodone, 50 mg/d as needed, to help her sleep
  
• stopped sumatriptan, as the headaches remitted after Julie’s eyes were tested and eyeglasses prescribed.
  

Initially, we managed Julie’s medications while she received psychotherapy from her counselor, but she eventually shifted her entire care to us. We then began seeing her weekly for psychoeducation and supportive therapy.

 

poll here

The authors’ observations

Medication. APA treatment guidelines support using SSRIs to treat all three PTSD symptom clusters—re-experiencing, avoidance, and hyperarousal—as well as coexisting depression. Evidence also supports use of the tricyclics amitriptyline and imipramine and some monoamine oxidase inhibitors (MAOIs).^6-10 Dietary restrictions associated with MAOIs, however, can pose a problem for teenagers.

Benzodiazepines can decrease anxiety and improve sleep, but they can be addictive and their efficacy in treating PTSD has not been established. Alpha-2-adrenergic agonists such as prazosin and clonidine may decrease hyperarousal and trauma-related nightmares.^11,12

Obtain informed parental consent before starting a child or adolescent on an antidepressant. These medications contain a black-box warning that the drug may increase suicide risk in youths.

Psychotherapy. Varying levels of evidence support psychotherapy models in PTSD (Box 2). Julie can benefit from psychoeducation, supportive therapy, psychodynamic psychotherapy, and cautious re-exposure to trauma where possible.

Psychoeducation provided a safe starting point for Julie’s therapy, engaged her parents and select school counselors and teachers, and helped her understand PTSD’s effects. This allowed us to teach stress reduction and coping strategies.

Supportive techniques helped Julie contain painful affects. She could then network with community resources such as AlaTeen and a peer support group via a local Native American mental health program. This approach helped us gain Julie’s trust, and we anticipate more in-depth work with time.

Trauma re-exposure helps some patients but worsens others’ symptoms. For Julie, trauma re-exposure has been minimal because of the many other issues she was facing.

Developing a trusting relationship over time is crucial to successful trauma re-exposure. Re-exposure should be gradual to keep affective arousal moderate. This will minimize dissociation and affective flooding, which can frustrate treatment.

Cognitive-behavioral therapy (CBT) might help Julie understand the automatic thoughts of failure and defeat that flood her when she is stressed. CBT could help her master her feelings and lay a foundation for improved coping.

Psychodynamic psychotherapy may be started later to help Julie verbalize feelings and modulate how she expresses affect. This model could promote her development, improve her self-image, and treat her depression.

Box 2

Follow-up: Back to school

After 2 months under our care, Julie begins to show improvement. Because of her progress and the fact that her parents drive 45 minutes each way to get to our clinic, we reduce visit frequency from weekly to biweekly.

Julie now attends school 2 hours daily, is earning additional credits through home study, and plans to graduate early and attend community college. Her depression has lifted, and she continues to take fluoxetine, 40 mg/d and extended-release dextroamphetamine, 20 mg/d. She still struggles with social isolation, failure to reach age-appropriate developmental milestones, and a poor body image.

Related resources

• American Psychiatric Association. Practice guideline for treating acute stress disorder and posttraumatic stress disorder. www.psych.org/psych_pract/treatg/pg/PTSD-PG-PartsA-B-C-New.pdf
  
• National Center for Post-Traumatic Stress Disorder. Information on obtaining Impact of Events Scale and Davidson Trauma Scale. www.ncptsd.va.gov/publications/assessment/adult_self_report.html
  

Drug brand names

• Amitriptyline • Elavil
  
• Aripiprazole • Abilify
  
• Clonidine • Catapres
  
• Dextroamphetamine (extended-release) • Adderall XR
  
• Duloxetine • Cymbalta
  
• Fluoxetine • Prozac
  
• Imipramine • Tofranil
  
• Phenelzine • Nardil
  
• Prazosin • Minipress
  
• Sumatriptan • Imitrex
  
• Trazodone • Desyrel
  

Disclosure

Dr. Matthews is an American Psychiatric Association Bristol-Myers Squibb Co. fellow in public and community psychiatry.

Dr. Mossefin reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

Acknowledgements

The authors thank Larry Schwartz, MD, for his help in preparing this article for publication.

History: A tortured past

Ms. A, age 46, is referred to us by her primary care physician for a psychiatric evaluation. The patient endorses longstanding depression but has never seen a psychiatrist. She also reports that she was raped several years ago.

Ms. A meets DSM-IV-TR criteria for major depressive disorder, recurrent moderate; and posttraumatic stress disorder (PTSD). She complains of depressed mood, lack of energy, poor concentration and memory, anxiety, feelings of hopelessness and worthlessness, insomnia, and poor appetite. She has nightmares, flashbacks of her rape, and decreased interest in activities. She says she tries to avoid thoughts associated with her rape, feels detached from others, is easily startled, and at times is irritable.

Approximately 8 years ago—shortly after she started taking bupropion, 150 mg/d, to help her quit smoking—Ms. A suffered her first seizure-like episode. A neurologist diagnosed her with epilepsy based on EEG findings. He started her on carbamazepine, 200 mg bid, and titrated the dosage to 900 mg/d. After 2 years, however, her spells continued. Usually, she would black out for a few minutes and forget what she was doing. During some spells she would jerk her hands and feet, stare into space, repeat words over and over, and/or fumble with her hands.

After changing health insurance plans, Ms. A saw another neurologist who switched her to divalproex, 250 mg bid. She began having nausea, vomiting, and alopecia, so she stopped taking divalproex after 2 weeks. The neurologist switched her to topiramate, 25 mg bid, and titrated the dosage to 400 mg/d over 8 weeks with no side effects but minimal response. Reducing topiramate to 200 mg/d and adding phenytoin, 300 mg/d, produced little improvement.

Ms. A says these spells now come once or twice daily. She denies aura, loss of consciousness, tongue biting, or incontinence during seizures.

Medical history. Ms. A has undergone posterior fossa decompression for Arnold-Chiari type I malformation, right nephrectomy for renal cell carcinoma, a complete hysterectomy, an appendectomy, and bilateral breast implants. She has also had venous angiomas with head and neck pain.

Ms. A is frustrated over her lack of independence, her limited social life, and her inability to drive because of her seizure disorder. Once employed full-time for 12 years in a doctor’s office, she now gets by on disability benefits, which she finds degrading. She feels hopeless and helpless, as antiepileptics have not worked.

poll here

The authors’ observations

Ms. A complained of depression, sleep problems secondary to depression and PTSD, poor appetite, underlying anxiety, and decreased concentration, energy, and interest. We decided to address these symptoms with mirtazapine. Because she is thin (126 lb, body mass index 19.2 kg/m²), potential for weight gain with mirtazapine was not a concern.

We gauged Ms. A’s response to mirtazapine and her seizure history at our next visit, during which we customarily continue taking the patient’s history.

Treatment: Marriage by force?

Ms. A begins taking mirtazapine, 15 mg/d. At her next appointment the following week, she says she has stopped it because it has increased her appetite, which she fears will cause weight gain. She says her seizures, which usually occur at home, have continued with the same frequency.

Upon exploring her history further, we discover that Ms. A’s father was rarely around, and when he was he physically abused her. As a child she struggled with dyslexia, for which she received special education. She became pregnant while finishing high school and feels her mother forced her to marry her first husband.

Ms. A added that her three former husbands were physically and/or emotionally abusive toward her. About 10 years ago, she says, her third husband raped her.

We begin to suspect that Ms. A might not have epilepsy because of the seizures’ distinct nature, her vague symptoms, minimal or no response to antiepileptics, and comorbid mood and anxiety disorders. We refer her to another neurologist for video EEG (VEEG). She reluctantly agrees to the test, unwilling to believe that her seizures might have a psychiatric cause.

poll here

The authors’ observations

Recurrent seizures characteristic of epilepsy can significantly impair quality of life. Although the diagnosis often is straightforward, distinguishing epilepsy from psychogenic nonepileptic seizures (PNES) can be difficult.

PNES are sudden, episodic changes in behavior, perception, thinking, or feeling. These changes resemble epileptic events but are not prompted by abnormal brain electrical discharges as measured by EEG.¹

Formerly called pseudoseizures, PNES can have a physiologic or psychological cause (Table 1). They often are a somatic response to unbearable past events and/or current psychological tension or conflict. Most patients with PNES cite domestic abuse or family conflicts as key stressors.²

 

Few systematic studies have addressed how life events contribute to PNES. Associated life events—described mostly in case reports—fall into three general categories:

• childhood and adult trauma
  
• bereavement or loss
  
• acute or situational stressors.³
  

PNES diagnosis has become progressively refined over the last three decades. VEEG is used to diagnose PNES. Neuropsychological evaluation and VEEG are used together if PNES is believed to coexist with epilepsy or psychiatric disorders.^4,5

Table 1

Physiologic and psychological causes of nonepileptic seizures

Physiologic
Autonomic disorders
Cerebrovascular disease
Cardiac disorders
Vasovagal syncope
Ischemic heart disease
Valvular heart disease
Arrythmias
Drug toxicity
Endocrine disturbance
Metabolic disorders
Migraines
Paroxysmal movement disorder
Sleep disorder
Psychological
Anxiety disorders
Conversion disorder
Dissociative disorder
Factitious disorder
Malingering
Victim of physical, emotional, or sexual abuse
Posttraumatic stress disorder
Psychotic disorder
Somatoform disorder
Substance abuse/dependence

Continued treatment: Wasted years

Two weeks after our referral, Ms. A reports that the neurologist discontinued topiramate and phenytoin after VEEG showed no epileptic activity.

Ms. A now realizes she does not have epilepsy. She is angry that her first neurologist had misdiag-nosed her, effectively sentencing her to 8 years of needless dependency and disability.

We prescribe escitalopram, starting at 10 mg/d and titrating to 20 mg/d, to address Ms. A’s depressive/PTSD symptoms. We also refer her to a psychotherapist, who schedules twice-weekly supportive psychotherapy sessions. The therapist plans to teach her coping techniques and provide ego support and encouragement.

Ms. A’s psychotherapy progresses slowly at first, but by the fourth session she sets goals, which include getting off disability as soon as possible. With careful ego strengthening, she resumes driving and searches for a job. During one session, she tells her therapist she has long wanted to become a nurse, so she is encouraged to see a nursing school counselor for advice on selecting prerequisite nursing classes.

The authors’ observations

As with Ms. A, an erroneous epilepsy diagnosis can cause physical, psychosocial, and socioeconomic grief for the patient and can lead to needless restrictions, unemployment or underemployment, and dependence on disability benefits. After the misdiagnosis, Ms. A lost control of her future and considered her life a burden, leading to depression and anxiety. Her seizures caused most of her physical and psychological disturbances and diminished her overall function.

PNES are often mistaken for epileptic seizures, and 26% of seizure patients experience both.⁶ In a study of 50 patients, between 5% and 20% of patients evaluated for epilepsy and 10% to 40% of patients referred to comprehensive epilepsy centers were later found to have PNES.⁷

Like Ms. A, many patients with undiagnosed PNES receive antiepileptics to treat apparent epilepsy. These medications can cause troublesome side effects—from GI problems, to respiratory arrest in patients with pseudostatus, to potential teratogenicity.

In addition, comorbid epilepsy often goes undetected in patients with PNES. This could lead to inadequate treatment, increasing the patient’s morbidity and mortality risk.⁸

poll here

The authors’ observations

Patient history. Take a thorough history for patients with a history of seizures.

Too often, doctors assume a previous epilepsy diagnosis is correct, especially if rendered by a neurologist. In the United Kingdom, 20% to 31% of epilepsy diagnoses are incorrect because of incomplete history and misinterpreted EEG findings.⁸ When taking a patient’s seizure history, clinicians often do not get:

• a detailed history of seizures or seizurelike events, including onset, frequency, observations from family or friends, and seizure duration
  
• information on whether the patient remembers seizure details; has had prespell aura or loss of consciousness, or cries during the spells
  
• history of physical and/or sexual abuse.
  

Multiple daily seizures, repeated hospitalizations or emergency room visits, minimal response to antiepileptics, and no history of injury after seizures could suggest nonepileptic seizures. Seizures may be psychogenic if the patient was sexually abused, has a comorbid psychiatric disorder, or suffers attacks only when alone or only in public (Table 2).

Refer patients with features that may suggest PNES to a neurologist for VEEG to confirm or rule out epilepsy, because roughly one-quarter of seizure patients can have both.

Table 2

Patient features that suggest nonepileptic seizures

Comorbid psychiatric disorder(s)
Events occur only in presence of others or only when alone
Lack of concern or excessive emotional response to seizures
Minimal or no response to antiepileptics
Multiple daily seizures
No history of injury resulting from seizures
Normal neurologic history and examination
Repeated hospitalizations or emergency room visits
Unremarkable EEG and MRI findings
Victim of sexual abuse

Finding psychological causes. Psychological investigations become paramount after physiologic causes for nonepileptic seizures are ruled out.

The Minnesota Multiphasic Personality Inventory (MMPI) is often used to discriminate PNES from epilepsy. Wilkus et al⁹ reported significant differences in scores of MMPI hypochondriasis, hysteria, and schizophrenia scales among patients with PNES and epilepsy. Patients with PNES may have higher MMPI hypochondriasis, hysteria, schizophrenia, and psychopathic deviate scores than do patients with epilepsy.

 

Other authors, however, have found more variable MMPI results when using the test to distinguish PNES from epilepsy. Thus, the MMPI may provide supportive data for PNES diagnosis but is not a definitive tool.

Explaining the findings. Getting the patient to accept that the epilepsy is “in your head” is crucial to engaging him or her in treatment. The clinician needs to be honest with the patient while projecting a positive approach to the diagnosis. Tell the patient that not having epilepsy is “good news,” that antiepileptics are not needed, and that he or she can gain better control once stress or emotional issues are resolved.¹⁰

Follow-up: A learning experience

Within 4 months of her last seizure, Ms. A showed dramatic improvement. She began driving, working part-time and enrolled in nursing school. Her disability benefits program provided tuition assistance.

Ms. A has now been seizure-free for 1 year. Motivated and determined, she is taking up to 8 credit hours per semester and earning As and Bs but at times is anxious and fears failure. She needs much support and encouragement. Multiple therapy techniques—including direct teaching, admiring her progress, offering support, explaining, and ego strengthening—have produced good results. She is still taking escitalopram, 20 mg/d, and sees her therapist every 2 weeks.

Related resources

• Adetunji B, Mathews M, Williams A, Verma S. Psychogenic or epileptic seizures? How to clinch the diagnosis. Current Psychiatry 2004;3(11):25-35.
  
• Privitera MD. EEGs and epilepsy: When seizures mimic psychiatric illness. Current Psychiatry 2002;1(9):14-21.
  

Drug brand names

• Bupropion • Wellbutrin, Zyban
  
• Carbamazepine • Tegretol
  
• Divalproex sodium • Depakote
  
• Escitalopram • Lexapro
  
• Mirtazapine • Remeron
  
• Phenytoin • Dilantin
  
• Topiramate • Topamax
  

Disclosure

Dr. Khan is a speaker for Pfizer and Wyeth.

Drs. Aziz and Syed report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: A tortured past

Ms. A, age 46, is referred to us by her primary care physician for a psychiatric evaluation. The patient endorses longstanding depression but has never seen a psychiatrist. She also reports that she was raped several years ago.

Ms. A meets DSM-IV-TR criteria for major depressive disorder, recurrent moderate; and posttraumatic stress disorder (PTSD). She complains of depressed mood, lack of energy, poor concentration and memory, anxiety, feelings of hopelessness and worthlessness, insomnia, and poor appetite. She has nightmares, flashbacks of her rape, and decreased interest in activities. She says she tries to avoid thoughts associated with her rape, feels detached from others, is easily startled, and at times is irritable.

Approximately 8 years ago—shortly after she started taking bupropion, 150 mg/d, to help her quit smoking—Ms. A suffered her first seizure-like episode. A neurologist diagnosed her with epilepsy based on EEG findings. He started her on carbamazepine, 200 mg bid, and titrated the dosage to 900 mg/d. After 2 years, however, her spells continued. Usually, she would black out for a few minutes and forget what she was doing. During some spells she would jerk her hands and feet, stare into space, repeat words over and over, and/or fumble with her hands.

After changing health insurance plans, Ms. A saw another neurologist who switched her to divalproex, 250 mg bid. She began having nausea, vomiting, and alopecia, so she stopped taking divalproex after 2 weeks. The neurologist switched her to topiramate, 25 mg bid, and titrated the dosage to 400 mg/d over 8 weeks with no side effects but minimal response. Reducing topiramate to 200 mg/d and adding phenytoin, 300 mg/d, produced little improvement.

Ms. A says these spells now come once or twice daily. She denies aura, loss of consciousness, tongue biting, or incontinence during seizures.

Medical history. Ms. A has undergone posterior fossa decompression for Arnold-Chiari type I malformation, right nephrectomy for renal cell carcinoma, a complete hysterectomy, an appendectomy, and bilateral breast implants. She has also had venous angiomas with head and neck pain.

Ms. A is frustrated over her lack of independence, her limited social life, and her inability to drive because of her seizure disorder. Once employed full-time for 12 years in a doctor’s office, she now gets by on disability benefits, which she finds degrading. She feels hopeless and helpless, as antiepileptics have not worked.

poll here

The authors’ observations

Ms. A complained of depression, sleep problems secondary to depression and PTSD, poor appetite, underlying anxiety, and decreased concentration, energy, and interest. We decided to address these symptoms with mirtazapine. Because she is thin (126 lb, body mass index 19.2 kg/m²), potential for weight gain with mirtazapine was not a concern.

We gauged Ms. A’s response to mirtazapine and her seizure history at our next visit, during which we customarily continue taking the patient’s history.

Treatment: Marriage by force?

Ms. A begins taking mirtazapine, 15 mg/d. At her next appointment the following week, she says she has stopped it because it has increased her appetite, which she fears will cause weight gain. She says her seizures, which usually occur at home, have continued with the same frequency.

Upon exploring her history further, we discover that Ms. A’s father was rarely around, and when he was he physically abused her. As a child she struggled with dyslexia, for which she received special education. She became pregnant while finishing high school and feels her mother forced her to marry her first husband.

Ms. A added that her three former husbands were physically and/or emotionally abusive toward her. About 10 years ago, she says, her third husband raped her.

We begin to suspect that Ms. A might not have epilepsy because of the seizures’ distinct nature, her vague symptoms, minimal or no response to antiepileptics, and comorbid mood and anxiety disorders. We refer her to another neurologist for video EEG (VEEG). She reluctantly agrees to the test, unwilling to believe that her seizures might have a psychiatric cause.

poll here

The authors’ observations

Recurrent seizures characteristic of epilepsy can significantly impair quality of life. Although the diagnosis often is straightforward, distinguishing epilepsy from psychogenic nonepileptic seizures (PNES) can be difficult.

PNES are sudden, episodic changes in behavior, perception, thinking, or feeling. These changes resemble epileptic events but are not prompted by abnormal brain electrical discharges as measured by EEG.¹

Formerly called pseudoseizures, PNES can have a physiologic or psychological cause (Table 1). They often are a somatic response to unbearable past events and/or current psychological tension or conflict. Most patients with PNES cite domestic abuse or family conflicts as key stressors.²

 

Few systematic studies have addressed how life events contribute to PNES. Associated life events—described mostly in case reports—fall into three general categories:

• childhood and adult trauma
  
• bereavement or loss
  
• acute or situational stressors.³
  

PNES diagnosis has become progressively refined over the last three decades. VEEG is used to diagnose PNES. Neuropsychological evaluation and VEEG are used together if PNES is believed to coexist with epilepsy or psychiatric disorders.^4,5

Table 1

Physiologic and psychological causes of nonepileptic seizures

Physiologic
Autonomic disorders
Cerebrovascular disease
Cardiac disorders
Vasovagal syncope
Ischemic heart disease
Valvular heart disease
Arrythmias
Drug toxicity
Endocrine disturbance
Metabolic disorders
Migraines
Paroxysmal movement disorder
Sleep disorder
Psychological
Anxiety disorders
Conversion disorder
Dissociative disorder
Factitious disorder
Malingering
Victim of physical, emotional, or sexual abuse
Posttraumatic stress disorder
Psychotic disorder
Somatoform disorder
Substance abuse/dependence

Continued treatment: Wasted years

Two weeks after our referral, Ms. A reports that the neurologist discontinued topiramate and phenytoin after VEEG showed no epileptic activity.

Ms. A now realizes she does not have epilepsy. She is angry that her first neurologist had misdiag-nosed her, effectively sentencing her to 8 years of needless dependency and disability.

We prescribe escitalopram, starting at 10 mg/d and titrating to 20 mg/d, to address Ms. A’s depressive/PTSD symptoms. We also refer her to a psychotherapist, who schedules twice-weekly supportive psychotherapy sessions. The therapist plans to teach her coping techniques and provide ego support and encouragement.

Ms. A’s psychotherapy progresses slowly at first, but by the fourth session she sets goals, which include getting off disability as soon as possible. With careful ego strengthening, she resumes driving and searches for a job. During one session, she tells her therapist she has long wanted to become a nurse, so she is encouraged to see a nursing school counselor for advice on selecting prerequisite nursing classes.

The authors’ observations

As with Ms. A, an erroneous epilepsy diagnosis can cause physical, psychosocial, and socioeconomic grief for the patient and can lead to needless restrictions, unemployment or underemployment, and dependence on disability benefits. After the misdiagnosis, Ms. A lost control of her future and considered her life a burden, leading to depression and anxiety. Her seizures caused most of her physical and psychological disturbances and diminished her overall function.

PNES are often mistaken for epileptic seizures, and 26% of seizure patients experience both.⁶ In a study of 50 patients, between 5% and 20% of patients evaluated for epilepsy and 10% to 40% of patients referred to comprehensive epilepsy centers were later found to have PNES.⁷

Like Ms. A, many patients with undiagnosed PNES receive antiepileptics to treat apparent epilepsy. These medications can cause troublesome side effects—from GI problems, to respiratory arrest in patients with pseudostatus, to potential teratogenicity.

In addition, comorbid epilepsy often goes undetected in patients with PNES. This could lead to inadequate treatment, increasing the patient’s morbidity and mortality risk.⁸

poll here

The authors’ observations

Patient history. Take a thorough history for patients with a history of seizures.

Too often, doctors assume a previous epilepsy diagnosis is correct, especially if rendered by a neurologist. In the United Kingdom, 20% to 31% of epilepsy diagnoses are incorrect because of incomplete history and misinterpreted EEG findings.⁸ When taking a patient’s seizure history, clinicians often do not get:

• a detailed history of seizures or seizurelike events, including onset, frequency, observations from family or friends, and seizure duration
  
• information on whether the patient remembers seizure details; has had prespell aura or loss of consciousness, or cries during the spells
  
• history of physical and/or sexual abuse.
  

Multiple daily seizures, repeated hospitalizations or emergency room visits, minimal response to antiepileptics, and no history of injury after seizures could suggest nonepileptic seizures. Seizures may be psychogenic if the patient was sexually abused, has a comorbid psychiatric disorder, or suffers attacks only when alone or only in public (Table 2).

Refer patients with features that may suggest PNES to a neurologist for VEEG to confirm or rule out epilepsy, because roughly one-quarter of seizure patients can have both.

Table 2

Patient features that suggest nonepileptic seizures

Comorbid psychiatric disorder(s)
Events occur only in presence of others or only when alone
Lack of concern or excessive emotional response to seizures
Minimal or no response to antiepileptics
Multiple daily seizures
No history of injury resulting from seizures
Normal neurologic history and examination
Repeated hospitalizations or emergency room visits
Unremarkable EEG and MRI findings
Victim of sexual abuse

Finding psychological causes. Psychological investigations become paramount after physiologic causes for nonepileptic seizures are ruled out.

The Minnesota Multiphasic Personality Inventory (MMPI) is often used to discriminate PNES from epilepsy. Wilkus et al⁹ reported significant differences in scores of MMPI hypochondriasis, hysteria, and schizophrenia scales among patients with PNES and epilepsy. Patients with PNES may have higher MMPI hypochondriasis, hysteria, schizophrenia, and psychopathic deviate scores than do patients with epilepsy.

 

Other authors, however, have found more variable MMPI results when using the test to distinguish PNES from epilepsy. Thus, the MMPI may provide supportive data for PNES diagnosis but is not a definitive tool.

Explaining the findings. Getting the patient to accept that the epilepsy is “in your head” is crucial to engaging him or her in treatment. The clinician needs to be honest with the patient while projecting a positive approach to the diagnosis. Tell the patient that not having epilepsy is “good news,” that antiepileptics are not needed, and that he or she can gain better control once stress or emotional issues are resolved.¹⁰

Follow-up: A learning experience

Within 4 months of her last seizure, Ms. A showed dramatic improvement. She began driving, working part-time and enrolled in nursing school. Her disability benefits program provided tuition assistance.

Ms. A has now been seizure-free for 1 year. Motivated and determined, she is taking up to 8 credit hours per semester and earning As and Bs but at times is anxious and fears failure. She needs much support and encouragement. Multiple therapy techniques—including direct teaching, admiring her progress, offering support, explaining, and ego strengthening—have produced good results. She is still taking escitalopram, 20 mg/d, and sees her therapist every 2 weeks.

Related resources

• Adetunji B, Mathews M, Williams A, Verma S. Psychogenic or epileptic seizures? How to clinch the diagnosis. Current Psychiatry 2004;3(11):25-35.
  
• Privitera MD. EEGs and epilepsy: When seizures mimic psychiatric illness. Current Psychiatry 2002;1(9):14-21.
  

Drug brand names

• Bupropion • Wellbutrin, Zyban
  
• Carbamazepine • Tegretol
  
• Divalproex sodium • Depakote
  
• Escitalopram • Lexapro
  
• Mirtazapine • Remeron
  
• Phenytoin • Dilantin
  
• Topiramate • Topamax
  

Disclosure

Dr. Khan is a speaker for Pfizer and Wyeth.

Drs. Aziz and Syed report no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.