Neeta Shenai, MD

CASE Improvement, then decline
Ms. M, age 37, is brought to the hospi­tal after her husband found her at home, after an unknown duration of impaired consciousness. Her husband reports that Ms. M had normal cognitive functioning before this event, with no difficulty complet­ing activities of daily living. Ms. M’s medi­cal and psychiatric histories are notable for type 2 diabetes mellitus, unspecified bipolar disorder, and opioid, cocaine, and alcohol use disorders. Her medications include parox­etine, 40 mg/d, and gabapentin, 1,200 mg/d.

First admission. Poor inspiratory effort and oxygen saturation of 70% leads to emergent intubation. Serum laboratory studies reveal a white blood cell (WBC) count at 10,900/μL and creatinine phos­phokinase level of 25,000 U/L. Urine drug screen is positive for tetrahydrocannabinol, cocaine, and opioids.

Ms. M is admitted to the ICU for manage­ment of rhabdomyolysis and multi-organ system failure, including acute hypoxic kid­ney injury.

By hospital Day 7, the tube is extubated with no recorded physical neurologic defi­cits. Mental status exam is normal, except for impaired memory of events surrounding the admission. Ms. M is discharged home with a recommendation for outpatient follow-up.

2 Weeks later. Ms. M is brought to the emergency department after a progressive decrease in social interaction, limited oral intake, decline in activities of daily living, and urinary incontinence. Results from laboratory studies are within normal limits; brain MRI is negative; EEG shows generalized moderate slowing.

During psychiatric evaluation, Ms. M is mute and staring continuously. Examination reveals oppositional paratonia (gegen­halten), catalepsy, prominent negativism, and waxy flexibility, all suggestive of cata­tonia. IV lorazepam is initiated at 1 mg every 8 hours, titrated to 2 mg, 3 times a day.

Ms. M is transferred to a psychiatric hospi­tal for further treatment of catatonia.

Second admission. Evaluation with the Bush-Francis Catatonia Rating Scale supported a diagnosis of catatonia, with the presence of >3 features from the 14-item screen and a score of 16 on the 23-item rating scale.¹ After titrat­ing lorazepam to 9 mg/d with minimal thera­peutic impact, the psychiatry team consults the electroconvulsive therapy (ECT) service, who deems Ms. M to be an appropriate candidate and petitions for court-ordered ECT.

On hospital Day 8, Ms. M has a fever of 104°F, tachycardia at 180 beats per minute, increased rigidity, and a WBC count of 17,800/μL. She is transferred to the ICU, with a presumptive diagnosis of malignant catatonia.

The medical evaluation, including general laboratory studies, EEG, and spinal fluid anal­ysis, is unremarkable. Because of vital sign instability, 2 ECT treatments are completed in the general hospital before Ms. M resumes psychiatric inpatient care.

By the tenth ECT treatment, Ms. M is no longer febrile and experiences no further autonomic instability or psychomotor fea­tures of catatonia. Despite these improve­ments, she is noted to have persistent word-finding difficulty.

Which test would you order as the next step in your work up?
   a) EEG
   b) lumbar puncture
   c) MRI
   d) CT

The authors’ observations
In approximately 25% of cases, catatonia is caused by a general medical condition²; as such, a comprehensive medical workup is vital for assessment and management of catatonic patients. In Ms. M’s case, we con­sidered several medical causes, including nutritional deficiency, infection, a toxin, renal or hepatic impairment, hypothyroidism, sei­zure, and stroke. Evaluation included measurement of thyroid-stimulating hormone, vitamin B₁₂, and folic acid levels; urinalysis and urine drug screen; chest radiography; lumbar puncture; neuroimaging; and EEG (Table 1).

Several conditions in the differen­tial diagnosis were noteworthy. Ms. M’s severe and sudden neurologic decline, along with a positive urine drug screen for substances of abuse, raised concern about overdose leading to toxic encephalopathy or hypoxic brain injury. Ms. M’s oxygen saturation when she was found was mod­erately hypoxic at 70%, which is not a level associated with hypoxic brain damage.

We also considered posterior reversible encephalopathy syndrome (PRES), which presents variably with nausea, visual impairment, disturbance in conscious­ness, seizures, and focal neurologic signs.³ Although 67% to 80% of patients with PRES also have acute hypertension, blood pressure elevation is not necessary for the diagnosis.⁴ Similar to toxic leukoencepha­lopathy, PRES is diagnosed by brain MRI, with classic signs of posterior white-matter edema.

Case reports also describe an uncom­mon demyelinating syndrome, delayed post-hypoxic leukoencephalopathy (DPHL), which develops several weeks or months after a cerebral anoxic insult.⁵ In Ms. M’s case, brain MRI performed during her sec­ond medical hospitalization, 7 days after the initial neuropsychiatric decline, was unremarkable. Using this result to rule out DPHL would have been premature because pathognomonic abnormalities can appear as long as 40 days after the anoxic insult. Given our differential diagnosis, we ordered a repeat MRI.

Etiology and pathophysiology
First described in 1979, DPHL is rare, pos­ing diagnostic challenges for clinical pro­viders.⁶ Although the exact incidence of DPHL is unknown, the precipitating event typically involves cerebral anoxia, which can occur through carbon monoxide (CO) poisoning, strangulation, cardiac arrest, respiratory failure, and overdose from sed­atives and narcotics (Table 2).⁷ DPHL was first observed in a small percentage (2.75%) of patients suffering from CO poison­ing.^8,9 Progression of the disease generally includes a period of unconsciousness, then a lucid interval that can last 2 to 40 days, followed by the abrupt onset of neuropsy­chiatric symptoms.¹⁰ The specific patho­physiologic mechanism is unknown, but has been hypothesized to involve inferior compensatory response to decreased oxy­genation in the white matter.

Diagnosis and clinical features
DPHL can be divided into 2 clinical varia­tions: parkinsonism and akinetic mutism. The former consists of conventional par­kinsonian features along with agitation, apathy, hallucinations, dystonic postur­ing, and odd behaviors. The latter variant presents with apathy, minimal response to pain, functional bowel and bladder inconti­nence, mutism, and, at times, inappropriate laughter or tearfulness.⁵ Both variants share similar features with hypokinetic forms of catatonia.

DPHL is a diagnosis of exclusion. A careful history is critical to establish the possibility of a recent anoxic event. MRI findings, including hyperintensities in the cerebral white matter on T2-based sequencing, are suggestive of the disease. A choline peak on magnetic resonance spectroscopy also might be present in patients with DPHL, although it is not spe­cific to the diagnosis.

Early reports of DPHL suggested an associated deficiency of arylsulfatase A, an enzyme required in the modulation of myelin; however, more recent case reports are conflicting.¹¹ Familial mutations in the gene for arylsulfatase A also result in meta­chromatic leukodystrophy, and adult onset can present with psychiatric symptoms, including delusions and hallucinations.¹²

Treatment and prognosis
The treatment of DPHL consists primarily of supportive care and rehabilitation with physical, occupational, and speech ther­apy.¹¹ With these measures, most patients improve after 3 to 6 months; however, a large percentage sustain some long-term cognitive deficit, the most prevalent symp­tom being frontal executive dysfunction.⁵

OUTCOME Supportive care
A second MRI shows diffuse hyperintensities in the white matter that spare the cerebel­lum and brainstem (Figure). This finding is pathognomonic for DPHL.

ECT is discontinued because there is no evidence to support ECT-associated improve­ment in DPHL. Moreover, ECT might worsen the clinical course through increased stress and metabolic demand on the brain.¹³

Because the primary treatment of DPHL is early rehabilitation, we consider that Ms. M would benefit most from increased sup­portive care and therapy. She is discharged to a brain injury rehabilitation facility, where metoprolol is prescribed for mild tachycardia, along with thiamine and vitamins B₁₂ and D. Physical, occupational, and speech therapy are continued.

Approximately 3 weeks after admission to the rehabilitation program, Ms. M is dis­charged home. Although she improves in overall activities of daily living, she continues to experience moderate communication def­icits and occasional external distractibility.

Bottom Line
Although delayed post-hypoxic leukoencephalopathy is considered rare, consider it in the differential diagnosis when a patient has a recent history of an anoxic event followed by the abrupt onset of neuropsychiatric symptoms. Keep in mind that the condition can be missed if an MRI is obtained too early, and the clinical signs can mimic hypokinetic catatonia.

Related Resources
• Meyer MA. Delayed post-hypoxic leukoencephalopathy: case report with a review of disease pathophysiology. Neurol Int. 2013;5(3):e13. doi: 10.4081/ni.2013.e13.
• Aljarallah S, Al-Hussain F. Acute fatal posthypoxic leukoencephalopathy following benzodiazepine overdose: a case report and review of the literature. BMC Neurol. 2015;15:69.

Drug Brand Names
Gabapentin • Neurontin
Lorazepam • Ativan
Metoprolol • Lopressor
Paroxetine • Paxil

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of com

CASE Improvement, then decline
Ms. M, age 37, is brought to the hospi­tal after her husband found her at home, after an unknown duration of impaired consciousness. Her husband reports that Ms. M had normal cognitive functioning before this event, with no difficulty complet­ing activities of daily living. Ms. M’s medi­cal and psychiatric histories are notable for type 2 diabetes mellitus, unspecified bipolar disorder, and opioid, cocaine, and alcohol use disorders. Her medications include parox­etine, 40 mg/d, and gabapentin, 1,200 mg/d.

First admission. Poor inspiratory effort and oxygen saturation of 70% leads to emergent intubation. Serum laboratory studies reveal a white blood cell (WBC) count at 10,900/μL and creatinine phos­phokinase level of 25,000 U/L. Urine drug screen is positive for tetrahydrocannabinol, cocaine, and opioids.

Ms. M is admitted to the ICU for manage­ment of rhabdomyolysis and multi-organ system failure, including acute hypoxic kid­ney injury.

By hospital Day 7, the tube is extubated with no recorded physical neurologic defi­cits. Mental status exam is normal, except for impaired memory of events surrounding the admission. Ms. M is discharged home with a recommendation for outpatient follow-up.

2 Weeks later. Ms. M is brought to the emergency department after a progressive decrease in social interaction, limited oral intake, decline in activities of daily living, and urinary incontinence. Results from laboratory studies are within normal limits; brain MRI is negative; EEG shows generalized moderate slowing.

During psychiatric evaluation, Ms. M is mute and staring continuously. Examination reveals oppositional paratonia (gegen­halten), catalepsy, prominent negativism, and waxy flexibility, all suggestive of cata­tonia. IV lorazepam is initiated at 1 mg every 8 hours, titrated to 2 mg, 3 times a day.

Ms. M is transferred to a psychiatric hospi­tal for further treatment of catatonia.

Second admission. Evaluation with the Bush-Francis Catatonia Rating Scale supported a diagnosis of catatonia, with the presence of >3 features from the 14-item screen and a score of 16 on the 23-item rating scale.¹ After titrat­ing lorazepam to 9 mg/d with minimal thera­peutic impact, the psychiatry team consults the electroconvulsive therapy (ECT) service, who deems Ms. M to be an appropriate candidate and petitions for court-ordered ECT.

On hospital Day 8, Ms. M has a fever of 104°F, tachycardia at 180 beats per minute, increased rigidity, and a WBC count of 17,800/μL. She is transferred to the ICU, with a presumptive diagnosis of malignant catatonia.

The medical evaluation, including general laboratory studies, EEG, and spinal fluid anal­ysis, is unremarkable. Because of vital sign instability, 2 ECT treatments are completed in the general hospital before Ms. M resumes psychiatric inpatient care.

By the tenth ECT treatment, Ms. M is no longer febrile and experiences no further autonomic instability or psychomotor fea­tures of catatonia. Despite these improve­ments, she is noted to have persistent word-finding difficulty.

Which test would you order as the next step in your work up?
   a) EEG
   b) lumbar puncture
   c) MRI
   d) CT

The authors’ observations
In approximately 25% of cases, catatonia is caused by a general medical condition²; as such, a comprehensive medical workup is vital for assessment and management of catatonic patients. In Ms. M’s case, we con­sidered several medical causes, including nutritional deficiency, infection, a toxin, renal or hepatic impairment, hypothyroidism, sei­zure, and stroke. Evaluation included measurement of thyroid-stimulating hormone, vitamin B₁₂, and folic acid levels; urinalysis and urine drug screen; chest radiography; lumbar puncture; neuroimaging; and EEG (Table 1).

Several conditions in the differen­tial diagnosis were noteworthy. Ms. M’s severe and sudden neurologic decline, along with a positive urine drug screen for substances of abuse, raised concern about overdose leading to toxic encephalopathy or hypoxic brain injury. Ms. M’s oxygen saturation when she was found was mod­erately hypoxic at 70%, which is not a level associated with hypoxic brain damage.

We also considered posterior reversible encephalopathy syndrome (PRES), which presents variably with nausea, visual impairment, disturbance in conscious­ness, seizures, and focal neurologic signs.³ Although 67% to 80% of patients with PRES also have acute hypertension, blood pressure elevation is not necessary for the diagnosis.⁴ Similar to toxic leukoencepha­lopathy, PRES is diagnosed by brain MRI, with classic signs of posterior white-matter edema.

Case reports also describe an uncom­mon demyelinating syndrome, delayed post-hypoxic leukoencephalopathy (DPHL), which develops several weeks or months after a cerebral anoxic insult.⁵ In Ms. M’s case, brain MRI performed during her sec­ond medical hospitalization, 7 days after the initial neuropsychiatric decline, was unremarkable. Using this result to rule out DPHL would have been premature because pathognomonic abnormalities can appear as long as 40 days after the anoxic insult. Given our differential diagnosis, we ordered a repeat MRI.

Etiology and pathophysiology
First described in 1979, DPHL is rare, pos­ing diagnostic challenges for clinical pro­viders.⁶ Although the exact incidence of DPHL is unknown, the precipitating event typically involves cerebral anoxia, which can occur through carbon monoxide (CO) poisoning, strangulation, cardiac arrest, respiratory failure, and overdose from sed­atives and narcotics (Table 2).⁷ DPHL was first observed in a small percentage (2.75%) of patients suffering from CO poison­ing.^8,9 Progression of the disease generally includes a period of unconsciousness, then a lucid interval that can last 2 to 40 days, followed by the abrupt onset of neuropsy­chiatric symptoms.¹⁰ The specific patho­physiologic mechanism is unknown, but has been hypothesized to involve inferior compensatory response to decreased oxy­genation in the white matter.

Diagnosis and clinical features
DPHL can be divided into 2 clinical varia­tions: parkinsonism and akinetic mutism. The former consists of conventional par­kinsonian features along with agitation, apathy, hallucinations, dystonic postur­ing, and odd behaviors. The latter variant presents with apathy, minimal response to pain, functional bowel and bladder inconti­nence, mutism, and, at times, inappropriate laughter or tearfulness.⁵ Both variants share similar features with hypokinetic forms of catatonia.

DPHL is a diagnosis of exclusion. A careful history is critical to establish the possibility of a recent anoxic event. MRI findings, including hyperintensities in the cerebral white matter on T2-based sequencing, are suggestive of the disease. A choline peak on magnetic resonance spectroscopy also might be present in patients with DPHL, although it is not spe­cific to the diagnosis.

Early reports of DPHL suggested an associated deficiency of arylsulfatase A, an enzyme required in the modulation of myelin; however, more recent case reports are conflicting.¹¹ Familial mutations in the gene for arylsulfatase A also result in meta­chromatic leukodystrophy, and adult onset can present with psychiatric symptoms, including delusions and hallucinations.¹²

Treatment and prognosis
The treatment of DPHL consists primarily of supportive care and rehabilitation with physical, occupational, and speech ther­apy.¹¹ With these measures, most patients improve after 3 to 6 months; however, a large percentage sustain some long-term cognitive deficit, the most prevalent symp­tom being frontal executive dysfunction.⁵

OUTCOME Supportive care
A second MRI shows diffuse hyperintensities in the white matter that spare the cerebel­lum and brainstem (Figure). This finding is pathognomonic for DPHL.

ECT is discontinued because there is no evidence to support ECT-associated improve­ment in DPHL. Moreover, ECT might worsen the clinical course through increased stress and metabolic demand on the brain.¹³

Because the primary treatment of DPHL is early rehabilitation, we consider that Ms. M would benefit most from increased sup­portive care and therapy. She is discharged to a brain injury rehabilitation facility, where metoprolol is prescribed for mild tachycardia, along with thiamine and vitamins B₁₂ and D. Physical, occupational, and speech therapy are continued.

Approximately 3 weeks after admission to the rehabilitation program, Ms. M is dis­charged home. Although she improves in overall activities of daily living, she continues to experience moderate communication def­icits and occasional external distractibility.

Bottom Line
Although delayed post-hypoxic leukoencephalopathy is considered rare, consider it in the differential diagnosis when a patient has a recent history of an anoxic event followed by the abrupt onset of neuropsychiatric symptoms. Keep in mind that the condition can be missed if an MRI is obtained too early, and the clinical signs can mimic hypokinetic catatonia.

Related Resources
• Meyer MA. Delayed post-hypoxic leukoencephalopathy: case report with a review of disease pathophysiology. Neurol Int. 2013;5(3):e13. doi: 10.4081/ni.2013.e13.
• Aljarallah S, Al-Hussain F. Acute fatal posthypoxic leukoencephalopathy following benzodiazepine overdose: a case report and review of the literature. BMC Neurol. 2015;15:69.

Drug Brand Names
Gabapentin • Neurontin
Lorazepam • Ativan
Metoprolol • Lopressor
Paroxetine • Paxil

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of com

CASE Improvement, then decline
Ms. M, age 37, is brought to the hospi­tal after her husband found her at home, after an unknown duration of impaired consciousness. Her husband reports that Ms. M had normal cognitive functioning before this event, with no difficulty complet­ing activities of daily living. Ms. M’s medi­cal and psychiatric histories are notable for type 2 diabetes mellitus, unspecified bipolar disorder, and opioid, cocaine, and alcohol use disorders. Her medications include parox­etine, 40 mg/d, and gabapentin, 1,200 mg/d.

First admission. Poor inspiratory effort and oxygen saturation of 70% leads to emergent intubation. Serum laboratory studies reveal a white blood cell (WBC) count at 10,900/μL and creatinine phos­phokinase level of 25,000 U/L. Urine drug screen is positive for tetrahydrocannabinol, cocaine, and opioids.

Ms. M is admitted to the ICU for manage­ment of rhabdomyolysis and multi-organ system failure, including acute hypoxic kid­ney injury.

By hospital Day 7, the tube is extubated with no recorded physical neurologic defi­cits. Mental status exam is normal, except for impaired memory of events surrounding the admission. Ms. M is discharged home with a recommendation for outpatient follow-up.

2 Weeks later. Ms. M is brought to the emergency department after a progressive decrease in social interaction, limited oral intake, decline in activities of daily living, and urinary incontinence. Results from laboratory studies are within normal limits; brain MRI is negative; EEG shows generalized moderate slowing.

During psychiatric evaluation, Ms. M is mute and staring continuously. Examination reveals oppositional paratonia (gegen­halten), catalepsy, prominent negativism, and waxy flexibility, all suggestive of cata­tonia. IV lorazepam is initiated at 1 mg every 8 hours, titrated to 2 mg, 3 times a day.

Ms. M is transferred to a psychiatric hospi­tal for further treatment of catatonia.

Second admission. Evaluation with the Bush-Francis Catatonia Rating Scale supported a diagnosis of catatonia, with the presence of >3 features from the 14-item screen and a score of 16 on the 23-item rating scale.¹ After titrat­ing lorazepam to 9 mg/d with minimal thera­peutic impact, the psychiatry team consults the electroconvulsive therapy (ECT) service, who deems Ms. M to be an appropriate candidate and petitions for court-ordered ECT.

On hospital Day 8, Ms. M has a fever of 104°F, tachycardia at 180 beats per minute, increased rigidity, and a WBC count of 17,800/μL. She is transferred to the ICU, with a presumptive diagnosis of malignant catatonia.

The medical evaluation, including general laboratory studies, EEG, and spinal fluid anal­ysis, is unremarkable. Because of vital sign instability, 2 ECT treatments are completed in the general hospital before Ms. M resumes psychiatric inpatient care.

By the tenth ECT treatment, Ms. M is no longer febrile and experiences no further autonomic instability or psychomotor fea­tures of catatonia. Despite these improve­ments, she is noted to have persistent word-finding difficulty.

Which test would you order as the next step in your work up?
   a) EEG
   b) lumbar puncture
   c) MRI
   d) CT

The authors’ observations
In approximately 25% of cases, catatonia is caused by a general medical condition²; as such, a comprehensive medical workup is vital for assessment and management of catatonic patients. In Ms. M’s case, we con­sidered several medical causes, including nutritional deficiency, infection, a toxin, renal or hepatic impairment, hypothyroidism, sei­zure, and stroke. Evaluation included measurement of thyroid-stimulating hormone, vitamin B₁₂, and folic acid levels; urinalysis and urine drug screen; chest radiography; lumbar puncture; neuroimaging; and EEG (Table 1).

Several conditions in the differen­tial diagnosis were noteworthy. Ms. M’s severe and sudden neurologic decline, along with a positive urine drug screen for substances of abuse, raised concern about overdose leading to toxic encephalopathy or hypoxic brain injury. Ms. M’s oxygen saturation when she was found was mod­erately hypoxic at 70%, which is not a level associated with hypoxic brain damage.

We also considered posterior reversible encephalopathy syndrome (PRES), which presents variably with nausea, visual impairment, disturbance in conscious­ness, seizures, and focal neurologic signs.³ Although 67% to 80% of patients with PRES also have acute hypertension, blood pressure elevation is not necessary for the diagnosis.⁴ Similar to toxic leukoencepha­lopathy, PRES is diagnosed by brain MRI, with classic signs of posterior white-matter edema.

Case reports also describe an uncom­mon demyelinating syndrome, delayed post-hypoxic leukoencephalopathy (DPHL), which develops several weeks or months after a cerebral anoxic insult.⁵ In Ms. M’s case, brain MRI performed during her sec­ond medical hospitalization, 7 days after the initial neuropsychiatric decline, was unremarkable. Using this result to rule out DPHL would have been premature because pathognomonic abnormalities can appear as long as 40 days after the anoxic insult. Given our differential diagnosis, we ordered a repeat MRI.

Etiology and pathophysiology
First described in 1979, DPHL is rare, pos­ing diagnostic challenges for clinical pro­viders.⁶ Although the exact incidence of DPHL is unknown, the precipitating event typically involves cerebral anoxia, which can occur through carbon monoxide (CO) poisoning, strangulation, cardiac arrest, respiratory failure, and overdose from sed­atives and narcotics (Table 2).⁷ DPHL was first observed in a small percentage (2.75%) of patients suffering from CO poison­ing.^8,9 Progression of the disease generally includes a period of unconsciousness, then a lucid interval that can last 2 to 40 days, followed by the abrupt onset of neuropsy­chiatric symptoms.¹⁰ The specific patho­physiologic mechanism is unknown, but has been hypothesized to involve inferior compensatory response to decreased oxy­genation in the white matter.

Diagnosis and clinical features
DPHL can be divided into 2 clinical varia­tions: parkinsonism and akinetic mutism. The former consists of conventional par­kinsonian features along with agitation, apathy, hallucinations, dystonic postur­ing, and odd behaviors. The latter variant presents with apathy, minimal response to pain, functional bowel and bladder inconti­nence, mutism, and, at times, inappropriate laughter or tearfulness.⁵ Both variants share similar features with hypokinetic forms of catatonia.

DPHL is a diagnosis of exclusion. A careful history is critical to establish the possibility of a recent anoxic event. MRI findings, including hyperintensities in the cerebral white matter on T2-based sequencing, are suggestive of the disease. A choline peak on magnetic resonance spectroscopy also might be present in patients with DPHL, although it is not spe­cific to the diagnosis.

Early reports of DPHL suggested an associated deficiency of arylsulfatase A, an enzyme required in the modulation of myelin; however, more recent case reports are conflicting.¹¹ Familial mutations in the gene for arylsulfatase A also result in meta­chromatic leukodystrophy, and adult onset can present with psychiatric symptoms, including delusions and hallucinations.¹²

Treatment and prognosis
The treatment of DPHL consists primarily of supportive care and rehabilitation with physical, occupational, and speech ther­apy.¹¹ With these measures, most patients improve after 3 to 6 months; however, a large percentage sustain some long-term cognitive deficit, the most prevalent symp­tom being frontal executive dysfunction.⁵

OUTCOME Supportive care
A second MRI shows diffuse hyperintensities in the white matter that spare the cerebel­lum and brainstem (Figure). This finding is pathognomonic for DPHL.

ECT is discontinued because there is no evidence to support ECT-associated improve­ment in DPHL. Moreover, ECT might worsen the clinical course through increased stress and metabolic demand on the brain.¹³

Because the primary treatment of DPHL is early rehabilitation, we consider that Ms. M would benefit most from increased sup­portive care and therapy. She is discharged to a brain injury rehabilitation facility, where metoprolol is prescribed for mild tachycardia, along with thiamine and vitamins B₁₂ and D. Physical, occupational, and speech therapy are continued.

Approximately 3 weeks after admission to the rehabilitation program, Ms. M is dis­charged home. Although she improves in overall activities of daily living, she continues to experience moderate communication def­icits and occasional external distractibility.

Bottom Line
Although delayed post-hypoxic leukoencephalopathy is considered rare, consider it in the differential diagnosis when a patient has a recent history of an anoxic event followed by the abrupt onset of neuropsychiatric symptoms. Keep in mind that the condition can be missed if an MRI is obtained too early, and the clinical signs can mimic hypokinetic catatonia.

Related Resources
• Meyer MA. Delayed post-hypoxic leukoencephalopathy: case report with a review of disease pathophysiology. Neurol Int. 2013;5(3):e13. doi: 10.4081/ni.2013.e13.
• Aljarallah S, Al-Hussain F. Acute fatal posthypoxic leukoencephalopathy following benzodiazepine overdose: a case report and review of the literature. BMC Neurol. 2015;15:69.

Drug Brand Names
Gabapentin • Neurontin
Lorazepam • Ativan
Metoprolol • Lopressor
Paroxetine • Paxil

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of com