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Erik Greb joined the staff of Neurology Reviews in January 2012. Since then, he has attended scientific conferences, conducted video interviews, and written about clinical research in multiple sclerosis, epilepsy, Parkinson's disease, Alzheimer's disease, stroke, and other neurologic disorders. In addition to news articles, Erik has written investigative stories about multiple sclerosis, headache, and epilepsy. He previously wrote about pharmaceutical manufacturing, drug formulation and delivery, quality assurance, and regulation for Pharmaceutical Technology.
Depression is linked to seizure frequency in patients with epilepsy
NEW ORLEANS –
The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively
Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.
Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”
The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.
“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”
Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.
“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”
This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
SOURCE: Kumar N et al. AES 2018, Abstract 1.371.
NEW ORLEANS –
The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively
Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.
Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”
The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.
“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”
Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.
“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”
This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
SOURCE: Kumar N et al. AES 2018, Abstract 1.371.
NEW ORLEANS –
The conclusion comes from a study of 120 people with epilepsy, 62 of whom had at least moderate depression based on the Patient Health Questionnaire-9 (PHQ-9). The Rapid Estimate of Adult Literacy in Medicine (REALM-R), Quality of Life in Epilepsy (QOLIE-10) and Charlson Comorbidity Index were used to assess patients’ health literacy, quality of life, and medical comorbidity, respectively
Among demographic characteristics, only inability to work was significantly associated with depression severity. Higher 30-day seizure frequency, panic disorder, and obsessive-compulsive disorder were correlated with more severe depression severity. Medical comorbidity was not associated with increased risk of depression.
Identifying and treating psychiatric comorbidities should be part of the management of patients with epilepsy, said Martha X. Sajatovic, MD, director of the Neurological and Behavioral Outcomes Center at Case Western Reserve University in Cleveland, who presented the data. “Following up to ensure they receive treatment is vital, because it can truly change patient outcomes and help them achieve their best quality of life.”
The study findings are consistent with those of previous research indicating that people with symptoms of depression are more likely to have more frequent seizures and decreased quality of life, said Dr. Sajatovic.
“Health care providers should screen their epilepsy patients for depression, but they shouldn’t stop there,” she advised. “A person may have depressive symptoms that don’t reach the level of depression but should be assessed for other types of mental health issues that could easily be overlooked.”
Patients with epilepsy should respond to the PHQ-9 annually, or more frequently, if warranted, she added.
“It’s important that people with epilepsy who have depression or other mental health issues get treatment such as cognitive behavioral therapy and medication,” said Dr. Sajatovic. “Even being in a self-management program helps, because the better they are at self management, the less likely they are to suffer negative health effects.”
This study was supported by a grant from the Centers for Disease Control and Prevention SIP 14-007 1U48DP005030.
SOURCE: Kumar N et al. AES 2018, Abstract 1.371.
REPORTING FROM AES 2018
Key clinical point: Identification and treatment of psychiatric comorbidities are appropriate components of epilepsy management.
Major finding: Half of participants in a randomized, controlled trial had depression of at least moderate severity.
Study details: Researchers analyzed data from a trial of 120 people with epilepsy.
Disclosures: This study was supported by a grant from the CDC SIP 14-007 1U48DP005030.
Source: Kumar N et al. Abstract 1.371.
Teenagers with epilepsy may benefit from depression screening
NEW ORLEANS – Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.
“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”
Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.
As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.
Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.
“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.
The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
SOURCE: Thomas HM et al. Abstract 1.388.
NEW ORLEANS – Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.
“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”
Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.
As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.
Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.
“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.
The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
SOURCE: Thomas HM et al. Abstract 1.388.
NEW ORLEANS – Referral to a mental health provider is adequate for most patients with moderately severe symptoms of depression, but some patients may require active intervention during the clinical visit, said the researchers.
“We know that depression is more common in people with epilepsy, compared to the general population, but there is less information about depression in children and teens than adults, and little is known about the factors that increase the likelihood of depressive symptoms,” said Hillary Thomas, PhD, a pediatric psychologist at Children’s Medical Center in Dallas. “Depression screening should be routine at epilepsy treatment centers and can identify children and teens who would benefit from intervention.”
Following 2015 guidelines from the American Academy of Neurology, the Comprehensive Epilepsy Center at Children’s Health System in Dallas developed a behavioral health screening protocol for teens with epilepsy. The center aims to identify patients with depressive symptoms and ensure that they are referred to appropriate behavioral health practitioners. Clinicians also review the screening data and seizure variables for their potential implications for clinical care. Researchers at the center also seek to elucidate the relationship between depressive symptoms and seizure diagnosis and treatment.
As part of the protocol, Dr. Thomas and her colleagues administer the Patient Health Questionnaire-9 (adolescent version) to all patients aged 15-18 years during their visit to the epilepsy clinic. Patients with intellectual disability or other factors that prevent them from providing valid responses are excluded. If a patient’s PHQ-9 score indicates at least moderately severe depressive symptoms, or if he or she reports suicidal ideation, clinicians follow a specific response protocol that includes providing referrals, encouraging follow-up with the patient’s current mental health provider, and obtaining a suicide risk assessment from a psychologist or social worker. After the screener is completed, clinicians retrieve demographic and clinical data (e.g., seizure diagnosis, medication, number of clinic or emergency department visits) from the patient’s medical record and include them in a database for subsequent analysis.
Dr. Thomas and her colleagues presented data from 394 youth with epilepsy whom they had screened. Patients’ mean age was 16 years, and half of the population was female. The study population had rates of depression similar to those identified in previous studies, said Dr. Thomas. Approximately 87% of patients had minimal or mild depressive symptoms, and 8% had moderately severe depressive symptoms. Furthermore, 5% of the patients reported suicidal ideation or previous suicide attempt. Several of the patients with suicidal ideation had a current mental health provider, and the others required an in-clinic risk assessment. Overall, 13% of the population required behavioral health referral or intervention. When the researchers conducted chi-squared analysis, they found no significant association between seizure type and depression severity.
“Our results don’t mean that only 13% of the teens with epilepsy had depressive symptoms,” said Susan Arnold, MD, director of the Comprehensive Epilepsy Center and a coauthor of the study. “They indicate the significant percentage of teens whose level of depressive symptoms warranted behavioral health referrals or further evaluation or even intervention during a clinic visit. Health care providers need to be vigilant about continually screening children and teens for depression.” As part of each patient’s comprehensive care, epilepsy treatment centers should provide psychosocial teams that include social workers or psychologists, she added.
The investigators plan to continue analyzing the data for specific depression symptoms that are most common in teens. These symptoms could be the basis for developing additional resources for families, such as lists of warning signs and guides to symptom management, as well as group therapy and support groups.
SOURCE: Thomas HM et al. Abstract 1.388.
REPORTING FROM AES 2018
Key clinical point: Screening children with epilepsy regularly for depression may be advisable.
Major finding: About 13% of patients screened required referral or intervention.
Study details: Prospective study of 394 patients with epilepsy.
Disclosures: The investigators have no disclosures and received no funding for this study.
Source: Thomas HM et al. Abstract 1.388.
Pseudobulbar Affect Is Common in Iraq and Afghanistan War Veterans With TBI
PHILADELPHIA—Between 60% and 70% of veterans of the wars in Iraq and Afghanistan who screened positive for traumatic brain injury (TBI) have symptoms of pseudobulbar affect (PBA), according to data presented at the 66th Annual Meeting of the American Academy of Neurology. Compared with those without PBA symptoms, veterans with PBA symptoms have higher rates of depression and posttraumatic stress disorder (PTSD) and use antidepressants, opioids, sedatives, and antiepileptic drugs more often.
Jennifer R. Fonda, a researcher at the Translational Research Center for Traumatic Brain Injury and Stress Disorders in the VA Boston Healthcare System, and colleagues conducted a cross-sectional study during which they searched VA clinical and demographic databases for veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who screened positive for TBI and who were receiving care from a VA facility in New England.
[To continue reading, click here.]
PHILADELPHIA—Between 60% and 70% of veterans of the wars in Iraq and Afghanistan who screened positive for traumatic brain injury (TBI) have symptoms of pseudobulbar affect (PBA), according to data presented at the 66th Annual Meeting of the American Academy of Neurology. Compared with those without PBA symptoms, veterans with PBA symptoms have higher rates of depression and posttraumatic stress disorder (PTSD) and use antidepressants, opioids, sedatives, and antiepileptic drugs more often.
Jennifer R. Fonda, a researcher at the Translational Research Center for Traumatic Brain Injury and Stress Disorders in the VA Boston Healthcare System, and colleagues conducted a cross-sectional study during which they searched VA clinical and demographic databases for veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who screened positive for TBI and who were receiving care from a VA facility in New England.
[To continue reading, click here.]
PHILADELPHIA—Between 60% and 70% of veterans of the wars in Iraq and Afghanistan who screened positive for traumatic brain injury (TBI) have symptoms of pseudobulbar affect (PBA), according to data presented at the 66th Annual Meeting of the American Academy of Neurology. Compared with those without PBA symptoms, veterans with PBA symptoms have higher rates of depression and posttraumatic stress disorder (PTSD) and use antidepressants, opioids, sedatives, and antiepileptic drugs more often.
Jennifer R. Fonda, a researcher at the Translational Research Center for Traumatic Brain Injury and Stress Disorders in the VA Boston Healthcare System, and colleagues conducted a cross-sectional study during which they searched VA clinical and demographic databases for veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn who screened positive for TBI and who were receiving care from a VA facility in New England.
[To continue reading, click here.]
IHS to Solicit Public Comment on Revised Headache Classification Criteria
STOWE, VERMONT—The third edition of the International Classification of Headache Disorders will soon be available on the website of the International Headache Society, Morris Levin, MD, reported at the 23rd Annual Headache Symposium of the Headache Cooperative of New England. The document will be presented in a “beta version,” and headache specialists are encouraged to review it and submit comments, said Dr. Levin, a neurologist at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. The classification will be incorporated into the 11th edition of the World Health Organization’s International Classification of Diseases, “which is unusual for a subset or specialty,” said Dr. Levin.
Frequency of Headaches in Chronic Migraine Has Decreased
The third edition of the classification contains various modifications to the section on primary headache. For example, the new definition of chronic migraine is eight migraine headaches or headaches that respond to migraine treatment per month and seven or more additional headaches per month. The previous definition of chronic migraine was 15 or more migraines per month.
Because of growing evidence that benign positional vertigo is a migraine variant, the condition was included in the migraine chapter of the new classification. In the same chapter, typical aura with migraine headache was renamed “migraine with typical aura.”
Basilar type migraine has been renamed “migraine with brainstem aura.” To receive this diagnosis, a patient must have at least two brainstem symptoms, which include dysarthria, vertigo, tinnitus, hypoacusis, diplopia, ataxia, and consciousness alteration. Neurologists may argue, however, that these symptoms indicate cortical dysfunction, rather than brainstem dysfunction, said Dr. Levin.
The chapter about trigeminal autonomic cephalalgias has undergone several changes in the new classification. Short, unilateral, neuralgiform (SUN) headaches were combined into one entity with two subcategories. SUN headaches accompanied by conjunctival injectional tearing are called SUNCT, and SUN headaches with other autonomic features are called SUNA. In addition, the duration of SUN headaches is now from one to 600 seconds instead of 0.5 to 600 seconds. SUN headaches can be episodic or chronic. Also, hemicrania continua is now in the chapter about trigeminal autonomic cephalalgias instead of the chapter about other primary headaches.
Cold stimulus headache and external compression headache were added to the chapter about other primary headaches. The same chapter contains primary headache associated with sexual activity, a new entity that combines orgasmic headache and preorgasmic headache. The definition of new daily persistent headache also was broadened to include migrainous headaches, which constitutes “an important change,” said Dr. Levin.
No Specific Features Required for Medication Overuse Headache
It can be difficult to know whether a headache is primary or secondary, noted Dr. Levin. A secondary headache should occur close in time to the cause of the disorder and often improves if the cause is removed. But a headache’s failure to resolve when its ostensible cause is removed “is not evidence against secondary headache,” he added. Unlike the previous edition of the classification, the new edition does not require the headache to resolve when the ostensible cause is removed.
“If the headache has features of a particular primary headache, but has arisen after a presumed secondary cause, classify it as a secondary headache,” said Dr. Levin. “That’s the best way to do it. On the other hand, [you should] treat it like the primary headache that it resembles.”
The description of medication overuse headache has changed in the new classification. Particular headache features are no longer required for this diagnosis, because “secondary headaches can take on many different morphologies,” said Dr. Levin. The new classification also does not require medication overuse headache to resolve after discontinuation of the overused medication.
Because medication overuse headache can be hard to distinguish from chronic migraine, the new classification suggests that clinicians who suspect medication overuse code a patient for probable medication overuse headache and probable chronic migraine. “When there are more data to support one or the other, you can change the diagnosis,” explained Dr. Levin.
Appendix Includes Various New Headaches
The new classification also includes various additions to the appendix, which is “probably the most interesting part of the whole document,” according to Dr. Levin. One addition, vestibular migraine, may be appropriate for patients who have episodic vertigo with or without headache. At least 50% of vestibular migraine episodes must be associated with at least one migraine feature, according to the classification. The diagnosis is important, because the condition “may respond to migraine treatment,” said Dr. Levin.
Although the new classification requires postconcussive headaches to appear within seven days of injury, the appendix now contains an entry called post-traumatic headache with delayed onset. The definition for cervicogenic headache has become broader, allowing for several more possible conditions to produce this type of secondary headache. Also, the appendix includes several more proposed subtypes of cervicogenic headache.
As with previous versions of the ICHD, the classification is intended for multiple uses, including research and clinical practice, but is still a work in progress. All of the headache types in the appendix are “fertile areas for research,” Dr. Levin concluded.
—Erik Greb
Senior Associate Editor
Suggested Reading
Buse DC, Lipton RB. Global perspectives on the burden of episodic and chronic migraine. Cephalalgia. 2013 Mar 12 [Epub ahead of print].
Pareja JA, Alvarez M, Montojo T. SUNCT and SUNA: recognition and treatment. Curr Treat Options Neurol. 2013;15(1):28-39.
Sances G, Galli F, Ghiotto N, et al. Factors associated with a negative outcome of medication-overuse headache: A 3-year follow-up (the ‘CARE’ protocol). Cephalalgia. 2013 Feb 26 [Epub ahead of print].
STOWE, VERMONT—The third edition of the International Classification of Headache Disorders will soon be available on the website of the International Headache Society, Morris Levin, MD, reported at the 23rd Annual Headache Symposium of the Headache Cooperative of New England. The document will be presented in a “beta version,” and headache specialists are encouraged to review it and submit comments, said Dr. Levin, a neurologist at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. The classification will be incorporated into the 11th edition of the World Health Organization’s International Classification of Diseases, “which is unusual for a subset or specialty,” said Dr. Levin.
Frequency of Headaches in Chronic Migraine Has Decreased
The third edition of the classification contains various modifications to the section on primary headache. For example, the new definition of chronic migraine is eight migraine headaches or headaches that respond to migraine treatment per month and seven or more additional headaches per month. The previous definition of chronic migraine was 15 or more migraines per month.
Because of growing evidence that benign positional vertigo is a migraine variant, the condition was included in the migraine chapter of the new classification. In the same chapter, typical aura with migraine headache was renamed “migraine with typical aura.”
Basilar type migraine has been renamed “migraine with brainstem aura.” To receive this diagnosis, a patient must have at least two brainstem symptoms, which include dysarthria, vertigo, tinnitus, hypoacusis, diplopia, ataxia, and consciousness alteration. Neurologists may argue, however, that these symptoms indicate cortical dysfunction, rather than brainstem dysfunction, said Dr. Levin.
The chapter about trigeminal autonomic cephalalgias has undergone several changes in the new classification. Short, unilateral, neuralgiform (SUN) headaches were combined into one entity with two subcategories. SUN headaches accompanied by conjunctival injectional tearing are called SUNCT, and SUN headaches with other autonomic features are called SUNA. In addition, the duration of SUN headaches is now from one to 600 seconds instead of 0.5 to 600 seconds. SUN headaches can be episodic or chronic. Also, hemicrania continua is now in the chapter about trigeminal autonomic cephalalgias instead of the chapter about other primary headaches.
Cold stimulus headache and external compression headache were added to the chapter about other primary headaches. The same chapter contains primary headache associated with sexual activity, a new entity that combines orgasmic headache and preorgasmic headache. The definition of new daily persistent headache also was broadened to include migrainous headaches, which constitutes “an important change,” said Dr. Levin.
No Specific Features Required for Medication Overuse Headache
It can be difficult to know whether a headache is primary or secondary, noted Dr. Levin. A secondary headache should occur close in time to the cause of the disorder and often improves if the cause is removed. But a headache’s failure to resolve when its ostensible cause is removed “is not evidence against secondary headache,” he added. Unlike the previous edition of the classification, the new edition does not require the headache to resolve when the ostensible cause is removed.
“If the headache has features of a particular primary headache, but has arisen after a presumed secondary cause, classify it as a secondary headache,” said Dr. Levin. “That’s the best way to do it. On the other hand, [you should] treat it like the primary headache that it resembles.”
The description of medication overuse headache has changed in the new classification. Particular headache features are no longer required for this diagnosis, because “secondary headaches can take on many different morphologies,” said Dr. Levin. The new classification also does not require medication overuse headache to resolve after discontinuation of the overused medication.
Because medication overuse headache can be hard to distinguish from chronic migraine, the new classification suggests that clinicians who suspect medication overuse code a patient for probable medication overuse headache and probable chronic migraine. “When there are more data to support one or the other, you can change the diagnosis,” explained Dr. Levin.
Appendix Includes Various New Headaches
The new classification also includes various additions to the appendix, which is “probably the most interesting part of the whole document,” according to Dr. Levin. One addition, vestibular migraine, may be appropriate for patients who have episodic vertigo with or without headache. At least 50% of vestibular migraine episodes must be associated with at least one migraine feature, according to the classification. The diagnosis is important, because the condition “may respond to migraine treatment,” said Dr. Levin.
Although the new classification requires postconcussive headaches to appear within seven days of injury, the appendix now contains an entry called post-traumatic headache with delayed onset. The definition for cervicogenic headache has become broader, allowing for several more possible conditions to produce this type of secondary headache. Also, the appendix includes several more proposed subtypes of cervicogenic headache.
As with previous versions of the ICHD, the classification is intended for multiple uses, including research and clinical practice, but is still a work in progress. All of the headache types in the appendix are “fertile areas for research,” Dr. Levin concluded.
—Erik Greb
Senior Associate Editor
Suggested Reading
Buse DC, Lipton RB. Global perspectives on the burden of episodic and chronic migraine. Cephalalgia. 2013 Mar 12 [Epub ahead of print].
Pareja JA, Alvarez M, Montojo T. SUNCT and SUNA: recognition and treatment. Curr Treat Options Neurol. 2013;15(1):28-39.
Sances G, Galli F, Ghiotto N, et al. Factors associated with a negative outcome of medication-overuse headache: A 3-year follow-up (the ‘CARE’ protocol). Cephalalgia. 2013 Feb 26 [Epub ahead of print].
STOWE, VERMONT—The third edition of the International Classification of Headache Disorders will soon be available on the website of the International Headache Society, Morris Levin, MD, reported at the 23rd Annual Headache Symposium of the Headache Cooperative of New England. The document will be presented in a “beta version,” and headache specialists are encouraged to review it and submit comments, said Dr. Levin, a neurologist at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. The classification will be incorporated into the 11th edition of the World Health Organization’s International Classification of Diseases, “which is unusual for a subset or specialty,” said Dr. Levin.
Frequency of Headaches in Chronic Migraine Has Decreased
The third edition of the classification contains various modifications to the section on primary headache. For example, the new definition of chronic migraine is eight migraine headaches or headaches that respond to migraine treatment per month and seven or more additional headaches per month. The previous definition of chronic migraine was 15 or more migraines per month.
Because of growing evidence that benign positional vertigo is a migraine variant, the condition was included in the migraine chapter of the new classification. In the same chapter, typical aura with migraine headache was renamed “migraine with typical aura.”
Basilar type migraine has been renamed “migraine with brainstem aura.” To receive this diagnosis, a patient must have at least two brainstem symptoms, which include dysarthria, vertigo, tinnitus, hypoacusis, diplopia, ataxia, and consciousness alteration. Neurologists may argue, however, that these symptoms indicate cortical dysfunction, rather than brainstem dysfunction, said Dr. Levin.
The chapter about trigeminal autonomic cephalalgias has undergone several changes in the new classification. Short, unilateral, neuralgiform (SUN) headaches were combined into one entity with two subcategories. SUN headaches accompanied by conjunctival injectional tearing are called SUNCT, and SUN headaches with other autonomic features are called SUNA. In addition, the duration of SUN headaches is now from one to 600 seconds instead of 0.5 to 600 seconds. SUN headaches can be episodic or chronic. Also, hemicrania continua is now in the chapter about trigeminal autonomic cephalalgias instead of the chapter about other primary headaches.
Cold stimulus headache and external compression headache were added to the chapter about other primary headaches. The same chapter contains primary headache associated with sexual activity, a new entity that combines orgasmic headache and preorgasmic headache. The definition of new daily persistent headache also was broadened to include migrainous headaches, which constitutes “an important change,” said Dr. Levin.
No Specific Features Required for Medication Overuse Headache
It can be difficult to know whether a headache is primary or secondary, noted Dr. Levin. A secondary headache should occur close in time to the cause of the disorder and often improves if the cause is removed. But a headache’s failure to resolve when its ostensible cause is removed “is not evidence against secondary headache,” he added. Unlike the previous edition of the classification, the new edition does not require the headache to resolve when the ostensible cause is removed.
“If the headache has features of a particular primary headache, but has arisen after a presumed secondary cause, classify it as a secondary headache,” said Dr. Levin. “That’s the best way to do it. On the other hand, [you should] treat it like the primary headache that it resembles.”
The description of medication overuse headache has changed in the new classification. Particular headache features are no longer required for this diagnosis, because “secondary headaches can take on many different morphologies,” said Dr. Levin. The new classification also does not require medication overuse headache to resolve after discontinuation of the overused medication.
Because medication overuse headache can be hard to distinguish from chronic migraine, the new classification suggests that clinicians who suspect medication overuse code a patient for probable medication overuse headache and probable chronic migraine. “When there are more data to support one or the other, you can change the diagnosis,” explained Dr. Levin.
Appendix Includes Various New Headaches
The new classification also includes various additions to the appendix, which is “probably the most interesting part of the whole document,” according to Dr. Levin. One addition, vestibular migraine, may be appropriate for patients who have episodic vertigo with or without headache. At least 50% of vestibular migraine episodes must be associated with at least one migraine feature, according to the classification. The diagnosis is important, because the condition “may respond to migraine treatment,” said Dr. Levin.
Although the new classification requires postconcussive headaches to appear within seven days of injury, the appendix now contains an entry called post-traumatic headache with delayed onset. The definition for cervicogenic headache has become broader, allowing for several more possible conditions to produce this type of secondary headache. Also, the appendix includes several more proposed subtypes of cervicogenic headache.
As with previous versions of the ICHD, the classification is intended for multiple uses, including research and clinical practice, but is still a work in progress. All of the headache types in the appendix are “fertile areas for research,” Dr. Levin concluded.
—Erik Greb
Senior Associate Editor
Suggested Reading
Buse DC, Lipton RB. Global perspectives on the burden of episodic and chronic migraine. Cephalalgia. 2013 Mar 12 [Epub ahead of print].
Pareja JA, Alvarez M, Montojo T. SUNCT and SUNA: recognition and treatment. Curr Treat Options Neurol. 2013;15(1):28-39.
Sances G, Galli F, Ghiotto N, et al. Factors associated with a negative outcome of medication-overuse headache: A 3-year follow-up (the ‘CARE’ protocol). Cephalalgia. 2013 Feb 26 [Epub ahead of print].
Is Parkinson’s Disease a Prion Disorder?
SAN DIEGO—An increasing body of evidence suggests that Parkinson’s disease is a prion disorder, according to a review presented at the 65th Annual Meeting of the American Academy of Neurology. If the prion hypothesis is confirmed, it could lead to the pursuit of novel therapeutic targets.
Developing new medical treatments will still require “an enormous amount of work,” said C. Warren Olanow, MD, Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine in New York City. “Many compounds will have to be tested in high-throughput studies to find lead compounds that interfere with the prion process, but this approach currently offers the best hope for finding a cure for Parkinson’s disease.”
Alpha Synuclein May Be a Prion
A prion is an infectious agent made solely of misfolded protein. The most common illness caused by prions in humans is Creutzfeldt–Jakob disease.
Parkinson’s disease may occur when native alpha synuclein, which normally exists in an alpha helical configuration, misfolds and forms beta sheets. Misfolding can result from an alpha synuclein gene mutation, excess production of or damage to alpha synuclein, or random chance, said Dr. Olanow. Normally, lysosomes or proteasomes clear the misfolded alpha synuclein. If it is not cleared, the protein can form aggregates that further interfere with lysosomal and proteasomal function. Misfolded alpha synuclein can promote the misfolding of wild-type alpha synuclein, and lead to the formation of toxic oligomers and aggregates that cause neurodegeneration.
“The significance of the Lewy body is not known, but it may represent a protective mechanism that forms in an attempt to clear and segregate misfolded protein aggregates,” said Dr. Olanow. “Furthermore, recent evidence demonstrates that misfolded alpha synuclein protein filaments and aggregates can transfer to unaffected cells to extend the disease process.”
Research Has Supported the Prion Hypothesis
The link between Parkinson’s disease and protein aggregates was established about 100 years ago when Lewy bodies were identified as a characteristic pathologic feature of the illness, said Dr. Olanow. In 1997, a mutation in the alpha synuclein gene was found to be responsible for some cases of Parkinson’s disease. Mutant alpha synuclein is more likely to misfold than wild-type alpha synuclein. Researchers subsequently demonstrated that alpha synuclein is the principal protein in Lewy bodies and Lewy neurites. Duplication or triplication of the alpha synuclein gene was found to cause a form of Parkinson’s disease, which indicated that overexpression of the normal protein itself could cause the disease.
Alpha synuclein staining in elderly controls and patients with Parkinson’s disease suggested that the earliest CNS changes in Parkinson’s disease occur in the dorsal motor nucleus of the vagus nerve and in the olfactory system. These regions’ proximity to the external environment suggested that exposure to toxins or infectious agents could initiate the disease process, which could then spread to other parts of the nervous system in a prion-like manner.
More recently, Dr. Olanow and colleagues examined transplanted fetal nigral neurons that had been implanted into patients with Parkinson’s disease 10 to 14 years previously. The implanted neurons showed evidence of Lewy pathology, which supported the possibility that Lewy pathology had extended from affected to unaffected neurons in a prion-like manner.
In 2012, Virginia Lee and colleagues injected synthetic alpha synuclein fibrils into the striatum of wild-type mice. This intervention was associated with the development of Lewy pathology and neurodegeneration in neighboring neurons with spread to the cortex and the olfactory bulb, as well as the substantia nigra and the contralateral cortex.
Prion Hypothesis Could Yield Novel Therapeutic Targets
Confirmation that Parkinson’s disease is a prion disorder would suggest novel targets for candidate neuroprotective therapies. Such approaches could include agents that prevent protein misfolding, immunization to remove toxic oligomers, and downregulation of native alpha synuclein to prevent its participation in prion reactions, said Dr. Olanow.
Studies are now beginning to test methods for removing toxic fibrils and aggregates through vaccination techniques. “But we don’t know yet for sure which component is toxic,” said Dr. Olanow, “and it is possible that we could be removing protective aggregates that could accelerate the disease process.”
Attempting to inhibit the prion conformer reaction could be a more promising approach, according to Dr. Olanow. If misfolded alpha synuclein causes native alpha synuclein to misfold through molecular mechanisms, these mechanisms “could be targets for a therapeutic intervention,” he added.
The best approach might be to eliminate native alpha synuclein entirely so that none of it could become misfolded. The approach could allow clearance systems to remove remaining misfolded alpha synuclein, potentially stopping the chain reaction of misfolding. “In experimental systems, knockout of alpha synuclein might remove substrate and slow down or stop the prion process,” said Dr. Olanow. “The prion concept is extremely exciting and hopefully will lead to an effective therapy.”
—Erik Greb
Senior Associate Editor
Suggested Reading
Bae EJ, Lee HJ, Rockenstein E, et al. Antibody-aided clearance of extracellular a-synuclein prevents cell-to-cell aggregate transmission. J Neurosci. 2012;32(39):13454-13469.
Luk KC, Kehm V, Carroll J, et al. Pathological a-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338(6109):949-953.
Olanow CW, Brundin P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov Disord. 2013;28(1):31-40.
SAN DIEGO—An increasing body of evidence suggests that Parkinson’s disease is a prion disorder, according to a review presented at the 65th Annual Meeting of the American Academy of Neurology. If the prion hypothesis is confirmed, it could lead to the pursuit of novel therapeutic targets.
Developing new medical treatments will still require “an enormous amount of work,” said C. Warren Olanow, MD, Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine in New York City. “Many compounds will have to be tested in high-throughput studies to find lead compounds that interfere with the prion process, but this approach currently offers the best hope for finding a cure for Parkinson’s disease.”
Alpha Synuclein May Be a Prion
A prion is an infectious agent made solely of misfolded protein. The most common illness caused by prions in humans is Creutzfeldt–Jakob disease.
Parkinson’s disease may occur when native alpha synuclein, which normally exists in an alpha helical configuration, misfolds and forms beta sheets. Misfolding can result from an alpha synuclein gene mutation, excess production of or damage to alpha synuclein, or random chance, said Dr. Olanow. Normally, lysosomes or proteasomes clear the misfolded alpha synuclein. If it is not cleared, the protein can form aggregates that further interfere with lysosomal and proteasomal function. Misfolded alpha synuclein can promote the misfolding of wild-type alpha synuclein, and lead to the formation of toxic oligomers and aggregates that cause neurodegeneration.
“The significance of the Lewy body is not known, but it may represent a protective mechanism that forms in an attempt to clear and segregate misfolded protein aggregates,” said Dr. Olanow. “Furthermore, recent evidence demonstrates that misfolded alpha synuclein protein filaments and aggregates can transfer to unaffected cells to extend the disease process.”
Research Has Supported the Prion Hypothesis
The link between Parkinson’s disease and protein aggregates was established about 100 years ago when Lewy bodies were identified as a characteristic pathologic feature of the illness, said Dr. Olanow. In 1997, a mutation in the alpha synuclein gene was found to be responsible for some cases of Parkinson’s disease. Mutant alpha synuclein is more likely to misfold than wild-type alpha synuclein. Researchers subsequently demonstrated that alpha synuclein is the principal protein in Lewy bodies and Lewy neurites. Duplication or triplication of the alpha synuclein gene was found to cause a form of Parkinson’s disease, which indicated that overexpression of the normal protein itself could cause the disease.
Alpha synuclein staining in elderly controls and patients with Parkinson’s disease suggested that the earliest CNS changes in Parkinson’s disease occur in the dorsal motor nucleus of the vagus nerve and in the olfactory system. These regions’ proximity to the external environment suggested that exposure to toxins or infectious agents could initiate the disease process, which could then spread to other parts of the nervous system in a prion-like manner.
More recently, Dr. Olanow and colleagues examined transplanted fetal nigral neurons that had been implanted into patients with Parkinson’s disease 10 to 14 years previously. The implanted neurons showed evidence of Lewy pathology, which supported the possibility that Lewy pathology had extended from affected to unaffected neurons in a prion-like manner.
In 2012, Virginia Lee and colleagues injected synthetic alpha synuclein fibrils into the striatum of wild-type mice. This intervention was associated with the development of Lewy pathology and neurodegeneration in neighboring neurons with spread to the cortex and the olfactory bulb, as well as the substantia nigra and the contralateral cortex.
Prion Hypothesis Could Yield Novel Therapeutic Targets
Confirmation that Parkinson’s disease is a prion disorder would suggest novel targets for candidate neuroprotective therapies. Such approaches could include agents that prevent protein misfolding, immunization to remove toxic oligomers, and downregulation of native alpha synuclein to prevent its participation in prion reactions, said Dr. Olanow.
Studies are now beginning to test methods for removing toxic fibrils and aggregates through vaccination techniques. “But we don’t know yet for sure which component is toxic,” said Dr. Olanow, “and it is possible that we could be removing protective aggregates that could accelerate the disease process.”
Attempting to inhibit the prion conformer reaction could be a more promising approach, according to Dr. Olanow. If misfolded alpha synuclein causes native alpha synuclein to misfold through molecular mechanisms, these mechanisms “could be targets for a therapeutic intervention,” he added.
The best approach might be to eliminate native alpha synuclein entirely so that none of it could become misfolded. The approach could allow clearance systems to remove remaining misfolded alpha synuclein, potentially stopping the chain reaction of misfolding. “In experimental systems, knockout of alpha synuclein might remove substrate and slow down or stop the prion process,” said Dr. Olanow. “The prion concept is extremely exciting and hopefully will lead to an effective therapy.”
—Erik Greb
Senior Associate Editor
Suggested Reading
Bae EJ, Lee HJ, Rockenstein E, et al. Antibody-aided clearance of extracellular a-synuclein prevents cell-to-cell aggregate transmission. J Neurosci. 2012;32(39):13454-13469.
Luk KC, Kehm V, Carroll J, et al. Pathological a-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338(6109):949-953.
Olanow CW, Brundin P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov Disord. 2013;28(1):31-40.
SAN DIEGO—An increasing body of evidence suggests that Parkinson’s disease is a prion disorder, according to a review presented at the 65th Annual Meeting of the American Academy of Neurology. If the prion hypothesis is confirmed, it could lead to the pursuit of novel therapeutic targets.
Developing new medical treatments will still require “an enormous amount of work,” said C. Warren Olanow, MD, Professor of Neurology and Neuroscience at the Mount Sinai School of Medicine in New York City. “Many compounds will have to be tested in high-throughput studies to find lead compounds that interfere with the prion process, but this approach currently offers the best hope for finding a cure for Parkinson’s disease.”
Alpha Synuclein May Be a Prion
A prion is an infectious agent made solely of misfolded protein. The most common illness caused by prions in humans is Creutzfeldt–Jakob disease.
Parkinson’s disease may occur when native alpha synuclein, which normally exists in an alpha helical configuration, misfolds and forms beta sheets. Misfolding can result from an alpha synuclein gene mutation, excess production of or damage to alpha synuclein, or random chance, said Dr. Olanow. Normally, lysosomes or proteasomes clear the misfolded alpha synuclein. If it is not cleared, the protein can form aggregates that further interfere with lysosomal and proteasomal function. Misfolded alpha synuclein can promote the misfolding of wild-type alpha synuclein, and lead to the formation of toxic oligomers and aggregates that cause neurodegeneration.
“The significance of the Lewy body is not known, but it may represent a protective mechanism that forms in an attempt to clear and segregate misfolded protein aggregates,” said Dr. Olanow. “Furthermore, recent evidence demonstrates that misfolded alpha synuclein protein filaments and aggregates can transfer to unaffected cells to extend the disease process.”
Research Has Supported the Prion Hypothesis
The link between Parkinson’s disease and protein aggregates was established about 100 years ago when Lewy bodies were identified as a characteristic pathologic feature of the illness, said Dr. Olanow. In 1997, a mutation in the alpha synuclein gene was found to be responsible for some cases of Parkinson’s disease. Mutant alpha synuclein is more likely to misfold than wild-type alpha synuclein. Researchers subsequently demonstrated that alpha synuclein is the principal protein in Lewy bodies and Lewy neurites. Duplication or triplication of the alpha synuclein gene was found to cause a form of Parkinson’s disease, which indicated that overexpression of the normal protein itself could cause the disease.
Alpha synuclein staining in elderly controls and patients with Parkinson’s disease suggested that the earliest CNS changes in Parkinson’s disease occur in the dorsal motor nucleus of the vagus nerve and in the olfactory system. These regions’ proximity to the external environment suggested that exposure to toxins or infectious agents could initiate the disease process, which could then spread to other parts of the nervous system in a prion-like manner.
More recently, Dr. Olanow and colleagues examined transplanted fetal nigral neurons that had been implanted into patients with Parkinson’s disease 10 to 14 years previously. The implanted neurons showed evidence of Lewy pathology, which supported the possibility that Lewy pathology had extended from affected to unaffected neurons in a prion-like manner.
In 2012, Virginia Lee and colleagues injected synthetic alpha synuclein fibrils into the striatum of wild-type mice. This intervention was associated with the development of Lewy pathology and neurodegeneration in neighboring neurons with spread to the cortex and the olfactory bulb, as well as the substantia nigra and the contralateral cortex.
Prion Hypothesis Could Yield Novel Therapeutic Targets
Confirmation that Parkinson’s disease is a prion disorder would suggest novel targets for candidate neuroprotective therapies. Such approaches could include agents that prevent protein misfolding, immunization to remove toxic oligomers, and downregulation of native alpha synuclein to prevent its participation in prion reactions, said Dr. Olanow.
Studies are now beginning to test methods for removing toxic fibrils and aggregates through vaccination techniques. “But we don’t know yet for sure which component is toxic,” said Dr. Olanow, “and it is possible that we could be removing protective aggregates that could accelerate the disease process.”
Attempting to inhibit the prion conformer reaction could be a more promising approach, according to Dr. Olanow. If misfolded alpha synuclein causes native alpha synuclein to misfold through molecular mechanisms, these mechanisms “could be targets for a therapeutic intervention,” he added.
The best approach might be to eliminate native alpha synuclein entirely so that none of it could become misfolded. The approach could allow clearance systems to remove remaining misfolded alpha synuclein, potentially stopping the chain reaction of misfolding. “In experimental systems, knockout of alpha synuclein might remove substrate and slow down or stop the prion process,” said Dr. Olanow. “The prion concept is extremely exciting and hopefully will lead to an effective therapy.”
—Erik Greb
Senior Associate Editor
Suggested Reading
Bae EJ, Lee HJ, Rockenstein E, et al. Antibody-aided clearance of extracellular a-synuclein prevents cell-to-cell aggregate transmission. J Neurosci. 2012;32(39):13454-13469.
Luk KC, Kehm V, Carroll J, et al. Pathological a-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338(6109):949-953.
Olanow CW, Brundin P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov Disord. 2013;28(1):31-40.
