Headache & Migraine

SAN FRANCISCO—Spontaneous intracranial hypotension (SIH) sometimes may go undiagnosed, partly because the disorder is uncommon. But patients will receive the care that they need if neurologists, particularly headache specialists, understand how to identify the disorder.

Misconceptions About SIH

The name of the disorder can be misleading, said Deborah I. Friedman, MD, at the 60th Annual Scientific Meeting of the American Headache Society. SIH is not always spontaneous; it often has an antecedent cause. Furthermore, the main problem is not intracranial, it is a leak in the spinal column, most often in the low cervical or thoracic zone. Finally, CSF pressure is usually normal in these patients, said Dr. Friedman, Chief of the Division of Headache Medicine, Professor of Neurology, and Professor of Ophthalmology at the University of Texas Southwestern Medical Center in Dallas.

SIH is considered a rare disorder, and its published annual incidence is five cases per 100,000 people. But this prevalence may be a gross underestimate that results from the absence of an ICD-9 or ICD-10 code for the condition, according to Dr. Friedman.

SIH is “much more common than we think,” she asserted. “These people are out there. They are in your offices. I can guarantee you, there are patients you have been seeing for years in your practice that have [SIH]. I have missed it. I bet you have, too.”

Guidelines for Identifying SIH

Dr. Friedman offered advice from the perspective of a headache specialist to guide the diagnosis of SIH. “Most of the literature that is out there, and it is good literature, was not written by headache medicine specialists, it was written by famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be challenging to diagnose because of its myriad presentations. “You need to be a detective,” said Dr. Friedman. The questions to ask center around whether the headache has postural, end-of-the-day, and Valsalva components. Joint hypermobility may provide another clue.

Headache is the most common symptom of SIH and the reason that patients with the disorder seek a headache specialist. A neurologist should consider the diagnosis in a patient with a new daily persistent headache or in a patient with a diagnosis of chronic migraine for whom no medication has worked. “The people who come in with a huge list of medications they have tried, and nothing works? That is unusual for migraine. Usually something works for migraine,” said Dr. Friedman.

SIH can result in a headache with an onset as sudden as that of thunderclap headache, but this characteristic is not necessary. The most common location of pain is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral pain.

The most typical headache is orthostatic or worsens at the end of the day. The longer a patient has SIH, the less likely that it will have a postural component. Most patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, or sexual activity. Caffeine often works well for people with SIH. A neurologist should ask the patient about these issues, said Dr. Friedman.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing (eg, hearing things as though one is underwater), neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Typical risk factors include joint hypermobility; previous lumbar puncture, epidural, or spinal anesthesia; known disc disease or a personal or family history of retinal detachment at a young age; aneurysm; dissection; and valvular heart disease. Joint hypermobility is widespread among patients with SIH. These patients often enjoy yoga and were exceptionally flexible as children. Many participated in gymnastics, ballet, or cheerleading as children.

Examining and Treating the Patient

On physical examination, a neurologist can look for joint hypermobility. He or she should examine the eyes for spontaneous retinal venous pulsations indicative of normal CSF pressure. A neurologist also can put the patient in 5° of the Trendelenburg position for five to 10 minutes to see whether it improves the headache and other symptoms.

One of the first things that Dr. Friedman does when she suspects SIH is to refer the patient to the website of the Spinal CSF Leak Foundation (spinalcsfleak.org). She asks him or her to review the site and tell her whether the descriptions sound familiar.

The medical consensus is that the first-line diagnostic test is brain MRI with gadolinium enhancement. The diagnostic challenge, however, is that 30% of patients with SIH have normal results.

There is no consensus about the next step when the brain MRI is negative. CT with or without MR myelography is one possibility, and a T2-weighted spine MRI is another. Despite a thorough search, however, neurologists find no leak in about half of individuals with SIH.

Conservative treatment measures do not work well, according to Dr. Friedman. A reasonable strategy, even if a leak site has not been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant. “It gives relief about a third of the time,” according to Dr. Friedman.

—Bruce Jancin

SAN FRANCISCO—Spontaneous intracranial hypotension (SIH) sometimes may go undiagnosed, partly because the disorder is uncommon. But patients will receive the care that they need if neurologists, particularly headache specialists, understand how to identify the disorder.

Misconceptions About SIH

The name of the disorder can be misleading, said Deborah I. Friedman, MD, at the 60th Annual Scientific Meeting of the American Headache Society. SIH is not always spontaneous; it often has an antecedent cause. Furthermore, the main problem is not intracranial, it is a leak in the spinal column, most often in the low cervical or thoracic zone. Finally, CSF pressure is usually normal in these patients, said Dr. Friedman, Chief of the Division of Headache Medicine, Professor of Neurology, and Professor of Ophthalmology at the University of Texas Southwestern Medical Center in Dallas.

SIH is considered a rare disorder, and its published annual incidence is five cases per 100,000 people. But this prevalence may be a gross underestimate that results from the absence of an ICD-9 or ICD-10 code for the condition, according to Dr. Friedman.

SIH is “much more common than we think,” she asserted. “These people are out there. They are in your offices. I can guarantee you, there are patients you have been seeing for years in your practice that have [SIH]. I have missed it. I bet you have, too.”

Guidelines for Identifying SIH

Dr. Friedman offered advice from the perspective of a headache specialist to guide the diagnosis of SIH. “Most of the literature that is out there, and it is good literature, was not written by headache medicine specialists, it was written by famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be challenging to diagnose because of its myriad presentations. “You need to be a detective,” said Dr. Friedman. The questions to ask center around whether the headache has postural, end-of-the-day, and Valsalva components. Joint hypermobility may provide another clue.

Headache is the most common symptom of SIH and the reason that patients with the disorder seek a headache specialist. A neurologist should consider the diagnosis in a patient with a new daily persistent headache or in a patient with a diagnosis of chronic migraine for whom no medication has worked. “The people who come in with a huge list of medications they have tried, and nothing works? That is unusual for migraine. Usually something works for migraine,” said Dr. Friedman.

SIH can result in a headache with an onset as sudden as that of thunderclap headache, but this characteristic is not necessary. The most common location of pain is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral pain.

The most typical headache is orthostatic or worsens at the end of the day. The longer a patient has SIH, the less likely that it will have a postural component. Most patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, or sexual activity. Caffeine often works well for people with SIH. A neurologist should ask the patient about these issues, said Dr. Friedman.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing (eg, hearing things as though one is underwater), neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Typical risk factors include joint hypermobility; previous lumbar puncture, epidural, or spinal anesthesia; known disc disease or a personal or family history of retinal detachment at a young age; aneurysm; dissection; and valvular heart disease. Joint hypermobility is widespread among patients with SIH. These patients often enjoy yoga and were exceptionally flexible as children. Many participated in gymnastics, ballet, or cheerleading as children.

Examining and Treating the Patient

On physical examination, a neurologist can look for joint hypermobility. He or she should examine the eyes for spontaneous retinal venous pulsations indicative of normal CSF pressure. A neurologist also can put the patient in 5° of the Trendelenburg position for five to 10 minutes to see whether it improves the headache and other symptoms.

One of the first things that Dr. Friedman does when she suspects SIH is to refer the patient to the website of the Spinal CSF Leak Foundation (spinalcsfleak.org). She asks him or her to review the site and tell her whether the descriptions sound familiar.

The medical consensus is that the first-line diagnostic test is brain MRI with gadolinium enhancement. The diagnostic challenge, however, is that 30% of patients with SIH have normal results.

There is no consensus about the next step when the brain MRI is negative. CT with or without MR myelography is one possibility, and a T2-weighted spine MRI is another. Despite a thorough search, however, neurologists find no leak in about half of individuals with SIH.

Conservative treatment measures do not work well, according to Dr. Friedman. A reasonable strategy, even if a leak site has not been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant. “It gives relief about a third of the time,” according to Dr. Friedman.

—Bruce Jancin

SAN FRANCISCO—Spontaneous intracranial hypotension (SIH) sometimes may go undiagnosed, partly because the disorder is uncommon. But patients will receive the care that they need if neurologists, particularly headache specialists, understand how to identify the disorder.

Misconceptions About SIH

The name of the disorder can be misleading, said Deborah I. Friedman, MD, at the 60th Annual Scientific Meeting of the American Headache Society. SIH is not always spontaneous; it often has an antecedent cause. Furthermore, the main problem is not intracranial, it is a leak in the spinal column, most often in the low cervical or thoracic zone. Finally, CSF pressure is usually normal in these patients, said Dr. Friedman, Chief of the Division of Headache Medicine, Professor of Neurology, and Professor of Ophthalmology at the University of Texas Southwestern Medical Center in Dallas.

SIH is considered a rare disorder, and its published annual incidence is five cases per 100,000 people. But this prevalence may be a gross underestimate that results from the absence of an ICD-9 or ICD-10 code for the condition, according to Dr. Friedman.

SIH is “much more common than we think,” she asserted. “These people are out there. They are in your offices. I can guarantee you, there are patients you have been seeing for years in your practice that have [SIH]. I have missed it. I bet you have, too.”

Guidelines for Identifying SIH

Dr. Friedman offered advice from the perspective of a headache specialist to guide the diagnosis of SIH. “Most of the literature that is out there, and it is good literature, was not written by headache medicine specialists, it was written by famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be challenging to diagnose because of its myriad presentations. “You need to be a detective,” said Dr. Friedman. The questions to ask center around whether the headache has postural, end-of-the-day, and Valsalva components. Joint hypermobility may provide another clue.

Headache is the most common symptom of SIH and the reason that patients with the disorder seek a headache specialist. A neurologist should consider the diagnosis in a patient with a new daily persistent headache or in a patient with a diagnosis of chronic migraine for whom no medication has worked. “The people who come in with a huge list of medications they have tried, and nothing works? That is unusual for migraine. Usually something works for migraine,” said Dr. Friedman.

SIH can result in a headache with an onset as sudden as that of thunderclap headache, but this characteristic is not necessary. The most common location of pain is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral pain.

The most typical headache is orthostatic or worsens at the end of the day. The longer a patient has SIH, the less likely that it will have a postural component. Most patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, or sexual activity. Caffeine often works well for people with SIH. A neurologist should ask the patient about these issues, said Dr. Friedman.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing (eg, hearing things as though one is underwater), neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Typical risk factors include joint hypermobility; previous lumbar puncture, epidural, or spinal anesthesia; known disc disease or a personal or family history of retinal detachment at a young age; aneurysm; dissection; and valvular heart disease. Joint hypermobility is widespread among patients with SIH. These patients often enjoy yoga and were exceptionally flexible as children. Many participated in gymnastics, ballet, or cheerleading as children.

Examining and Treating the Patient

On physical examination, a neurologist can look for joint hypermobility. He or she should examine the eyes for spontaneous retinal venous pulsations indicative of normal CSF pressure. A neurologist also can put the patient in 5° of the Trendelenburg position for five to 10 minutes to see whether it improves the headache and other symptoms.

One of the first things that Dr. Friedman does when she suspects SIH is to refer the patient to the website of the Spinal CSF Leak Foundation (spinalcsfleak.org). She asks him or her to review the site and tell her whether the descriptions sound familiar.

The medical consensus is that the first-line diagnostic test is brain MRI with gadolinium enhancement. The diagnostic challenge, however, is that 30% of patients with SIH have normal results.

There is no consensus about the next step when the brain MRI is negative. CT with or without MR myelography is one possibility, and a T2-weighted spine MRI is another. Despite a thorough search, however, neurologists find no leak in about half of individuals with SIH.

Conservative treatment measures do not work well, according to Dr. Friedman. A reasonable strategy, even if a leak site has not been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant. “It gives relief about a third of the time,” according to Dr. Friedman.

—Bruce Jancin

Anatomic localization (the hypothalamus as a key and early mediator in the pathophysiology of migraine), common mediating signaling molecules (such as serotonin and dopamine), and the discovery of a new central nervous system waste removal system, the glymphatic system, all point to a common pathophysiology manifesting in migraine and sleep problems, according to recent research. Patients consistently report poor sleep prior to migraine attacks and during them, identifying poor sleep as a migraine trigger. However, anecdotally, sleep is reported to serve a therapeutic role in terminating headache. Researchers reviewed studies of sleep and migraine from the last 2 decades, utilizing validated subjective and objective measures of sleep and to explore potential mechanisms underlying this complex relationship by incorporating recent advances in neuroscience. They specifically focused on:

• insomnia,
• obstructive sleep apnea,
• parasomnias,
• sleep-related movement disorders, and
• rapid eye movement (REM) sleep-related disorders and their relationship to migraine.

In addition, parts of brainstem‐cortical networks involved in sleep physiology are unintentionally being identified as important factors in the common migraine pathway.

Vgontzas A, Pavlović JM. Sleep disorders and migraine: Review of literature and potential pathophysiology mechanisms. [Published online ahead of print August 8, 2018]. Headache. doi:10.1111/head.13358.

Anatomic localization (the hypothalamus as a key and early mediator in the pathophysiology of migraine), common mediating signaling molecules (such as serotonin and dopamine), and the discovery of a new central nervous system waste removal system, the glymphatic system, all point to a common pathophysiology manifesting in migraine and sleep problems, according to recent research. Patients consistently report poor sleep prior to migraine attacks and during them, identifying poor sleep as a migraine trigger. However, anecdotally, sleep is reported to serve a therapeutic role in terminating headache. Researchers reviewed studies of sleep and migraine from the last 2 decades, utilizing validated subjective and objective measures of sleep and to explore potential mechanisms underlying this complex relationship by incorporating recent advances in neuroscience. They specifically focused on:

• insomnia,
• obstructive sleep apnea,
• parasomnias,
• sleep-related movement disorders, and
• rapid eye movement (REM) sleep-related disorders and their relationship to migraine.

In addition, parts of brainstem‐cortical networks involved in sleep physiology are unintentionally being identified as important factors in the common migraine pathway.

Vgontzas A, Pavlović JM. Sleep disorders and migraine: Review of literature and potential pathophysiology mechanisms. [Published online ahead of print August 8, 2018]. Headache. doi:10.1111/head.13358.

Anatomic localization (the hypothalamus as a key and early mediator in the pathophysiology of migraine), common mediating signaling molecules (such as serotonin and dopamine), and the discovery of a new central nervous system waste removal system, the glymphatic system, all point to a common pathophysiology manifesting in migraine and sleep problems, according to recent research. Patients consistently report poor sleep prior to migraine attacks and during them, identifying poor sleep as a migraine trigger. However, anecdotally, sleep is reported to serve a therapeutic role in terminating headache. Researchers reviewed studies of sleep and migraine from the last 2 decades, utilizing validated subjective and objective measures of sleep and to explore potential mechanisms underlying this complex relationship by incorporating recent advances in neuroscience. They specifically focused on:

• insomnia,
• obstructive sleep apnea,
• parasomnias,
• sleep-related movement disorders, and
• rapid eye movement (REM) sleep-related disorders and their relationship to migraine.

In addition, parts of brainstem‐cortical networks involved in sleep physiology are unintentionally being identified as important factors in the common migraine pathway.

Vgontzas A, Pavlović JM. Sleep disorders and migraine: Review of literature and potential pathophysiology mechanisms. [Published online ahead of print August 8, 2018]. Headache. doi:10.1111/head.13358.

The presence of a sleep disorder is associated with more frequent and severe migraine and portends a poorer headache prognosis, according to recent research that focuses on clinical assessment and treatment of sleep disorders. Interestingly, the disorders linked to migraine are quite varied, including insomnia, snoring and obstructive sleep apnea, restless legs, circadian rhythm disorders, and narcolepsy. Insomnia is by far the most common sleep disorder in headache patients.  New developments in treatment have produced abbreviated and cost‐effective therapies for insomnia and obstructive sleep apnea that may reach a larger population. Recommendations include:

• behavioral sleep regulation, shown in recent controlled trials to decrease migraine frequency,
• management for sleep apnea headache, and
• cognitive behavioral therapy (CBT) for insomnia abbreviated for the physician practice setting.

There is no empirical evidence that sleep evaluation should delay or supersede usual headache care. Rather, sleep management is complimentary to standard headache practice.

Rains JC. Sleep and migraine: Assessment and treatment of comorbid sleep disorders. [Published online ahead of print August 10, 2018]. Headache. doi:10.1111/head.13357.

The presence of a sleep disorder is associated with more frequent and severe migraine and portends a poorer headache prognosis, according to recent research that focuses on clinical assessment and treatment of sleep disorders. Interestingly, the disorders linked to migraine are quite varied, including insomnia, snoring and obstructive sleep apnea, restless legs, circadian rhythm disorders, and narcolepsy. Insomnia is by far the most common sleep disorder in headache patients.  New developments in treatment have produced abbreviated and cost‐effective therapies for insomnia and obstructive sleep apnea that may reach a larger population. Recommendations include:

• behavioral sleep regulation, shown in recent controlled trials to decrease migraine frequency,
• management for sleep apnea headache, and
• cognitive behavioral therapy (CBT) for insomnia abbreviated for the physician practice setting.

There is no empirical evidence that sleep evaluation should delay or supersede usual headache care. Rather, sleep management is complimentary to standard headache practice.

Rains JC. Sleep and migraine: Assessment and treatment of comorbid sleep disorders. [Published online ahead of print August 10, 2018]. Headache. doi:10.1111/head.13357.

The presence of a sleep disorder is associated with more frequent and severe migraine and portends a poorer headache prognosis, according to recent research that focuses on clinical assessment and treatment of sleep disorders. Interestingly, the disorders linked to migraine are quite varied, including insomnia, snoring and obstructive sleep apnea, restless legs, circadian rhythm disorders, and narcolepsy. Insomnia is by far the most common sleep disorder in headache patients.  New developments in treatment have produced abbreviated and cost‐effective therapies for insomnia and obstructive sleep apnea that may reach a larger population. Recommendations include:

• behavioral sleep regulation, shown in recent controlled trials to decrease migraine frequency,
• management for sleep apnea headache, and
• cognitive behavioral therapy (CBT) for insomnia abbreviated for the physician practice setting.

There is no empirical evidence that sleep evaluation should delay or supersede usual headache care. Rather, sleep management is complimentary to standard headache practice.

Rains JC. Sleep and migraine: Assessment and treatment of comorbid sleep disorders. [Published online ahead of print August 10, 2018]. Headache. doi:10.1111/head.13357.

Patients with comorbid fibromyalgia and migraine report more depressive symptoms, higher headache intensity, and are more likely to have severe headache-related disability as compared to controls without fibromyalgia, according to a recent study. Cases of comorbid fibromyalgia and migraine were identified using a prospectively maintained headache database at Mayo Clinic Rochester. Depressive symptoms as assessed by Patient Health Questionnaire (PHQ)-9, intensity of headache, and migraine-related disability as assessed by Migraine Disability Assessment (MIDAS) were primary measures used to compare migraine patients with comorbid fibromyalgia vs those without. One hundred and fifty-seven cases and 471 controls were identified. Researchers found:

• Patients with comorbid fibromyalgia reported significantly higher PHQ-9 scores (OR 1.08) and headache intensity scores (odds ratio [OR] 1.149).
• There was no significant difference in migraine-related disability (OR 1.002).
• Patients with fibromyalgia were more likely to score in a higher category of depression severity (OR 1.467) and more likely to score in a higher category of migraine-related disability (OR 1.23).

Whealy M, Nanda S, Vincent A, Mandrekar J, Cutrer FM. Fibromyalgia in migraine: A retrospective cohort study. J Headache Pain. 2018;19(1):61. doi:10.1186/s10194-018-0892-9.

Patients with comorbid fibromyalgia and migraine report more depressive symptoms, higher headache intensity, and are more likely to have severe headache-related disability as compared to controls without fibromyalgia, according to a recent study. Cases of comorbid fibromyalgia and migraine were identified using a prospectively maintained headache database at Mayo Clinic Rochester. Depressive symptoms as assessed by Patient Health Questionnaire (PHQ)-9, intensity of headache, and migraine-related disability as assessed by Migraine Disability Assessment (MIDAS) were primary measures used to compare migraine patients with comorbid fibromyalgia vs those without. One hundred and fifty-seven cases and 471 controls were identified. Researchers found:

• Patients with comorbid fibromyalgia reported significantly higher PHQ-9 scores (OR 1.08) and headache intensity scores (odds ratio [OR] 1.149).
• There was no significant difference in migraine-related disability (OR 1.002).
• Patients with fibromyalgia were more likely to score in a higher category of depression severity (OR 1.467) and more likely to score in a higher category of migraine-related disability (OR 1.23).

Whealy M, Nanda S, Vincent A, Mandrekar J, Cutrer FM. Fibromyalgia in migraine: A retrospective cohort study. J Headache Pain. 2018;19(1):61. doi:10.1186/s10194-018-0892-9.

Patients with comorbid fibromyalgia and migraine report more depressive symptoms, higher headache intensity, and are more likely to have severe headache-related disability as compared to controls without fibromyalgia, according to a recent study. Cases of comorbid fibromyalgia and migraine were identified using a prospectively maintained headache database at Mayo Clinic Rochester. Depressive symptoms as assessed by Patient Health Questionnaire (PHQ)-9, intensity of headache, and migraine-related disability as assessed by Migraine Disability Assessment (MIDAS) were primary measures used to compare migraine patients with comorbid fibromyalgia vs those without. One hundred and fifty-seven cases and 471 controls were identified. Researchers found:

• Patients with comorbid fibromyalgia reported significantly higher PHQ-9 scores (OR 1.08) and headache intensity scores (odds ratio [OR] 1.149).
• There was no significant difference in migraine-related disability (OR 1.002).
• Patients with fibromyalgia were more likely to score in a higher category of depression severity (OR 1.467) and more likely to score in a higher category of migraine-related disability (OR 1.23).

Whealy M, Nanda S, Vincent A, Mandrekar J, Cutrer FM. Fibromyalgia in migraine: A retrospective cohort study. J Headache Pain. 2018;19(1):61. doi:10.1186/s10194-018-0892-9.

SAN FRANCISCO – Spontaneous intracranial hypotension couldn’t have a more misleading moniker.

Bruce Jancin/MDedge News

First of all, spontaneous intracranial hypotension (SIH) is not always spontaneous; often there is an antecedent causal event. Second, the main problem isn’t intracranial, it’s a leak in the spinal column, most often in the low cervical or thoracic zone. And cerebrospinal fluid (CSF) pressure is usually normal in these patients, Deborah I. Friedman, MD, said in the annual Seymour Solomon Award Lecture at the annual meeting of the American Headache Society.

Moreover, although SIH is usually labeled a rare disorder, with a published annual incidence of 5 cases per 100,000, that’s doubtless a gross underestimate stemming from the absence of an ICD-9 or -10 code for the condition, according to Dr. Friedman, chief of the division of headache medicine, professor of neurology, and professor of ophthalmology at the University of Texas Southwestern Medical Center, Dallas.

“[SIH is] much more common than we think,” she asserted. “These people are out there. They’re in your offices. I can guarantee you, there are patients you’ve been seeing for years in your practice that have [SIH]. I’ve missed it. I bet you have, too.”

She focused her award lecture on the diagnosis of SIH from the perspective of a headache specialist.

“Most of the literature that’s out there – and it is good literature – wasn’t written by headache medicine specialists, it was written by very famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be a challenging diagnosis because of its myriad presentations.

“You need to be a detective,” she emphasized. The questions to ask center around whether postural, end-of-the-day, and Valsalva components to the headache are present, along with the clue provided by joint hypermobility.

Headache is the most common symptom of SIH and the reason patients with the disorder seek out a headache specialist. It’s time to consider the diagnosis in a patient with a new daily persistent headache, or in the patient running around with a diagnosis of chronic migraine for which nothing works.

“The people who come in with a huge list of medications they’ve tried and nothing works? That’s unusual for migraine. Usually something works for migraine,” she observed.

The headache of SIH can be thunderclap in onset, although not necessarily so. The most common location is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral.

The most typical headache pattern is one that’s orthostatic or gets worse at the end of the day. The longer a patient has SIH, though, the less likely that they’ll have a postural component. The majority of patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, and/or sexual activity. People with SIH often find that caffeine works very well for them. Ask nonleading questions about these issues, she suggested.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing as if underwater, neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Risk factors that are a tipoff include joint hypermobility, previous lumbar puncture, epidural or spinal anesthesia, known disc disease, or a personal or family history of retinal detachment at a young age, aneurysm, dissection, or valvular heart disease.

Joint hypermobility is really common in patients with SIH. These are often headache patients who enjoy yoga and were superflexible as children, participating in gymnastics, ballet, or cheerleading.

“We’re looking for Cirque du Soleil here, so you have to ask the Cirque du Soleil questions,” Dr. Friedman said.

On physical examination, she looks for joint hypermobility, makes sure that spontaneous retinal venous pulsations indicative of normal CSF pressure are present when she looks in the eyes, and puts the patient in 5 degrees of Trendelenburg position for 5-10 minutes to see if that improves the headache and other symptoms.

One of the first things Dr. Friedman does when she suspects the diagnosis is to send a patient to the recommended website of the Spinal CSF Leak Foundation. She asks them to take a look around the site and tell her if the descriptions sound like them.

There is broad agreement that the first-line diagnostic test is brain imaging via MRI with gadolinium enhancement. The diagnostic challenge posed by SIH is that the test is normal in 30% of affected patients.

At present there is no consensus as to the next move when the brain MRI is negative. Some favor CT with or without MR myelography, others a T2-weighted spine MRI. But despite a thorough search, no leak is found in about half of individuals with SIH.

Although Dr. Friedman focused on diagnosis, she turned briefly to treatment. She has found that conservative measures don’t work very well. A reasonable strategy, even if a leak site hasn’t been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant.

“It gives relief about a third of the time each time you do it,” according to Dr. Friedman.

[email protected]

SAN FRANCISCO – Spontaneous intracranial hypotension couldn’t have a more misleading moniker.

Bruce Jancin/MDedge News

First of all, spontaneous intracranial hypotension (SIH) is not always spontaneous; often there is an antecedent causal event. Second, the main problem isn’t intracranial, it’s a leak in the spinal column, most often in the low cervical or thoracic zone. And cerebrospinal fluid (CSF) pressure is usually normal in these patients, Deborah I. Friedman, MD, said in the annual Seymour Solomon Award Lecture at the annual meeting of the American Headache Society.

Moreover, although SIH is usually labeled a rare disorder, with a published annual incidence of 5 cases per 100,000, that’s doubtless a gross underestimate stemming from the absence of an ICD-9 or -10 code for the condition, according to Dr. Friedman, chief of the division of headache medicine, professor of neurology, and professor of ophthalmology at the University of Texas Southwestern Medical Center, Dallas.

“[SIH is] much more common than we think,” she asserted. “These people are out there. They’re in your offices. I can guarantee you, there are patients you’ve been seeing for years in your practice that have [SIH]. I’ve missed it. I bet you have, too.”

She focused her award lecture on the diagnosis of SIH from the perspective of a headache specialist.

“Most of the literature that’s out there – and it is good literature – wasn’t written by headache medicine specialists, it was written by very famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be a challenging diagnosis because of its myriad presentations.

“You need to be a detective,” she emphasized. The questions to ask center around whether postural, end-of-the-day, and Valsalva components to the headache are present, along with the clue provided by joint hypermobility.

Headache is the most common symptom of SIH and the reason patients with the disorder seek out a headache specialist. It’s time to consider the diagnosis in a patient with a new daily persistent headache, or in the patient running around with a diagnosis of chronic migraine for which nothing works.

“The people who come in with a huge list of medications they’ve tried and nothing works? That’s unusual for migraine. Usually something works for migraine,” she observed.

The headache of SIH can be thunderclap in onset, although not necessarily so. The most common location is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral.

The most typical headache pattern is one that’s orthostatic or gets worse at the end of the day. The longer a patient has SIH, though, the less likely that they’ll have a postural component. The majority of patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, and/or sexual activity. People with SIH often find that caffeine works very well for them. Ask nonleading questions about these issues, she suggested.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing as if underwater, neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Risk factors that are a tipoff include joint hypermobility, previous lumbar puncture, epidural or spinal anesthesia, known disc disease, or a personal or family history of retinal detachment at a young age, aneurysm, dissection, or valvular heart disease.

Joint hypermobility is really common in patients with SIH. These are often headache patients who enjoy yoga and were superflexible as children, participating in gymnastics, ballet, or cheerleading.

“We’re looking for Cirque du Soleil here, so you have to ask the Cirque du Soleil questions,” Dr. Friedman said.

On physical examination, she looks for joint hypermobility, makes sure that spontaneous retinal venous pulsations indicative of normal CSF pressure are present when she looks in the eyes, and puts the patient in 5 degrees of Trendelenburg position for 5-10 minutes to see if that improves the headache and other symptoms.

One of the first things Dr. Friedman does when she suspects the diagnosis is to send a patient to the recommended website of the Spinal CSF Leak Foundation. She asks them to take a look around the site and tell her if the descriptions sound like them.

There is broad agreement that the first-line diagnostic test is brain imaging via MRI with gadolinium enhancement. The diagnostic challenge posed by SIH is that the test is normal in 30% of affected patients.

At present there is no consensus as to the next move when the brain MRI is negative. Some favor CT with or without MR myelography, others a T2-weighted spine MRI. But despite a thorough search, no leak is found in about half of individuals with SIH.

Although Dr. Friedman focused on diagnosis, she turned briefly to treatment. She has found that conservative measures don’t work very well. A reasonable strategy, even if a leak site hasn’t been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant.

“It gives relief about a third of the time each time you do it,” according to Dr. Friedman.

[email protected]

SAN FRANCISCO – Spontaneous intracranial hypotension couldn’t have a more misleading moniker.

Bruce Jancin/MDedge News

First of all, spontaneous intracranial hypotension (SIH) is not always spontaneous; often there is an antecedent causal event. Second, the main problem isn’t intracranial, it’s a leak in the spinal column, most often in the low cervical or thoracic zone. And cerebrospinal fluid (CSF) pressure is usually normal in these patients, Deborah I. Friedman, MD, said in the annual Seymour Solomon Award Lecture at the annual meeting of the American Headache Society.

Moreover, although SIH is usually labeled a rare disorder, with a published annual incidence of 5 cases per 100,000, that’s doubtless a gross underestimate stemming from the absence of an ICD-9 or -10 code for the condition, according to Dr. Friedman, chief of the division of headache medicine, professor of neurology, and professor of ophthalmology at the University of Texas Southwestern Medical Center, Dallas.

“[SIH is] much more common than we think,” she asserted. “These people are out there. They’re in your offices. I can guarantee you, there are patients you’ve been seeing for years in your practice that have [SIH]. I’ve missed it. I bet you have, too.”

She focused her award lecture on the diagnosis of SIH from the perspective of a headache specialist.

“Most of the literature that’s out there – and it is good literature – wasn’t written by headache medicine specialists, it was written by very famous and prominent neurosurgeons and neuroradiologists. But the people we see are not necessarily the people they see,” Dr. Friedman explained.

SIH can be a challenging diagnosis because of its myriad presentations.

“You need to be a detective,” she emphasized. The questions to ask center around whether postural, end-of-the-day, and Valsalva components to the headache are present, along with the clue provided by joint hypermobility.

Headache is the most common symptom of SIH and the reason patients with the disorder seek out a headache specialist. It’s time to consider the diagnosis in a patient with a new daily persistent headache, or in the patient running around with a diagnosis of chronic migraine for which nothing works.

“The people who come in with a huge list of medications they’ve tried and nothing works? That’s unusual for migraine. Usually something works for migraine,” she observed.

The headache of SIH can be thunderclap in onset, although not necessarily so. The most common location is posterior, but the pain can be centered anywhere in the head or face. Bilateral pain is more common than unilateral.

The most typical headache pattern is one that’s orthostatic or gets worse at the end of the day. The longer a patient has SIH, though, the less likely that they’ll have a postural component. The majority of patients are awakened by their headache in the middle of the night. The headache is often exertional and usually worsens with Valsalva maneuvers, including coughing, sneezing, lifting, bending forward, straining, singing, and/or sexual activity. People with SIH often find that caffeine works very well for them. Ask nonleading questions about these issues, she suggested.

Besides headache, other common symptoms of SIH include tinnitus, abnormal hearing as if underwater, neck pain, imbalance, pain between the shoulder blades, and blurred or double vision.

Risk factors that are a tipoff include joint hypermobility, previous lumbar puncture, epidural or spinal anesthesia, known disc disease, or a personal or family history of retinal detachment at a young age, aneurysm, dissection, or valvular heart disease.

Joint hypermobility is really common in patients with SIH. These are often headache patients who enjoy yoga and were superflexible as children, participating in gymnastics, ballet, or cheerleading.

“We’re looking for Cirque du Soleil here, so you have to ask the Cirque du Soleil questions,” Dr. Friedman said.

On physical examination, she looks for joint hypermobility, makes sure that spontaneous retinal venous pulsations indicative of normal CSF pressure are present when she looks in the eyes, and puts the patient in 5 degrees of Trendelenburg position for 5-10 minutes to see if that improves the headache and other symptoms.

One of the first things Dr. Friedman does when she suspects the diagnosis is to send a patient to the recommended website of the Spinal CSF Leak Foundation. She asks them to take a look around the site and tell her if the descriptions sound like them.

There is broad agreement that the first-line diagnostic test is brain imaging via MRI with gadolinium enhancement. The diagnostic challenge posed by SIH is that the test is normal in 30% of affected patients.

At present there is no consensus as to the next move when the brain MRI is negative. Some favor CT with or without MR myelography, others a T2-weighted spine MRI. But despite a thorough search, no leak is found in about half of individuals with SIH.

Although Dr. Friedman focused on diagnosis, she turned briefly to treatment. She has found that conservative measures don’t work very well. A reasonable strategy, even if a leak site hasn’t been identified, is to treat with a high-volume epidural CT-guided targeted blood patch with fibrin sealant.

“It gives relief about a third of the time each time you do it,” according to Dr. Friedman.

[email protected]

SAN FRANCISCO – Galcanezumab, the investigational calcitonin gene-related peptide inhibitor under development as preventive therapy for migraine, looks like a triple threat: Multiple phase 3 randomized trials have not only demonstrated safety and efficacy of the monoclonal antibody for prevention of both episodic and chronic migraine but for prevention of episodic cluster headache as well.

Bruce Jancin/MDedge News

Galcanezumab

Sheena K. Aurora, MD, presented the results of the GCAL study, a phase 3 randomized, double-blind, 8-week study of subcutaneous galcanezumab at 300 mg once monthly or placebo administered for 2 months in 106 patients with ongoing episodic cluster headache attacks at baseline.

“This is really uncharted territory. The American Headache Society, in its 2016 cluster headache guidelines, reported that there was no high-quality evidence for prophylactic therapy,” noted Dr. Aurora of Eli Lilly in Indianapolis.

After the GCAL study, that’s no longer true. Study participants were a typical population of episodic cluster headache patients: that is, mostly middle-aged men. They averaged more than 17 cluster headache attacks per week during the baseline period, or 2-3 daily, with roughly a 16-year history of episodic cluster headaches, which typically occur in bursts lasting 6-8 weeks before temporarily fading. Of note, 14 of the 106 patients reported a history of prior suicidal ideation; while disturbing, that’s actually a lower rate than in some epidemiologic studies examining patients with this excruciating form of head pain.

The primary endpoint was the mean change in weekly cluster headache attack frequency during weeks 1-3. The difference was significant: a reduction of 8.7 attacks per week in the galcanezumab group, compared with 5.2 fewer in controls. The key secondary endpoint was the proportion of patients with at least a 50% reduction in weekly cluster attack frequency from baseline at week 3: This was achieved in 76% in the galcanezumab arm, versus 57% for placebo, again a significant difference.

At week 4, 73% of patients on galcanezumab rated themselves as very much or much better on the Patient Global Impression of Improvement, significantly greater than the 46% rate in controls. By week 8, this difference – while trending favorably – was no longer statistically significant, but it must be noted that by then 8 of the original 57 patients randomized to placebo had discontinued treatment because of the lack of efficacy, compared with just 1 of 49 in the galcanezumab group.

Adverse events in the two treatment arms were essentially the same as placebo except for an 8% rate of mild injection site reactions in the active treatment group.

Another double-blind, placebo-controlled phase 3 trial known as the CGAM study was conducted in 237 patients with chronic rather than episodic cluster headache. However, it proved negative for the same endpoints, Dr. Aurora said.

Separately, she presented a new post hoc analysis of the recently published EVOLVE-1 (JAMA Neurol. 2018 May 29. doi: 10.1001/jamaneurol.2018.1212) and EVOLVE-2 (Cephalalgia. 2018 Jul;38[8]:1442-54) trials. These two mirror-image pivotal phase 3, double-blind, placebo-controlled, 6-month studies of galcanezumab at 120 or 240 mg once monthly included a collective 1,773 episodic migraine patients with a baseline mean of 9.1 migraine headache days per month. Her analysis focused on the rapidity of onset of the humanized monoclonal antibody’s preventive effect.

“As most clinicians are aware, the current oral preventive treatments that we use require titration, and we don’t really see a good effect for maybe 2-3 months,” she observed.

In an ordinal logistic regression analysis, she and her coinvestigators first determined that the galcanezumab group separated from placebo in terms of reduced migraine headache days as early as 1 month in both studies. Next, they drilled down deeper into the participants’ daily headache diaries and determined that the onset of effect was seen at week 1, at which point the odds of a significant reduction in weekly migraine headache days were 2.71-fold greater with galcanezumab than placebo in EVOLVE-1 and 2.88-fold greater in EVOLVE-2.

“Patients would like to know how quickly they might see an effect, so the fact that we start seeing it for patients who’ve had migraine for 20 years with an average of 9.1 migraine headache days per month as early as week 1 is gratifying, even though the absolute numbers who benefit at that point are small,” Dr. Aurora said.

Fremanezumab

Fremanezumab is a fully humanized monoclonal antibody selectively targeting CGRP. Like galcanezumab and eptinezumab, it is now supported by phase 3 data from short-term, double-blind, placebo-controlled trials backed up by reassuring results from long-term, open-label studies.

Eptinezumab

Unlike other anti-CGRP antibodies, eptinezumab is administered intravenously, once every 3 months, rather than by subcutaneous injection. This IgG1 anti-CGRP monoclonal antibody was engineered for reduced immune activation and a 30-day half-life. It’s onset of action is extremely rapid, with 100% of the agent being bioavailable within a few hours after administration.

The positive 12-week outcomes of the phase 3 randomized, double-blind, placebo-controlled PROMISE-2 trial of eptinezumab for prophylaxis against chronic migraine have previously been presented, as have the 1-year results in episodic migraine patients in PROMISE-1.

[email protected]

SAN FRANCISCO – Galcanezumab, the investigational calcitonin gene-related peptide inhibitor under development as preventive therapy for migraine, looks like a triple threat: Multiple phase 3 randomized trials have not only demonstrated safety and efficacy of the monoclonal antibody for prevention of both episodic and chronic migraine but for prevention of episodic cluster headache as well.

Bruce Jancin/MDedge News

Galcanezumab

Sheena K. Aurora, MD, presented the results of the GCAL study, a phase 3 randomized, double-blind, 8-week study of subcutaneous galcanezumab at 300 mg once monthly or placebo administered for 2 months in 106 patients with ongoing episodic cluster headache attacks at baseline.

“This is really uncharted territory. The American Headache Society, in its 2016 cluster headache guidelines, reported that there was no high-quality evidence for prophylactic therapy,” noted Dr. Aurora of Eli Lilly in Indianapolis.

After the GCAL study, that’s no longer true. Study participants were a typical population of episodic cluster headache patients: that is, mostly middle-aged men. They averaged more than 17 cluster headache attacks per week during the baseline period, or 2-3 daily, with roughly a 16-year history of episodic cluster headaches, which typically occur in bursts lasting 6-8 weeks before temporarily fading. Of note, 14 of the 106 patients reported a history of prior suicidal ideation; while disturbing, that’s actually a lower rate than in some epidemiologic studies examining patients with this excruciating form of head pain.

The primary endpoint was the mean change in weekly cluster headache attack frequency during weeks 1-3. The difference was significant: a reduction of 8.7 attacks per week in the galcanezumab group, compared with 5.2 fewer in controls. The key secondary endpoint was the proportion of patients with at least a 50% reduction in weekly cluster attack frequency from baseline at week 3: This was achieved in 76% in the galcanezumab arm, versus 57% for placebo, again a significant difference.

At week 4, 73% of patients on galcanezumab rated themselves as very much or much better on the Patient Global Impression of Improvement, significantly greater than the 46% rate in controls. By week 8, this difference – while trending favorably – was no longer statistically significant, but it must be noted that by then 8 of the original 57 patients randomized to placebo had discontinued treatment because of the lack of efficacy, compared with just 1 of 49 in the galcanezumab group.

Adverse events in the two treatment arms were essentially the same as placebo except for an 8% rate of mild injection site reactions in the active treatment group.

Another double-blind, placebo-controlled phase 3 trial known as the CGAM study was conducted in 237 patients with chronic rather than episodic cluster headache. However, it proved negative for the same endpoints, Dr. Aurora said.

Separately, she presented a new post hoc analysis of the recently published EVOLVE-1 (JAMA Neurol. 2018 May 29. doi: 10.1001/jamaneurol.2018.1212) and EVOLVE-2 (Cephalalgia. 2018 Jul;38[8]:1442-54) trials. These two mirror-image pivotal phase 3, double-blind, placebo-controlled, 6-month studies of galcanezumab at 120 or 240 mg once monthly included a collective 1,773 episodic migraine patients with a baseline mean of 9.1 migraine headache days per month. Her analysis focused on the rapidity of onset of the humanized monoclonal antibody’s preventive effect.

“As most clinicians are aware, the current oral preventive treatments that we use require titration, and we don’t really see a good effect for maybe 2-3 months,” she observed.

In an ordinal logistic regression analysis, she and her coinvestigators first determined that the galcanezumab group separated from placebo in terms of reduced migraine headache days as early as 1 month in both studies. Next, they drilled down deeper into the participants’ daily headache diaries and determined that the onset of effect was seen at week 1, at which point the odds of a significant reduction in weekly migraine headache days were 2.71-fold greater with galcanezumab than placebo in EVOLVE-1 and 2.88-fold greater in EVOLVE-2.

“Patients would like to know how quickly they might see an effect, so the fact that we start seeing it for patients who’ve had migraine for 20 years with an average of 9.1 migraine headache days per month as early as week 1 is gratifying, even though the absolute numbers who benefit at that point are small,” Dr. Aurora said.

Fremanezumab

Fremanezumab is a fully humanized monoclonal antibody selectively targeting CGRP. Like galcanezumab and eptinezumab, it is now supported by phase 3 data from short-term, double-blind, placebo-controlled trials backed up by reassuring results from long-term, open-label studies.

Eptinezumab

Unlike other anti-CGRP antibodies, eptinezumab is administered intravenously, once every 3 months, rather than by subcutaneous injection. This IgG1 anti-CGRP monoclonal antibody was engineered for reduced immune activation and a 30-day half-life. It’s onset of action is extremely rapid, with 100% of the agent being bioavailable within a few hours after administration.

The positive 12-week outcomes of the phase 3 randomized, double-blind, placebo-controlled PROMISE-2 trial of eptinezumab for prophylaxis against chronic migraine have previously been presented, as have the 1-year results in episodic migraine patients in PROMISE-1.

[email protected]

SAN FRANCISCO – Galcanezumab, the investigational calcitonin gene-related peptide inhibitor under development as preventive therapy for migraine, looks like a triple threat: Multiple phase 3 randomized trials have not only demonstrated safety and efficacy of the monoclonal antibody for prevention of both episodic and chronic migraine but for prevention of episodic cluster headache as well.

Bruce Jancin/MDedge News

Galcanezumab

Sheena K. Aurora, MD, presented the results of the GCAL study, a phase 3 randomized, double-blind, 8-week study of subcutaneous galcanezumab at 300 mg once monthly or placebo administered for 2 months in 106 patients with ongoing episodic cluster headache attacks at baseline.

“This is really uncharted territory. The American Headache Society, in its 2016 cluster headache guidelines, reported that there was no high-quality evidence for prophylactic therapy,” noted Dr. Aurora of Eli Lilly in Indianapolis.

After the GCAL study, that’s no longer true. Study participants were a typical population of episodic cluster headache patients: that is, mostly middle-aged men. They averaged more than 17 cluster headache attacks per week during the baseline period, or 2-3 daily, with roughly a 16-year history of episodic cluster headaches, which typically occur in bursts lasting 6-8 weeks before temporarily fading. Of note, 14 of the 106 patients reported a history of prior suicidal ideation; while disturbing, that’s actually a lower rate than in some epidemiologic studies examining patients with this excruciating form of head pain.

The primary endpoint was the mean change in weekly cluster headache attack frequency during weeks 1-3. The difference was significant: a reduction of 8.7 attacks per week in the galcanezumab group, compared with 5.2 fewer in controls. The key secondary endpoint was the proportion of patients with at least a 50% reduction in weekly cluster attack frequency from baseline at week 3: This was achieved in 76% in the galcanezumab arm, versus 57% for placebo, again a significant difference.

At week 4, 73% of patients on galcanezumab rated themselves as very much or much better on the Patient Global Impression of Improvement, significantly greater than the 46% rate in controls. By week 8, this difference – while trending favorably – was no longer statistically significant, but it must be noted that by then 8 of the original 57 patients randomized to placebo had discontinued treatment because of the lack of efficacy, compared with just 1 of 49 in the galcanezumab group.

Adverse events in the two treatment arms were essentially the same as placebo except for an 8% rate of mild injection site reactions in the active treatment group.

Another double-blind, placebo-controlled phase 3 trial known as the CGAM study was conducted in 237 patients with chronic rather than episodic cluster headache. However, it proved negative for the same endpoints, Dr. Aurora said.

Separately, she presented a new post hoc analysis of the recently published EVOLVE-1 (JAMA Neurol. 2018 May 29. doi: 10.1001/jamaneurol.2018.1212) and EVOLVE-2 (Cephalalgia. 2018 Jul;38[8]:1442-54) trials. These two mirror-image pivotal phase 3, double-blind, placebo-controlled, 6-month studies of galcanezumab at 120 or 240 mg once monthly included a collective 1,773 episodic migraine patients with a baseline mean of 9.1 migraine headache days per month. Her analysis focused on the rapidity of onset of the humanized monoclonal antibody’s preventive effect.

“As most clinicians are aware, the current oral preventive treatments that we use require titration, and we don’t really see a good effect for maybe 2-3 months,” she observed.

In an ordinal logistic regression analysis, she and her coinvestigators first determined that the galcanezumab group separated from placebo in terms of reduced migraine headache days as early as 1 month in both studies. Next, they drilled down deeper into the participants’ daily headache diaries and determined that the onset of effect was seen at week 1, at which point the odds of a significant reduction in weekly migraine headache days were 2.71-fold greater with galcanezumab than placebo in EVOLVE-1 and 2.88-fold greater in EVOLVE-2.

“Patients would like to know how quickly they might see an effect, so the fact that we start seeing it for patients who’ve had migraine for 20 years with an average of 9.1 migraine headache days per month as early as week 1 is gratifying, even though the absolute numbers who benefit at that point are small,” Dr. Aurora said.

Fremanezumab

Fremanezumab is a fully humanized monoclonal antibody selectively targeting CGRP. Like galcanezumab and eptinezumab, it is now supported by phase 3 data from short-term, double-blind, placebo-controlled trials backed up by reassuring results from long-term, open-label studies.

Eptinezumab

Unlike other anti-CGRP antibodies, eptinezumab is administered intravenously, once every 3 months, rather than by subcutaneous injection. This IgG1 anti-CGRP monoclonal antibody was engineered for reduced immune activation and a 30-day half-life. It’s onset of action is extremely rapid, with 100% of the agent being bioavailable within a few hours after administration.

The positive 12-week outcomes of the phase 3 randomized, double-blind, placebo-controlled PROMISE-2 trial of eptinezumab for prophylaxis against chronic migraine have previously been presented, as have the 1-year results in episodic migraine patients in PROMISE-1.

[email protected]

SAN FRANCISCO—Among patients with episodic cluster headache, galcanezumab significantly reduced weekly attack frequency, according to the results of a phase III trial presented at the 60th Annual Scientific Meeting of the American Headache Society. Results of an eight-week, double-blind, placebo-controlled clinical trial showed that galcanezumab (300 mg SC) significantly reduced the weekly cluster headache attack frequency across weeks one to three, which was the study’s primary end point, and resulted in a significantly greater percentage of patients achieving a 50% or greater reduction in their weekly cluster headache attack frequency at week three.

James M. Martinez, MD, a medical fellow at Eli Lilly, Indianapolis, Indiana, and study collaborators sought to determine if galcanezumab (aka LY2951742), a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide (CGRP), is efficacious as a preventive treatment of episodic cluster headache.

A phase III study was designed to assess the efficacy and safety of galcanezumab in individuals with episodic cluster headache, as defined by ICHD-3 beta criteria. This study comprised a screening period; a prospective baseline period; an eight-week, double-blind, placebo-controlled treatment period; and a four-month posttreatment washout period.

In the double-blind treatment period, participants were randomized 1:1 to galcanezumab 300 mg SC (n = 49) or placebo (n = 57) once monthly for two months. The primary end point was the overall mean change from baseline in weekly cluster headache attack frequency across weeks one to three. The key secondary end point was the proportion of participants achieving a response, defined as a reduction from baseline of 50% or greater in the weekly cluster headache attack frequency at week three. Other secondary end points included proportion of participants very much or much better based on Patient Global Impression of Improvement (PGI-I) at weeks four and eight.

Baseline demographics of the galcanezumab and placebo groups were similar. Mean age was 47 and 45, respectively; 84% and 82%, respectively, were male. The mean number of weekly cluster headache attacks in the baseline period was 17.8 for the galcanezumab group and 17.3 for the placebo group. Overall, four participants (8%) in the galcanezumab treatment group discontinued therapy during the double-blind period versus 12 (21%) in the placebo group. In the placebo group, eight participants (14%) discontinued treatment due to lack of efficacy versus one (2%) in the galcanezumab group. The mean change in weekly cluster headache attack frequency across weeks one to three was –8.7 for galcanezumab versus –5.2 for placebo (difference between treatment groups in mean change, –3.5). The proportion of participants achieving a 50% or greater reduction in weekly cluster headache attack frequency was 76% for galcanezumab versus 57% for placebo. The proportion of participants very much or much better based on PGI-I was significantly greater with galcanezumab versus placebo at week four (73% vs 46%) but not at week eight (72% vs 66%). There were no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a statistically significantly greater incidence of injection site pain with galcanezumab versus placebo (8.2% vs 0%), which was similar to the safety profile seen previously in patients with episodic and chronic migraine.

—Glenn S. Williams

SAN FRANCISCO—Among patients with episodic cluster headache, galcanezumab significantly reduced weekly attack frequency, according to the results of a phase III trial presented at the 60th Annual Scientific Meeting of the American Headache Society. Results of an eight-week, double-blind, placebo-controlled clinical trial showed that galcanezumab (300 mg SC) significantly reduced the weekly cluster headache attack frequency across weeks one to three, which was the study’s primary end point, and resulted in a significantly greater percentage of patients achieving a 50% or greater reduction in their weekly cluster headache attack frequency at week three.

James M. Martinez, MD, a medical fellow at Eli Lilly, Indianapolis, Indiana, and study collaborators sought to determine if galcanezumab (aka LY2951742), a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide (CGRP), is efficacious as a preventive treatment of episodic cluster headache.

A phase III study was designed to assess the efficacy and safety of galcanezumab in individuals with episodic cluster headache, as defined by ICHD-3 beta criteria. This study comprised a screening period; a prospective baseline period; an eight-week, double-blind, placebo-controlled treatment period; and a four-month posttreatment washout period.

In the double-blind treatment period, participants were randomized 1:1 to galcanezumab 300 mg SC (n = 49) or placebo (n = 57) once monthly for two months. The primary end point was the overall mean change from baseline in weekly cluster headache attack frequency across weeks one to three. The key secondary end point was the proportion of participants achieving a response, defined as a reduction from baseline of 50% or greater in the weekly cluster headache attack frequency at week three. Other secondary end points included proportion of participants very much or much better based on Patient Global Impression of Improvement (PGI-I) at weeks four and eight.

Baseline demographics of the galcanezumab and placebo groups were similar. Mean age was 47 and 45, respectively; 84% and 82%, respectively, were male. The mean number of weekly cluster headache attacks in the baseline period was 17.8 for the galcanezumab group and 17.3 for the placebo group. Overall, four participants (8%) in the galcanezumab treatment group discontinued therapy during the double-blind period versus 12 (21%) in the placebo group. In the placebo group, eight participants (14%) discontinued treatment due to lack of efficacy versus one (2%) in the galcanezumab group. The mean change in weekly cluster headache attack frequency across weeks one to three was –8.7 for galcanezumab versus –5.2 for placebo (difference between treatment groups in mean change, –3.5). The proportion of participants achieving a 50% or greater reduction in weekly cluster headache attack frequency was 76% for galcanezumab versus 57% for placebo. The proportion of participants very much or much better based on PGI-I was significantly greater with galcanezumab versus placebo at week four (73% vs 46%) but not at week eight (72% vs 66%). There were no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a statistically significantly greater incidence of injection site pain with galcanezumab versus placebo (8.2% vs 0%), which was similar to the safety profile seen previously in patients with episodic and chronic migraine.

—Glenn S. Williams

SAN FRANCISCO—Among patients with episodic cluster headache, galcanezumab significantly reduced weekly attack frequency, according to the results of a phase III trial presented at the 60th Annual Scientific Meeting of the American Headache Society. Results of an eight-week, double-blind, placebo-controlled clinical trial showed that galcanezumab (300 mg SC) significantly reduced the weekly cluster headache attack frequency across weeks one to three, which was the study’s primary end point, and resulted in a significantly greater percentage of patients achieving a 50% or greater reduction in their weekly cluster headache attack frequency at week three.

James M. Martinez, MD, a medical fellow at Eli Lilly, Indianapolis, Indiana, and study collaborators sought to determine if galcanezumab (aka LY2951742), a humanized monoclonal antibody that selectively binds to calcitonin gene-related peptide (CGRP), is efficacious as a preventive treatment of episodic cluster headache.

A phase III study was designed to assess the efficacy and safety of galcanezumab in individuals with episodic cluster headache, as defined by ICHD-3 beta criteria. This study comprised a screening period; a prospective baseline period; an eight-week, double-blind, placebo-controlled treatment period; and a four-month posttreatment washout period.

In the double-blind treatment period, participants were randomized 1:1 to galcanezumab 300 mg SC (n = 49) or placebo (n = 57) once monthly for two months. The primary end point was the overall mean change from baseline in weekly cluster headache attack frequency across weeks one to three. The key secondary end point was the proportion of participants achieving a response, defined as a reduction from baseline of 50% or greater in the weekly cluster headache attack frequency at week three. Other secondary end points included proportion of participants very much or much better based on Patient Global Impression of Improvement (PGI-I) at weeks four and eight.

Baseline demographics of the galcanezumab and placebo groups were similar. Mean age was 47 and 45, respectively; 84% and 82%, respectively, were male. The mean number of weekly cluster headache attacks in the baseline period was 17.8 for the galcanezumab group and 17.3 for the placebo group. Overall, four participants (8%) in the galcanezumab treatment group discontinued therapy during the double-blind period versus 12 (21%) in the placebo group. In the placebo group, eight participants (14%) discontinued treatment due to lack of efficacy versus one (2%) in the galcanezumab group. The mean change in weekly cluster headache attack frequency across weeks one to three was –8.7 for galcanezumab versus –5.2 for placebo (difference between treatment groups in mean change, –3.5). The proportion of participants achieving a 50% or greater reduction in weekly cluster headache attack frequency was 76% for galcanezumab versus 57% for placebo. The proportion of participants very much or much better based on PGI-I was significantly greater with galcanezumab versus placebo at week four (73% vs 46%) but not at week eight (72% vs 66%). There were no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a statistically significantly greater incidence of injection site pain with galcanezumab versus placebo (8.2% vs 0%), which was similar to the safety profile seen previously in patients with episodic and chronic migraine.

—Glenn S. Williams

SAN FRANCISCO—Patients with chronic migraine are significantly more likely than those with episodic migraine to report that headaches contribute to relationship problems and have a detrimental effect on family life, researchers said at the 60th Annual Scientific Meeting of the American Headache Society. Negative effects on family life include a delay in having children and having fewer children.

Migraine can detract from many aspects of family life and affect all members of the patient’s family. Dawn C. Buse, PhD, Clinical Professor of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to understand the effects of episodic and chronic migraine on a person’s relationships and family life.

An Analysis of CaMEO Data

The CaMEO study is a prospective, longitudinal, web-based survey designed to characterize the impact of migraine, among other objectives, in a systematic US sample of people meeting modified ICHD-2R criteria. A total of 19,891 respondents met study criteria, including criteria for migraine, and were invited to complete the Family Burden Module (FBM), which assessed the impact, perception, and emotions related to living with migraine among people with migraine and their family members.

Dr. Buse and colleagues presented the results of migraineurs’ responses to the FBM regarding relationships with spouses or significant others and relationships with children living at home. The investigators stratified migraineurs by episodic migraine (ie, those with fewer than 14 headache days per month) and chronic migraine (ie, those with 15 or more headache days per month). Migraineurs were asked about their current relationship status (ie, in a current relationship or not, living together or not). Questions evaluated how headaches had affected past or current relationships with Likert-type response options that corresponded to degrees of disagreement or agreement. Dr. Buse’s group analyzed items by relationship status, episodic or chronic migraine status, and gender.

Women and Men Were Affected Similarly

In all, 13,064 respondents provided valid data. Of this population, 11,938 (91.4%) had episodic migraine and 1,126 (8.6%) had chronic migraine. Of those not currently in a relationship (n = 3,189), respondents with chronic migraine were significantly more likely to indicate that headaches had contributed to relationship problems (37.0%), compared with patients with episodic migraine (15.0%). Of those in a relationship but not living together (n = 1,323), 43.9% of respondents with chronic migraine indicated that headaches were causing relationship concerns or were preventing a closer relationship, such as moving in together or getting married, compared with 15.8% of patients with episodic migraine. The responses were similar among men (18.0%) and women (17.8%).

About 47% of respondents with chronic migraine reported that headaches have caused one or more previous relationship to end or have other problems, compared with 18.2% of respondents with episodic migraine. Headache contributions to relationship problems (ie, breakup or other difficulties) were similar among men (20.6%) and women (19.9%).

Of those in a relationship and living together (n = 8,127), 78.2% of respondents with chronic migraine agreed that they would be a better partner if they did not have headaches, compared with 46.2% of respondents with episodic migraine. Furthermore, 9.6% of patients with chronic migraine had delayed having children or had fewer children, compared with 2.6% of patients with episodic migraine. The researchers observed no differences between men and women.

SAN FRANCISCO—Patients with chronic migraine are significantly more likely than those with episodic migraine to report that headaches contribute to relationship problems and have a detrimental effect on family life, researchers said at the 60th Annual Scientific Meeting of the American Headache Society. Negative effects on family life include a delay in having children and having fewer children.

Migraine can detract from many aspects of family life and affect all members of the patient’s family. Dawn C. Buse, PhD, Clinical Professor of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to understand the effects of episodic and chronic migraine on a person’s relationships and family life.

An Analysis of CaMEO Data

The CaMEO study is a prospective, longitudinal, web-based survey designed to characterize the impact of migraine, among other objectives, in a systematic US sample of people meeting modified ICHD-2R criteria. A total of 19,891 respondents met study criteria, including criteria for migraine, and were invited to complete the Family Burden Module (FBM), which assessed the impact, perception, and emotions related to living with migraine among people with migraine and their family members.

Dr. Buse and colleagues presented the results of migraineurs’ responses to the FBM regarding relationships with spouses or significant others and relationships with children living at home. The investigators stratified migraineurs by episodic migraine (ie, those with fewer than 14 headache days per month) and chronic migraine (ie, those with 15 or more headache days per month). Migraineurs were asked about their current relationship status (ie, in a current relationship or not, living together or not). Questions evaluated how headaches had affected past or current relationships with Likert-type response options that corresponded to degrees of disagreement or agreement. Dr. Buse’s group analyzed items by relationship status, episodic or chronic migraine status, and gender.

Women and Men Were Affected Similarly

In all, 13,064 respondents provided valid data. Of this population, 11,938 (91.4%) had episodic migraine and 1,126 (8.6%) had chronic migraine. Of those not currently in a relationship (n = 3,189), respondents with chronic migraine were significantly more likely to indicate that headaches had contributed to relationship problems (37.0%), compared with patients with episodic migraine (15.0%). Of those in a relationship but not living together (n = 1,323), 43.9% of respondents with chronic migraine indicated that headaches were causing relationship concerns or were preventing a closer relationship, such as moving in together or getting married, compared with 15.8% of patients with episodic migraine. The responses were similar among men (18.0%) and women (17.8%).

About 47% of respondents with chronic migraine reported that headaches have caused one or more previous relationship to end or have other problems, compared with 18.2% of respondents with episodic migraine. Headache contributions to relationship problems (ie, breakup or other difficulties) were similar among men (20.6%) and women (19.9%).

Of those in a relationship and living together (n = 8,127), 78.2% of respondents with chronic migraine agreed that they would be a better partner if they did not have headaches, compared with 46.2% of respondents with episodic migraine. Furthermore, 9.6% of patients with chronic migraine had delayed having children or had fewer children, compared with 2.6% of patients with episodic migraine. The researchers observed no differences between men and women.

SAN FRANCISCO—Patients with chronic migraine are significantly more likely than those with episodic migraine to report that headaches contribute to relationship problems and have a detrimental effect on family life, researchers said at the 60th Annual Scientific Meeting of the American Headache Society. Negative effects on family life include a delay in having children and having fewer children.

Migraine can detract from many aspects of family life and affect all members of the patient’s family. Dawn C. Buse, PhD, Clinical Professor of Neurology at Albert Einstein College of Medicine in the Bronx, New York, and colleagues analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to understand the effects of episodic and chronic migraine on a person’s relationships and family life.

An Analysis of CaMEO Data

The CaMEO study is a prospective, longitudinal, web-based survey designed to characterize the impact of migraine, among other objectives, in a systematic US sample of people meeting modified ICHD-2R criteria. A total of 19,891 respondents met study criteria, including criteria for migraine, and were invited to complete the Family Burden Module (FBM), which assessed the impact, perception, and emotions related to living with migraine among people with migraine and their family members.

Dr. Buse and colleagues presented the results of migraineurs’ responses to the FBM regarding relationships with spouses or significant others and relationships with children living at home. The investigators stratified migraineurs by episodic migraine (ie, those with fewer than 14 headache days per month) and chronic migraine (ie, those with 15 or more headache days per month). Migraineurs were asked about their current relationship status (ie, in a current relationship or not, living together or not). Questions evaluated how headaches had affected past or current relationships with Likert-type response options that corresponded to degrees of disagreement or agreement. Dr. Buse’s group analyzed items by relationship status, episodic or chronic migraine status, and gender.

Women and Men Were Affected Similarly

In all, 13,064 respondents provided valid data. Of this population, 11,938 (91.4%) had episodic migraine and 1,126 (8.6%) had chronic migraine. Of those not currently in a relationship (n = 3,189), respondents with chronic migraine were significantly more likely to indicate that headaches had contributed to relationship problems (37.0%), compared with patients with episodic migraine (15.0%). Of those in a relationship but not living together (n = 1,323), 43.9% of respondents with chronic migraine indicated that headaches were causing relationship concerns or were preventing a closer relationship, such as moving in together or getting married, compared with 15.8% of patients with episodic migraine. The responses were similar among men (18.0%) and women (17.8%).

About 47% of respondents with chronic migraine reported that headaches have caused one or more previous relationship to end or have other problems, compared with 18.2% of respondents with episodic migraine. Headache contributions to relationship problems (ie, breakup or other difficulties) were similar among men (20.6%) and women (19.9%).

Of those in a relationship and living together (n = 8,127), 78.2% of respondents with chronic migraine agreed that they would be a better partner if they did not have headaches, compared with 46.2% of respondents with episodic migraine. Furthermore, 9.6% of patients with chronic migraine had delayed having children or had fewer children, compared with 2.6% of patients with episodic migraine. The researchers observed no differences between men and women.

SAN FRANCISCO—Among a cohort of recently deployed soldiers, headaches were frequent but were more severe, frequent, and migrainous if associated with concussion, according to a report presented at the 60th Annual Scientific Meeting of the American Headache Society. At one-year follow-up, headache frequency had decreased in soldiers with posttraumatic headache (PTH) but remained higher in this group than in those whose headaches were presumed to be unrelated to head injury, said Ann I. Scher, PhD, Director and Professor of Preventive Medicine and Biostatistics at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues.

“There are limited data on the phenotypic differences between headaches related to mild traumatic brain injury and ‘regular’ headaches,” Dr. Scher said. “A better understanding of the posttraumatic headache phenotype will inform the design of interventional studies for this difficult to treat population.”

SAN FRANCISCO—Among a cohort of recently deployed soldiers, headaches were frequent but were more severe, frequent, and migrainous if associated with concussion, according to a report presented at the 60th Annual Scientific Meeting of the American Headache Society. At one-year follow-up, headache frequency had decreased in soldiers with posttraumatic headache (PTH) but remained higher in this group than in those whose headaches were presumed to be unrelated to head injury, said Ann I. Scher, PhD, Director and Professor of Preventive Medicine and Biostatistics at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues.

“There are limited data on the phenotypic differences between headaches related to mild traumatic brain injury and ‘regular’ headaches,” Dr. Scher said. “A better understanding of the posttraumatic headache phenotype will inform the design of interventional studies for this difficult to treat population.”

SAN FRANCISCO—Among a cohort of recently deployed soldiers, headaches were frequent but were more severe, frequent, and migrainous if associated with concussion, according to a report presented at the 60th Annual Scientific Meeting of the American Headache Society. At one-year follow-up, headache frequency had decreased in soldiers with posttraumatic headache (PTH) but remained higher in this group than in those whose headaches were presumed to be unrelated to head injury, said Ann I. Scher, PhD, Director and Professor of Preventive Medicine and Biostatistics at the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues.

“There are limited data on the phenotypic differences between headaches related to mild traumatic brain injury and ‘regular’ headaches,” Dr. Scher said. “A better understanding of the posttraumatic headache phenotype will inform the design of interventional studies for this difficult to treat population.”

Thrombectomy Is Feasible for the Elderly, but Entails Risks

Mechanical thrombectomy is an increasingly important therapy for acute stroke that can benefit the very old, assuming a careful selection of patients and risk assessment, according to a Portuguese study.

For several years, endovascular thrombectomy has been a way of removing larger vascular obstructions. In this procedure, the thrombus is extracted from the cerebral vessel via a catheter inserted in the groin. Numerous international studies have shown that endovascular treatment is a substantial improvement over purely drug-based therapy. The procedure is especially effective in dealing with extremely long blood clots and large obstructions of the cerebral arteries and often yields positive results. Thanks to this procedure, more than 60% of patients treated survive the stroke with no or minor subsequent impairment.

“More and more study results show the high effectiveness of mechanical removal of blood clots after a stroke. But researchers are still trying to determine the type of patient for whom this relatively new procedure is the best treatment option,” said Ary Lopes de Sousa, MD, a neurology resident at Central Lisbon Hospital Center.

Dr. de Sousa and his colleagues reviewed the treatment success of thrombectomy in more than 200 patients with anterior acute ischemic stroke and no or slight disability prior to this event. The researchers separated patients into two groups: one with individuals younger than 80 and one with individuals age 80 and older.

In the group of patients age 80 and older, hypertension and transient ischemic attacks were more frequent. The treatment did not differ between the two groups (eg, in terms of the time frame of the revascularization). But in the older group, two-thirds of the patients exhibited a poor functional outcome at three months after the treatment (ie, they were moderately or severely limited in their ability to handle their daily tasks). The number of impaired individuals in that group was substantially larger than in the younger group, where 46% faced limitations in their everyday lives. On the other hand, one-third of the patients age 80 and older were able to handle their everyday lives three months after the treatment with no or mild impairments from the stroke. No difference in mortality was observed between the two age groups.

“For patients over 80, thrombectomy appears to be riskier than for younger patients,” said Dr. de Sousa. “But one third of the patients over 80 can be fully functional in their everyday lives after the procedure, so we must identify the factors associated with this favorable outcome. This [step] will support us applying this modern procedure efficiently to those individuals among the very old who can benefit from it.”

Studies Gauge the Cost of Migraine

A pair of studies have evaluated the cost of migraine to individuals, society, and businesses. A French study looked at the socioeconomic impact of the condition. In a survey of more than 7,700 people, a representative sample of the general population, 3.8% indicated that they experienced severe migraines on at least eight days per month. “Two-thirds of those [patients] were women, and the average age of those affected was 41, meaning that migraines significantly affect people at the peak of their careers, and who have families to provide for. These regular attacks represent a serious problem as far as keeping their jobs is concerned,” said Dr. Guillaume Leiba, Pricing and Market Access Manager at Novartis in Paris. In the current study, patients with severe migraine reported missing 33 working days per year because of their condition. This absence translates into a cost to society of approximately EUR 3.8 billion. Migraine also has an impact on patients’ social environment: 14% of respondents indicated that family members had to adjust their working hours because of patients’ migraine headaches. The study also quantified the financial burden placed on migraineurs: 58% reported an average monthly cost of more than EUR 30 per month for nonreimbursed medicines. Approximately 43% spent more than EUR 50 each month on other, nonpharmaceutical therapies. Despite the high level of public and private spending associated with the condition, quality of life for migraineurs remains far from satisfactory. More than three-quarters have sleep disorders and benefit less from their free time than healthy controls.

A Swiss study obtained more detailed results regarding absenteeism in the workplace. A group of 700 working migraineurs reported losing an average of 32 days per year because of migraine. This rate is similar to that reported in the French study. But there were significant differences depending on the specific type of headache, according to study author François Cadiou, CEO of Healint in Singapore. “With an average of more than 56 working days missed per year, patients with chronic migraine had the highest rate of absenteeism. People with episodic migraine were unable to go to work on 33 days of the year, while those with low-frequency episodic migraine took an average of 15 days off because of their condition.” Another finding has implications for preventive measures: the number of sick days was not always constant. In fact, the total steadily increased, and with it the amount of medication taken if patients indicated anxiety or depression as a symptom or trigger at least once within the 28-day observation period. In light of the outcomes presented, experts at the EAN Congress have issued a call for increased investment in migraine research and prevention, citing the advantages to society.

Both studies were funded by Novartis Pharma.

Parkinson’s Disease Progression Varies by Gender

A current study has now furnished the first neurophysiologic evidence that Parkinson’s disease progresses differently in women than in men. “Numerous demographic studies have provided evidence that men contract Parkinson’s disease nearly twice as often as women. What was unclear, however, was whether a gender-specific pathophysiology exists as soon as the first symptoms appear,” said Maja Kojovic, MD, PhD, a consultant neurologist at Ljubljana University Medical Center in Slovenia.

The international research team proceeded from the concept that in early Parkinson’s disease, functional changes can be detected in the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). If pathophysiology differs between genders in Parkinson’s disease, they hypothesized, it will be reflected in differences of M1 TMS measurements.

Thirty-nine newly diagnosed and untreated patients with Parkinson’s disease (23 males) were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Then the patients and a group of healthy controls underwent TMS measurements of motor thresholds of the brain, input–output curve, short interval intracortical inhibition, cortical silent period, and intracortical facilitation. Brain plasticity was also measured using paired associative stimulation.

The UPDRS tests did not yield any differences in motor scores between the genders. However, the female patients had a less steep input–output curve than the male patients on the side of the brain more affected by Parkinson’s disease.

The women with Parkinson’s disease also exhibited better preserved short interval intracortical inhibition in both hemispheres, compared with affected men, and tended to have a better response to the paired associative stimulation protocol on the side less affected by symptoms. No gender-specific differences were determined, however, in the motor thresholds, intracortical facilitation, and the cortical silent period. The healthy control group did not show any gender or interhemispheric differences for any of the TMS parameters measured. “The detected gender differences in corticospinal and intracortical excitability in patients with early untreated Parkinson’s disease represent differences in disease pathophysiology. Gender may also prove to be a relevant factor when choosing appropriate treatment,” said Dr. Kojovic.

EAN Develops Guideline on Palliative Care of Patients With Severe MS

A cohort of 934 individuals affected by multiple sclerosis (MS) from seven European countries played an instrumental part in developing the European Academy of Neurology’s (EAN) new guideline on palliative care for people with severe MS. “There were 751 MS patients and 183 caregiver relatives involved,” said Sascha Köpke, PhD, Professor of Nursing Research at the University of Lübeck in Germany.

With the involvement of patients and their families in a new guideline, the EAN is emphasizing shared decision-making as an increasingly important concept that underscores patient autonomy and promotes the individualization of diagnosis and therapy. According to this approach, patients and physicians undergo a detailed consultation and then choose the medical treatment. The EAN has supported this patient-centered approach for a long time, and it is becoming increasingly established in other medical areas as well.

“It was resource- and time-intensive to include consumers in the guideline process, but also highly rewarding,” said Prof. Köpke. “Patients and caregivers really helped us to formulate the guideline in a way that was in line with actual practice and their own needs. We were able to see clearly which of our ideas met with approval or rejection.” The comments were also instructive for the group of EAN experts. They raised new aspects as well as sensitive issues that had been left out of the first draft.

Two approaches were chosen to ensure that consumers would participate. “First, there was an international online survey launched by national MS societies following a trial run involving 20 patients and 18 caregivers. Second, we invited MS patients and caregiver relatives to focus group meetings,” said Prof. Köpke. The majority of participants approved the topics proposed by the EAN group of experts. About 98% agreed to incorporate the subject of multidisciplinary rehabilitation in the guideline. There were 569 free comments, of which 182 (32%) pertained to the specified topics. A further 227 comments (40%) addressed additional topics, of which 16 were pertinent to the guideline. Five of the focus group meetings corroborated the results of the online survey and helped to work out important issues for the individuals affected. “The involvement of patients and caregivers increases the reliability and relevance of the guideline for clinical practice,” said Prof. Köpke.

Thrombectomy Is Feasible for the Elderly, but Entails Risks

Mechanical thrombectomy is an increasingly important therapy for acute stroke that can benefit the very old, assuming a careful selection of patients and risk assessment, according to a Portuguese study.

For several years, endovascular thrombectomy has been a way of removing larger vascular obstructions. In this procedure, the thrombus is extracted from the cerebral vessel via a catheter inserted in the groin. Numerous international studies have shown that endovascular treatment is a substantial improvement over purely drug-based therapy. The procedure is especially effective in dealing with extremely long blood clots and large obstructions of the cerebral arteries and often yields positive results. Thanks to this procedure, more than 60% of patients treated survive the stroke with no or minor subsequent impairment.

“More and more study results show the high effectiveness of mechanical removal of blood clots after a stroke. But researchers are still trying to determine the type of patient for whom this relatively new procedure is the best treatment option,” said Ary Lopes de Sousa, MD, a neurology resident at Central Lisbon Hospital Center.

Dr. de Sousa and his colleagues reviewed the treatment success of thrombectomy in more than 200 patients with anterior acute ischemic stroke and no or slight disability prior to this event. The researchers separated patients into two groups: one with individuals younger than 80 and one with individuals age 80 and older.

In the group of patients age 80 and older, hypertension and transient ischemic attacks were more frequent. The treatment did not differ between the two groups (eg, in terms of the time frame of the revascularization). But in the older group, two-thirds of the patients exhibited a poor functional outcome at three months after the treatment (ie, they were moderately or severely limited in their ability to handle their daily tasks). The number of impaired individuals in that group was substantially larger than in the younger group, where 46% faced limitations in their everyday lives. On the other hand, one-third of the patients age 80 and older were able to handle their everyday lives three months after the treatment with no or mild impairments from the stroke. No difference in mortality was observed between the two age groups.

“For patients over 80, thrombectomy appears to be riskier than for younger patients,” said Dr. de Sousa. “But one third of the patients over 80 can be fully functional in their everyday lives after the procedure, so we must identify the factors associated with this favorable outcome. This [step] will support us applying this modern procedure efficiently to those individuals among the very old who can benefit from it.”

Studies Gauge the Cost of Migraine

A pair of studies have evaluated the cost of migraine to individuals, society, and businesses. A French study looked at the socioeconomic impact of the condition. In a survey of more than 7,700 people, a representative sample of the general population, 3.8% indicated that they experienced severe migraines on at least eight days per month. “Two-thirds of those [patients] were women, and the average age of those affected was 41, meaning that migraines significantly affect people at the peak of their careers, and who have families to provide for. These regular attacks represent a serious problem as far as keeping their jobs is concerned,” said Dr. Guillaume Leiba, Pricing and Market Access Manager at Novartis in Paris. In the current study, patients with severe migraine reported missing 33 working days per year because of their condition. This absence translates into a cost to society of approximately EUR 3.8 billion. Migraine also has an impact on patients’ social environment: 14% of respondents indicated that family members had to adjust their working hours because of patients’ migraine headaches. The study also quantified the financial burden placed on migraineurs: 58% reported an average monthly cost of more than EUR 30 per month for nonreimbursed medicines. Approximately 43% spent more than EUR 50 each month on other, nonpharmaceutical therapies. Despite the high level of public and private spending associated with the condition, quality of life for migraineurs remains far from satisfactory. More than three-quarters have sleep disorders and benefit less from their free time than healthy controls.

A Swiss study obtained more detailed results regarding absenteeism in the workplace. A group of 700 working migraineurs reported losing an average of 32 days per year because of migraine. This rate is similar to that reported in the French study. But there were significant differences depending on the specific type of headache, according to study author François Cadiou, CEO of Healint in Singapore. “With an average of more than 56 working days missed per year, patients with chronic migraine had the highest rate of absenteeism. People with episodic migraine were unable to go to work on 33 days of the year, while those with low-frequency episodic migraine took an average of 15 days off because of their condition.” Another finding has implications for preventive measures: the number of sick days was not always constant. In fact, the total steadily increased, and with it the amount of medication taken if patients indicated anxiety or depression as a symptom or trigger at least once within the 28-day observation period. In light of the outcomes presented, experts at the EAN Congress have issued a call for increased investment in migraine research and prevention, citing the advantages to society.

Both studies were funded by Novartis Pharma.

Parkinson’s Disease Progression Varies by Gender

A current study has now furnished the first neurophysiologic evidence that Parkinson’s disease progresses differently in women than in men. “Numerous demographic studies have provided evidence that men contract Parkinson’s disease nearly twice as often as women. What was unclear, however, was whether a gender-specific pathophysiology exists as soon as the first symptoms appear,” said Maja Kojovic, MD, PhD, a consultant neurologist at Ljubljana University Medical Center in Slovenia.

The international research team proceeded from the concept that in early Parkinson’s disease, functional changes can be detected in the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). If pathophysiology differs between genders in Parkinson’s disease, they hypothesized, it will be reflected in differences of M1 TMS measurements.

Thirty-nine newly diagnosed and untreated patients with Parkinson’s disease (23 males) were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Then the patients and a group of healthy controls underwent TMS measurements of motor thresholds of the brain, input–output curve, short interval intracortical inhibition, cortical silent period, and intracortical facilitation. Brain plasticity was also measured using paired associative stimulation.

The UPDRS tests did not yield any differences in motor scores between the genders. However, the female patients had a less steep input–output curve than the male patients on the side of the brain more affected by Parkinson’s disease.

The women with Parkinson’s disease also exhibited better preserved short interval intracortical inhibition in both hemispheres, compared with affected men, and tended to have a better response to the paired associative stimulation protocol on the side less affected by symptoms. No gender-specific differences were determined, however, in the motor thresholds, intracortical facilitation, and the cortical silent period. The healthy control group did not show any gender or interhemispheric differences for any of the TMS parameters measured. “The detected gender differences in corticospinal and intracortical excitability in patients with early untreated Parkinson’s disease represent differences in disease pathophysiology. Gender may also prove to be a relevant factor when choosing appropriate treatment,” said Dr. Kojovic.

EAN Develops Guideline on Palliative Care of Patients With Severe MS

A cohort of 934 individuals affected by multiple sclerosis (MS) from seven European countries played an instrumental part in developing the European Academy of Neurology’s (EAN) new guideline on palliative care for people with severe MS. “There were 751 MS patients and 183 caregiver relatives involved,” said Sascha Köpke, PhD, Professor of Nursing Research at the University of Lübeck in Germany.

With the involvement of patients and their families in a new guideline, the EAN is emphasizing shared decision-making as an increasingly important concept that underscores patient autonomy and promotes the individualization of diagnosis and therapy. According to this approach, patients and physicians undergo a detailed consultation and then choose the medical treatment. The EAN has supported this patient-centered approach for a long time, and it is becoming increasingly established in other medical areas as well.

“It was resource- and time-intensive to include consumers in the guideline process, but also highly rewarding,” said Prof. Köpke. “Patients and caregivers really helped us to formulate the guideline in a way that was in line with actual practice and their own needs. We were able to see clearly which of our ideas met with approval or rejection.” The comments were also instructive for the group of EAN experts. They raised new aspects as well as sensitive issues that had been left out of the first draft.

Two approaches were chosen to ensure that consumers would participate. “First, there was an international online survey launched by national MS societies following a trial run involving 20 patients and 18 caregivers. Second, we invited MS patients and caregiver relatives to focus group meetings,” said Prof. Köpke. The majority of participants approved the topics proposed by the EAN group of experts. About 98% agreed to incorporate the subject of multidisciplinary rehabilitation in the guideline. There were 569 free comments, of which 182 (32%) pertained to the specified topics. A further 227 comments (40%) addressed additional topics, of which 16 were pertinent to the guideline. Five of the focus group meetings corroborated the results of the online survey and helped to work out important issues for the individuals affected. “The involvement of patients and caregivers increases the reliability and relevance of the guideline for clinical practice,” said Prof. Köpke.

Thrombectomy Is Feasible for the Elderly, but Entails Risks

Mechanical thrombectomy is an increasingly important therapy for acute stroke that can benefit the very old, assuming a careful selection of patients and risk assessment, according to a Portuguese study.

For several years, endovascular thrombectomy has been a way of removing larger vascular obstructions. In this procedure, the thrombus is extracted from the cerebral vessel via a catheter inserted in the groin. Numerous international studies have shown that endovascular treatment is a substantial improvement over purely drug-based therapy. The procedure is especially effective in dealing with extremely long blood clots and large obstructions of the cerebral arteries and often yields positive results. Thanks to this procedure, more than 60% of patients treated survive the stroke with no or minor subsequent impairment.

“More and more study results show the high effectiveness of mechanical removal of blood clots after a stroke. But researchers are still trying to determine the type of patient for whom this relatively new procedure is the best treatment option,” said Ary Lopes de Sousa, MD, a neurology resident at Central Lisbon Hospital Center.

Dr. de Sousa and his colleagues reviewed the treatment success of thrombectomy in more than 200 patients with anterior acute ischemic stroke and no or slight disability prior to this event. The researchers separated patients into two groups: one with individuals younger than 80 and one with individuals age 80 and older.

In the group of patients age 80 and older, hypertension and transient ischemic attacks were more frequent. The treatment did not differ between the two groups (eg, in terms of the time frame of the revascularization). But in the older group, two-thirds of the patients exhibited a poor functional outcome at three months after the treatment (ie, they were moderately or severely limited in their ability to handle their daily tasks). The number of impaired individuals in that group was substantially larger than in the younger group, where 46% faced limitations in their everyday lives. On the other hand, one-third of the patients age 80 and older were able to handle their everyday lives three months after the treatment with no or mild impairments from the stroke. No difference in mortality was observed between the two age groups.

“For patients over 80, thrombectomy appears to be riskier than for younger patients,” said Dr. de Sousa. “But one third of the patients over 80 can be fully functional in their everyday lives after the procedure, so we must identify the factors associated with this favorable outcome. This [step] will support us applying this modern procedure efficiently to those individuals among the very old who can benefit from it.”

Studies Gauge the Cost of Migraine

A pair of studies have evaluated the cost of migraine to individuals, society, and businesses. A French study looked at the socioeconomic impact of the condition. In a survey of more than 7,700 people, a representative sample of the general population, 3.8% indicated that they experienced severe migraines on at least eight days per month. “Two-thirds of those [patients] were women, and the average age of those affected was 41, meaning that migraines significantly affect people at the peak of their careers, and who have families to provide for. These regular attacks represent a serious problem as far as keeping their jobs is concerned,” said Dr. Guillaume Leiba, Pricing and Market Access Manager at Novartis in Paris. In the current study, patients with severe migraine reported missing 33 working days per year because of their condition. This absence translates into a cost to society of approximately EUR 3.8 billion. Migraine also has an impact on patients’ social environment: 14% of respondents indicated that family members had to adjust their working hours because of patients’ migraine headaches. The study also quantified the financial burden placed on migraineurs: 58% reported an average monthly cost of more than EUR 30 per month for nonreimbursed medicines. Approximately 43% spent more than EUR 50 each month on other, nonpharmaceutical therapies. Despite the high level of public and private spending associated with the condition, quality of life for migraineurs remains far from satisfactory. More than three-quarters have sleep disorders and benefit less from their free time than healthy controls.

A Swiss study obtained more detailed results regarding absenteeism in the workplace. A group of 700 working migraineurs reported losing an average of 32 days per year because of migraine. This rate is similar to that reported in the French study. But there were significant differences depending on the specific type of headache, according to study author François Cadiou, CEO of Healint in Singapore. “With an average of more than 56 working days missed per year, patients with chronic migraine had the highest rate of absenteeism. People with episodic migraine were unable to go to work on 33 days of the year, while those with low-frequency episodic migraine took an average of 15 days off because of their condition.” Another finding has implications for preventive measures: the number of sick days was not always constant. In fact, the total steadily increased, and with it the amount of medication taken if patients indicated anxiety or depression as a symptom or trigger at least once within the 28-day observation period. In light of the outcomes presented, experts at the EAN Congress have issued a call for increased investment in migraine research and prevention, citing the advantages to society.

Both studies were funded by Novartis Pharma.

Parkinson’s Disease Progression Varies by Gender

A current study has now furnished the first neurophysiologic evidence that Parkinson’s disease progresses differently in women than in men. “Numerous demographic studies have provided evidence that men contract Parkinson’s disease nearly twice as often as women. What was unclear, however, was whether a gender-specific pathophysiology exists as soon as the first symptoms appear,” said Maja Kojovic, MD, PhD, a consultant neurologist at Ljubljana University Medical Center in Slovenia.

The international research team proceeded from the concept that in early Parkinson’s disease, functional changes can be detected in the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). If pathophysiology differs between genders in Parkinson’s disease, they hypothesized, it will be reflected in differences of M1 TMS measurements.

Thirty-nine newly diagnosed and untreated patients with Parkinson’s disease (23 males) were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). Then the patients and a group of healthy controls underwent TMS measurements of motor thresholds of the brain, input–output curve, short interval intracortical inhibition, cortical silent period, and intracortical facilitation. Brain plasticity was also measured using paired associative stimulation.

The UPDRS tests did not yield any differences in motor scores between the genders. However, the female patients had a less steep input–output curve than the male patients on the side of the brain more affected by Parkinson’s disease.

The women with Parkinson’s disease also exhibited better preserved short interval intracortical inhibition in both hemispheres, compared with affected men, and tended to have a better response to the paired associative stimulation protocol on the side less affected by symptoms. No gender-specific differences were determined, however, in the motor thresholds, intracortical facilitation, and the cortical silent period. The healthy control group did not show any gender or interhemispheric differences for any of the TMS parameters measured. “The detected gender differences in corticospinal and intracortical excitability in patients with early untreated Parkinson’s disease represent differences in disease pathophysiology. Gender may also prove to be a relevant factor when choosing appropriate treatment,” said Dr. Kojovic.

EAN Develops Guideline on Palliative Care of Patients With Severe MS

A cohort of 934 individuals affected by multiple sclerosis (MS) from seven European countries played an instrumental part in developing the European Academy of Neurology’s (EAN) new guideline on palliative care for people with severe MS. “There were 751 MS patients and 183 caregiver relatives involved,” said Sascha Köpke, PhD, Professor of Nursing Research at the University of Lübeck in Germany.

With the involvement of patients and their families in a new guideline, the EAN is emphasizing shared decision-making as an increasingly important concept that underscores patient autonomy and promotes the individualization of diagnosis and therapy. According to this approach, patients and physicians undergo a detailed consultation and then choose the medical treatment. The EAN has supported this patient-centered approach for a long time, and it is becoming increasingly established in other medical areas as well.

“It was resource- and time-intensive to include consumers in the guideline process, but also highly rewarding,” said Prof. Köpke. “Patients and caregivers really helped us to formulate the guideline in a way that was in line with actual practice and their own needs. We were able to see clearly which of our ideas met with approval or rejection.” The comments were also instructive for the group of EAN experts. They raised new aspects as well as sensitive issues that had been left out of the first draft.

Two approaches were chosen to ensure that consumers would participate. “First, there was an international online survey launched by national MS societies following a trial run involving 20 patients and 18 caregivers. Second, we invited MS patients and caregiver relatives to focus group meetings,” said Prof. Köpke. The majority of participants approved the topics proposed by the EAN group of experts. About 98% agreed to incorporate the subject of multidisciplinary rehabilitation in the guideline. There were 569 free comments, of which 182 (32%) pertained to the specified topics. A further 227 comments (40%) addressed additional topics, of which 16 were pertinent to the guideline. Five of the focus group meetings corroborated the results of the online survey and helped to work out important issues for the individuals affected. “The involvement of patients and caregivers increases the reliability and relevance of the guideline for clinical practice,” said Prof. Köpke.