Medical Marijuana May Alleviate MS Symptoms

PHILADELPHIA—Certain forms of medical marijuana can help treat symptoms of multiple sclerosis (MS), but they may not be helpful in treating levodopa-induced movements in Parkinson’s disease, researchers reported at the 66th Annual Meeting of the American Academy of Neurology (AAN).

The researchers did not find enough evidence to show whether medical marijuana is helpful in treating motor problems in Huntington’s disease, tics in Tourette syndrome, cervical dystonia, and seizures in epilepsy. These conclusions are part of AAN’s review of scientific research on the use of medical marijuana in brain diseases. The findings were published in the April 29, 2014, print issue of Neurology.

“This review by the world’s largest association for neurologists is intended to help neurologists and their patients understand the current research on medical marijuana for the treatment of certain brain diseases,” said review author Barbara S. Koppel, MD, of New York Medical College in Valhalla, and Fellow of the AAN. “The AAN review also highlights the need for more high-quality studies of the long-term efficacy and safety of medical marijuana in the treatment of neurologic diseases.”

The AAN review concluded that only the pill or oral spray forms of medical marijuana can help treat symptoms of MS, including spasticity, certain types of pain (ie, pain related to spasticity, including painful spasms, and painful burning and numbness), and overactive bladder. Most of the MS studies examined pill or oral spray forms of medical marijuana. Two studies examined smoked medical marijuana for treating MS symptoms, but these studies did not provide enough information to show whether smoked medical marijuana is effective. “It’s important to note that medical marijuana can worsen thinking and memory problems, and this is a concern, since many people with MS suffer from these problems already due to the disease itself,” said Dr. Koppel.

In addition, the AAN review concluded that medical marijuana, in the form of synthetic tetrahydrocannabinol (THC) pills, likely does not help relieve abnormal movements that can develop in the late stages of Parkinson’s disease as a result of levodopa.

Medical marijuana use does entail safety concerns. In at least two studies, participants reported side effects such as nausea, increased weakness, behavioral or mood changes, suicidal thoughts or hallucinations, dizziness or fainting symptoms, fatigue, and feelings of intoxication. There were reports of two seizures. Mood changes and suicidal thoughts are of special concern for people with neurologic illness, who are at an increased risk for depression and suicide. The risk of serious psychologic effects is approximately 1%, according to the studies.

The only two medical marijuana pills with FDA approval contain THC. “The psychoactive side effects, such as feeling intoxicated, seemed to come from the THC,” said Dr. Koppel. “They’re trying to create pills that are leaning more toward the cannabinoid, which has the therapeutic effects with fewer psychoactive side effects.”

Clinicians who practice in states where medical marijuana is legal may recommend the drug for the MS symptoms that respond to it, Dr. Koppel added. “The problem is that the studies are done very rigorously with a certain amount of THC versus cannabinoid. The type of marijuana you can buy so far is not so rigorously defined.” Clinicians also should warn their patients about marijuana’s potential side effects.

In general, medical marijuana is prescribed as a treatment only when standard treatment has not helped. In most of the studies reviewed, patients were allowed to continue their standard treatments. The AAN review is endorsed by the American Autonomic Society, the American Epilepsy Society, and the International Rett Syndrome Foundation.

—Erik Greb

New Drugs May Offer Hope for Migraine Prevention
Two new studies may offer hope for patients with migraine. Both studies involve drugs for migraine prophylaxis rather than acute treatment. These studies are among the first to test monoclonal antibodies for the prevention of migraine, and both are directed against calcitonin gene-related peptide (CGRP), a relatively new target in migraine prevention. Both are phase II studies.

One study involved 163 patients who had migraine from five to 14 days per month. The patients received either a placebo or a single IV dose of a drug called ALD403. After the initial injection, study participants were followed for 24 weeks. Those who received the drug had an average of 5.6 fewer migraine days per month, a 66% decrease, compared with 4.6 fewer days per month for those who received a placebo, or a 52% decrease. Sixteen percent of those who received the drug had no migraine days at 12 weeks, while none of those who received the placebo were free from migraine at that point.

There were no differences in side effects between those receiving the drug and those receiving the placebo.

“These results may potentially represent a new era in preventive therapy for migraine,” said Peter Goadsby, MD, PhD, of the University of California, San Francisco, who was an investigator in both studies.

“Migraine remains poorly treated, and there are few effective and well-tolerated treatments approved that prevent attacks from occurring,” said coinvestigator David Dodick, MD, of Mayo Clinic Arizona in Phoenix. “There is a huge treatment need for migraine—the third most common and seventh most disabling medical disorder in the world.”

In the second study, 217 patients who had migraine four to 14 days per month received biweekly subcutaneous injections of either a placebo or a drug called LY2951742 for 12 weeks.

Those who received the drug had an average of 4.2 fewer migraine days per month at 12 weeks, or a 63% decrease, while those who received placebo had three fewer migraine days per month, or a 42% decrease. Those who received the drug were more likely to have side effects including pain at the injection site, upper respiratory tract infections, and abdominal pain, but overall the drug was considered to be safe and well tolerated.

“We’re cautiously optimistic that a new era of mechanism-based migraine prevention is beginning,” Dr. Dodick said.

Botulinum Toxin for Poststroke Spasticity—Could a Higher Dosage Yield Greater Benefit?
Although patients with poststroke spasticity are generally satisfied with their botulinum toxin treatment, many individuals may derive additional benefit with higher dosages and shorter injection intervals than the standard 12-week regimen, researchers reported at the 66th Annual Meeting of the American Academy of Neurology.

Djamel Bensmail, MD, PhD, and colleagues conducted two cross-sectional surveys among patients and physicians in Canada, France, Germany, and the United States. A total of 79 eligible patients had received two or more treatments of abobotulinumtoxinA, incobotulinumtoxinA, or onabotulinumtoxinA for poststroke spasticity. The investigators gathered data regarding current and prior botulinum toxin treatments along with physician and patient treatment satisfaction. All 105 participating physicians had treated patients with poststroke spasticity and had three or more years’ experience of injecting botulinum toxin.

“Botulinum toxin injections are the first-line treatment for patients with poststroke spasticity,” stated Dr. Bensmail, from the Department of Physical Medicine and Rehabilitation, R. Poincaré Hospital, AP-HP, University of Versailles Saint Quentin in Garches, France. “However, for some patients, treatment at the standard-of-care 12‑week interval may result in re-emergence of symptoms before reinjection.”

Sixty-one patients (77%) received onabotulinumtoxinA, 15 patients (19%) received abobotulinumtoxinA, and three patients (4%) received incobotulinumtoxinA. The researchers found that 40.5% of patients were overall very satisfied with the treatment, and 48.1% were somewhat satisfied with their current treatment.

“Satisfaction was highest at the time of peak effect and lowest just before reinjection,” stated the investigators. “While 78.9% of patients preferred injection intervals of less than or equal to 12 weeks, only 45.6% received such intervals. Intervals of 10 weeks or fewer were preferred by 43.4% of patients but received by just 6.3%. The mean interval was 13.7 weeks.”

Among the physicians surveyed, most (57.7%) were moderately or very satisfied (36.5%) with botulinum
toxin treatment for poststroke spasticity. However, the physicians also believed, on average, that 16.2% of patients would benefit from shorter injection intervals and that 24.6% would benefit from higher doses than those that are approved.

—Colby Stong

Potential Targets and Interventions for Parkinson’s Disease
A trio of studies from researchers at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia demonstrate new approaches to understanding, treating, and potentially staving off Parkinson’s disease. Studies show that factors such as estrogen exposure and statin use have an impact on the onset of Parkinson’s disease. And a new look at telemedicine demonstrates feasibility in providing care for patients with Parkinson’s disease using remote video visits to expand access and center care around the needs of the patients.

Statins May Delay Onset of Parkinson’s Disease
Research presented by Yosef Berlyand, an undergraduate in the laboratory of Alice Chen-Plotkin, MD, MSc, Assistant Professor of Neurology, suggests that statins may be beneficial in Parkinson’s disease. In collaboration with Roy Alcalay, MD, and colleagues at the Columbia University School of Medicine, members of Dr. Chen-Plotkin’s research group demonstrated that blood levels of the protein apolipoprotein A1 (ApoA1) are lower in people with Parkinson’s disease than in those without the disease. Patients with Parkinson’s disease taking statins, which can elevate levels of ApoA1, had an older age of disease onset, which appears to be driven by taking statins.

Previous work led by Dr. Chen-Plotkin suggested that ApoA1 levels may be a new biomarker for Parkinson’s disease risk. The team is now conducting a follow-up study on plasma ApoA1 and statins, evaluating participants in the Michael J. Fox Foundation’s Parkinson’s Progression Marker Initiative cohort to confirm whether ApoA1-modifying drugs such as statins may be a promising neuroprotective therapy for Parkinson’s disease.

Estrogen Investigated for Protection From Parkinson’s Disease
In another study, an analysis by Kara Smith, MD, a movement disorders fellow in Neurology at the Perelman School of Medicine, and colleagues investigated the role that estrogen plays in decreasing the lifetime risk of Parkinson’s disease, in light of the fact that men have a relative risk of 1.5 for having Parkinson’s disease compared with women. In a systematic review of studies using animal models of Parkinson’s disease, the research team found consistent evidence that 17β-estradiol, in particular, may play a key role in binding to the estrogen receptor and protecting cells from Parkinson’s pathology. The team said that further research needs to look at 17β-estradiol in more accurate models of Parkinson’s disease before results can be translated to clinical trials in patients with Parkinson’s disease.

Telemedicine Improves Access to Specialty Parkinson’s Care
To help remove barriers to specialty care experienced by many patients who live far from care or have disabilities that make it difficult to travel, University of Pennsylvania researchers examined use of telemedicine visits to increase access to specialty care for patients with Parkinson’s disease.

A research team led by Jayne Wilkinson, MD, and Meredith Spinder, MD, conducted a randomized controlled trial using video telemedicine in the patient’s home or at a facility near the patient. In the case of this study, that location was VA Community-Based Outpatient Clinics, which connected them to a neurologist specializing in movement disorders and Parkinson’s disease who was based at the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center.

Early results demonstrate that the process of using telemedicine for Parkinson’s disease care is feasible, provided similar quality of life, care, and communication, and significantly decreased travel.

Acetazolamide May Improve Vision in Patients With Idiopathic Intracranial Hypertension
When administered with a low-sodium weight-reduction diet, acetazolamide modestly improves visual field function in patients with idiopathic intracranial hypertension, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The drug and diet together may be more effective than the diet alone for improving vision. Acetazolamide also may prevent further progression of visual loss in these patients.

Michael Wall, MD, Professor of Neurology at the University of Iowa Carver College of Medicine in Iowa City, and colleagues enrolled 165 participants with idiopathic intracranial hypertension and mild visual loss in a multicenter study. Patients’ mean age was 29, and all but four participants were women. All patients received a low-sodium weight-reduction diet. Participants were randomized to as much as 4 g/day of acetazolamide or matching placebo and followed up for six months.

The trial’s primary end point was the change in perimetric mean deviation (PMD) from baseline to month six in the most affected eye, as measured by Humphrey Field Analyzer. PMD is a measure of global visual field loss with a range of 2 to −32 dB. Larger negative values indicate greater vision loss.

At six months, the mean improvement in PMD was greater with acetazolamide (1.43 dB) than with placebo (0.71 dB). In addition, papilledema grade improved from 2.76 to 1.45 for patients receiving acetazolamide, compared with an improvement from 2.76 to 2.15 for patients receiving placebo. Vision-related quality of life, as measured by the Visual Function Questionnaire 25, improved from 82.97 to 91.30 for patients receiving acetazolamide, compared with an improvement from 82.97 to 84.95 for patients receiving placebo. Participants assigned to acetazolamide also lost 7.50 kg, compared with 3.45 kg for patients receiving placebo.

Idiopathic intracranial hypertension primarily affects young women who are overweight or obese. The disease’s incidence ranges from 10 to 20 patients per 100,000, and incidence increases with increasing BMI. The condition presents with persistent debilitating headaches and visual loss.

Acetazolamide previously has been used to treat idiopathic and secondary intracranial hypertension syndromes. The drug has been on the market “for a long time” and “is a fairly benign medication,” said Natalia Rost, MD, Associate Director of Acute Stroke Services at Massachusetts General Hospital in Boston. Some patients who take acetazolamide report tremors, added Dr. Rost, who described Dr. Wall’s study.

—Erik Greb

A Link Between Caffeinated Soda and Huntington’s Disease?
Total lifetime caffeinated soda consumption may be associated with an earlier onset of Huntington’s disease, reported Caroline Tanner, MD, PhD, and colleagues at the 66th Annual Meeting of the American Academy of Neurology.

The researchers sought to assess the role of various health and lifestyle factors on phenoconversion in persons who are at risk for Huntington’s disease with the CAG expansion (CAG >37). All participants were enrolled in the Prospective Huntington at Risk Observational Study. Previous research has found that the environment may cause 60% of the variance in disease onset age that is not due to CAGn, as well as an association between caffeine use and an earlier age of Huntington’s disease onset.

With the use of self-report questionnaires, the investigators analyzed participants’ exposure to tobacco, caffeine, alcohol, nonsteroidal anti-inflammatory drugs, vitamins, estrogen in women, head injury, physical activity, and cognitive activity. The researchers compared the time from baseline to motor phenoconversion between exposure groups in CAG >37 subjects by using Cox proportional hazards analyses that were adjusted for age, gender, and CAGn.

A total of 247 persons with CAG >37 completed the questionnaire. Some risk factors, such as caffeine, were “very common,” occurring in 99% of subjects, noted Dr. Tanner, who is the Director of Clinical Research at the Parkinson’s Institute and Clinical Center in Sunnyvale, California. The mean follow-up was 4.2 years (SD, 2), during which 36 persons phenoconverted.

“Drinking larger amounts of caffeinated soda predicted shorter time to phenoconversion,” said Dr. Tanner. “Six percent of low lifetime caffeinated soda consumers phenoconverted, compared with 13% of moderate consumers and 22% of high consumers.”

The hazard ratios for phenoconversion were 3.08 for moderate caffeinated soda consumers and 5.86 for high caffeinated soda consumers. Dr. Tanner noted that the association between lifetime caffeinated soda consumption and earlier onset of Huntington’s disease “was not seen with other caffeinated beverages and may be spurious. Other lifestyle risk factors associated with Parkinson’s disease or Alzheimer’s disease did not modify time to phenoconversion in Huntington’s disease.”

—Colby Stong

PHILADELPHIA—Certain forms of medical marijuana can help treat symptoms of multiple sclerosis (MS), but they may not be helpful in treating levodopa-induced movements in Parkinson’s disease, researchers reported at the 66th Annual Meeting of the American Academy of Neurology (AAN).

The researchers did not find enough evidence to show whether medical marijuana is helpful in treating motor problems in Huntington’s disease, tics in Tourette syndrome, cervical dystonia, and seizures in epilepsy. These conclusions are part of AAN’s review of scientific research on the use of medical marijuana in brain diseases. The findings were published in the April 29, 2014, print issue of Neurology.

“This review by the world’s largest association for neurologists is intended to help neurologists and their patients understand the current research on medical marijuana for the treatment of certain brain diseases,” said review author Barbara S. Koppel, MD, of New York Medical College in Valhalla, and Fellow of the AAN. “The AAN review also highlights the need for more high-quality studies of the long-term efficacy and safety of medical marijuana in the treatment of neurologic diseases.”

The AAN review concluded that only the pill or oral spray forms of medical marijuana can help treat symptoms of MS, including spasticity, certain types of pain (ie, pain related to spasticity, including painful spasms, and painful burning and numbness), and overactive bladder. Most of the MS studies examined pill or oral spray forms of medical marijuana. Two studies examined smoked medical marijuana for treating MS symptoms, but these studies did not provide enough information to show whether smoked medical marijuana is effective. “It’s important to note that medical marijuana can worsen thinking and memory problems, and this is a concern, since many people with MS suffer from these problems already due to the disease itself,” said Dr. Koppel.

In addition, the AAN review concluded that medical marijuana, in the form of synthetic tetrahydrocannabinol (THC) pills, likely does not help relieve abnormal movements that can develop in the late stages of Parkinson’s disease as a result of levodopa.

Medical marijuana use does entail safety concerns. In at least two studies, participants reported side effects such as nausea, increased weakness, behavioral or mood changes, suicidal thoughts or hallucinations, dizziness or fainting symptoms, fatigue, and feelings of intoxication. There were reports of two seizures. Mood changes and suicidal thoughts are of special concern for people with neurologic illness, who are at an increased risk for depression and suicide. The risk of serious psychologic effects is approximately 1%, according to the studies.

The only two medical marijuana pills with FDA approval contain THC. “The psychoactive side effects, such as feeling intoxicated, seemed to come from the THC,” said Dr. Koppel. “They’re trying to create pills that are leaning more toward the cannabinoid, which has the therapeutic effects with fewer psychoactive side effects.”

Clinicians who practice in states where medical marijuana is legal may recommend the drug for the MS symptoms that respond to it, Dr. Koppel added. “The problem is that the studies are done very rigorously with a certain amount of THC versus cannabinoid. The type of marijuana you can buy so far is not so rigorously defined.” Clinicians also should warn their patients about marijuana’s potential side effects.

In general, medical marijuana is prescribed as a treatment only when standard treatment has not helped. In most of the studies reviewed, patients were allowed to continue their standard treatments. The AAN review is endorsed by the American Autonomic Society, the American Epilepsy Society, and the International Rett Syndrome Foundation.

—Erik Greb

New Drugs May Offer Hope for Migraine Prevention
Two new studies may offer hope for patients with migraine. Both studies involve drugs for migraine prophylaxis rather than acute treatment. These studies are among the first to test monoclonal antibodies for the prevention of migraine, and both are directed against calcitonin gene-related peptide (CGRP), a relatively new target in migraine prevention. Both are phase II studies.

One study involved 163 patients who had migraine from five to 14 days per month. The patients received either a placebo or a single IV dose of a drug called ALD403. After the initial injection, study participants were followed for 24 weeks. Those who received the drug had an average of 5.6 fewer migraine days per month, a 66% decrease, compared with 4.6 fewer days per month for those who received a placebo, or a 52% decrease. Sixteen percent of those who received the drug had no migraine days at 12 weeks, while none of those who received the placebo were free from migraine at that point.

There were no differences in side effects between those receiving the drug and those receiving the placebo.

“These results may potentially represent a new era in preventive therapy for migraine,” said Peter Goadsby, MD, PhD, of the University of California, San Francisco, who was an investigator in both studies.

“Migraine remains poorly treated, and there are few effective and well-tolerated treatments approved that prevent attacks from occurring,” said coinvestigator David Dodick, MD, of Mayo Clinic Arizona in Phoenix. “There is a huge treatment need for migraine—the third most common and seventh most disabling medical disorder in the world.”

In the second study, 217 patients who had migraine four to 14 days per month received biweekly subcutaneous injections of either a placebo or a drug called LY2951742 for 12 weeks.

Those who received the drug had an average of 4.2 fewer migraine days per month at 12 weeks, or a 63% decrease, while those who received placebo had three fewer migraine days per month, or a 42% decrease. Those who received the drug were more likely to have side effects including pain at the injection site, upper respiratory tract infections, and abdominal pain, but overall the drug was considered to be safe and well tolerated.

“We’re cautiously optimistic that a new era of mechanism-based migraine prevention is beginning,” Dr. Dodick said.

Botulinum Toxin for Poststroke Spasticity—Could a Higher Dosage Yield Greater Benefit?
Although patients with poststroke spasticity are generally satisfied with their botulinum toxin treatment, many individuals may derive additional benefit with higher dosages and shorter injection intervals than the standard 12-week regimen, researchers reported at the 66th Annual Meeting of the American Academy of Neurology.

Djamel Bensmail, MD, PhD, and colleagues conducted two cross-sectional surveys among patients and physicians in Canada, France, Germany, and the United States. A total of 79 eligible patients had received two or more treatments of abobotulinumtoxinA, incobotulinumtoxinA, or onabotulinumtoxinA for poststroke spasticity. The investigators gathered data regarding current and prior botulinum toxin treatments along with physician and patient treatment satisfaction. All 105 participating physicians had treated patients with poststroke spasticity and had three or more years’ experience of injecting botulinum toxin.

“Botulinum toxin injections are the first-line treatment for patients with poststroke spasticity,” stated Dr. Bensmail, from the Department of Physical Medicine and Rehabilitation, R. Poincaré Hospital, AP-HP, University of Versailles Saint Quentin in Garches, France. “However, for some patients, treatment at the standard-of-care 12‑week interval may result in re-emergence of symptoms before reinjection.”

Sixty-one patients (77%) received onabotulinumtoxinA, 15 patients (19%) received abobotulinumtoxinA, and three patients (4%) received incobotulinumtoxinA. The researchers found that 40.5% of patients were overall very satisfied with the treatment, and 48.1% were somewhat satisfied with their current treatment.

“Satisfaction was highest at the time of peak effect and lowest just before reinjection,” stated the investigators. “While 78.9% of patients preferred injection intervals of less than or equal to 12 weeks, only 45.6% received such intervals. Intervals of 10 weeks or fewer were preferred by 43.4% of patients but received by just 6.3%. The mean interval was 13.7 weeks.”

Among the physicians surveyed, most (57.7%) were moderately or very satisfied (36.5%) with botulinum
toxin treatment for poststroke spasticity. However, the physicians also believed, on average, that 16.2% of patients would benefit from shorter injection intervals and that 24.6% would benefit from higher doses than those that are approved.

—Colby Stong

Potential Targets and Interventions for Parkinson’s Disease
A trio of studies from researchers at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia demonstrate new approaches to understanding, treating, and potentially staving off Parkinson’s disease. Studies show that factors such as estrogen exposure and statin use have an impact on the onset of Parkinson’s disease. And a new look at telemedicine demonstrates feasibility in providing care for patients with Parkinson’s disease using remote video visits to expand access and center care around the needs of the patients.

Statins May Delay Onset of Parkinson’s Disease
Research presented by Yosef Berlyand, an undergraduate in the laboratory of Alice Chen-Plotkin, MD, MSc, Assistant Professor of Neurology, suggests that statins may be beneficial in Parkinson’s disease. In collaboration with Roy Alcalay, MD, and colleagues at the Columbia University School of Medicine, members of Dr. Chen-Plotkin’s research group demonstrated that blood levels of the protein apolipoprotein A1 (ApoA1) are lower in people with Parkinson’s disease than in those without the disease. Patients with Parkinson’s disease taking statins, which can elevate levels of ApoA1, had an older age of disease onset, which appears to be driven by taking statins.

Previous work led by Dr. Chen-Plotkin suggested that ApoA1 levels may be a new biomarker for Parkinson’s disease risk. The team is now conducting a follow-up study on plasma ApoA1 and statins, evaluating participants in the Michael J. Fox Foundation’s Parkinson’s Progression Marker Initiative cohort to confirm whether ApoA1-modifying drugs such as statins may be a promising neuroprotective therapy for Parkinson’s disease.

Estrogen Investigated for Protection From Parkinson’s Disease
In another study, an analysis by Kara Smith, MD, a movement disorders fellow in Neurology at the Perelman School of Medicine, and colleagues investigated the role that estrogen plays in decreasing the lifetime risk of Parkinson’s disease, in light of the fact that men have a relative risk of 1.5 for having Parkinson’s disease compared with women. In a systematic review of studies using animal models of Parkinson’s disease, the research team found consistent evidence that 17β-estradiol, in particular, may play a key role in binding to the estrogen receptor and protecting cells from Parkinson’s pathology. The team said that further research needs to look at 17β-estradiol in more accurate models of Parkinson’s disease before results can be translated to clinical trials in patients with Parkinson’s disease.

Telemedicine Improves Access to Specialty Parkinson’s Care
To help remove barriers to specialty care experienced by many patients who live far from care or have disabilities that make it difficult to travel, University of Pennsylvania researchers examined use of telemedicine visits to increase access to specialty care for patients with Parkinson’s disease.

A research team led by Jayne Wilkinson, MD, and Meredith Spinder, MD, conducted a randomized controlled trial using video telemedicine in the patient’s home or at a facility near the patient. In the case of this study, that location was VA Community-Based Outpatient Clinics, which connected them to a neurologist specializing in movement disorders and Parkinson’s disease who was based at the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center.

Early results demonstrate that the process of using telemedicine for Parkinson’s disease care is feasible, provided similar quality of life, care, and communication, and significantly decreased travel.

Acetazolamide May Improve Vision in Patients With Idiopathic Intracranial Hypertension
When administered with a low-sodium weight-reduction diet, acetazolamide modestly improves visual field function in patients with idiopathic intracranial hypertension, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The drug and diet together may be more effective than the diet alone for improving vision. Acetazolamide also may prevent further progression of visual loss in these patients.

Michael Wall, MD, Professor of Neurology at the University of Iowa Carver College of Medicine in Iowa City, and colleagues enrolled 165 participants with idiopathic intracranial hypertension and mild visual loss in a multicenter study. Patients’ mean age was 29, and all but four participants were women. All patients received a low-sodium weight-reduction diet. Participants were randomized to as much as 4 g/day of acetazolamide or matching placebo and followed up for six months.

The trial’s primary end point was the change in perimetric mean deviation (PMD) from baseline to month six in the most affected eye, as measured by Humphrey Field Analyzer. PMD is a measure of global visual field loss with a range of 2 to −32 dB. Larger negative values indicate greater vision loss.

At six months, the mean improvement in PMD was greater with acetazolamide (1.43 dB) than with placebo (0.71 dB). In addition, papilledema grade improved from 2.76 to 1.45 for patients receiving acetazolamide, compared with an improvement from 2.76 to 2.15 for patients receiving placebo. Vision-related quality of life, as measured by the Visual Function Questionnaire 25, improved from 82.97 to 91.30 for patients receiving acetazolamide, compared with an improvement from 82.97 to 84.95 for patients receiving placebo. Participants assigned to acetazolamide also lost 7.50 kg, compared with 3.45 kg for patients receiving placebo.

Idiopathic intracranial hypertension primarily affects young women who are overweight or obese. The disease’s incidence ranges from 10 to 20 patients per 100,000, and incidence increases with increasing BMI. The condition presents with persistent debilitating headaches and visual loss.

Acetazolamide previously has been used to treat idiopathic and secondary intracranial hypertension syndromes. The drug has been on the market “for a long time” and “is a fairly benign medication,” said Natalia Rost, MD, Associate Director of Acute Stroke Services at Massachusetts General Hospital in Boston. Some patients who take acetazolamide report tremors, added Dr. Rost, who described Dr. Wall’s study.

—Erik Greb

A Link Between Caffeinated Soda and Huntington’s Disease?
Total lifetime caffeinated soda consumption may be associated with an earlier onset of Huntington’s disease, reported Caroline Tanner, MD, PhD, and colleagues at the 66th Annual Meeting of the American Academy of Neurology.

The researchers sought to assess the role of various health and lifestyle factors on phenoconversion in persons who are at risk for Huntington’s disease with the CAG expansion (CAG >37). All participants were enrolled in the Prospective Huntington at Risk Observational Study. Previous research has found that the environment may cause 60% of the variance in disease onset age that is not due to CAGn, as well as an association between caffeine use and an earlier age of Huntington’s disease onset.

With the use of self-report questionnaires, the investigators analyzed participants’ exposure to tobacco, caffeine, alcohol, nonsteroidal anti-inflammatory drugs, vitamins, estrogen in women, head injury, physical activity, and cognitive activity. The researchers compared the time from baseline to motor phenoconversion between exposure groups in CAG >37 subjects by using Cox proportional hazards analyses that were adjusted for age, gender, and CAGn.

A total of 247 persons with CAG >37 completed the questionnaire. Some risk factors, such as caffeine, were “very common,” occurring in 99% of subjects, noted Dr. Tanner, who is the Director of Clinical Research at the Parkinson’s Institute and Clinical Center in Sunnyvale, California. The mean follow-up was 4.2 years (SD, 2), during which 36 persons phenoconverted.

“Drinking larger amounts of caffeinated soda predicted shorter time to phenoconversion,” said Dr. Tanner. “Six percent of low lifetime caffeinated soda consumers phenoconverted, compared with 13% of moderate consumers and 22% of high consumers.”

The hazard ratios for phenoconversion were 3.08 for moderate caffeinated soda consumers and 5.86 for high caffeinated soda consumers. Dr. Tanner noted that the association between lifetime caffeinated soda consumption and earlier onset of Huntington’s disease “was not seen with other caffeinated beverages and may be spurious. Other lifestyle risk factors associated with Parkinson’s disease or Alzheimer’s disease did not modify time to phenoconversion in Huntington’s disease.”

—Colby Stong

PHILADELPHIA—Certain forms of medical marijuana can help treat symptoms of multiple sclerosis (MS), but they may not be helpful in treating levodopa-induced movements in Parkinson’s disease, researchers reported at the 66th Annual Meeting of the American Academy of Neurology (AAN).

The researchers did not find enough evidence to show whether medical marijuana is helpful in treating motor problems in Huntington’s disease, tics in Tourette syndrome, cervical dystonia, and seizures in epilepsy. These conclusions are part of AAN’s review of scientific research on the use of medical marijuana in brain diseases. The findings were published in the April 29, 2014, print issue of Neurology.

“This review by the world’s largest association for neurologists is intended to help neurologists and their patients understand the current research on medical marijuana for the treatment of certain brain diseases,” said review author Barbara S. Koppel, MD, of New York Medical College in Valhalla, and Fellow of the AAN. “The AAN review also highlights the need for more high-quality studies of the long-term efficacy and safety of medical marijuana in the treatment of neurologic diseases.”

The AAN review concluded that only the pill or oral spray forms of medical marijuana can help treat symptoms of MS, including spasticity, certain types of pain (ie, pain related to spasticity, including painful spasms, and painful burning and numbness), and overactive bladder. Most of the MS studies examined pill or oral spray forms of medical marijuana. Two studies examined smoked medical marijuana for treating MS symptoms, but these studies did not provide enough information to show whether smoked medical marijuana is effective. “It’s important to note that medical marijuana can worsen thinking and memory problems, and this is a concern, since many people with MS suffer from these problems already due to the disease itself,” said Dr. Koppel.

In addition, the AAN review concluded that medical marijuana, in the form of synthetic tetrahydrocannabinol (THC) pills, likely does not help relieve abnormal movements that can develop in the late stages of Parkinson’s disease as a result of levodopa.

Medical marijuana use does entail safety concerns. In at least two studies, participants reported side effects such as nausea, increased weakness, behavioral or mood changes, suicidal thoughts or hallucinations, dizziness or fainting symptoms, fatigue, and feelings of intoxication. There were reports of two seizures. Mood changes and suicidal thoughts are of special concern for people with neurologic illness, who are at an increased risk for depression and suicide. The risk of serious psychologic effects is approximately 1%, according to the studies.

The only two medical marijuana pills with FDA approval contain THC. “The psychoactive side effects, such as feeling intoxicated, seemed to come from the THC,” said Dr. Koppel. “They’re trying to create pills that are leaning more toward the cannabinoid, which has the therapeutic effects with fewer psychoactive side effects.”

Clinicians who practice in states where medical marijuana is legal may recommend the drug for the MS symptoms that respond to it, Dr. Koppel added. “The problem is that the studies are done very rigorously with a certain amount of THC versus cannabinoid. The type of marijuana you can buy so far is not so rigorously defined.” Clinicians also should warn their patients about marijuana’s potential side effects.

In general, medical marijuana is prescribed as a treatment only when standard treatment has not helped. In most of the studies reviewed, patients were allowed to continue their standard treatments. The AAN review is endorsed by the American Autonomic Society, the American Epilepsy Society, and the International Rett Syndrome Foundation.

—Erik Greb

New Drugs May Offer Hope for Migraine Prevention
Two new studies may offer hope for patients with migraine. Both studies involve drugs for migraine prophylaxis rather than acute treatment. These studies are among the first to test monoclonal antibodies for the prevention of migraine, and both are directed against calcitonin gene-related peptide (CGRP), a relatively new target in migraine prevention. Both are phase II studies.

One study involved 163 patients who had migraine from five to 14 days per month. The patients received either a placebo or a single IV dose of a drug called ALD403. After the initial injection, study participants were followed for 24 weeks. Those who received the drug had an average of 5.6 fewer migraine days per month, a 66% decrease, compared with 4.6 fewer days per month for those who received a placebo, or a 52% decrease. Sixteen percent of those who received the drug had no migraine days at 12 weeks, while none of those who received the placebo were free from migraine at that point.

There were no differences in side effects between those receiving the drug and those receiving the placebo.

“These results may potentially represent a new era in preventive therapy for migraine,” said Peter Goadsby, MD, PhD, of the University of California, San Francisco, who was an investigator in both studies.

“Migraine remains poorly treated, and there are few effective and well-tolerated treatments approved that prevent attacks from occurring,” said coinvestigator David Dodick, MD, of Mayo Clinic Arizona in Phoenix. “There is a huge treatment need for migraine—the third most common and seventh most disabling medical disorder in the world.”

In the second study, 217 patients who had migraine four to 14 days per month received biweekly subcutaneous injections of either a placebo or a drug called LY2951742 for 12 weeks.

Those who received the drug had an average of 4.2 fewer migraine days per month at 12 weeks, or a 63% decrease, while those who received placebo had three fewer migraine days per month, or a 42% decrease. Those who received the drug were more likely to have side effects including pain at the injection site, upper respiratory tract infections, and abdominal pain, but overall the drug was considered to be safe and well tolerated.

“We’re cautiously optimistic that a new era of mechanism-based migraine prevention is beginning,” Dr. Dodick said.

Botulinum Toxin for Poststroke Spasticity—Could a Higher Dosage Yield Greater Benefit?
Although patients with poststroke spasticity are generally satisfied with their botulinum toxin treatment, many individuals may derive additional benefit with higher dosages and shorter injection intervals than the standard 12-week regimen, researchers reported at the 66th Annual Meeting of the American Academy of Neurology.

Djamel Bensmail, MD, PhD, and colleagues conducted two cross-sectional surveys among patients and physicians in Canada, France, Germany, and the United States. A total of 79 eligible patients had received two or more treatments of abobotulinumtoxinA, incobotulinumtoxinA, or onabotulinumtoxinA for poststroke spasticity. The investigators gathered data regarding current and prior botulinum toxin treatments along with physician and patient treatment satisfaction. All 105 participating physicians had treated patients with poststroke spasticity and had three or more years’ experience of injecting botulinum toxin.

“Botulinum toxin injections are the first-line treatment for patients with poststroke spasticity,” stated Dr. Bensmail, from the Department of Physical Medicine and Rehabilitation, R. Poincaré Hospital, AP-HP, University of Versailles Saint Quentin in Garches, France. “However, for some patients, treatment at the standard-of-care 12‑week interval may result in re-emergence of symptoms before reinjection.”

Sixty-one patients (77%) received onabotulinumtoxinA, 15 patients (19%) received abobotulinumtoxinA, and three patients (4%) received incobotulinumtoxinA. The researchers found that 40.5% of patients were overall very satisfied with the treatment, and 48.1% were somewhat satisfied with their current treatment.

“Satisfaction was highest at the time of peak effect and lowest just before reinjection,” stated the investigators. “While 78.9% of patients preferred injection intervals of less than or equal to 12 weeks, only 45.6% received such intervals. Intervals of 10 weeks or fewer were preferred by 43.4% of patients but received by just 6.3%. The mean interval was 13.7 weeks.”

Among the physicians surveyed, most (57.7%) were moderately or very satisfied (36.5%) with botulinum
toxin treatment for poststroke spasticity. However, the physicians also believed, on average, that 16.2% of patients would benefit from shorter injection intervals and that 24.6% would benefit from higher doses than those that are approved.

—Colby Stong

Potential Targets and Interventions for Parkinson’s Disease
A trio of studies from researchers at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia demonstrate new approaches to understanding, treating, and potentially staving off Parkinson’s disease. Studies show that factors such as estrogen exposure and statin use have an impact on the onset of Parkinson’s disease. And a new look at telemedicine demonstrates feasibility in providing care for patients with Parkinson’s disease using remote video visits to expand access and center care around the needs of the patients.

Statins May Delay Onset of Parkinson’s Disease
Research presented by Yosef Berlyand, an undergraduate in the laboratory of Alice Chen-Plotkin, MD, MSc, Assistant Professor of Neurology, suggests that statins may be beneficial in Parkinson’s disease. In collaboration with Roy Alcalay, MD, and colleagues at the Columbia University School of Medicine, members of Dr. Chen-Plotkin’s research group demonstrated that blood levels of the protein apolipoprotein A1 (ApoA1) are lower in people with Parkinson’s disease than in those without the disease. Patients with Parkinson’s disease taking statins, which can elevate levels of ApoA1, had an older age of disease onset, which appears to be driven by taking statins.

Previous work led by Dr. Chen-Plotkin suggested that ApoA1 levels may be a new biomarker for Parkinson’s disease risk. The team is now conducting a follow-up study on plasma ApoA1 and statins, evaluating participants in the Michael J. Fox Foundation’s Parkinson’s Progression Marker Initiative cohort to confirm whether ApoA1-modifying drugs such as statins may be a promising neuroprotective therapy for Parkinson’s disease.

Estrogen Investigated for Protection From Parkinson’s Disease
In another study, an analysis by Kara Smith, MD, a movement disorders fellow in Neurology at the Perelman School of Medicine, and colleagues investigated the role that estrogen plays in decreasing the lifetime risk of Parkinson’s disease, in light of the fact that men have a relative risk of 1.5 for having Parkinson’s disease compared with women. In a systematic review of studies using animal models of Parkinson’s disease, the research team found consistent evidence that 17β-estradiol, in particular, may play a key role in binding to the estrogen receptor and protecting cells from Parkinson’s pathology. The team said that further research needs to look at 17β-estradiol in more accurate models of Parkinson’s disease before results can be translated to clinical trials in patients with Parkinson’s disease.

Telemedicine Improves Access to Specialty Parkinson’s Care
To help remove barriers to specialty care experienced by many patients who live far from care or have disabilities that make it difficult to travel, University of Pennsylvania researchers examined use of telemedicine visits to increase access to specialty care for patients with Parkinson’s disease.

A research team led by Jayne Wilkinson, MD, and Meredith Spinder, MD, conducted a randomized controlled trial using video telemedicine in the patient’s home or at a facility near the patient. In the case of this study, that location was VA Community-Based Outpatient Clinics, which connected them to a neurologist specializing in movement disorders and Parkinson’s disease who was based at the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center.

Early results demonstrate that the process of using telemedicine for Parkinson’s disease care is feasible, provided similar quality of life, care, and communication, and significantly decreased travel.

Acetazolamide May Improve Vision in Patients With Idiopathic Intracranial Hypertension
When administered with a low-sodium weight-reduction diet, acetazolamide modestly improves visual field function in patients with idiopathic intracranial hypertension, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The drug and diet together may be more effective than the diet alone for improving vision. Acetazolamide also may prevent further progression of visual loss in these patients.

Michael Wall, MD, Professor of Neurology at the University of Iowa Carver College of Medicine in Iowa City, and colleagues enrolled 165 participants with idiopathic intracranial hypertension and mild visual loss in a multicenter study. Patients’ mean age was 29, and all but four participants were women. All patients received a low-sodium weight-reduction diet. Participants were randomized to as much as 4 g/day of acetazolamide or matching placebo and followed up for six months.

The trial’s primary end point was the change in perimetric mean deviation (PMD) from baseline to month six in the most affected eye, as measured by Humphrey Field Analyzer. PMD is a measure of global visual field loss with a range of 2 to −32 dB. Larger negative values indicate greater vision loss.

At six months, the mean improvement in PMD was greater with acetazolamide (1.43 dB) than with placebo (0.71 dB). In addition, papilledema grade improved from 2.76 to 1.45 for patients receiving acetazolamide, compared with an improvement from 2.76 to 2.15 for patients receiving placebo. Vision-related quality of life, as measured by the Visual Function Questionnaire 25, improved from 82.97 to 91.30 for patients receiving acetazolamide, compared with an improvement from 82.97 to 84.95 for patients receiving placebo. Participants assigned to acetazolamide also lost 7.50 kg, compared with 3.45 kg for patients receiving placebo.

Idiopathic intracranial hypertension primarily affects young women who are overweight or obese. The disease’s incidence ranges from 10 to 20 patients per 100,000, and incidence increases with increasing BMI. The condition presents with persistent debilitating headaches and visual loss.

Acetazolamide previously has been used to treat idiopathic and secondary intracranial hypertension syndromes. The drug has been on the market “for a long time” and “is a fairly benign medication,” said Natalia Rost, MD, Associate Director of Acute Stroke Services at Massachusetts General Hospital in Boston. Some patients who take acetazolamide report tremors, added Dr. Rost, who described Dr. Wall’s study.

—Erik Greb

A Link Between Caffeinated Soda and Huntington’s Disease?
Total lifetime caffeinated soda consumption may be associated with an earlier onset of Huntington’s disease, reported Caroline Tanner, MD, PhD, and colleagues at the 66th Annual Meeting of the American Academy of Neurology.

The researchers sought to assess the role of various health and lifestyle factors on phenoconversion in persons who are at risk for Huntington’s disease with the CAG expansion (CAG >37). All participants were enrolled in the Prospective Huntington at Risk Observational Study. Previous research has found that the environment may cause 60% of the variance in disease onset age that is not due to CAGn, as well as an association between caffeine use and an earlier age of Huntington’s disease onset.

With the use of self-report questionnaires, the investigators analyzed participants’ exposure to tobacco, caffeine, alcohol, nonsteroidal anti-inflammatory drugs, vitamins, estrogen in women, head injury, physical activity, and cognitive activity. The researchers compared the time from baseline to motor phenoconversion between exposure groups in CAG >37 subjects by using Cox proportional hazards analyses that were adjusted for age, gender, and CAGn.

A total of 247 persons with CAG >37 completed the questionnaire. Some risk factors, such as caffeine, were “very common,” occurring in 99% of subjects, noted Dr. Tanner, who is the Director of Clinical Research at the Parkinson’s Institute and Clinical Center in Sunnyvale, California. The mean follow-up was 4.2 years (SD, 2), during which 36 persons phenoconverted.

“Drinking larger amounts of caffeinated soda predicted shorter time to phenoconversion,” said Dr. Tanner. “Six percent of low lifetime caffeinated soda consumers phenoconverted, compared with 13% of moderate consumers and 22% of high consumers.”

The hazard ratios for phenoconversion were 3.08 for moderate caffeinated soda consumers and 5.86 for high caffeinated soda consumers. Dr. Tanner noted that the association between lifetime caffeinated soda consumption and earlier onset of Huntington’s disease “was not seen with other caffeinated beverages and may be spurious. Other lifestyle risk factors associated with Parkinson’s disease or Alzheimer’s disease did not modify time to phenoconversion in Huntington’s disease.”

—Colby Stong