Neurology News

Follow our Neurology News blog for the latest news on neurologic diseases and research.

Tuesday, March 20, 2018

By Michael Shen

Living close to a major urban roadway is associated with a higher risk for ischemic stroke, according to a new analysis published in the March 14 online edition of the journal Stroke.

Pulling medical records and data from the Northern Manhattan Study, a prospective population-based study of stroke risk factors in a multiethnic population in northern Manhattan, the study followed 3,287 individuals over the course of 15 years. During that period, 11 percent were diagnosed with ischemic stroke, and 11.2 percent had a myocardial infarction (MI). The researchers found that those living within 100 meters from a major roadway had a 42 percent higher rate of ischemic stroke compared to those living more than 400 meters away.

"The evidence supporting the deleterious health effects of living near a major roadway is growing," the researchers, led by Erin R. Kulick, MPH, a PhD student at the Mailman School of Public Health at Columbia University in New York City, wrote. She and her team attributed their findings to traffic-related air pollution, which has been weakly linked to cardiovascular and stroke risk in past studies.

The researchers noted that there are several hypothesized mechanisms for this association. Animal studies have suggested that pollution-related particles in the air enter the nervous system through the circulatory system and contribute directly or indirectly to inflammatory changes and microvascular damage. Over time, this may pave the way for the development of stroke and cardiovascular disease.

At enrollment, participants were at least 40 years of age and had no prior history of stroke. Researchers reviewed medical records and phoned participants annually to assess the onset of new neurological or cardiac symptoms. Major roadways were defined according to classifications set by the U.S. Census Bureau, and included federal and interstate highways, and some larger state and county highways.

In addition to incident ischemic stroke, researchers also looked at secondary outcomes, including incident MI, all-cause death, and vascular death, defined as death due to heart disease or stroke. They found no clear associations for any of these secondary outcomes, which they attributed to the fact that the study did not exclude individuals with a history of heart disease or those who were being treated for heart disease.

The analysis accounted for socioeconomic status and cardiovascular risk factors such as smoking, alcohol use, hypertension, diabetes mellitus, body mass index, and HDL levels. Interestingly, for those living within 100 meters of a major roadway, noncurrent smokers — which include former smokers and those who never smoked — were 1.54 times more likely to get an ischemic stroke than their smoking counterparts.

As a limitation, Kulick and her team acknowledged that their study looked at a very limited geographic area and is specific to the urban setting. Furthermore, given the observational study design, no causal relationship between proximity to major roadways and stroke can be concluded from their results. They said further studies should be done using measured levels of air pollutants to confirm their findings.


Kulick ER, Wellenius GA, Boehme AK, et al. Residential proximity to major roadways and risk of incident ischemic stroke in NOMAS (The Northern Manhattan Study)​Stroke 2018; Epub 2018 Mar 14.​

Tuesday, March 13, 2018


Mossy cells of the hippocampus are partially lost in temporal lobe epilepsy (TLE), and that loss is thought to contribute to seizure activity. But exactly how they contribute — whether the remaining cells are overall excitatory or inhibitory within the complex hippocampal network —has been unclear, and so designing treatment strategies to compensate for mossy cell loss has been hampered.

Now, a new study in the February 16 issue of Science reveals that increasing mossy cell firing can reduce electrographic seizure duration and reduce the likelihood they will generalize to become convulsive seizures.

The results indicate that the remaining mossy cells continue to inhibit aberrant electrical activity in the hippocampus. Further, the study shows that a decrease in mossy cell activity can produce cognitive deficits in otherwise normal mice, suggesting that loss of mossy cells may be the source of similar deficits in people with TLE.

"It has been a longstanding question in temporal lobe epilepsy whether it is the loss of mossy cells themselves, or an overall change in the network that allows seizures to develop," said the first author of the new study, Anh Bui, PhD, currently a medical student at University of California, Irvine, and formerly in the laboratory of Ivan Soltesz, PhD, James R. Doty professor of neurosurgery and neurosciences at Stanford University School of Medicine. "Our study suggests that the loss of mossy cells is sufficient to allow seizures to generalize."


Dr. Bui and colleagues weren't the first to attempt to solve the puzzle of the mossy cell in TLE, but previous work has been hindered by the inability to target mossy cells specifically. To overcome that obstacle, the team turned to optogenetics, the technique of using light to selectively turn on or turn off neuronal firing.

Mice were produced to express one of two light-sensitive rhodopsin proteins only in their mossy cells. Both proteins were ion channels, one of which decreased membrane polarization and thus promoted firing, while the other increased polarization and inhibited firing. The proteins were activated when light was delivered to the hippocampus via an implanted optical fiber, allowing the mossy cells to be switched on or off. The mice received unilateral injections to the hippocampus of the excitotoxin kainic acid, a standard way to induce an experimental form of TLE, and seizure-recording electrodes were implanted as well.

To test how activity of the remaining mossy cells affected electrographic, non-convulsive seizure activity, Dr. Bui recorded seizure onset, then randomly delivered either no light (as a control), or light sufficient to trigger the ion channels. In mice bearing the inhibitory ion channel, electrographic seizure dynamics following light administration were no different from the control. But in those bearing the excitatory ion channel, light reduced the duration of the seizures.

"Stimulation of mossy cells controls seizures rather than inhibition," Dr. Bui said, "presumably because they are overall inhibitory in the network," with synapses reaching multiple cell types, including inhibitory interneurons. "When you excite the mossy cells, that leads to more inhibition of the network, so that is able to stop the seizures."

As in humans with TLE, a small proportion of electrographic seizures evolve into convulsive seizures. To test the role of mossy cells in that evolution, Dr. Bui recorded seizure electrographic activity continuously for up to six months, "enough time to collect sufficient data for statistical analysis," she said. They used light to inhibit mossy cells. She found that inhibition of mossy cells during an electrographic seizure increased the likelihood of the seizure generalizing to convulsion but had no effect on the duration of the resulting convulsive seizure. Conversely, exciting mossy cells during the electrographic stage reduced the number of seizures that generalized, but again had no effect on duration of those that did.

"What we think is going on is that decreased mossy cell activity is allowing seizures to propagate and to generalize," but without affecting the dynamics of the generalized seizure itself.

Finally, Dr. Bui and colleagues asked whether the loss of mossy cell activity might also contribute to the cognitive deficits that are commonly seen in TLE. To do this, they examined the ability to learn in mice without kainate-induced TLE but with an inhibitory rhodopsin in place. They found that when the mice experienced a light-induced inhibition of their mossy cells, they were less able to encode new spatial memories. The effect seemed to be highly selective, as inhibition did not interfere with recall of previously encoded spatial memories, or with learning or recall of object recognition. The next step for the team is to test whether exciting the remaining mossy cells in epileptic mice might restore cognitive function.

The study was funded by the National Institute of Neurological Disorders and Stroke.


This study nicely tests two competing hypotheses — aberrant excitation versus incomplete inhibition — of residual mossy cell function in TLE, said Kazutoshi Nakazawa, MD, PhD, associate professor of psychiatry and neurobiology at the University of Alabama School of Medicine in Birmingham. Previous studies, including Dr. Nakazawa's own work, have suggested an overall inhibitory role for mossy cells, and the new study "confirms that convincingly in the TLE model," he said.

The study also highlights the importance of mossy cells during acquisition of spatial information. "It remains unknown whether, in an epilepsy model, cognitive function can be rescued by manipulating mossy cells," he said. "That is the next important question to be addressed."

 "The idea that mossy cells contribute to temporal lobe epilepsy has been hypothesized for over 25 years, but it has been very hard to explore without the selectivity used in this study," said Helen Scharfman, PhD, professor in the departments of child and adolescent psychiatry, neuroscience and physiology, and psychiatry at NYU Langone Medical Center. Mossy cells are known to have synapses on both inhibitory and excitatory neurons, "so it has been hard to predict the effect on the network of their loss. This study, because of its ability to manipulate mossy cells so selectively, really moves the field forward," suggesting that mossy cells normally inhibit the brain.

The study also provides a proof of principle that "direct manipulation of mossy cells may be therapeutic," although there are many steps before that possibility could be realized, she said, and there may be more practical ways to control seizures for those currently untreated by anti-seizure drugs.

"This study also suggests the mossy cells may contribute to cognitive impairment. It's important to think not only about controlling seizures in temporal lobe epilepsy, but also improving the quality-of-life issues that people with epilepsy experience," including cognitive deficits, she said.

Neither the study author nor the independent experts had disclosures relevant to this study.


Bui AD, Nguyen TM, Limouse C, et al. Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory. Science 2018; 359(6377):787-790.

Scharfman HE. The enigmatic mossy cell of the dentate gyrus​. Nat Rev Neurosci 2016; 17(9): 562–575.

Wednesday, March 7, 2018


High-dose oral doses of corticosteroid were as effective as intravenous corticosteroid for treating acute optic neuritis, a common condition among people with multiple sclerosis (MS), according to a study published online on March 5 in JAMA Neurology.

The present study supports the use of either IV or oral administration for ON treatment, but "oral medication may be more convenient, minimizing travel to an infusion center, especially for those residing in rural locations," wrote the researchers, led by Sarah A. Morrow, MD, MS, FRCPC, an associate professor of neurology at Western University in London, Ontario, Canada.

Oral administration is also more cost-effective than IV administration and preferred by most multiple sclerosis patients, according to the researchers.

The IV administration of corticosteroids has been the standard practice for treating acute demyelinating events such as optic neuritis for vision recovery based on findings from the Optic Neuritis Treatment Trial (ONTT), reported in The New England Journal of Medicine in 1992. But, the authors pointed out, the treatments studied were not pharmacologically equivalent. Subsequent studies have found that oral and IV corticosteroid treatment for optic neuritis have similar effects on magnetic resonance imaging outcomes and similar clinical effects on MS relapse.

In the current study, the IV group received treatment either at a hospital outpatient infusion center, or when feasible, in a hospital outpatient infusion center for the first dose, and then at home for subsequent doses. Participants in the oral group were given 75 tablets of 50 mg of prednisone, or 25 tablets daily, to consume at home. No tapering was used after the three-day treatment.

Throughout the study, the researchers assessed measures of vision recovery, including visual evoked potential P100 latency and high- and low-contrast best-corrected visual acuity.

At one-month and six-months' recovery, there were no significant differences in visual evoked potential P100 latency between the two groups. Adverse effects between the two treatment groups did not differ significantly. Among the most frequently events reported were gastrointestinal effects, insomnia, and tiredness or fatigue.

The study did present several limitations, according to the study authors. Among the limitations, they failed to address other important clinical issues, specifically who will benefit from corticosteroid treatment and when the ideal time is to start therapy to the lack of use of optical coherence tomography.

The authors reported several conflicts of interest: Dr. Morrow has received honoraria for speaking, consulting, and participating on advisory boards from Biogen Idec, EMD Serono Inc, Genzyme, Novartis, and Roche. The paper lists other disclosures reported.


Morrow SA, Fraser A, Day C et al. Effect of Treating Acute Optic Neuritis With Bioequivalent Oral vs Intravenous Corticosteroids A Randomized Clinical Trial. JAMA Neurology 2018; Epub 2018 Mar 5.​

Thursday, March 1, 2018


A once-monthly subcutaneous injection of the monoclonal antibody erenumab significantly reduced migraine frequency, use of acute migraine-specific medications, and disability in patients with episodic migraine, according to a study published online on February 22 in the journal Cephalagia.

In the ARISE randomized, double-blind, placebo-controlled, phase 3 study, erenumab at a dosage of 70 mg monthly, reduced monthly migraine days by 2.9 days and migraine-specific medication treatment days by 1.2 days.

Erenumab, developed by Amgen, works by targeting and blocking the calcitonin gene-related (CGRP) receptor, a neuropeptide implicated in migraine pathophysiology. Previous phase 2 and phase 3 studies of erenumab use in episodic and chronic migraine have reported that doses at 70 mg, the minimally effective dose in this population, and 140 mg led to a reduction in monthly migraine days at three months and six months.

"Compared to currently available therapies, the good safety and tolerability profile of erenumab may help promote better adherence to treatment in a condition with high unmet needs," the researchers, led by David W. Dodick, MD, FAAN, professor of neurology at the Mayo Clinic College of Medicine and a consultant in neurology at the Mayo Clinic in Scottsdale, AZ, wrote.

To test the efficacy of erenumab in episodic migraine, defined as four to less than 15 migraine days per month, 577 adults were randomized 1:1 to a monthly placebo or erenumab 70 mg, administered subcutaneously. To be eligible, participants had to experience fewer than 15 headache days per month for at least 12 months prior to the study. The study consisted of a screening phase (up to three weeks), a four-week baseline phase, a 12-week double-blind treatment phase, and a 28-week open-label treatment phase. Twelve weeks after the last dose, researchers conducted a safety follow-up visit.

Throughout the baseline phase and 12-week double-blind treatment phase, researchers assessed erenumab efficacy from patient-reported outcomes via the Migraine Physical Function Impact Diary and other measures, including the Headache Impact Test (HIT-6T), Modified Migraine Disability Assessment (mMIDAS), and Migraine-Specific Quality-of-Life (MSQ).

At baseline, patients had a mean of 8.3 monthly migraine days and 3.6 migraine-specific medication days, with 61 percent of patients using acute migraine medications. At week 12, a dose of erenumab 70 mg reduced the mean migraine days by 2.9 compared to 1.8 days for placebo; migraine-specific medication treatment days were reduced by 1.2 days and 0.6 days, for erenumab and placebo, respectively. A 50 percent reduction in monthly migraine days was achieved by 39.7 percent in the erenumab and 29.5 percent in the placebo group.

Common adverse effects reported in both erenumab and placebo groups were upper respiratory tract infection, injection site pain, influenza, fatigue, nausea, migraine, sinusitis, nasopharyngitis and constipation, the researchers wrote. In regard to serious adverse effects, there were no clinically apparent differences among the two groups. No significant changes were observed in patients' serum chemistry, hematology laboratory values, electrocardiogram, or vital signs.

The findings warrant further investigation into the efficacy of erenumab in more diverse patient populations, the study authors wrote. This includes patients who do not respond to multiple preventive medications that were not eligible for this study. Results from the open-label treatment and safety follow-up phases will provide more information on patients who have been treated up to 40 weeks.

The authors declared several conflicts of interest, including serving on the advisory board of Amgen, which funded the study, and receiving speaker bureau fees from Amgen, Teva, Allergan, and other pharmaceutical companies.


Dodick DW, Ashina M, Brandes JL et al. ARISE: A phase 3 randomized trial of erenumab for episodic migraine. Cephalagia 2018; Epub 2018 Feb 22. ​

Monday, February 26, 2018


Midthoracic epidural spinal cord stimulation was safe and led to significant improvement in axial motor symptoms in patients with advanced Parkinson's disease (PD), researchers reported in a paper published online on February 14 in the journal Movement Disorders.

In the small, open-label, nonrandomized pilot study, spinal cord stimulation provided an overall improvement in motor and gait measurements and reduced the number of freezing of gait (FOG) episodes from 16 at presurgery to 0 at six months following surgery for participants on levodopa and off stimulation.

Therapeutic interventions to alleviate axial motor symptoms are limited, the study authors pointed out. Gait dysfunction, FOG, and postural instability are mainly resistant to dopamine replacement therapy and deep brain stimulation (DBS) that targets the subthalamic nucleus (STN) or globus pallidus interna (GPi) is limited, unpredictable, and not available to all patients, they wrote. The study was led by Olivia Samotus, a clinical research associate at the London Movement Disorders Centre in London, Ontario, Canada.

This is the first study that uses objective gait technology to assess the effectiveness of spinal cord stimulation for gait in advanced PD patients, according to the researchers. "A novel therapeutic intervention is a significant unmet need for alleviating axial disability in advanced PD patients," the researchers said.

Researchers recruited a total of five men with PD who had significant gait dysfunction and postural instability while on oral medication. Two cylindrical percutaneous electrodes with eight contacts per lead were implanted in the medial epidural space at T8-T10 spinal segments, and they tested the effectiveness at different stimulation settings. The electrodes were positioned to cover both lower limbs and feet to produce paresthesias.

Nine study visits averaging four to five hours each were conducted throughout the study to assess one or two spinal cord stimulation settings and their effect on clinical outcomes. The research team assessed gait and motor function using the Unified Parkinson's Disease Rating Scale motor scores (UPDRS III), 30 Parkinson's Disease Questionnaire (PDQ-8), Freezing of Gait Questionnaire (FOG-Q), and activities-specific balance confidence scale (ABC) on medications. On each visit, participants walked across a 20-foot hallway without shoes. The researchers used a software program to process participants' footstep patterns to provide accurate gait measurements.

After six months, mean step length, stride velocity, and sit-to-stand functions improved by 38.8 percent, 42.3 percent, and 50.3 percent, respectively, while participants were on medication and undergoing spinal cord stimulation. Mean UPDRS, (FOG-Q), and activities-specific balance confidence scales improved 33.5 percent, 26.8 percent, and 71.4 percent, respectively. FOG-Q scores had a mean change of 26.8 percent by six months.

There were several limitations in the study, including the lack of repetition of spinal cord stimulation programs on different days to avoid fatigue. Assessment of spinal cord stimulations programs was conducted over four months in a small cohort, but changes in gait could be different between one to four months, regardless of the intervention, the researchers pointed out.

AbbVie, Allergan Inc.,Boston Scientific, Ipsen, MDDT Inc., Medtronic, Merz Pharma, Novartis, and Teva Pharmaceuticals provided financial support to study author Mandar Jog, MD. The other two authors do not report any conflicts of interest.


Samotus O, Parrent A, and Jog M. Spinal Cord Stimulation Therapy for Gait Dysfunction in Advanced Parkinson's Disease Patients. Movement Disorders 2018; Epub 2018 Feb 14. ​