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

Friday, June 16, 2017


Eight children in Colorado who had been diagnosed with acute flaccid myelitis (AFM) in 2014 had lingering motor and functional deficits one year later, despite functional improvements in some areas, according to a new study published online on June 14 in Neurology.

Nationwide cases of AFM, a neurologic condition associated with enterovirus infections that causes weakness and loss of muscle tone and reflexes, rose to 120 in 34 states in 2014, correlating with an outbreak of severe respiratory illness. [Earlier this year, Neurology Today reported on another widespread outbreak in the US and Europe in 2016.] Because the disease's clinical course and long-term outcomes remain unknown, researchers enrolled a small cluster of children with the aim of characterizing short- and long-term outcomes using clinical, neuroimaging and electrophysiological assessments.

The findings suggest that functional deficits due to AFM are "severe and are likely permanent," the study authors, led by Jan A. Martin, MD, assistant professor of pediatric neurology at the University of Colorado School of Medicine, wrote. "Future studies should investigate tools to accurately predict the course of this disease and identify effective treatments to prevent the severe long-term outcomes observed in this cohort."

For the study, researchers enrolled 12 children in Colorado who had been diagnosed with acute flaccid myelitis between August and October of 2014. Every three months for one year or until the clinical resolution of symptoms, children were given a neurologic examination, magnetic resonance imaging (MRI) scans, electromyography (EMG)/nerve conduction studies (NCS), tests of functional measures, and questionnaires of patient-reported outcomes.

Eight of the 12 children completed the year-long study; of these, six children had persistent motor deficits at the study's endpoint on clinical assessments, while two demonstrated a full recovery. The patients' proximal muscles were the weakest, demonstrating significant atrophy and minimal to no movement at the end of the study period, while distal muscles showed some functional improvement.

On MRI scans, seven children showed hyperintensities on initial T2-weighted imaging; these had resolved in six of eight children by the final scan. On NCS, three of eight children showed ongoing nerve deterioration and chronic reinnervation. Overall, changes on EMG tests correlated with functional deficits better than neuroimaging, the researchers noted.

Among notable patient-reported outcomes were symptoms of fatigue in one patient and depressive symptoms in three of eight patients; the children also reported anxiety and depression and behavioral outbursts.

The findings demonstrate that AFM has "substantial long-term functional effects on affected children," the study authors concluded. In addition, the occurrence of depression in over a third of the patients suggests that AFM can have "a substantial psychosocial effect."

Also, they wrote, the finding that EMG/NCS tests correlated better than MRI with functional assessments "provides important insights into the ability of diagnostic tools to evaluate recovery in AFM… EMG/NCS [rather than imaging] may be a useful tool to evaluate recovery of affected muscles and warrants further evaluation as a diagnostic tool in late presentations of illness."

The researchers noted several limitations to their study. Among them were the small cohort size, the lack of follow-up among four of the 12 original patients, and the fact that the functional testing measures used have not been validated for AFM.


Thursday, June 15, 2017


Taking once-daily extended-release capsules of ADS-5012 (amantadine) at bedtime was safe and effective for reducing levodopa-induced dyskinesia (LID) and helped reduce off-times in patients with Parkinson's disease, according to the results of a randomized, double-blind, placebo-controlled clinical trial published online on June 12 in JAMA Neurology.

LID is common among patients with PD who take levodopa, but there are no approved Food and Drug Administration (FDA) treatments to treat it. Small, preliminary studies have suggested that amantadine-immediate release (IR) can have an antidyskinetic effect, but those findings have not yet been studied in well-controlled clinical trials. And at higher doses, amantadine IR has been associated with increased adverse events.

The study authors wanted to see if the extended-release capsules of ADS-5012 was safe and effective for LID. They concluded that based on the data on efficacy and safety, "these data support the use of ADS-5102 for patients with PD with LID, irrespective of its severity and duration, as well as off time. ADS-5012, 274 mg once daily at bedtime, should therefore be considered for the primary treatment of LID in patients with LID," wrote the study authors, led by Rajesh Pahwa, MD, FAAN, professor of neurology at the University of Kansas Medical Center.

For the study, researchers enrolled 126 patients with PD who were taking levodopa and had drug-associated dyskinesia at 44 sites in North America; 121 patients were included in the modified intent-to-treat population. They randomly assigned the patients to take 274 mg of extended-release amantadine  at bedtime (n=63) or placebo (n=58) for up to 25 weeks. Their primary efficacy endpoint was the change from baseline to week 12 in the Unified Dyskinesia Rating Scale, which assesses involuntary movements associated with Parkinson's disease, with higher scores indicating greater involuntary movement.

They found that extended-release amantadine significantly reduced the duration, severity, and impact of levodopa-induced dyskinea compared with placebo. At the end of the 12-week study period, the least-squares mean (SE) change (the group change after adjusting for covariables) in the Unified Dyskinesia Rating Scale score was –15.9 (1.6) in the amantadine group and –8.0 (1.6) in the placebo group (treatment difference, –7.9; 95%CI, –12.5 to –3.3; p<0.001). The study was stopped early, at week 12, by the sponsor to accelerate the availability of primary efficacy data. However, the benefit of the treatment was sustained in a subgroup of patients (n=39 for ADS-5102 n=45 for placebo) who continued treatment until 24 weeks (least-squares mean treatment difference, –9.3; 95% CI, –14.7 to –4.0; p<0.001).

Additionally, extended-release amantadine was effective at reducing off-times associated with levodopa; off-time decreased by a mean (SE) of 0.6 (0.3) hours in the amantadine group, while it increased by 0.3 (0.3) hours in the placebo group (treatment difference, –0.9 hours; 95%CI, –1.6 to –0.2; p=0.02).

The most common adverse events associated with ADS-5102 vs placebo included visual hallucinations (15 [23.8 percent] vs 1 [1.7 percent]), peripheral edema (15 [23.8 percent] vs 0), and dizziness (14 [22.2 percent] vs 0). Thirteen patients receiving extended-release amantadine (20.6 percent) discontinued treatment, compared to four patients receiving placebo (6.9 percent).

The researchers noted several limitations to their study. Among them, the study was stopped early, which decreased the number of patients contributing to the secondary endpoint assessments; and conclusions about the safety and efficacy of extended release amantadine relative to amantadine-IR require comparison in a randomized clinical trial.


Monday, June 12, 2017


Patients with ischemic stroke and a complete vessel occlusion who were treated with the next-generation thrombolytic tenecteplase had greater complete recanalization rates and better early clinical improvement at 24 hours, according to a new study published online on June 2 in Neurology.

Those on tenecteplase also had a higher chance of a favorable outcome at 90 days, compared to patients treated with the standard-of-care alteplase, the study authors found.

Though the present findings on the superiority of tenecteplase remain preliminary, if confirmed in larger, blinded trials, they have "major potential relevance given the limited access to endovascular therapy in much of the world," the study authors, led by Andrew Bivard, PhD, of the School of Medicine and Public Health at the University of Newcastle in Australia, wrote.

For their study, researchers at several institutions in Australia pooled clinical and imaging data from two randomized, prospective, open-label phase 2 trials comparing tenecteplase with alteplase for the treatment of ischemic stroke – the Australian-TNK and ATTEST trials. In both trials, patients presenting with a large vessel occlusion on CT angiography scans were randomized to receive 0.25 mg/kg of tenecteplase or 0.9 mg/kg of alteplase. A total of 146 patients were included in the pooled analysis; of these, 69 had a total vessel occlusion at baseline.

They found that patients who had a complete vessel occlusion and were treated with tenecteplase had superior recanalization rates (71 percent for tenecteplase vs. 43 percent for alteplase, p<0.001). In fact, the study authors noted, the recanalization rates in patients treated with tenecteplase "were approaching rates seen in the recent endovascular trials."

Additionally, among patients with a complete occlusion at baseline, those treated with tenecteplase had better early neurologic recovery (median NIHSS change with tenecteplase = 9, interquartile range [IQR] 6, alteplase 1, IQR 1, p=0.001) as well as higher rates of a favorable 90-day functional outcome (mRS 0–1 of tenecteplase compared with alteplase, odds ratio [OR] 4.82, 95% confidence interval 1.02–7.84, p=0.05). They also had a better rate of hemorrhage transformation (3 percent for tenecteplase vs. 7 percent for alteplase, p=0.002) and reduced symptomatic intracranial hemorrhage (0 percent for tenecteplase vs 3 percent for alteplase, p=0.04).

However, the researchers noted, there was no significant difference between treatment groups in patients with a partial occlusion on rates of recanalization and 90-day outcomes.

The findings, the study authors concluded, "indicate that tenecteplase produces significantly higher rates of recanalization of occluded vessels." While tenecteplase was superior only for patients with a complete occlusion, they added, "this does not mean that there is no treatment benefit [for patients with a partial occlusion] as our study may lack power to measure the treatment effect in this group."

The researchers noted several limitations to their study. Among them were the small size of the datasets and that the data were from 2 small, open-label trials, which could have included biases in decision-making, clinical assessments, and patient motivation and compliance.


Wednesday, May 31, 2017



Cannabidiol, a compound derived from cannabis, significantly reduced the frequency of convulsive seizures but also increased the risk of adverse events in children with drug-resistant Dravet syndrome, a devastating form of epilepsy, according to findings from a randomized, double-blind, placebo-controlled trial published online on May 25 in the New England Journal of Medicine.

Dravet syndrome is a rare, genetic, early-onset form of epileptic encephalopathy that typically does not respond to antiepileptic drugs, has a high mortality rate, and is associated with convulsive seizures that increase risk of sudden unexpected death in epilepsy. Interest in pharmaceutical-grade cannabidiol for Dravet syndrome and other epilepsies has been growing based on findings from small, preliminary trials, although some yielded mixed results. The current findings, which were first presented at the AAN Annual Meeting in April, show that cannabidiol is effective for reducing seizure frequency over 14 weeks, although its long-term effects remain unknown.

"Additional data are needed to determine the long-term efficacy and safety of cannabidiol for the Dravet syndrome," the study authors, led by Orrin Devinsky, MD, FAAN, director of the Comprehensive Epilepsy Center at New York University Langone Medical Center, wrote.

For the study, researchers enrolled 120 children and young adults who had been diagnosed with Dravet syndrome and randomly assigned them to receive, in addition to their standard antiepileptic treatment, 20 mg of cannabidiol per kilogram of body weight per day or placebo for 14 weeks. The study's primary endpoint was a change in the frequency of convulsive seizures over the treatment period, measured against a four-week baseline period.

They found that among participants in the cannabidiol group, the median frequency of convulsive seizures per month decreased from 12.4 to 5.9, compared to a decrease from 14.9 to 14.1 among children in the placebo arm (p=0.01). Forty-three percent of the participants in the treatment group had at least a 50 percent reduction in frequency, compared with 27 percent of participants in the placebo group (p=0.08). While cannabidiol was associated with a significant reduction in seizures of all types (p=0.03), there was no significant reduction in nonconvulsive seizures.

However, adverse events were more commonly reported in the treatment group than in the placebo group. These included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. Overall, more participants withdrew from the trial in the cannabidiol group than the placebo group.

The results "showed that cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo among children and young adults with drug-resistant Dravet syndrome," the study authors wrote. The lack of a significant reduction in non-convulsive seizures "suggests that the antiseizure effect of cannabidiol may be specific to convulsive seizures in the Dravet syndrome," they noted.

As limitations, the researchers noted the trial's short 14-week duration, and that the high occurrence of adverse events and differences in palatability may have un-blinded some of the participants in the active treatment arm.


Friday, May 26, 2017


Patients with polyneuropathy who took opioids continuously for at least 90 days had no improvement in functional status and had a higher risk of adverse events, including overdose, compared to patients who had a shorter duration of opioid use, according to a new study published in the May 22 online edition of JAMA Neurology.

Short-term trials have suggested that opioids can be effective for treating non-cancer pain, but data from long-term trials are less substantial, and long-term opioid use has been linked with a higher risk of opioid use disorders. Still, opioids are commonly prescribed to treat neuropathic pain associated with polyneuropathy, a prevalent disorder in the elderly, despite rising concerns about an opioid-related morbidity pandemic.

"Our results suggest unintended consequences of long-term opioid therapy when it is used for or in the setting of polyneuropathy," the study authors, led by E. Matthew Hoffman, DO, PhD, a resident in adult neurology at the Mayo Clinic School of Graduate Medical Education in Rochester, MN, wrote.

For the study, researchers retrospectively analyzed a cohort of participants in the Rochester Epidemiology Project living in Olmsted County, MN, who received prescriptions between January 1, 2006 and December 31, 2010; patients were followed through November 25, 2016.

They found that among 2,892 patients with polyneuropathy and 14,435 controls, the patients with polyneuropathy were significantly more likely to receive long-term opioids than controls (18.8 percent vs. 5.4 percent, respectively). Among patients with polyneuropathy, those with long-term opioid use had no improvement in functional status markers, and in fact had several markers that were somewhat poorer, including reliance on gait aids (adjusted odds ratio, 1.9; 95% CI, 1.4-2.6), even after adjusting to account for medical comorbidities.

Additionally, of the 1,993 patients with polyneuropathy who were prescribed opioids, patients who received long-term opioid therapy (one or multiple consecutive opioid prescriptions resulting in ≥90 days of continuous use) were significantly more likely to experience an adverse event, including depression, opioid dependence, or opioid overdose, to those who were on opioid therapy for a shorter duration.

The findings, the study authors concluded, show that long-term opioid therapy "appears to increase the risk of adverse outcomes without benefiting functional status" among patients with polyneuropathy. The findings "should be considered by physicians counseling patients with neuropathic pain who are considering opioid analgesic therapy, as well as by authors of guidelines, policy, and consensus statements," they concluded.

The researchers noted several limitations to their study. Among them were the retrospective study design; that they used administrative codes, which may be subject to error, to ascertain polyneuropathy and to identify adverse outcomes; and a dose effect could not be determined because daily morphine equivalents were not calculated.

For more on the safety and efficacy of opioids for neurological conditions, read