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

Friday, March 24, 2017

BY SARAH OWENS

Over one year of follow-up, neurovascular thrombectomy reduced post-stroke disability and improved health-related quality of life compared to medical therapy alone when performed up to eight hours after the onset of symptoms, according to the results of a new randomized, open-label trial published online on March 16 in The Lancet Neurology.

Current guidelines recommend that thrombectomy, a surgical procedure that recanalizes large-vessel occlusions, be performed on patients with acute ischemic stroke within six hours of symptom onset. The Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) meta-analysis, which pooled the results of five randomized, controlled trials testing the efficacy time window for thrombectomy, found last year that the procedure's benefit lasted up until 7.3 hours. The current study suggests that window may extend up to eight hours – or beyond – and that the benefit is sustained one year later, rather than the 90 days or three months used as a benchmark by many trials.

"Our results provide reassurance to clinicians that the benefit of thrombectomy is sustained long term and validates the hitherto unproven hypothesis of sustained treatment effect used in cost-effective analyses of thrombectomy in acute stroke," the study authors, led by Antoni Davalos, MD, PhD, wrote.

For their study, researchers at four stroke centers in Barcelona, Spain enrolled 206 patients who presented with acute ischemic stroke between November 2012 and December 2014. They randomly assigned the patients to receive either medical therapy alone (n=103) or endovascular thrombectomy (n=103). Patients underwent thrombectomy up to eight hours after the onset of symptoms.

At five days, 90 days, three months, and one year post-stroke, masked investigators assessed a number of outcome measures, including disability, health-related quality of life, functional independence, and cognitive function. All but one (n=205) of the population was available for complete follow-up at one year. At one year, patients in the thrombectomy group had lower disability scores on the modified Rankin scale (a 0 to 6 scale of degree of disability, with higher scores indicating greater disability). Additionally, patients in the thrombectomy group had significantly better health-related quality of life, functional independence, and cognitive function.

The results have several important implications, the study authors noted. Since outcomes remained essentially unchanged from three months to one year, the results provide reassurance of the long-term benefit of thrombectomy, and may also suggest that "outcomes beyond 90 days in acute stroke trials might not be necessary." Further, the treatment effect was similar at five days post-stroke and 90 days post-randomization, which justifies further studies that seek to establish the five-day modified Rankin scale as a surrogate outcome measure.

However, the authors did note several limitations to their study. Among them, their trial was open-label, so patients and investigators were aware of treatment assignments; and the trial was stopped before the formal three-month stopping boundary was reached, although the prespecified 12-month secondary analysis showed that three-month benefits were sustained.

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Thursday, March 16, 2017

BY SARAH OWENS

Eighty-four percent of patients who had an acute ischemic stroke and a history of atrial fibrillation were not receiving guideline-recommended therapeutic anticoagulation before the stroke, according to a new study published online on March 14 in the Journal of the American Medical Association.

Those who did receive adequate anticoagulation before the stroke had better stroke severity scores, lower in-hospital mortality, and better functional outcomes, the study authors found.

The findings, the study authors wrote, demonstrate that there are "potentially preventable strokes in high-risk patients with AF who either were not treated with anticoagulants or did not receive adequate anticoagulation" and "highlight the opportunities for stroke prevention by improving appropriate AF treatment."

Atrial fibrillation (AF) is a substantial, but potentially modifiable, risk factor for stroke, and guidelines recommend treatment for patients with AF with vitamin K antagonists (warfarin) and non-vitamin K antagonist oral anticoagulants (NOACs). Previous studies have suggested these medicines are underused, but they tended to examine treatment patterns for AF only post-stroke. The present study, instead, examines how patients with acute ischemic stroke were treated prior to the event.

"A substantial number of strokes may be due to underuse of or inadequate anticoagulation in AF," the study authors, led by Ying Xian, MD, PhD, assistant professor of neurology and assistant professor of clinical pharmacology at the Duke University Medical Center and Duke Clinical Research Institute, wrote.

For their retrospective, observational study, researchers at Duke analyzed 94,474 patients who were participating in the Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study. All participants had been diagnosed with AF, had a stroke between October 2012 and March 2015, and had been admitted to hospitals participating in the American Heart Association/American Stroke Association's Get With The Guidelines-Stroke registry program. The research assessed anticoagulant use in the study population at the time of hospital admission.

They found that 7,176 (7.6 percent) of participants were receiving warfarin, and 8,290 (8.8 percent) were receiving NOACs. That left 79,008 patients (83.6 percent) who were receiving no anticoagulation therapy. Moreover, among the 91,155 patients defined as having a high risk of stroke according to their CHA2DS2–VASc score, which is designed to estimate the risk of stroke in patients with AF, 83.5 percent were not receiving adequate therapeutic anticoagulation (either warfarin or NOACs) before their stroke.

Those patients who did receive adequate anticoagulation before a stroke had lower rates of moderate or severe stroke:  15.8 percent (warfarin) and 17.5 percent (NOACs) compared with 27.1 percent [no therapy), 24.8 percent (antiplatelet therapy only), and 25.8 percent (subtherapeutic warfarin). Likewise, patients who received anticoagulation had lower rates of in-hospital mortality: 6.4 percent (warfarin) and 6.3 percent (NOACs) compared with 9.3 percent (no therapy), 8.1 percent (antiplatelet therapy only), and 8.8 percent [subtherapeutic warfarin).

Finally, patients receiving anticoagulation pre-stroke had higher odds of a better functional outcome, defined as a modified Rankin score (a functional scale measuring degree of disability or dependence after stroke, with higher scores indicating worse outcomes) of 0-1 or 0-2 at discharge.

The researchers noted several limitations to their study. Among them, the fact that the study analyzed treatment prior to stroke prevented randomization; the study excluded patients with AF who did not have a stroke, which prevented a case-control design; and some patients did not have available measures of stroke severity or functional outcome.

Look for expanded coverage of this study in an upcoming edition of Neurology Today​.

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Monday, March 13, 2017

BY SARAH OWENS

Levels of neurofilament light chain (NFL) may help doctors distinguish subtypes of amyotrophic lateral sclerosis (ALS) and differentiate ALS from other neurodegenerative diseases, according to a new study published online on March 6 in JAMA Neurology.

Moreover, cerebrospinal fluid NFL levels may guide disease prognosis in patients with lower motor neuron signs of the disease, the researchers reported.

"NFL measurement is probably heading to the ALS clinic," the study authors, led by Alessandra Gaiani, MD, neurologist at the University of Padua in Padova, Italy, wrote. "Further evidence of the diagnostic and prognostic role of NFL will have a profound effect on the selection of patients to enroll in clinical trials."

For their study, researchers at the University of Padua enrolled 176 patients who underwent a spinal tap at the university's department of neurosciences between January 2010 and February 2016. The participants included 94 patients with ALS, 20 patients with frontotemporal dementia (FTD), 18 patients with motor neuropathies (MN), and 44 controls. The researchers used an NFL enzyme-linked immunosorbent assay to quantify NFL levels in the cerebrospinal fluid samples.

They found that NFL concentrations were higher in the ALS and FTD groups compared to the MN and control groups (p<0.001). NFL levels correlated with ALS subtypes; patients with typical ALS (hazard ratio (HR) 1.0 [reference]), progressive bulbar palsy (HR, 1.48; p=0.41) and upper motor neuron dominant ALS (HR, 0.12; p<0.01) had higher NFL levels compared to those with flail arm or leg syndrome (HR, 0.28; p<0.049) and progressive muscular atrophy (HR 0.17, p=0.10).

Additionally, researchers found that NFL concentration was inversely correlated with overall survival (p<0.001), suggesting that NFL has prognostic value in ALS.

The authors hypothesized that elevated NFL levels in patients with upper motor neuron involvement and in patients with FTD might reflect the degeneration of the corticospinal tract, which has motor neurons that are believed to be rich in neurofilament. They also proposed that low NFL levels in patients with ALS and lower motor neuron signs "might be a prognostic indicator of milder phenotypes of disease."

The researchers noted a few limitations to their study. Among them, the study's retrospective design may have limited the results; and the researchers studied a small number of patients, especially considering their division into different clinical subtypes.

To read our collection of reports on NFL as a biomarker of neurological disease, visit http://bit.ly/NT-Neurofilament.

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Wednesday, March 8, 2017

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BY SARAH OWENS

A history of migraine, particularly of migraine without aura, was associated with the occurrence of spontaneous cervical artery dissection during young adulthood, according to a new study published online on March 6 in JAMA Neurology. The association was greater for men than for women and for younger patients than for older.

The finding persisted even after factoring in traditional vascular risk factors, including hypertension, diabetes, cigarette smoking, hypercholesterolemia, and migraine.

Ischemic stroke is on the rise among young adults, and cervical artery dissection is the most frequent cause, yet the mechanisms and risk factors are poorly defined. The current findings suggest that migraine should be considered a marker of increased risk for cervical dissection and support additional research into the possible shared biologic pathways of the two conditions.

"This finding emphasizes the need for further analyses to investigate the nature and mechanisms of elevated risk in migraineurs and to elucidate whether this risk applies to only specific subsets of patients with migraine," the study authors, led by Valeria De Giuli, MD, resident physician in neurology at Università degli Studi di Brescia in Brescia, Italy, wrote.

For the study, researchers at the University of Brescia prospectively studied all patients between ages 18 and 45 who had a first-ever ischemic stroke and were participating in the multicenter Italian Project on Stroke in Young Adults between January 2000 and June 2015 (n=2,485). Of all patients, 334 (13.4 percent) had a stroke due to a spontaneous cervical artery dissection (CEAD), and 2,151 (86.6 percent) had a stroke due to another reason.

The researchers found that migraine was significantly more common in the CEAD group than in the non-CEAD group: 103 (30.8 percent) vs. 525 (24.4 percent), respectively (p=0.01). The study authors attributed this to  the difference in occurrence of migraine without aura: 80 (24 percent) vs 335 (15.6 percent), respectively, (p<0.01). By contrast, the frequency of migraine with aura did not differ significantly between the CEAD and non-CEAD group (p=0.12).

Furthermore, the magnitude of the association between migraine without aura and CEAD was greater in men than in women (odds ratio [OR], 1.99; 95% CI, 1.31-3.04 vs OR, 1.53; 95% CI, 1.04-2.25) and in younger versus older patients (OR, 1.82; 95% CI, 1.22-2.71 vs OR, 1.55; 95% CI, 1.04-2.31).

  .The researchers noted several limitations to their study. Among them, the study was based on data from hospitals, which may have subjected the findings to hospital referral selection bias; and the study did not assess migraine frequency or severity, which prevents an interpretation of the association according to migraine patterns.

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Monday, March 6, 2017

BY SARAH OWENS

Worsening depression appeared to increase the risk of epilepsy as well as worse outcomes after a seizure, according to a new study published online on February 27 in JAMA Neurology. Moreover, depression appeared to mediate the influence of independent risk factors for epilepsy.

Previous research has found that depression and epilepsy share pathophysiological mechanisms, affecting many of the same brain areas. The current study establishes a gradient in that relationship, suggesting that as depression worsens, epilepsy risk increases and seizure outcomes worsen.

The findings, which "indicate a shared relationship between depression and epilepsy, with each appearing to act as a risk factor for the other," should "have a direct effect on counseling and management," the study authors, led by Colin B. Josephson, MD, assistant professor of neurology at the University of Calgary, wrote. "Depression-specific interventions might reduce the overall effect of each of these variables on epilepsy," they concluded.

For the study, researchers at the University of Calgary assessed data on more than 10 million patients in The Health Improvement Network (THIN) database, a population-based general-practice cohort of patients in the United Kingdom. They identified 229,164 patients (2.2 percent) who developed depression and 91,177 (0.9 percent) with epilepsy.

Incident epilepsy was associated with an increased risk of developing depression (hazard ratio [HR], 2.04 [95% CI, 1.97-2.09]; p<0.001), and incident depression was linked with an increased risk of developing epilepsy (HR, 2.55 [95% CI, 2.49-2.60]; p<0.001). Patients with treated epilepsy had the highest increased risk of incident epilepsy (HR, 3.42 [95% CI, 3.37-3.47]; p<0.001).

Among patients who developed epilepsy, the researchers found that past or current depression was linked with a higher risk of failing to achieve seizure freedom over the previous year compared to people who did not have depression (p =0.03). In addition, patients with epilepsy and depression who were treated with antidepressants and/or counseling had a statistically significant higher chance of failing to achieve freedom from seizures after 1 year (p=0.03).

Finally, they found that depression appeared to partially mediate the influence of independent risk factors, including sex, socioeconomic deprivation, and the Charlson Comorbidity Index (CCI) – which captures the prevalence of patient comorbidities – and the risk of developing epilepsy.

The researchers noted several limitations to their study. Among them, the database did not allow the researchers to control for etiology, epilepsy subtypes, or other conditions that could cause epilepsy or depression; the THIN database may have underreported epilepsy and depression; and the analysis was not able to establish a cause-effect relationship.

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