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Friday, December 2, 2016

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BY SARAH OWENS

Newborns who had low concentrations of vitamin D in blood spot samples had an increased risk of developing multiple sclerosis (MS) as adults, according to a new study published online on November 30 in Neurology.

Growing research evidence supports an association between low vitamin D levels and an increased risk of MS, and studies have shown that vitamin D dietary supplementation confers an MS-protective effect. Additionally, patients with MS who live in the Northern hemisphere seem slightly more likely to have been born in April or May, suggesting that low exposure to vitamin D in utero during low-sunlight months may increase MS risk.

The results of the current study, which corroborate previous findings, "provide a rationale for universal vitamin D supplementation in pregnancy," the study authors, led by Nete Munk Nielsen, MD, MSc, PhD, researcher in epidemiology at the Statens Serum Institut in Copenhagen, Denmark, wrote.

For the study, researchers identified 521 adult patients with MS and 972 age- and sex-matched controls in Denmark who as babies had provided dried blood spot samples to the Danish Newborn Screening Biobank. The researchers used liquid chromatography tandem mass spectroscopy to measure levels of 25-hydroxyvitamin D (25[OH]D) in these samples.

They found that lower levels of 25[OH]D in neonates' blood samples were associated with an increased risk of developing MS. After dividing the neonates' vitamin D levels into quintiles, the researchers found that the risk of developing MS as an adult was highest among patients who had the lowest concentrations of vitamin D as newborns (<20.7 nmol/L), and lowest among patients with the highest concentrations of vitamin D (≥48.9 nmol/L).

Overall, treating blood vitamin D concentrations as a continuous variable, the researchers calculated that every 25 nmol/L increase in 25[OH]D resulted in a 30 percent reduced risk of developing MS. The results remained consistent after the researchers adjusted for parental ethnicity, birthweight, and gestational age in a multivariable analysis.

The results, the study authors say, support two sets of findings: that vitamin D plays a protective role in the development of MS, and that vitamin D levels in utero affect the risk of developing MS as an adult. The mechanism of this effect is not yet understood, but animal studies suggest it may relate to the effect of vitamin D deficiency in altering mitochondrial, cytoskeletal, and synaptic brain functions, the study authors noted.

Since vitamin D deficiency among pregnant women is highly prevalent globally, the researchers concluded, vitamin D supplementation should be strongly considered during pregnancy to potentially protect both mother and newborn.

The researchers noted several limitations to their study. Among them, 25[OH]D stored in the Biobank may have degraded due to storage conditions and levels of 25[OH]D measured in neonatal blood may be different from 25[OH]D levels in utero.

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Wednesday, November 30, 2016

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BY SARAH OWENS

US veterans with epilepsy who were deployed in the Iraq and Afghanistan conflicts were twice as likely to die between 2011 and 2015 as veterans without epilepsy, according to an analysis of Veterans Health Administration (VA) data in the November 11 Morbidity and Mortality Weekly Report published by the Centers for Disease Control and Prevention.

Seizure disorders like epilepsy have been associated with traumatic brain injuries sustained during active duty, the study authors noted. In addition, people who have epilepsy are generally more likely to die than people without epilepsy, partly because of the high number of associated comorbidities. But they said the study is the first to identify a specific link between epilepsy and mortality for US veterans of the Iraq and Afghanistan conflicts.

The findings suggest that clinicians should seek out evidence-based interventions to help manage epilepsy and related comorbidities, the study authors wrote.

Led by Mary Jo Pugh, PhD, associate professor of epidemiology and biostatistics at the University of Texas Health Science Center at San Antonio, the researchers assessed data on US veterans who received VA care in 2010 and 2011. To ensure they were active VA users, all veterans included in the study cohort had at least one inpatient or outpatient visit in both years. Using diagnostic codes and records of prescriptions for antiseizure drugs, the researchers identified 2,187 veterans with epilepsy; the remaining 318,396 were considered not to have epilepsy. Then they used VA vital status files to determine the occurrence and date of death.

The researchers used the VA's vital status records to identify five-year mortality (2011-2015). They found that  between January 2011 and December 2015, nearly five times more veterans with epilepsy from the Afghanistan and Iraqi conflicts (4.6 percent) had died by the end of the follow-up period compared to those without epilepsy (1 percent), comprising a 2.6 times higher risk of mortality. The results remained consistent after controlling for demographic characteristics and other comorbidities associated with death (adjusted hazard ratio = 2.6; CI = 2.1-3.2).

Additionally, the vets in the epilepsy cohort were more likely to have other comorbidities, including post-traumatic stress disorder, depression, substance abuse disorder, suicidality, hypertension, and traumatic brain injury.

Health care providers should ensure that veterans with epilepsy are receiving appropriate care and filling their prescriptions for antiseizure medications, the study authors wrote. Additionally, public health agencies like the VA should implement evidence-based self-management programs for those with chronic diseases. Such programs, they wrote, should study the participants' long-term outcomes and support linkages with community health care and social service providers.

The researchers noted several limitations to the findings; among them,  the study excluded veterans who were not treated in VA facilities during the study period, which limits the generalizability of the results; epilepsy care received outside of the VA was not accounted for; and some of the veterans may have been misdiagnosed with epilepsy after a psychogenic nonepileptic seizure.

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Monday, November 14, 2016

​BY SARAH OWENS

People in late middle age who had migraine with aura had a significantly increased risk of cardioembolic stroke over the course of 20 years, according to a new study published online on November 9 in Neurology.

The researchers examined the association in three stroke subtypes, including thrombotic, cardioembolic, and lacunar strokes, but the association was only significant in cardioembolic stroke. Migraneurs without visual aura did not have a significant risk for cardioembolic stroke.

"The results suggest that visual aura symptoms may be related to distal emboli, and there may be shared pathogenesis for migraine with visual aura and cardiac emboli," the authors, led by Michelle Androulakis, MD, MS, assistant professor of clinical neurology at the University of South Carolina, wrote.

Based on the findings, "clinicians might consider initiation of workup for assessment of factors predisposing to cardioembolism in migraine with visual aura patients, especially among those who have other coexisting stroke risk factors," said the study authors.

For their study, researchers analyzed data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing, prospective, longitudinal, community-based study investigating the etiology of atherosclerosis and atherosclerotic diseases. Among 12,758 participants averaging 59 years in age, the researchers identified 1,622 participants (12.6 percent) who had migraine and completed at least three clinical visits as part of the study. Of these, 3.6 percent had migraine with visual aura and 9 percent had migraine without visual aura.

Over a follow-up period of at least six years, they found that the link between migraine with visual aura and ischemic stroke was significant (p=0.014),.The risk was specific to cardioembolic stroke; migraineurs with visual aura had a significantly increased risk of cardioembolic stroke (p=0.003) but not of lacunar stroke (p=0.07) or of non-lacunar thrombotic stroke (p=0.09).

The authors speculated that  luctuations in calcitonin gene-related peptide (CGRP) throughout a migraine attack may induce changes in coronary blood flow and velocity, in turn increasing the risk of atrial fibrillation and the risk of stroke. But, they wrote, "While it may be true in general that migraineurs, regardless of their status of visual aura, have elevated CGRP levels, we do not know if there is differential expression of CGRP levels in older migraineurs with or without visual aura."

They also pointed out that because the study did not enroll people younger than 45, the findings cannot be generalized to younger populations.

The researchers noted several limitations to their study, including that their algorithm for calculating stroke subtype required a cardioembolic source for classification of cardioembolic stroke, even though cardioembolism may not be the stroke etiology; and that they only counted visual aura as aura and may have excluded other auras, including sensory, motor, and brainstem aura.

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Wednesday, November 9, 2016

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​​BY SARAH OWENS

Poorer children with epilepsy had worse social outcomes, but no difference in the clinical course of epilepsy or seizure relapse rates, compared to wealthier children with epilepsy, according to a new study published online on November 4 in Epilepsia.

Chronic diseases are generally more common and more severe in poorer families than in wealthier ones, the study authors noted. However, this association has not been established specifically for childhood-onset epilepsy. If such a link existed, the researchers added, it could provide a target for enhanced treatment and counseling. The results, however, suggest that family socioeconomic status does not affect disease severity for children with epilepsy – but it does affect their social outcomes.

"This information should be reassuring to families of low income and physicians who care for their children with epilepsy," the study's authors, led by Carol Camfield, MD, of Dalhousie University in Halifax, Nova Scotia, wrote. "Although long-term social outcome is significantly less successful in poor children, it remains an issue for children from all socioeconomic groups." And, they added, it speaks to the need for increased counseling services for poorer children.

For their study, researchers in Nova Scotia assessed data on 421 children who were enrolled in the Nova Scotia childhood-onset epilepsy cohort. All study participants were between one month and 16 years old and had new-onset epilepsy at the beginning of the study.

Over at least 10 years and as many as 25 years of follow-up, the researchers used a variety of measures to determine the clinical outcomes of children with epilepsy. These included the use of antiepileptic drugs; the total number of generalized tonic-clonic seizures, focal seizures; intellectual disability related to epilepsy; and major neurologic deficits related to epilepsy.

The researchers measured each child's socioeconomic status using three metrics: income (divided into five quintiles, with the first representing "poor," the second and third representing "adequate" income, and the fourth and fifth representing "well off"); family home ownership; and level of parent education.

Finally, researchers conducted interviews by telephone or face-to-face with each participant to assess their social outcomes. The interviews asked participants about their employment and education status, as well as their social status – whether they lived alone or had romantic relationships, for example – and any psychiatric diagnoses.

While the researchers found that income, family home ownership, and parental education did not affect clinical status, it did have an effect on social outcomes. Compared to the "well-off" group, children in the "poor" group were significantly more likely to have failed to complete high school (42 percent vs. 6 percent, p<0.001); to be unemployed (37 percent vs. 11 percent, p< 0.001); to be poor (56 percent vs. 19 percent, p<0.001); to have an inadvertent pregnancy (50 percent vs. 18 percent, p<0.001); and to have a psychiatric diagnosis other than attention-deficit hyperactivity disorder (34 percent vs. 14 percent).

Overall, wealthy children were significantly more likely to have no adverse outcomes at all (56 percent vs. 17 percent, p< 0.001), and poor children were significantly more likely to have had more than two adverse outcomes (33 percent vs. 9 percent, p< 0.001).

The researchers noted several limitations to their study: among them, the sample size may have been too small to detect minor variations in severity of epilepsy and their measures of socioeconomic status are not standardized.

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Friday, October 28, 2016

BY SARAH OWENS

Researchers have developed a new clinical risk stratification tool called the Surviving Penetrating Injury to the Brain (SPIN) scale based on an analysis of factors associated with survival from penetrating traumatic injury (pTBI). A report on the methodology for the scale was published in a paper online October 26 in Neurology.

The SPIN score, which has not yet been validated, may presently serve as "a preliminary tool that may provide guidance for physicians and families in their direction-of-care decision-making in patients with pTBI," and future external validation should expand its use, the study authors, led by Susanne Muehlschelegel, MD, MPH, critical care neurologist at UMass Memorial Medical Center, wrote.

The main cause of pTBI — gunshot wounds — is a serious public health problem, the study authors noted, adding that  mortality rates for pTBI vary widely between trauma centers. A comprehensive, multivariable score for estimating survival after pTBI is necessary to identify ways to improve patient outcomes, they said.

For their study, the researchers retrospectively analyzed data on 413 pTBI patients using local trauma registries at two level-one trauma centers in the United States: the University of Maryland Shock-Trauma Center (n=377) in an urban setting and the UMass Memorial Medical Center, n=36) in a rural area. The patients were an average age of 33 years and were predominantly male; patients who were dead upon arrival at the trauma center were excluded.

They found that 175 patients (42.4 percent) survived to hospital discharge (the researchers' primary endpoint) and six months after pTBI (the secondary endpoint); there were no additional deaths at either center between hospital discharge and six months.

Additionally, the researchers found a wide range of factors associated with likelihood of survival. These included higher scores on the motor Glasgow Coma Scale subscore and pupillary reactivity, which were the two strongest predictors of survival. Injury that was not self-inflicted transfer status from another hospital, female gender, a lower Injury Severity Score, and a lower international normalized ratio were all independently associated with survival (p<0.001).

The researchers developed the SPIN score as a sum of individual points, with greater points allocated to stronger predictors of survival. However, they did not include radiologic factors in the scale, as these would have introduced too many parameters and limited predictive power. The score ranges from four to 52; higher scores indicate a stronger likelihood of survival.​

Among their findings, 98 percent of the patients with a SPIN score of 35 and above survived, while only 3 percent of patients with a score of 20 or below survived, and no patients with a score of 16 or below survived.

The researchers noted several limitations to their study, including the lack of score validation; the retrospective nature of the study, which may have resulted in incomplete collection of some outcome variables; and that most of the study participants were from the University of Maryland Shock-Trauma Center, which potentially biased the results toward an urban pTBI population.

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