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Thursday, August 27, 2015



Vitamin D pathway. In blue are the genes containing, or in proximity to, SNPs that were genome-wide significant for 25OHD level in SUNLIGHT (n = 33,996). The p-values for the association with 25OHD level were 1.9 × 10−109 for GC, 2.1 × 10−27 for DHCR7, 3.3 × 10−20 forCYP2R1, and 6.0 × 10−10 for CYP24A1. Note that each gene plays an independent role in modulating the level of 25OHD.


A new genetic analysis strengthens the association between low circulating levels of vitamin D and an increased risk of multiple sclerosis (MS). Past epidemiological and observational studies have hinted at this association, but could not establish a causal link, the study authors wrote in the Aug. 25 online edition of PLOS Medicine.


The findings provide “strong evidence in support of a causal role of vitamin D in MS susceptibility,” the researchers wrote. “These findings are consistent with evidence from observational studies that have demonstrated that low vitamin D levels influence MS risk."


The study is particularly important because vitamin D insufficiency appears to be increasing among American adults, they added, citing statistics from the US Centers for Disease Control and Prevention (CDC)’s National Health and Nutrition Examination Survey. The survey found that in 2005, 41.6 percent of adult Americans had insufficient vitamin D. As vitamin D supplementation is relatively safe and effective, the study authors said, positive findings from randomized controlled trials of the therapy could have an important impact on public health and the overall burden of MS in the population.


The researchers from Canada, the US, and the United Kingdom used Mendelian randomization — which “uses genetic associations to test the effects of biomarkers” on the risk of disease — to determine whether there was an association between genetically lowered circulating levels of 25-hydroxyvitamin D (25OHD), the clinical determinant of vitamin D status, and risk of MS among 14,498 MS patients and 24,091 healthy controls enrolled in the International Multiple Sclerosis Genetics Consortium (IMSGC).


First, the researchers identified four significant single nucleotide polymorphisms (SNPs) that appeared to be associated with decreased 25OHD levels in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT), a genome-wide association study involving 33,996 participants. They then confirmed that these SNPs had a significant effect on 25OHD levels among 2,347 individuals enrolled in the population-based Canadian Multicentre Osteoporosis Study (CaMos).


Lastly, the researchers evaluated the effect of these SNPs on 25OHD levels among the participants in the IMSGC, in an effort to determine whether lowered levels of vitamin D were associated with increased MS risk.


All four 25OHD-decreasing alleles were associated with an increased risk of MS, the researchers reported. They found that for each standard deviation decrease in genetic vitamin D levels, a participants’ risk for MS increased twofold (OR=2.02, 95% CI, 1.7-2.5; p=7.7 X 10-12).


“This evidence provides rationale to further investigate whether vitamin D supplementation may reduce MS susceptibility in those most at risk,” the researchers wrote, noting that a “reasonable first step” might be to look at whether vitamin D therapy can delay the onset or severity of MS in patients with clinically isolated syndrome, who are most at risk of developing MS. Some randomized controlled trials of the therapy are already underway, they noted.


Look for more coverage of this study in a future issue of Neurology Today. For more articles about vitamin D and MS risk, browse our archives here.


Image via Mokry LE, Ross S, Ahmad OS, et al. Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study. PLOS Medicine 2015: Epub 2015 Aug. 25.

Tuesday, August 25, 2015




Researchers have identified nine modifiable risk factors that may contribute to up to two-thirds of Alzheimer’s cases globally. The findings, published in the Aug. 20 online edition of the Journal of Neurology, Neurosurgery & Psychiatry, suggest that preventive strategies targeting these risk factors — including diet, medications, mental health, pre-existing conditions, and lifestyle — may help reduce the burden of dementia worldwide.


The researchers, from Qingdao Municipal Hospital, Ocean University of China, and the University of California, San Francisco, conducted the largest systematic review and meta-analysis to date of potential modifiable risk factors for Alzheimer’s disease (AD). They looked at all studies published in English between 1968 and July 2014 and identified 323 out of nearly 17,000 that met inclusion criteria. They identified 93 potential modifiable risk factors for AD for which there was relatively strong evidence, defined having a pooled study population of at least 5,000 people, and rated the level of evidence for each risk factor.


They found strong evidence (grade 1) that estrogen, statins, antihypertensive medications, and non-steroidal anti-inflammatory drugs (NSAIDs), as well as dietary intake of folate, vitamins C and E, and coffee, were associated with a lower risk of AD. Estrogen was found to reduce AD risk by about 40 percent, NSAIDs by about 26 percent, and current or longer-term use of statins by 48 and 76 percent, respectively. Folate reduced AD risk by about 49 percent, vitamins C and E by about 26 percent, and caffeine by about 46 percent. There was also grade 1 evidence to suggest that consumption of fish reduced the risk by 36 percent. Physical activity, cognitive activity, and socioeconomic status trended toward a lowered risk by 28, 13, and 43 percent, respectively.


There was grade 1 evidence to suggest that depression and high levels of the amino acid homocysteine were associated with an increased risk of developing AD. Pre-existing medical conditions associated with a higher risk for AD included frailty, carotid artherosclerosis, hypertension, low diastolic blood pressure, and type 2 diabetes (but only in the Asian population). Low education was also associated with an increased risk.


The interaction between pre-existing conditions in AD is a complicated one, however. The authors noted that a history of arthritis, heart disease, metabolic syndrome, and cancer were linked to a decreased risk of AD. Certain factors also had a different risk profile at different points in the life cycle. For example, high body mass index (BMI) was associated with an increased risk of AD in mid-life, but was linked to lower risk in late life. Current smoking (in the Western population), light to moderate drinking, and stress in late life were also associated with a lowered risk.


The researchers also calculated the proportion of global disease that could be attenuated by eliminating these risk factors. They identified nine with the strongest association with AD risk for which data about global prevalence was available: obesity (3.4 percent of the population worldwide), current smoking in the Asian population (34.7 to 61.1 percent for men and 0.5 to 2.6 percent for women), carotid atherosclerosis, type 2 diabetes (in Asians), low educational attainment, high levels of homocysteine, depression, hypertension, and frailty. These risk factors combined may contribute to up to two-thirds of all dementia cases worldwide, they said.


“The current meta-analysis emphasized the heterogeneity of modifiable risk factors of AD and the complexity of its etiology, and indicated that the effective interventions in diet, medications, biochemical exposures, psychological condition, pre-existing disease and lifestyle may be promising options for preventive strategies,” the authors concluded. “Further good-quality cohort studies and randomized controlled trials targeting these elements are necessary.”


For more articles about risk factors for AD, browse our archives here.


Image via Wikimedia Commons.

Friday, August 21, 2015




The sudden onset of a severe headache in pregnant women with high blood pressure and no history of headaches may signal a more serious condition or pregnancy complication, such as preeclampsia, according to a new study.


Clinicians need to be vigilant in screening pregnant women with severe headaches for complications, the researchers from the Montefiore Health System and Albert Einstein College of Medicine of Yeshiva University in the Bronx, NY, wrote in the Aug. 19 online edition of Neurology. “Diagnostic vigilance should be heightened in the absence of a headache history and if seizures, hypertension, or fever are present,” they said.


For the study, the researchers looked for factors that could help determine whether to make a diagnosis of primary headache or whether the pain is a symptom of another, potentially life-threatening condition.


“It is not always easy to distinguish between a recurring, pre-existing migraine condition and a headache caused by a pregnancy complication. Our study suggests that physicians should pay close attention when a pregnant woman presents with a severe headache, especially if she has elevated blood pressure or lack of past headache history. Those patients should be referred immediately for neuroimaging and monitoring for preeclampsia,” said lead author Matthew S. Robbins, MD, director of inpatient services at Montefiore Headache Center, chief of neurology at the Jack D. Wiler Hospital of Montefiore, and an associate professor of clinical neurology at Einstein, in a news release.


For the five-year, single-center retrospective study, Dr. Robbins and his colleagues looked at records from every pregnant woman aged 18 or older complaining of severe headache referred to Wiler Hospital from July 2009 through June 2014. They consulted records for a total of 140 women with an average age of 29, 56.4 percent of whom presented during their third trimester.


Among the findings, 78.6 percent of the women reported a history of headaches. They found that 91 of the 140 women, or 65 percent, were diagnosed with primary headaches, most commonly migraines (91.2 percent). However, 49 women, or 35 percent, received a diagnosis of headache secondary to other conditions such as hypertension disorders (51 percent), including 38 percent who had preeclampsia. (Common symptoms of preeclampsia include hypertension, headaches, blurry vision, and abdominal pain, but some women show no symptoms.)


Women with headache and high blood pressure were 17 times more likely to have a secondary diagnosis of headache than a primary diagnosis (55.1 percent vs. 8.8 percent; OR 17.0, 95% CI, 4.2-56.0; p<0.0001), the researchers found. And women without a history of headache were 4.9 times more likely to have a secondary headache disorder (35.7 percent vs. 13.2 percent; OR 4.9, 95% CI, 1.7-14.5; p=0.0012).


Seizures (12.2 percent vs. 0 percent, p=0.0015), fever (8.2 percent vs. 0 percent, p=0.014), and an abnormal neurologic examination (34.7 percent vs. 16.5 percent, p=0.014) were all more strongly associated with secondary headache disorders.


Psychiatric comorbidities such as depression, anxiety, or bipolar disorder (OR 1.3, 95% CI, 0.021-0.78) and phonophobia (OR 0.29, 95% CI, 0.09-0.91) were more strongly associated with primary headache.


“Aside from a lack of phonophobia and a self-report of increased headache duration relative to past headache, secondary headache features did not differ from those of primary headache,” Dr. Robbins and his colleagues noted. “Since the headache and related symptoms of preeclampsia and migraine may overlap, close follow-up with monitoring for signs of preeclampsia is…reasonable.”


For more coverage of neurologic conditions in pregnancy, browse our archives here.


Image via Tatiana Vdb on Flickr.

Wednesday, August 19, 2015




Children with multiple sclerosis (MS) who exercise regularly have less disease activity and fewer relapses than those who exercise less, according to a new study. But they’re also less likely to get regular strenuous exercise than children with a similar condition, monophasic acquired demyelinating syndrome (mono-ADS), the researchers wrote in the Aug. 12 online edition of Neurology.


The findings “add to the possibility that physical activity may have a beneficial effect on the health of the brain,” study author E. Ann Yeh, MD, a neurologist at the Hospital for Sick Children in Toronto and an associate professor at the University of Toronto, said in a news release.


The researchers looked at 31 children with MS and 79 with mono-ADS (a single inflammatory neurologic event) between the ages of five and 18 who presented to the Hospital for Sick Children’s Pediatric MS and Demyelinating Disorders Center in June through December 2013. All 110 children or their caregivers reported on their levels of fatigue and depression. They also indicated how often they participated in strenuous physical activity such as running or jogging, moderate activity such as fast walking, and mild activity such as leisurely walking for a period of at least 15 minutes during a usual week.


A subset of 60 children — 13 with MS and 47 with mono-ADS — also received magnetic resonance imaging (MRI) scans, which Dr. Yeh and her colleagues used to measure whole brain and T2 lesion volume.


Among the findings, 45 percent of the children with MS reported participating in strenuous physical activity, compared with 82 percent among children with mono-ADS. Kids with MS also reported more fatigue and depression than those with mono-ADS.


Exercise appeared to be neuroprotective for children with MS, Dr. Yeh and colleagues reported: Children with MS who reported more strenuous physical activity had a lower volume of T2 lesions than those who did not report strenuous exercise (0.46 cm3 vs. 3.4 cm3). Those who exercised more strenuously also had fewer annual relapses (0.5 relapses vs. 1 relapse per year) and reported less fatigue and depression. The researchers found no associations between total brain volume and level of physical activity.


Because of the study’s cross-sectional design, the researchers could not establish cause and effect. “Does less physical activity worsen fatigue and depression? Or are fatigue and depression among the reasons for reduced physical activity?” questioned Maria A. Rocca, MD, and Massimo Filippi, MD, of the Neuroimaging Institute at Vita-Salute San Raffaele University in Milan, and Kumaran Deiva, MD, PhD, of Assistance Publique-Hôpitaux de Paris, in an accompanying editorial in Neurology.


If confirmed in future studies, the findings suggest that interventions that encourage physical activity may help slow disease progression and improve depression and fatigue among children with MS, Dr. Yeh and her colleagues wrote.


Drs. Rocca, Filippi, and Deiva agreed. “The current study offers tantalizing results that have the potential to guide future studies, which ideally would be longitudinal, to allow some statements about causality,” they wrote in their editorial. “A strong message from this study is that implementing physical activity may represent an easy approach that could favorably influence disease outcome in the long term.”


For more articles about pediatric MS, browse our archives here.


Image via peace6x on Flickr.

Tuesday, August 18, 2015




Smokers who experience migraines may have an increased risk for stroke, according to a study published in the July 22 online edition of Neurology.


For the study, led by Teshamae Monteith, MD, an assistant professor of clinical neurology and chief of the Headache Division at the University of Miami’s Miller School of Medicine, the researchers looked at available data on 1,292 participants over age 40 who were enrolled in the Northern Manhattan Study, a population-based cohort study of stroke incidence. The participants were on average 68 years old and were followed for an average of 11 years; 198 said they were current smokers. Of the 262 patients (20 percent) who reported experiencing migraines, 187 had migraine without aura and 75 had migraine with aura. There were 114 strokes, 94 heart attacks, and 178 vascular deaths during the study period.


The researchers did not find any association between migraine with or without aura and risk of stroke or heart attacks. However, migraine was associated with a three-fold increased risk of stroke among the 35 smokers who reported having migraines (hazard ratio [HR] 3.17, 95% confidence interval [CI] 1.13-8.85; p=0.02). Current smokers with migraines also had an increased risk for vascular events including stroke, heart attack, and vascular deaths (HR 1.83, 95% CI, 0.89-3.75, p=0.03).


Migraine was not associated with a higher risk of stroke among non-smokers (HR 0.49, 95% CI, 0.19-1.27) or former smokers (HR 0.87, 95% CI 0.41-1.84), or for combined vascular events (HR 0.63, 95% CI 0.43-0.94) after controlling for socioeconomic and vascular risk factors.  


“Statistically, we could not rule out the possibility that the relationship between migraine and stroke in smokers was due to chance,” the researchers noted. “However, we believe the association is biologically plausible” and consistent with past research, they said.


While the analysis found no association between migraine of either type and stroke risk, past research has shown that women under age 45 who have migraine with aura have an increased risk of stroke independent of smoking status, they noted.


“As smoking may be common among migraineurs, smoking cessation counseling should be encouraged as part of routine migraine care throughout the lifetime,” they said. “Taken together, the identification of modifiable vascular risk factors and treatments may have beneficial outcomes for stroke reduction in the elderly population with migraine.”


For more articles on migraine and stroke risk, browse our archives here.


Image via Matt Trostle on Flickr.