News Roundup

New and Noteworthy Information—June 2017


Can Biomarkers Predict Cognitive Deficits in Parkinson’s Disease?

Biomarkers may predict which patients with Parkinson’s disease will have significant cognitive deficits within the first three years after diagnosis, according to a study published May 17 in PLOS One. Researchers conducted an international, prospective study of 423 newly diagnosed and untreated patients with Parkinson’s disease with no signs of cognitive impairment at the time of enrollment in 2010. Investigators conducted brain scans, genetic tests, and analyses of CSF at baseline and during follow-up. At three years, between 15% and 38% of participants had developed cognitive impairment. Brain scans identified dopamine deficiency and decreased brain volume as predictors of cognitive decline. Low CSF beta-amyloid level and single-nucleotide polymorphisms (SNPs) in COMT and BDNF also predicted cognitive decline. These SNPs previously had been associated with cognitive impairment.

Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One. 2017 May 17;12(5):e0175674.

Service Members With Concussive Blast TBI Have Worsening Outcomes

Military service members with concussive blast traumatic brain injury (TBI) have considerable decline in clinical outcomes over five years, according to a study published online ahead of print May 1 in JAMA Neurology. This prospective longitudinal study enrolled active-duty US military after concussive blast injury in the acute to subacute stage and combat-deployed control individuals in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. Physicians in the United States performed one- and five-year clinical evaluations. Among the 94 participants, global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI, compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the five-year evaluation.

Mac Donald CL, Barber J, Jordan M, et al. Early clinical predictors of 5-year outcome after concussive blast traumatic brain injury. JAMA Neurol. 2017 May 1 [Epub ahead of print].

Biomarker Linked to Increased Risk of Ischemic Stroke in Women

High levels of β2-microglobulin are associated with an increased risk of ischemic stroke among women, according to a study published online ahead of print May 10 in Neurology. Researchers performed a nested case–control study among women enrolled in the Nurses’ Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. Investigators measured β2-microglobulin levels in 473 ischemic stroke cases and 473 controls matched on age, race, and other variables. Median levels of β2-microglobulin were 1.86 mg/L in cases and 1.80 mg/L in controls. Women in the highest β2-microglobulin quartile had a multivariable-adjusted increased risk of ischemic stroke, compared with women in the lowest quartile (odds ratio, 1.56). Results were similar when restricted to those without chronic kidney disease.

Rist PM, Jiménez MC, Rexrode KM. Prospective association between β2-microglobulin levels and ischemic stroke risk among women. Neurology. 2017 May 10 [Epub ahead of print].

Female Hormones May Cause Headache in Girls With Migraine

Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine, according to a study published online ahead of print May 8 in Cephalalgia. The study included 34 girls with migraine grouped into three age strata (ie, prepubertal, pubertal, and postpubertal). Participants collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide and pregnandiol glucuronide, and the daily change in each was calculated. The primary outcome measures were headache onset days and headache severity. Models of headache onset days demonstrated a significant interaction between age and pregnandiol glucuronide. Change in pregnandiol glucuronide was associated with headache severity.

Martin VT, Allen JR, Houle TT, et al. Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: an observational cohort study. Cephalalgia. 2017 Jan 1 [Epub ahead of print].

PTSD Is Associated With Risk for Dementia Diagnosis

Posttraumatic stress disorder (PTSD) diagnosis is associated with an increased risk for dementia diagnosis that varies with psychotropic medication, according to a study published in the May issue of the Journal of the American Geriatrics Society. Researchers examined information from 417,172 veterans age 56 and older without dementia or mild cognitive impairment. During the study’s nine-year follow-up period, participants had a clinical encounter every two years. PTSD diagnosis significantly increased the risk for dementia diagnosis. The hazard ratio for dementia diagnosis among veterans diagnosed with PTSD who did not use psychotropic medications was 1.55. Among veterans diagnosed with PTSD and prescribed psychotropic medication, the hazard ratio for dementia diagnosis ranged from 1.99 for SSRIs to 4.21 for atypical antipsychotics.

Mawanda F, Wallace RB, McCoy K, Abrams TE. PTSD, psychotropic medication use, and the risk of dementia among US veterans: a retrospective cohort study. J Am Geriatr Soc. 2017;65(5):1043-1050.

Screening for Atrial Fibrillation Recommended

Screening for asymptomatic atrial fibrillation in people age 65 and older and treating it with anticoagulant medications could greatly reduce the risk of stroke and premature death, according to the AF-SCREEN International Collaboration report published May 9 in Circulation. In 2016, 60 members of the collaboration, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare a draft document. They concluded that screen-detected atrial fibrillation found at a single timepoint or by intermittent ECG recordings over two weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. Handheld ECG devices are preferred as screening tools because they provide a verifiable ECG trace that guidelines require for diagnosis, said the authors.

Freedman B, Camm J, Calkins H, et al. Screening for atrial fibrillation: a report of the AF-SCREEN international collaboration. Circulation. 2017;135(19):1851-1867.

Can Music Reduce Depressive Symptoms in Dementia?

Providing people with dementia with at least five sessions of a music-based therapeutic intervention probably reduces depressive symptoms, but has little or no effect on agitation or aggression, according to a study published online ahead of print May 2 in the Cochrane Database of Systematic Reviews. Researchers searched ALOIS on April 14, 2010, using the terms “music therapy,” “music,” “singing,” “sing,” and “auditory stimulation.” Sixteen studies with a total of 620 participants contributed data to meta-analyses. Participants in the studies had dementia of varying severity. The investigators found that music-based therapeutic interventions may have little or no effect on emotional well-being and quality of life, overall behavior problems, and cognition. Study authors also found moderate-quality evidence that these interventions reduce depressive symptoms, but do not decrease agitation or aggression.

van der Steen JT, van Soest-Poortvliet MC, van der Wouden JC, et al. Music-based therapeutic interventions for people with dementia. Cochrane Database Syst Rev. 2017 May 2 [Epub ahead of print].

FDA Approves Radicava for Treatment of ALS

The FDA has approved Radicava (edaravone) as an IV treatment for amyotrophic lateral sclerosis (ALS). A phase III study evaluated the efficacy and safety of Radicava, compared with placebo, in 137 people with ALS. After a 12-week preobservation period, eligible patients were randomized 1:1 to receive 60 mg of Radicava in an IV for 60 minutes or placebo during a six-month double-blind phase. People given Radicava showed significantly less decline in physical function, compared with controls, as measured by the ALS Functional Rating Scale-Revised. The most common adverse reactions that occurred in greater than 10% of patients and greater than placebo were bruising, walking difficulties, and headache. Radicava is administered in 28-day cycles. MT Pharma America, headquartered in Jersey City, New Jersey, markets Radicava.

Can Cooling the Body Reduce Brain Injury?

Cooling the body may reduce brain injury for people in a coma after being revived from cardiac arrest, according to a guideline published online ahead of print May 10 in Neurology. Researchers reviewed evidence from studies of methods to reduce brain injury in people who are comatose after resuscitation from cardiac arrest. The guideline found that for patients who are treated with electric shocks to the heart after out-of-hospital cardiac arrest and who are in a coma, cooling the body to 89.6 to 93.2 °F for 24 hours effectively improves the chance of recovering brain function. The authors also found that keeping the body cooled to 96.8 °F for 24 hours, followed by rewarming to 99.5 °F over eight hours, effectively reduces brain injury after cardiac arrest.

Geocadin RG, Wijdicks E, Armstrong MJ, et al. Practice guideline summary: reducing brain injury following cardiopulmonary resuscitation: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 May 10 [Epub ahead of print].

Granger Causality Analysis Can Localize Ictal Networks

Granger causality analysis has the potential to help localize ictal networks from interictal data, according to a study published online ahead of print May 2 in Neurosurgery. For this study, 20-minute interictal baselines were obtained from 25 patients with hard-to-treat epilepsy who previously had had long-term EEG monitoring. The Granger causality maps were quantitatively compared with conventionally constructed surgical plans by using rank order and Cartesian distance statistics. In 16 of 25 participants, the interictal Granger causality rankings of the electrodes in the ictally active electrode set were lower than predicted by chance. The Granger causality maps thus likely correlated with ictal networks. The distance from the highest Granger causality electrode to the ictally active electrode set and to the resection averaged 6 and 4 mm, respectively.

Park EH, Madsen JR. Granger causality analysis of interictal iEEG predicts seizure focus and ultimate resection. Neurosurgery. 2017 May 2 [Epub ahead of print].

Tourette Disorder Risk Genes Identified

Researchers have identified the first risk gene for Tourette disorder and three other probable risk genes, according to a study published May 3 in Neuron. Researchers analyzed genomic data from 311 trios of children with Tourette disorder and their parents. Data were collected by the Tourette International Collaborative Genetics group. The authors found strong evidence that variants of WWC1 can play a significant role in triggering the disorder. Investigators conducted a replication study in 173 trios and found the same results. Extrapolating from the number of de novo variants, investigators estimated that approximately 12% of Tourette disorder cases are likely to involve de novo variants. The genes CELSR3, NIPBL, and FN1 were identified as having at least 70% probability of contributing to Tourette disorder.

Willsey AJ, Fernandez TV, Yu D, et al. De novo coding variants are strongly associated with Tourette disorder. Neuron. 2017;94(3):486-499.

Kimberly Williams

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