Neurology September 2012 Volume 79 Issue 12

Objective: To determine the association between silent ischemic lesions (SILs) on baseline brain MRI and recurrent stroke in young adults with first-ever ischemic stroke.Methods: This was a single-center retrospective study of adult patients aged 18-50 years with first-ever ischemic stroke investigated by brain MRI between 2002 and 2009. Silent brain infarcts (SBIs) were defined as focal T2 hyperintensities >=3 mm without corresponding focal symptoms, and leukoaraiosis was defined as focal, multifocal, or confluent hyperintensities on T2-weighted sequences. The primary outcome was recurrent stroke. A forward stepwise Cox regression model was used to determine whether SILs were independently associated with recurrent stroke.Results: A total of 271 eligible patients were identified in the database: 89 did not undergo MRI imaging and 12 patients had inadequate follow-up, leaving a study population of 170 patients. MRI demonstrated SILs in 48 of 170 (28.2) patients. No patients had isolated leukoaraiosis. Hypertension (p = 0.049), migraine with aura (p = 0.02), and cardiovascular disease (p = 0.04) were associated with SIL. Mean follow-up duration was 25 +/- 7 months. Among patients with SILs, 11 of 48 (23%) had a recurrent stroke vs 8 of 122 (6.5%) patients without SIL (p = 0.003). After multivariate Cox regression, SILs remained independently associated with recurrent stroke (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.2-8.6, p = 0.02), as did the combination of SBIs and leukoaraiosis (HR 7.3, 95% CI 2.3-22.9, p = 0.003).Conclusions: In adults <=50 years old with first-ever ischemic stroke, SILs are common and independently predict recurrent stroke.GLOSSARY: ACS : acute coronary syndromeCI : confidence intervalFLAIR : fluid-attenuated inversion recoveryNIHSS : NIH Stroke ScaleSBI : silent brain infarctSIL : silent ischemic lesionTOAST : Trial of ORG 10172 in Acute Stroke Treatment(C)2012 American Academy of Neurology

Objective: To investigate the association between chocolate consumption and risk of stroke in men and conduct a meta-analysis to summarize available evidence from prospective studies of chocolate consumption and stroke.Methods: We prospectively followed 37,103 men in the Cohort of Swedish Men. Chocolate consumption was assessed at baseline using a food-frequency questionnaire. Cases of first stroke were ascertained from the Swedish Hospital Discharge Registry. For the meta-analysis, pertinent studies were identified by searching the PubMed and EMBASE databases through January 13, 2012. Study-specific results were combined using a random-effects model.Results: During 10.2 years of follow-up, we ascertained 1,995 incident stroke cases, including 1,511 cerebral infarctions, 321 hemorrhagic strokes, and 163 unspecified strokes. High chocolate consumption was associated with a lower risk of stroke. The multivariable relative risk of stroke comparing the highest quartile of chocolate consumption (median 62.9 g/week) with the lowest quartile (median 0 g/week) was 0.83 (95 % CI 0.70-0.99). The association did not differ by stroke subtypes. In a meta-analysis of 5 studies, with a total of 4,260 stroke cases, the overall relative risk of stroke for the highest vs lowest category of chocolate consumption was 0.81 (95% CI 0.73-0.90), without heterogeneity among studies (p = 0.47).Conclusion: These findings suggest that moderate chocolate consumption may lower the risk of stroke.GLOSSARY: BMI: body mass indexCI: confidence intervalICD-10: International Classification of Diseases, 10th revisionLDL: low-density lipoproteinMET: metabolic equivalent(C)2012 American Academy of Neurology

Objective: This study evaluated usage of the Army Knowledge Online (AKO) Telemedicine Consultation Program for neurology and traumatic brain injury (TBI) cases in remote overseas areas with limited access to subspecialists. We performed a descriptive analysis of quantity of consults, response times, sites where consults originated, military branches that benefitted, anatomic locations of problems, and diagnoses.Methods: This was a retrospective analysis that searched electronic databases for neurology consults from October 2006 to December 2010 and TBI consults from March 2008 to December 2010.Results: A total of 508 consults were received for neurology, and 131 consults involved TBI. For the most part, quantity of consults increased over the years. Meanwhile, response times decreased, with a mean response time of 8 hours, 14 minutes for neurology consults and 2 hours, 44 minutes for TBI consults. Most neurology consults originated in Iraq (67.59%) followed by Afghanistan (16.84%), whereas TBI consults mainly originated from Afghanistan (40.87%) followed by Iraq (33.91%). The most common consultant diagnoses were headaches, including migraines (52.1%), for neurology cases and mild TBI/concussion (52.3%) for TBI cases. In the majority of cases, consultants recommended in-theater management. After receipt of consultant's recommendation, 84 known neurology evacuations were facilitated, and 3 known neurology evacuations were prevented.Conclusions: E-mail-based neurology and TBI subspecialty teleconsultation is a viable method for overseas providers in remote locations to receive expert recommendations for a range of neurologic conditions. These recommendations can facilitate medically necessary patient evacuations or prevent evacuations for which on-site care is preferable.GLOSSARY: AKO: Army Knowledge OnlineIED: improvised explosive devicePTSD: posttraumatic stress disorderTBI: traumatic brain injury.(C)2012 American Academy of Neurology

Objective: To develop and validate a measure of antiepileptic drug (AED) side effects in children with a variety of seizure types, treatments, and therapy durations.Methods: Content for an initial 44-item measure was developed using the previously published Hague Scale and expert opinion from recognized pediatric epileptologists (n = 12) and caregivers of children with epilepsy (n = 21). The measure was completed by caregivers during routine clinic visits. Demographic and medical data were collected through chart reviews. Factor analysis was conducted and internal consistency, test-retest reliability, and construct validity were assessed.Results: Questionnaires were analyzed from 495 children with epilepsy (Mage = 10.1 years; range 2-21 years; 42% female; 14% African American; 32% new onset vs 68% chronic epilepsy). The final questionnaire, the Pediatric Epilepsy Side Effects Questionnaire (PESQ), is a 19-item measure with 5 subscales (i.e., cognitive, motor, behavioral, general neurological, and weight) that accounts for 99% of the variance. Internal consistency coefficients and test-retest reliabilities ranged from 0.72 to 0.93 and 0.74 to 0.97, respectively. Construct validity was demonstrated by increasing side effects as the number of drugs increased. Participants on valproic acid had significantly higher scores on the Weight Scale compared to those on carbamazepine.Conclusions: The PESQ is a reliable and valid measure of AED side effects in children across the epilepsy spectrum that can be used in both clinical and research settings.GLOSSARY: AED : antiepileptic drugCBZ : carbamazepineICC : intraclass correlation coefficientsIRB : Institutional Review BoardMCID : minimal clinically important differencePESQ : Pediatric Epilepsy Side Effects QuestionnaireVPA : valproate(C)2012 American Academy of Neurology

Objectives: Patients surviving retinopathy-positive cerebral malaria (CM) are at high risk for the development of epilepsy, developmental disabilities, and behavioral abnormalities. We aimed to establish whether retinopathy-negative CM is also a risk factor for these outcomes.Methods: Between 2005 and 2007, survivors of CM and concurrently hospitalized controls in Blantyre, Malawi, were followed to assess the development of neurologic abnormalities. At discharge and every 3 months thereafter, incident cases of epilepsy and developmental disabilities were ascertained using screening questionnaires and confirmatory neurologic examinations. Incident cases of epilepsy and developmental disabilities were compared in retinopathy-negative CM survivors to controls and retinopathy-positive CM survivors.Results: Thirty-five retinopathy-negative CM survivors were enrolled. Their neurologic outcomes were compared to 132 retinopathy-positive CM survivors and 272 controls. Compared to survivors of retinopathy-positive CM, children without malaria retinopathy have an equal odds of adverse neurologic outcome (odds ratio [OR] = 1.0, 95% confidence interval [CI] 0.4-2.2). Eleven of 35 survivors of retinopathy-negative CM had at least 1 adverse neurologic outcome compared to 2 of 272 controls (OR 61.9, 95% CI 13.0-295.5). In retinopathy-negative CM survivors, a Blantyre Coma Scale score <=1 on admission was associated with an adverse outcome.Conclusions: Compared with controls, children surviving either retinopathy-negative or -positive CM are at similar high risk for adverse neurologic outcomes. Studies to evaluate preventive and therapeutic strategies in children with both retinopathy-negative and -positive CM are needed to improve mortality, morbidity, or both.GLOSSARY: CI: confidence intervalCM: cerebral malariaOR: odds ratio(C)2012 American Academy of Neurology

Objective: To determine whether Ginkgo biloba extract (ginkgo) improves cognitive function in persons with multiple sclerosis (MS).Methods: Persons with MS from the Seattle and Portland VA clinics and adjacent communities who scored 1 SD or more below the mean on one of 4 neuropsychological tests (Stroop Test, California Verbal Learning Test II [CVLT-II], Controlled Oral Word Association Test [COWAT], and Paced Auditory Serial Addition Task [PASAT]) were randomly assigned to receive either one 120-mg tablet of ginkgo (EGb-761; Willmar Schwabe GmbH & Co, Germany) or one placebo tablet twice a day for 12 weeks. As the primary outcome, we compared the performance of the 2 groups on the 4 tests at exit after adjusting for baseline performance.Results: Fifty-nine subjects received placebo and 61 received ginkgo; 1 participant receiving placebo and 3 receiving ginkgo were lost to follow-up. Two serious adverse events (AEs) (myocardial infarction and severe depression) believed to be unrelated to the treatment occurred in the ginkgo group; otherwise, there were no significant differences in AEs. The differences (ginkgo - placebo) at exit in the z scores for the cognitive tests were as follows: PASAT -0.2 (95% confidence interval [CI] -0.5 to 0.1); Stroop Test -0.5 (95% CI -0.9 to -0.1); COWAT 0.0 (95% CI -0.2 to 0.3); and CVLT-II 0.0 (95% CI -0.3 to 0.3); none was statistically significant.Conclusions: Treatment with ginkgo 120 mg twice a day did not improve cognitive performance in persons with MS.Classification of evidence: This study provides Class I evidence that treatment with ginkgo 120 mg twice a day for 12 weeks does not improve cognitive performance in people with MS.GLOSSARY: AD: Alzheimer diseaseAE: adverse eventBDI-II: Beck Depression Inventory IICI: cognitive impairmentCOWAT: Controlled Word Association TestCVLT-II: California Verbal Learning Test IIEDSS: Expanded Disability Status ScaleMFIS: Modified Fatigue Impact ScaleMS: multiple sclerosisMSNSQ: Multiple Sclerosis Neuropsychological Screening QuestionnairePAF: platelet-activating factorPASAT: Paced Auditory Serial Addition TestPDQ: Perceived Deficits Questionnaire(C)2012 American Academy of Neurology

GLOSSARY: ALS: amyotrophic lateral sclerosisBMP: bone morphogenic proteinCMT: Charcot-Marie-ToothCMT2: Charcot-Marie-Tooth type IICOP: coat complexdHMN: distal hereditary motor neuronopathyER: endoplasmic reticulumERGIC: endoplasmic reticulum-Golgi complex intermediate compartmentESCRT: endosomal sorting complex required for transportGTPase: guanidine triphosphataseHAP: huntingtin-associated proteinHSAN: hereditary sensory and autonomic neuropathyHSP: hereditary spastic paraplegiaMFN2: mitofusin 2MVB: multivesicular bodyPI: phosphoinositideREEP: receptor-expression-enhancing proteinRTN: reticulonSNARE: soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptorTGN: trans-Golgi networkVAMP: vesicle associated membrane proteinVAPB: vesicle-associated membrane protein-associated protein B.(C)2012 American Academy of Neurology