Neurology June 2012 Volume 78 Issue 23

Objective: To characterize saccadic eye movements, as a marker of decision-making processes, in frontotemporal dementia (FTD).Methods: Saccadometry was performed on a cross-section of patients with FTD, using a portable saccadometer, and results compared to matched control subjects. We used the Linear Approach to Threshold with Ergodic Rate model to generate measures of decision-making speed and incidence of early saccades. Patterns of cortical atrophy were related to decision-making processes using voxel-based morphometry (VBM) analysis.Results: A total of 45 subjects (22 FTD: 10 with behavioral variant FTD and 12 with primary progressive aphasia, and 23 controls) were studied. A measure of decision-making speed, [mu], was reduced in FTD, resulting in prolonged saccadic latency, but the incidence of early saccades was increased compared to controls. In addition, performance on an antisaccade task was poor in FTD compared to controls. Decision-making speed and the incidence of early saccades were independently correlated with atrophy of the left frontal eye field, and decision-making speed also correlated with atrophy of the left cingulate eye field.Conclusion: Saccades are abnormal in FTD, reflecting reduced decision-making speed, and these abnormalities related to atrophy of the left frontal eye field. In addition, patients with FTD had an increased incidence of early saccades, which may be due to reduced inhibition of primitive responses.GLOSSARY: ALS: amyotrophic lateral sclerosisbvFTD: behavioral variant frontotemporal dementiaCEF: cingulate eye fieldFEF: frontal eye fieldFTD: frontotemporal dementiaLATER: Linear Approach to Threshold with Ergodic RateMNI: Montreal Neurological InstitutePNFA: progressive nonfluent aphasiaPPA: primary progressive aphasiaSemD: semantic dementiaVBM: voxel-based morphometry(C)2012 American Academy of Neurology

Objective: The widely reported associations between various nutrients and cognition may occur through many biologic pathways including those of [beta]-amyloid (A[beta]). However, little is known about the possible associations of dietary factors with plasma A[beta]40 or A[beta]42. The aim of the current study was to evaluate the association between nutrient intake and plasma A[beta] levels.Methods: In this cross-sectional study, plasma A[beta]40 and A[beta]42 and dietary data were obtained from 1,219 cognitively healthy elderly (age >65 years), who were participants in a community-based multiethnic cohort. Information on dietary intake was obtained 1.2 years, on average, before A[beta] assay. The associations of plasma A[beta]40 and A[beta]42 levels and dietary intake of 10 nutrients were examined using linear regression models, adjusted for age, gender, ethnicity, education, caloric intake, apolipoprotein E genotype, and recruitment wave. Nutrients examined included saturated fatty acid, monounsaturated fatty acid, [omega]-3 polyunsaturated fatty acid (PUFA), [omega]-6 PUFA, vitamin E, vitamin C, [beta]-carotene, vitamin B12, folate, and vitamin D.Results: In unadjusted models that simultaneously included all nutrients, higher intake of [omega]-3 PUFA was associated with lower levels of A[beta]40 ([beta] = -24.7, p < 0.001) and lower levels of A[beta]42 ([beta] = -12.3, p < 0.001). In adjusted models, [omega]-3 PUFA remained a strong predictor of A[beta]42 ([beta] = -7.31, p = 0.02), whereas its association with A[beta]40 was attenuated ([beta] = -11.96, p = 0.06). Other nutrients were not associated with plasma A[beta] levels.Conclusions: Our data suggest that higher dietary intake of [omega]-3 PUFA is associated with lower plasma levels of A[beta]42, a profile linked with reduced risk of incident AD and slower cognitive decline in our cohort.GLOSSARY: A[beta]: [beta]-amyloidAD: Alzheimer diseaseDHA: docosahexaenoic acidMCI: mild cognitive impairmentMUFA: monounsaturated fatty acidPUFA: polyunsaturated fatty acidSFA: saturated fatty acidSFFQ: semiquantitative food frequency questionnaireWHICAP: Washington Heights/Hamilton Heights Columbia Aging Project(C)2012 American Academy of Neurology

Background: In this feasibility study, we tested whether prehospital diagnostic stroke workup enables rational decision-making regarding treatment and the target hospital in persons with suspected stroke.Methods: A mobile stroke unit that delivers imaging (including multimodal brain imaging with CT angiography and CT perfusion), point-of-care-laboratory analysis, and neurologic expertise directly at the emergency site was analyzed for its use in prehospital diagnosis-based triage of suspected stroke patients.Results: We present 4 complementary cases with suspected stroke who underwent prehospital diagnostic workup that enabled direct diagnosis-based treatment decisions and reliable triage regarding the most appropriate medical facility for that individual, e.g., a primary hospital vs specialized centers of a tertiary hospital.Conclusions: This preliminary report demonstrates the feasibility of prehospital diagnostic stroke workup for immediate etiology-specific decision-making regarding the necessary time-sensitive stroke treatment and the most appropriate target hospital.GLOSSARY: MSU: mobile stroke unitNIHSS: NIH Stroke Scale(C)2012 American Academy of Neurology

Objective: To address the need for brief, reliable, valid, and standardized quality of life (QOL) assessment applicable across neurologic conditions.Methods: Drawing from larger calibrated item banks, we developed short measures (8-9 items each) of 13 different QOL domains across physical, mental, and social health and evaluated their validity and reliability. Three samples were utilized during short form development: general population (Internet-based, n = 2,113); clinical panel (Internet-based, n = 553); and clinical outpatient (clinic-based, n = 581). All short forms are expressed as T scores with a mean of 50 and SD of 10.Results: Internal consistency (Cronbach [alpha]) of the 13 short forms ranged from 0.85 to 0.97. Correlations between short form and full-length item bank scores ranged from 0.88 to 0.99 (0.82-0.96 after removing common items from banks). Online respondents were asked whether they had any of 19 different chronic health conditions, and whether or not those reported conditions interfered with ability to function normally. All short forms, across physical, mental, and social health, were able to separate people who reported no health condition from those who reported 1-2 or 3 or more. In addition, scores on all 13 domains were worse for people who acknowledged being limited by the health conditions they reported, compared to those who reported conditions but were not limited by them.Conclusion: These 13 brief measures of self-reported QOL are reliable and show preliminary evidence of concurrent validity inasmuch as they differentiate people based upon number of reported health conditions and whether those reported conditions impede normal function.GLOSSARY: ALS: amyotrophic lateral sclerosisCAT: computerized adaptive testIRT: item response theoryMS: multiple sclerosisNINDS: National Institute of Neurologic Disorders and StrokePD: Parkinson diseaseQOL: quality of life.(C)2012 American Academy of Neurology

Objective: To evaluate teriflunomide as add-on therapy to ongoing stable-dosed interferon-[beta] (IFN[beta]) in patients with relapsing forms of multiple sclerosis (RMS).Methods: A total of 118 patients with RMS were randomly assigned 1:1:1 to receive oral placebo or teriflunomide, 7 or 14 mg, once daily for 24 weeks; 86 patients entered the 24-week extension. The primary objective was to evaluate safety; secondary objectives were to evaluate the effects of treatment on disease activity assessed by MRI and relapse rate.Results: Teriflunomide was well tolerated with a low and similar incidence of treatment-emergent adverse events (TEAEs) across the 3 groups; TEAEs led to treatment discontinuation of 4.9%, 8.1%, and 7.9% of patients in the placebo, 7-mg, and 14-mg groups, respectively. The number of gadolinium-enhancing T1 (T1-Gd) lesions was reduced in both teriflunomide groups, with relative risk reductions (RRRs) of 84.6% (p = 0.0005) and 82.8% (p < 0.0001) for 7 and 14 mg, respectively, compared with IFN[beta] alone at 48 weeks. T1-Gd lesion volume was also reduced in the 7-mg group (RRR 72.1%, p = 0.1104) and 14-mg group (RRR 70.6%, p = 0.0154). A trend toward dose-dependent reduction in annualized relapse rate was also noted (RRRs 32.6% [p = 0.4355] and 57.9% [p = 0.1005] for 7 and 14 mg, respectively).Conclusion: Teriflunomide as add-on therapy to IFN[beta] had acceptable safety and tolerability and reduced MRI disease activity compared with IFN[beta] alone.Classification of evidence: This study provides Class II evidence that teriflunomide, 7 and 14 mg, added to IFN[beta], is safe. The T1-Gd lesion burden was significantly reduced with both teriflunomide doses.GLOSSARY: AE: adverse eventALT: alanine aminotransferaseARR: annualized relapse rateDMT: disease-modifying therapyEDSS: Expanded Disability Status ScaleIFN[beta]: interferon-[beta]MS: multiple sclerosisNAb: neutralizing antibodyPML: progressive multifocal leukoencephalopathyRMS: relapsing multiple sclerosisRRR: relative risk reductionTEAE: treatment-emergent adverse eventTEMSO: Teriflunomide Multiple Sclerosis OralT1-Gd: gadolinium-enhancing T1ULN: upper limit of normal(C)2012 American Academy of Neurology

Objective: Spinal muscular atrophy (SMA) is a group of progressive and fatal neurodegenerative disorders that are characterized by destruction of the anterior horn cells of the spinal cord. In this case report we outline the medical and ethical issues involved in a 7-year-old boy with SMA type 2 who experienced acute respiratory failure.Methods: A review of the literature was conducted focusing particularly on the pathology, presentation, and outcomes of SMA and end-of-life decision-making in pediatrics.Results: In a world where 40%-60% of deaths in pediatric intensive care units are a result of withdrawal or limitation of life-sustaining treatment, end-of-life decision-making has become an integral and difficult part of pediatric practice.Conclusion: Limitation or withdrawal of life-sustaining treatment in a cognitively normal child with SMA poses a significant medical and ethical dilemma. This difficult decision is influenced by confluence of parental, doctor, social, cultural, moral, religious, legal, and economic factors and more recently the media.GLOSSARY: SMA: spinal muscular atrophy(C)2012 American Academy of Neurology