Neurology June 2009 Volume 72 Issue 23

Objective: We assessed the hypotheses that non-major histocompatibility complex multiple sclerosis (MS) susceptibility loci would be common to sporadic cases and multiplex families, that they would have larger effects in multiplex families, and that the aggregation of susceptibility loci contributes to the increased prevalence of MS in such families.Methods: A set of 43 multiplex families comprising 732 individuals and 211 affected subjects was genotyped for 13 MS candidate genes identified by genome-wide association. A control data set of 182 healthy individuals was also genotyped to perform a case-control analysis alongside the family-based pedigree disequilibrium association test, although this may have been underpowered.Results: An effect of the IL2RA and CD58 loci was shown in multiplex families as in sporadic MS. The aggregate of the IL2RA, IL7R, EVI5, KIAA0350, and CD58 risk genotypes in affected individuals from multiplex families was found to be notably different from controls ([chi]2 = 112, p = 1 x 10-22).Conclusions: Although differences between individual families can only be suggested, the aggregate results in multiplex families demonstrate effect sizes that are increased as compared with those reported in previous studies for sporadic cases. In addition, they imply that concentrations of susceptibility alleles at IL2RA, IL7R, EVI5, KIAA0350, and CD58 are partly responsible for the heightened prevalence of multiple sclerosis within multiplex families.(C)2009AAN Enterprises, Inc.

Background: With respect to sporadic Creutzfeldt-Jakob disease (sCJD), six molecular subtypes (MM1, MM2, MV1, MV2, VV1, and VV2) have been described, which vary with respect to age at disease onset, disease duration, early symptoms, and neuropathology. MRI signal alterations were reported to correlate with distinct Creutzfeldt-Jakob disease (CJD) subtypes. This multicenter, international study aimed to describe the brain MRI findings associated with each of the sCJD molecular subtypes.Methods: Pathologically confirmed sCJD cases with codon 129 genotype (MM, MV, and VV), PrPSc type, and fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted imaging (DWI) were collected in seven countries. All MRI scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus, and cerebellum.Results: MRI scans were evaluated in 211 CJD patients (98 MM1, 23 MM2, 19 MV1, 30 MV2, 9 VV1, and 32 VV2). Basal ganglia hyperintensities occurred most frequently in MV2, VV2, and MM1 subtypes (79, 77, and 70%). Wide cerebral cortical signal increase was most common in VV1, MM2, and MV1 subtypes (86, 77, and 77%). Thalamic hyperintensities occurred most often in VV2 (45%) and MV2 (43%). The most consistent finding across most subtypes was high signal in basal ganglia, with these abnormalities found in 63% (FLAIR) and 71% (DWI).Conclusion: Cortical signal increase and hyperintensities in the basal ganglia and thalamus are detected by MRI across all molecular sporadic Creutzfeldt-Jakob disease subtypes. Our findings argue that characteristic MRI lesion patterns may occur for each molecular subtype.(C)2009AAN Enterprises, Inc.

Background: Unsteadiness during standing and walking is a frequent complaint of patients with polyneuropathy (PNP).Objective: To determine whether balance disorders in patients with PNP may be caused by reduced proprioceptive input from the feet alone or whether impaired vestibular input, resulting from involvement of the vestibular nerve, can be an additional factor.Methods: A total of 37 patients (mean age 65 years +/- 12 SD; 12 women) with electrodiagnostically confirmed PNP (predominantly axonal: 18; predominantly demyelinating: 19) underwent horizontal search-coil head-impulse testing, which assesses the high-acceleration vestibulo-ocular reflex (VOR).Results: Relative to a healthy comparison group, the gains (eye velocity divided by head velocity) of the horizontal VOR were reduced in 27 of 37 patients (unilateral: 13; bilateral: 14). The percentages of patients with unilateral or bilateral VOR deficits were not significantly different between patients with axonal or demyelinating PNP.Conclusions: Two thirds of patients with axonal or demyelinating polyneuropathy (PNP) showed unilateral (~50%) or bilateral (~50%) gain reductions of the horizontal high-acceleration vestibulo-ocular reflex. This finding suggests that, in many patients with PNP, the neuropathic process includes the vestibular nerve. Such information is highly relevant for subsequent physical therapy, since vestibular exercise improves balance control and reduces disability.(C)2009AAN Enterprises, Inc.

Background: Graduating medical students often identify the neurologic examination (NE) as one of the clinical skills with which they are least comfortable. We hypothesized that this is because they are unsure about which elements of the NE are important, and conducted a study 1) to identify whether neurologists agree about the essential elements of the NE and 2) to determine whether the views of medical students about what is essential differ from those of neurologists.Methods: Using a Delphi process, we asked McGill University neurologists which elements of the NE they would perform at least 80% of the time in a common clinical scenario. We confirmed the results in a sample of Canadian neurologists, and then compared the results of the McGill neurologists to a sample of graduating McGill University medical students.Results: The neurologists surveyed rated 22 items of the NE as essential, and there was a high degree of consensus about which items were essential. Medical student ratings of the importance of NE items were largely similar to those of the neurologists, although there were some noteworthy discrepancies.Conclusions: The anxiety felt by medical students regarding the neurologic examination (NE) seems unlikely to be solely due to uncertainty about which elements of the NE are important. Expert consensus about the essential elements of the NE and awareness of areas where neurologist and student views differ should be used to guide teaching of the NE.(C)2009AAN Enterprises, Inc.

Background: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age.Methods: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope >=0), minor decliners (slope <0 and >1 SD below mean), or major decliners (slope <=1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner.Results: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55-0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30-2.28), high school education level or greater (OR = 2.75, 95% CI 1.78-4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00-7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06-1.62), and not smoking (OR = 1.84, 95% CI 1.14-2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported.Conclusion: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies.(C)2009AAN Enterprises, Inc.