Neurology September 2009 Volume 73 Issue 11

Background: It is unclear which factors lead to progressive neuronal damage in mesial temporal lobe epilepsy (MTLE). The objective of this study was to evaluate whether progressive hippocampal and extrahippocampal atrophy occur in patients with MTLE and whether this atrophy is related to seizures.Method: We performed 2 MRI scans in 33 patients with clinical and electroencephalographic diagnosis of MTLE and in 24 healthy controls. MRI was performed in a 2-T scanner, and a T1-weighted gradient-echo sequence with 1 mm thickness was used for voxel-based morphometry analysis. Follow-up images were obtained at least 7 months after the first baseline MRI. Comparisons between the patient's follow-up and baseline MRIs, and between patients and controls, were performed. A corrected p value of 0.05 was set as the threshold for the statistical analysis.Results: Follow-up MRI was performed after a median interval of 39 months (range 7-85 months). Three patients were seizure-free between the first and second MRIs. We observed progressive white and gray matter atrophy (p < 0.05) in patients with MTLE. This progression was more intense in patients with left MTLE compared with right MTLE. A higher frequency of seizures and a longer duration of epilepsy were associated with progression of gray and white matter atrophy in patients with MTLE.Conclusion: The progression of white and gray matter atrophy in patients with mesial temporal lobe epilepsy (MTLE) was more intense in patients with left MTLE and was associated with poorer seizure control and a longer duration of epilepsy.(C)2009AAN Enterprises, Inc.

Objective: Several lines of evidence indicate that a decrease in the CSF concentration of amyloid [beta]42 (A[beta]42) is a potential biomarker for incident Alzheimer disease. In contrast, studies on plasma A[beta]1-40 and A[beta]1-42 peptide levels have yielded contradictory results. Here, we explored the links between incident dementia and plasma A[beta]1-40 and A[beta]1-42 peptide concentrations in the prospective, population-based Three-City (3C) Study. We also assessed the association between plasma concentrations of truncated A[beta] (A[beta]n-40 and A[beta]n-42) and the risk of dementia.Methods: During a subsequent 4-year follow-up period, 257 individuals presented incident dementia from 8,414 participants, and a subcohort of 1,185 individuals without dementia was drawn as a control cohort. Plasma levels of A[beta]1-40, A[beta]1-42, A[beta]n-40, and A[beta]n-42 were measured using an xMAP-based assay technology. The association between plasma A[beta] peptide levels and the risk of dementia was assessed using Cox proportional hazard models.Results: Of the various A[beta] variables analyzed, the A[beta]1-42/A[beta]1-40 and A[beta]n-42/A[beta]n-40 ratios presented the strongest association with the risk of dementia: people with a high A[beta]1-42/A[beta]1-40 or A[beta]n-42/A[beta]n-40 ratio had a lower risk of developing dementia. These associations were restricted to individuals diagnosed at 2 years of follow-up and the A[beta]n-42/A[beta]n-40 ratio was mainly associated with the risk of mixed/vascular dementia.Conclusion: Plasma A[beta] peptide concentrations and A[beta]1-42/A[beta]1-40 and A[beta]n-42/A[beta]n-40 ratios may be useful markers to indicate individuals susceptible to short-term risk of dementia.(C)2009AAN Enterprises, Inc.

Background: Because retinal and cerebral arterioles share similar pathologic processes, retinal microvascular changes are expected to be markers of cerebral small vessel disease (SVD). To better understand the role of SVD in cognitive function, we investigated the relationship between retinal microvascular abnormalities and longitudinal changes in cognitive function in a community-based study.Methods: A total of 803 participants underwent 4 cognitive assessments between 1990-1992 and 2004-2006, using the Word Fluency (WF) test, Digit Symbol Substitution (DSS), and Delayed Word Recall as well as retinal photography in 1993-1995. Covariate adjusted random effects linear models for repeated measures were used to determine the associations of cognitive change with specific retinal vascular abnormalities.Results: Individuals with retinopathy showed declines in executive function and psychomotor speed, with 1) an average decline in WF of -1.64 words per decade (95% confidence interval [CI] -3.3, -0.02) compared to no decline in those without retinopathy +0.06 (95% CI -0.6, 0.8) and 2) a higher frequency of rapid decliners on the DSS test.Conclusion: Signs of retinal vascular changes, as markers of the cerebral microvasculature, are associated with declines in executive function and psychomotor speed, adding to the growing evidence for the role of microvascular disease in cognitive decline in the elderly.(C)2009AAN Enterprises, Inc.

Background: Drug users who crush, dissolve, and inject buprenorphine tablets parenterally may be at risk of severe thromboembolic complications or death. We describe patients with neurologic complications after injecting buprenorphine tablets.Methods: Brain MRI including diffusion-weighted imaging (DWI) in patients admitted to the neurologic department after injecting buprenorphine tablets were reviewed.Results: Seven men had neurologic complications after buprenorphine tablet injection. In 5 patients, multiple small scattered hyperintense lesions were detected on DWI in the cortex, white matter, and basal ganglia of the cerebral hemisphere; one patient had a single small lesion. The side of MRI abnormality corresponded to the side of needle marks on the neck except in one patient who had bilateral injections. One patient, who denied injecting into the neck, had DWI abnormalities in the middle cerebral artery territory on one side and occlusion of the ipsilateral internal carotid artery.Conclusions: Buprenorphine tablets can be intentionally or inadvertently injected into the carotid artery, causing a characteristic appearance on diffusion-weighted imaging, consistent with embolic cerebral infarction.(C)2009AAN Enterprises, Inc.

Objective: To make evidence-based recommendations concerning the evaluation of the child with microcephaly.Methods: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a 4-tiered scheme of evidence classification.Results: Microcephaly is an important neurologic sign but there is nonuniformity in its definition and evaluation. Microcephaly may result from any insult that disturbs early brain growth and can be seen in association with hundreds of genetic syndromes. Annually, approximately 25,000 infants in the United States will be diagnosed with microcephaly (head circumference <-2 SD). Few data are available to inform evidence-based recommendations regarding diagnostic testing. The yield of neuroimaging ranges from 43% to 80%. Genetic etiologies have been reported in 15.5% to 53.3%. The prevalence of metabolic disorders is unknown but is estimated to be 1%. Children with severe microcephaly (head circumference <-3 SD) are more likely (~80%) to have imaging abnormalities and more severe developmental impairments than those with milder microcephaly (-2 to -3 SD; ~40%). Coexistent conditions include epilepsy (~40%), cerebral palsy (~20%), mental retardation (~50%), and ophthalmologic disorders (~20% to ~50%).Recommendations: Neuroimaging may be considered useful in identifying structural causes in the evaluation of the child with microcephaly (Level C). Targeted and specific genetic testing may be considered in the evaluation of the child with microcephaly who has clinical or imaging abnormalities that suggest a specific diagnosis or who shows no evidence of an acquired or environmental etiology (Level C). Screening for coexistent conditions such as cerebral palsy, epilepsy, and sensory deficits may also be considered (Level C). Further study is needed regarding the yield of diagnostic testing in children with microcephaly.(C)2009AAN Enterprises, Inc.

Objective: The American Board of Psychiatry and Neurology (ABPN) has recently replaced the traditional, centralized oral examination with the locally administered Neurology Clinical Skills Examination (NEX). The ABPN postulated the experience with the NEX would be similar to the Mini-Clinical Evaluation Exercise, a reliable and valid assessment tool. The reliability and validity of the NEX has not been established.Methods: NEX encounters were videotaped at 4 neurology programs. Local faculty and ABPN examiners graded the encounters using 2 different evaluation forms: an ABPN form and one with a contracted rating scale. Some NEX encounters were purposely failed by residents. Cohen's kappa and intraclass correlation coefficients (ICC) were calculated for local vs ABPN examiners.Results: Ninety-eight videotaped NEX encounters of 32 residents were evaluated by 20 local faculty evaluators and 18 ABPN examiners. The interrater reliability for a determination of pass vs fail for each encounter was poor (kappa 0.32; 95% confidence interval [CI] = 0.11, 0.53). ICC between local faculty and ABPN examiners for each performance rating on the ABPN NEX form was poor to moderate (ICC range 0.14-0.44), and did not improve with the contracted rating form (ICC range 0.09-0.36). ABPN examiners were more likely than local examiners to fail residents.Conclusions: There is poor interrater reliability between local faculty and American Board of Psychiatry and Neurology examiners. A bias was detected for favorable assessment locally, which is concerning for the validity of the examination. Further study is needed to assess whether training can improve interrater reliability and offset bias.(C)2009AAN Enterprises, Inc.