Neurology December 2012 Volume 79 Issue 24

Objectives: Patients with idiopathic REM sleep behavior disorder (IRBD) are at risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB). We aimed to identify functional brain imaging patterns predicting the emergence of PD and DLB in patients with IRBD, using SPECT with 99mTc-ethylene cysteinate dimer (ECD).Methods: Twenty patients with IRBD were scanned at baseline during wakefulness using 99mTc-ECD SPECT. After a follow-up of 3 years on average, patients were divided into 2 groups according to whether or not they developed defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing regional cerebral blood flow (rCBF) between groups assessed whether specific brain perfusion patterns were associated with subsequent clinical evolution. Regression analysis between rCBF and clinical markers of neurodegeneration (motor, color vision, olfaction) looked for neural structures involved in this process.Results: Of the 20 patients with IRBD recruited for this study, 10 converted to PD or DLB during the follow-up. rCBF at baseline was increased in the hippocampus of patients who would later convert compared with those who would not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and color vision scores across all IRBD patients.Conclusions: 99mTc-ECD SPECT identifies patients with IRBD at risk for conversion to other neurodegenerative disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal perfusion in the hippocampus at baseline. Perfusion within this structure is correlated with clinical markers of neurodegeneration, further suggesting its involvement in the development of presumed synucleinopathies.(C)2012 American Academy of Neurology

Objective: Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 (ATXN-2) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 (ATXN-1) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy.Methods: We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders.Results: We found significantly higher intermediate PolyQ expansions >=32 for ATXN-1 alleles and >=28 for ATXN-2 alleles in the sALS cohort (ATXN-1: ALS, 7.07% vs controls, 2.38%; p = 0.0001; ATXN-2: ALS, 2.72% vs controls, 0.5%; p = 0.001). ATXN-1 CAT and ATXN-2 CAA interruptions were detected in patients with ALS only. Age at onset, site of onset, and sex were not significantly related to the ATXN-1 or ATXN-2 PolyQ repeat length expansions.Conclusions: Both ATXN-1 and ATXN-2 PolyQ intermediate expansions are independently associated with an increased risk for ALS.(C)2012 American Academy of Neurology

Objective: Brain changes occurring early in HIV infection are not well characterized. The Chicago Early HIV Infection Study aimed to evaluate the presence and extent of structural brain alterations using quantitative MRI.Methods: Forty-three HIV and 21 control subjects were enrolled. Mean length of infection was estimated as less than 1 year based on assay results. High-resolution neuroanatomical images were acquired. Automated image analysis was used to derive measurements for total brain, ventricular volume, and for tissue classes (total and cortical gray matter, white matter, and CSF). A separate image analysis algorithm was used to calculate measurements for individual brain regions. Cognitive function was assessed by neuropsychological evaluation.Results: Reductions were quantified in total (p = 0.0547) and cortical (p = 0.0109) gray matter in the HIV group. Analysis of individual brain regions with a separate image analysis algorithm revealed consistent findings of reductions in cerebral cortex (p = 0.042) and expansion of third ventricle (p = 0.046). The early HIV group also demonstrated weaker performance on several neuropsychological tests, with the most pronounced difference in psychomotor speed (p = 0.001).Conclusions: This cross-sectional brain volumetric study indicates structural alterations early in HIV infection. The findings challenge the prevailing assumption that the brain is spared in this period. Revisiting the question of the brain's vulnerability to processes unfolding in the initial virus-host interaction and the early natural history may yield new insights into neurologic injury in HIV infection and inform neuroprotection strategies.(C)2012 American Academy of Neurology

Objective: We hypothesized that cryptogenic forms of arterial ischemic stroke (AIS) in children may present better outcomes than symptomatic ones.Methods: We conducted a single-centered retrospective cohort study using chart reviews of all inpatients aged 0.25-16 years and admitted for AIS or TIA between 1994 and 2007. Sixty-three consecutive children with AIS were divided into 2 stroke categories: first, AIS with an established cause, considered as symptomatic (S), and second, AIS only associated with risk factors, and considered as cryptogenic (C). AIS were further subclassified according to the CASCADE stroke classification system. We measured long-term outcome with 2 endpoints: recurrence rate and neurologic impairment score (NIS). We used univariate analysis to compare the clinical and radiologic characteristics of both groups.Results: AIS were cryptogenic in 28 patients (44%) and symptomatic in 35 (56%). Compared to patients in group S, patients in group C showed an absence of stroke recurrence under prolonged aspirin treatment (0% vs 30.3%; p < 0.01), a predominance of nonprogressive arteriopathies (p = 0.02), unilateral infarcts (p = 0.01), M1 segment stenosis (p = 0.02), and better stroke outcomes (mean NIS 2.7 vs 4.2; p = 0.04). Within group C, patients with post-varicella arteriopathy (PVA) had a profile comparable to that of patients with non-PVA strokes in terms of infarct topography, localization of vascular lesions, recurrence rate, and neurologic outcome.Conclusion: Cryptogenic AIS during childhood is a homogeneous clinical and radiologic entity, likely reflecting similar underlying pathophysiologic mechanisms. Under early and prolonged treatment with aspirin, cryptogenic AIS does not recur.(C)2012 American Academy of Neurology

Objective: To evaluate the natural history and outcome predictors in familial mesial temporal lobe epilepsy (FMTLE).Methods: We conducted a longitudinal study of 103 individuals from 17 FMTLE families (mean follow-up: 7.6 years). We divided subjects into 3 groups: FMTLE (n = 53), unclassified seizure (n = 18), and asymptomatics (n = 32). We divided FMTLE patients into 3 subgroups: seizure-free (n = 19), infrequent (n = 17) seizures, and frequent (n = 17) seizures and further reclassified them into favorable and poor outcome. We defined hippocampal atrophy (HA) by visual MRI analysis and performed volumetry in those who had 2 MRIs.Results: FMTLE patients with infrequent seizures evolved to either frequent seizures (17.6%) or seizure freedom (23.5%). In the seizure-free group, most remained seizure-free and 21% developed infrequent seizures. All patients with frequent seizures remained in the same status or underwent surgery. Twelve percent of the asymptomatics and 22% of the unclassified-seizure group evolved to FMTLE with infrequent seizures. Predictive factors of poor outcome were presence of HA (p = 0.0192) and interictal epileptiform discharges (p = 0.0174). The relationship between initial precipitating incidents and clinical outcome was not significant although a tendency was observed (p = 0.055). Use of antiepileptic drugs and secondary generalized seizures during the patient's lifetime did not predict poor outcome. We observed progression of HA only in the group with frequent seizures.Conclusion: Most patients with FMTLE continued in the same clinical status. However, patients with frequent seizures had progression of HA and none improved except those who underwent surgery. Interictal epileptiform discharges and HA predicted poorer outcome in FMTLE, and there was a tendency in favor of initial precipitating incidents as outcome predictors.(C)2012 American Academy of Neurology