Neurology January 2013 Volume 80 Issue 3

Objectives: To assess in a large population of patients with clinically isolated syndrome (CIS) the relevance of brain lesion location and frequency in predicting 1-year conversion to multiple sclerosis (MS).Methods: In this multicenter, retrospective study, clinical and MRI data at onset and clinical follow-up at 1 year were collected for 1,165 patients with CIS. On T2-weighted MRI, we generated lesion probability maps of white matter (WM) lesion location and frequency. Voxelwise analyses were performed with a nonparametric permutation-based approach (p < 0.05, cluster-corrected).Results: In CIS patients with hemispheric, multifocal, and brainstem/cerebellar onset, lesion probability map clusters were seen in clinically eloquent brain regions. Significant lesion clusters were not found in CIS patients with optic nerve and spinal cord onset. At 1 year, clinically definite MS developed in 26% of patients. The converting group, despite a greater baseline lesion load compared with the nonconverting group (7 +/- 8.1 cm3 vs 4.6 +/- 6.7 cm3, p < 0.001), showed less widespread lesion distribution (18% vs 25% of brain voxels occupied by lesions). High lesion frequency was found in the converting group in projection, association, and commissural WM tracts, with larger clusters being in the corpus callosum, corona radiata, and cingulum.Conclusions: Higher frequency of lesion occurrence in clinically eloquent WM tracts can characterize CIS subjects with different types of onset. The involvement of specific WM tracts, in particular those traversed by fibers involved in motor function and near the corpus callosum, seems to be associated with a higher risk of clinical conversion to MS in the short term.(C)2013 American Academy of Neurology

Objective: Presently there is no clinically feasible imaging modality that can effectively detect cortical demyelination in patients with multiple sclerosis (MS). The objective of this study is to determine if clinically feasible magnetization transfer ratio (MTR) imaging is sensitive to cortical demyelination in MS.Methods: MRI were acquired in situ on 7 recently deceased patients with MS using clinically feasible sequences at 3 T, including relatively high-resolution T1-weighted and proton density-weighted images with/without a magnetization transfer pulse for calculation of MTR. The brains were rapidly removed and placed in fixative. Multiple cortical regions from each brain were immunostained for myelin proteolipid protein and classified as mostly myelinated (MMctx), mostly demyelinated (MDctx), or intermediately demyelinated (IDctx). MRIs were registered with the cortical sections so that the cortex corresponding to each cortical section could be identified, along with adjacent subcortical white matter (WM). Mean cortical MTR normalized to mean WM MTR was calculated for each cortical region. Linear mixed-effects models were used to test if mean normalized cortical MTR was significantly lower in demyelinated cortex.Results: We found that mean normalized cortical MTR was significantly lower in cortical tissue with any demyelination (IDctx or MDctx) compared to MMctx (demyelinated cortex: least-squares mean [LSM] = 0.797, SE = 0.007; MMctx: LSM = 0.837, SE = 0.006; p = 0.01, n = 89).Conclusions: This result demonstrates that clinically feasible MTR imaging is sensitive to cortical demyelination and suggests that MTR will be a useful tool to help detect MS cortical lesions in living patients with MS.(C)2013 American Academy of Neurology

Objective: To investigate the clinical, genetic, and neuroradiologic data of biotin-responsive basal ganglia disease (BBGD) and clarify the disease spectrum.Methods: We first investigated all patients attending our Division of Pediatric Neurology with a genetically proven diagnosis of BBGD between 2009 and 2011. All patients underwent a detailed medical history and clinical examination, extensive laboratory investigations including genetic tests, and brain MRI. Finally, we conducted a systematic review of the literature.Results: We enrolled 10 patients meeting the diagnostic criteria for BBGD, and analyzed the data on 14 patients from 4 previous reports. The BBGD occurred predominantly in preschool/school-aged patients in the Saudi population, but it was also observed in other ethnic groups. The typical clinical picture consisted of recurrent subacute encephalopathy leading to coma, seizures, and extrapyramidal manifestations. The brain MRI typically showed symmetric and bilateral lesions in the caudate nucleus and putamen, infra- and supratentorial brain cortex, and in the brainstem. Vasogenic edema characterized the acute crises as demonstrated by diffusion-weighted imaging/apparent diffusion coefficient MRI. Atrophy and gliosis in the affected regions were observed in patients with chronic disease. Early treatment with a combination of biotin and thiamine resulted in clinical and neuroradiologic improvement. Death and neurologic sequelae including dystonia, mental retardation, and epilepsy were observed in those who were not treated or were treated late.Conclusion: BBGD is an underdiagnosed pan-ethnic treatable condition. Clinicians caring for patients with unexplained encephalopathy and neuroimaging showing vasogenic edema in the bilateral putamen and caudate nuclei, infra- and supratentorial cortex, and brainstem should consider this disorder early in the hospital course because a therapeutic trial with biotin and thiamine can be lifesaving.(C)2013 American Academy of Neurology

Objective: Nonmotor symptoms (NMS) are common in patients with established Parkinson disease (PD) but their frequency in early PD has not been extensively studied. Our aim was to determine the frequency of NMS in a cohort of patients with newly diagnosed PD.Methods: A total of 159 patients with early PD and 99 healthy controls participated in this study. NMS were screened for using the Nonmotor Symptom Questionnaire. Other assessments included measures of motor disability (Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale [MDS-UPDRS]), disease severity (Hoehn & Yahr staging), depression (Geriatric Depression Scale), and global cognitive function (Mini-Mental State Examination and Montreal Cognitive Assessment).Results: The PD group reported a significantly greater number of NMS compared with controls (8.4 [4.3] vs 2.8 [2.6]). In the PD group, the most commonly experienced NMS were excessive saliva, forgetfulness, urinary urgency, hyposmia, and constipation. Patients with higher MDS-UPDRS III scores and those with the postural instability gait subtype experienced a greater number of NMS.Conclusion: NMS are common in early PD and reflect the multisystem nature of the disorder. Even in the earliest stages of PD, NMS may be detrimental to patients' functional status and sense of well-being.(C)2013 American Academy of Neurology

Objective: Transverse sinus stenosis (TSS) is common in idiopathic intracranial hypertension (IIH), but its effect on the course and outcome of IIH is unknown. We evaluated differences in TSS characteristics between patients with IIH with "good" vs "poor" clinical courses.Methods: All patients with IIH seen in our institution after September 2009 who underwent a high-quality standardized brain magnetic resonance venogram (MRV) were included. Patients were categorized as having a good or poor clinical course based on medical record review. The location and percent of each TSS were determined for each patient, and were correlated to the clinical outcome.Results: We included 51 patients. Forty-six patients had bilateral TSS. The median average percent stenosis was 56%. Seventy-one percent of patients had stenoses >50%. Thirty-five of the 51 patients (69%) had no final visual field loss. Eight patients (16%) had a clinical course classified as poor. There was no difference in the average percent stenosis between those with good clinical courses vs those with poor courses (62% vs 56%, p = 0.44). There was no difference in the percent stenosis based on the visual field grade (p = 0.38). CSF opening pressure was not associated with either location or degree of TSS.Conclusion: TSS is common, if not universal, among patients with IIH, and is almost always bilateral. There is no correlation between the degree of TSS and the clinical course, including visual field loss, among patients with IIH, suggesting that clinical features, not the degree of TSS, should be used to determine management in IIH.(C)2013 American Academy of Neurology

Objective: To quantitatively characterize domain-specific cognition in individuals with symptomatic lacunar stroke in a systematic review.Methods: Systematic searches of MEDLINE and EMBASE were conducted. Inclusion criteria were all articles published prior to December 2011 evaluating domain-specific cognitive status in individuals with a symptomatic lacunar infarct. Data extraction identified cognitive domains with reported impairment and effect size calculations and heterogeneity analyses were completed to assess the magnitude of this impairment for all studies with control group data.Results: Results of the search yielded 12 cross-sectional and 5 longitudinal studies that met inclusion criteria. Effect size calculations revealed small to medium effect sizes (ES) estimations for impairment after stroke in the domains of executive function (ES -0.44, 95% confidence interval [CI] -0.83, -0.50), memory (ES -0.55, 95% CI -0.96, -0.13), language (ES -0.63, 95% CI -0.92, -0.33), attention (ES -0.37, 95% CI -0.67, -0.07), and visuospatial abilities (ES -0.61, 95% CI -1.03, 0.19), and large effect sizes for global cognition (ES -0.90, 95% CI -1.48, -0.31) and information processing speed (ES -0.93, 95% CI -1.63, -0.23). Heterogeneity analyses revealed that a subset of these domains were heterogeneous and identified moderating factors accounting for this heterogeneity.Conclusions: Results of this systematic review are consistent with previous characterizations of cognitive impairment associated with lacunar strokes. However, impaired cognition in this stroke subtype appears less selective than previously thought, involving all major cognitive domains.(C)2013 American Academy of Neurology