Neurology November 2009 Volume 73 Issue 18

Background: Right temporal frontotemporal dementia (FTD) is an anatomic variant of FTD associated with relatively distinct behavioral and cognitive symptoms. We aimed to determine whether right temporal FTD is a homogeneous clinical, imaging, and pathologic/genetic entity.Methods: In this case-control study, 101 subjects with FTD were identified. Atlas-based parcellation generated temporal, frontal, and parietal grey matter volumes which were used to identify subjects with a right temporal dominant atrophy pattern. Clinical, neuropsychological, genetic, and neuropathologic features were reviewed. The subjects with right temporal FTD were grouped by initial clinical diagnosis and voxel-based morphometry was used to assess grey matter loss in the different groups, compared to controls, and each other.Results: We identified 20 subjects with right temporal FTD. Twelve had been initially diagnosed with behavioral variant FTD (bvFTD), and the other 8 with semantic dementia (SMD). Personality change and inappropriate behaviors were more frequent in the bvFTD group, while prosopagnosia, word-finding difficulties, comprehension problems, and topographagnosia were more frequent in the SMD group. The bvFTD group showed greater loss in frontal lobes than the SMD group. The SMD group showed greater fusiform loss than the bvFTD group. All 8 bvFTD subjects with pathologic/genetic diagnosis showed abnormalities in tau protein (7 with tau mutations), while all three SMD subjects with pathology showed abnormalities in TDP-43 (p = 0.006).Conclusions: We have identified 2 subtypes of right temporal variant frontotemporal dementia (FTD) allowing further differentiation of FTD subjects with underlying tau pathology from those with TDP-43 pathology.(C)2009AAN Enterprises, Inc.

Objective: In patients who remain in a coma after cardiopulmonary resuscitation (CPR), the bilateral absence of cortical N20 responses of median nerve somatosensory evoked potentials (SSEP) 24 hours after admission invariably correlates with a poor neurologic outcome. Nowadays, CPR patients are treated with mild hypothermia, with simultaneously administered sedative drugs, hampering clinical neurologic assessment. We investigated whether SSEP performed during hypothermia can reliably predict a poor neurologic outcome.Methods: Between July 2006 and April 2008, this multicenter prospective cohort study included adult comatose patients admitted after CPR and treated with induced mild hypothermia (32-34[degrees]C). SSEP was performed during hypothermia, and in patients who remained comatose after rewarming, a second SSEP was performed. Neurologic outcome was assessed 30 days after admission with the Glasgow Outcome Scale.Results: Seventy-seven consecutive patients were included in 2 hospitals. In 13 patients (17%), the cortical N20 response during hypothermia was bilaterally absent. In 9 of these 13 patients in whom SSEP could be repeated during normothermia, the N20 response was also absent, yielding a positive predictive value of 1.00 (95% confidence interval [CI] 0.70-1.00). All 13 patients with absent SSEP during hypothermia had a poor neurologic outcome, yielding a positive predictive value of 1.00 (95% CI 0.77-1.00).Conclusions: The results of this pilot study show that bilaterally absent cortical N20 responses of median nerve somatosensory evoked potentials performed during mild hypothermia after resuscitation can predict a poor neurologic outcome. We started a larger multicenter prospective cohort study to confirm these results.(C)2009AAN Enterprises, Inc.

Objective: To investigate the incidence of and risk factors for cognitive impairment in a large, well-defined clinical trial cohort of patients with early Parkinson disease (PD).Methods: The Mini-Mental State Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age- and education-adjusted MMSE norms.Results: Cumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 +/- 9.6 years, Hoehn-Yahr stage 1-2.5) was 2.4% (95% confidence interval: 1.2%-3.5%) at 2 years and 5.8% (3.7%-7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline.Conclusions: The relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination-based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease.(C)2009AAN Enterprises, Inc.

Background: Interferon beta (IFN[beta]) administered subcutaneously is immunogenic in some patients with multiple sclerosis (MS) and leads to the development of neutralizing antibodies (NAbs). Considerable evidence has accumulated that NAbs diminish or abolish IFN[beta] bioactivity, but there is less evidence that NAbs impact clinical efficacy of the drug.Methods: Because a robust effect of IFN[beta] is a decrease in enhancing lesions on brain MRI scans, the Betaseron Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints (BECOME) study, a head-to-head study of IFN[beta]-1b vs glatiramer acetate with a primary endpoint of enhancing lesions on MRI, provided an excellent opportunity to determine the effect of NAbs on MRI activity. We measured NAbs and IFN[beta] bioactivity by myxovirus resistance protein A gene expression and identified 2 groups of patients: one labeled "bioactivity preserved," with absent NAbs and robust IFN[beta] bioactivity (n = 8), and the other labeled "bioactivity lost," with high levels of NAbs and diminished bioactivity (n = 7). The development of enhancing lesions in the groups was then compared.Results: The incidence of NAbs and effect of NAbs on bioactivity were consistent with previous studies. We analyzed MRI outcomes in patients with NAbs at levels high enough to abolish bioactivity relative to patients without NAbs. For the preserved bioactivity group, the enhancing lesion/scan ratio decreased from 7.6 in the pretreatment period to 2.6 in the posttreatment period, a 66% decrease. For the lost bioactivity group, the decrease was 8.5 to 5.8, only a 32% decrease. Thus, lost bioactivity from high levels of NAbs resulted in reduced therapeutic efficacy of IFN[beta] as manifested by diminished reductions in enhancing lesions on MRI.Conclusions: High levels of anti-interferon beta (IFN[beta]) antibodies, which result in diminished bioactivity, are correlated with reduced therapeutic efficacy of IFN[beta].(C)2009AAN Enterprises, Inc.

Background: Autoimmune autonomic ganglionopathy is characterized by impairment of multiple autonomic domains of which sudomotor function is among the most common. Many patients with this disorder have difficulties with thermoregulation and anhidrosis. Our objective was to characterize the distribution and severity of sudomotor dysfunction in this disorder.Methods: Sudomotor function was analyzed in a cohort of 21 patients with ganglionic [alpha]3 nicotinic acetylcholine receptor (nAChR) antibody positive autoimmune autonomic ganglionopathy. Standard measurements of sudomotor function were used including the Thermoregulatory Sweat Test and Quantitative Sudomotor Axon Reflex Test.Results: The clinical presentation in all patients was characterized by widespread sudomotor dysfunction. Sudomotor impairment was predominantly postganglionic in 17 of the 21 patients studied. Higher ganglionic [alpha]3 nAChR antibody levels resulted in progressive postganglionic predominant dysfunction (postganglionic, r = 0.637, p = 0.002; mixed ganglionic, r = 0.709, p < 0.001). The pattern of anhidrosis on Thermoregulatory Sweat Testing was consistent with a ganglionopathy in the majority of patients (14 of 21) and a distal pattern in a minority of patients (8 of 21). These patterns of anhidrosis coupled with increasing postganglionic dysfunction in a proximal to distal pattern (foot > distal leg > proximal leg > forearm) indicate lesions at both the ganglia and distal axon of the postganglionic sudomotor sympathetic neuron.Conclusions: Our data characterize the unique sudomotor dysfunction in autoimmune autonomic ganglionopathy as widespread, predominantly postganglionic, and a result of lesions at both the ganglia and distal axon. This study provides important support to the hypothesis that this disorder represents a ganglionic neuropathy.(C)2009AAN Enterprises, Inc.