Neurology Journal

Background: Based on the higher frequency of paroxysmal atrial fibrillation during night and early morning hours, we sought to analyze the association between newly diagnosed atrial fibrillation and wake-up ischemic cerebrovascular events.Methods: We prospectively assessed every acute ischemic stroke and TIA patient admitted to our hospital between 2008 and 2011. We used a forward step-by-step multiple logistic regression analysis to assess the relationship between newly diagnosed atrial fibrillation and wake-up ischemic stroke or TIA, after adjusting for significant covariates.Results: The study population comprised 356 patients, 274 (77.0%) with a diagnosis of acute ischemic stroke and 82 (23.0%) with TIA. A total of 41 (11.5%) of these events occurred during night sleep. A newly diagnosed atrial fibrillation was detected in 27 patients of 272 without known atrial fibrillation (9.9%). We found an independent association between newly diagnosed atrial fibrillation and wake-up ischemic stroke and TIA (odds ratio 3.6, 95% confidence interval 1.2-7.7, p = 0.019).Conclusions: The odds of detecting a newly diagnosed atrial fibrillation were 3-fold higher among wake-up cerebrovascular events than among non-wake-up events. The significance of this independent association between newly diagnosed atrial fibrillation and wake-up ischemic stroke and TIA and the role of other comorbidities should be investigated in future studies.(C)2013 American Academy of Neurology

Objective: The underlying pathophysiology of tremor in Parkinson disease (PD) is unclear; however, it is known that tremor does not appear to be as responsive to dopaminergic medication as bradykinesia or rigidity. It is suggested that serotonergic dysfunction could have a role in tremor development.Methods: Using 11C-DASB PET, a marker of serotonin transporter binding, and clinical observations, we have investigated function of serotonergic terminals in 12 patients with tremor-predominant and 12 with akinetic-rigid PD. Findings were compared with those of 12 healthy controls.Results: Reductions of 11C-DASB in caudate, putamen, and raphe nuclei significantly correlated with tremor severity on posture and action, but not with resting tremor. The tremor-predominant group also showed reductions of 11C-DASB in other regions involved in motor circuitry, including the thalamus and Brodmann areas 4 and 10.Conclusions: Our findings support a role for serotonergic dysfunction in motor circuitries in the generation of postural tremor in PD.(C)2013 American Academy of Neurology

Objective: The objective of this randomized, double-blind, placebo-controlled, crossover study was to examine if patients with optic neuropathy would derive a therapeutic benefit from 4-aminopyridine (4-AP) treatment. Furthermore, the study was intended to determine if patients with certain P100 latencies or retinal nerve fiber layer (RNFL) measures would be more likely to respond to therapy.Methods: Patients were enrolled in a randomized, placebo-controlled, double-blind, crossover study of 10 weeks duration. Patients underwent visual evoked potentials (VEP), optical coherence tomography (OCT), and visual acuity before starting 5 weeks of either placebo or 4-AP. After 5 weeks, they completed a second evaluation (VEP, OCT, and visual acuity) and were crossed over between treatment arms. Five weeks later, they had their final evaluation. All investigators were blinded to treatment arm until after data analysis.Results: On average, patients had faster P100s on 4-AP when compared to placebo. A subset of patients had distinct responses to 4-AP as measured by improvements in visual acuity. Finally, eyes with an RNFL measure between 60 and 80 [micro]m had the highest response rate.Conclusions: 4-Aminopyridine is useful for improving vision in patients with demyelinating optic neuropathy. Future clinical trials may be able to enrich a patient population for potential responders using OCT and VEP measures. Selecting patients for future trials should use RNFL measures as part of inclusion/exclusion criteria.Classification of evidence: This study provides Class IV evidence supporting the use of 4-AP in certain patients with optic neuropathy to improve visual function (patients with RNFL between 60 and 80 [micro]m).(C)2013 American Academy of Neurology

Objective: To explore the putative connection between inclusion body myopathy, Paget disease, frontotemporal dementia (IBMPFD) and motor neuron disease (MND).Methods: Clinical, genetic, and EMG characterization of 17 patients from 8 IBMPFD families.Results: Limb weakness was the most common clinical manifestation (present in 15 patients, median onset age 38 years, range 25-52), with unequivocal evidence of upper motor neuron dysfunction in 3. EMG, abnormal in all 17, was purely neurogenic in 4, purely myopathic in 6, and mixed neurogenic/myopathic in 7. Cognitive/behavioral impairment was detected in at least 8. Mutations in VCP (R155H, R159G, R155C) were identified in 6 families, and in hnRNPA2B1 (D290V) in another family. The genetic cause in the eighth family has not yet been identified.Conclusion: Mutations in at least 4 genes may cause IBMPFD, and its phenotypic spectrum extends beyond IBM, Paget disease, and frontotemporal dementia (FTD). Weakness, the most common and disabling manifestation, may be caused by muscle disease or MND. The acronym IBMPFD is, therefore, insufficient to describe disorders due to VCP mutations or other recently identified IBMPFD-associated genes. Instead, we favor the descriptor multisystem proteinopathy (MSP), which encompasses both the extended clinical phenotype and the previously described prominent pathologic feature of protein aggregation in affected tissues. The nomenclature MSP1, MSP2, and MSP3 may be used for VCP-, HNRNPA2B1-, and HNRNPA1-associated disease, respectively. Genetic defects in MSP implicate a range of biological mechanisms including RNA processing and protein homeostasis, both with potential relevance to the pathobiology of more common MNDs such as amyotrophic lateral sclerosis (ALS) and providing an additional link between ALS and FTD.(C)2013 American Academy of Neurology

Objective: To explore whether prevalence, survival, and incidence of dementia have changed from 1987-1994 to 2001-2008 in Stockholm, Sweden.Methods: This study is based on 2 cross-sectional surveys of people aged 75 years or over conducted in central Stockholm: the Kungsholmen Project (KP) (1987-1989, n = 1,700) and the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) (2001-2004, n = 1,575). In both surveys we diagnosed dementia according to DSM-III-R criteria, following the identical diagnostic procedure. Death certificates were used to determine survival status of KP participants as of December 1994 and SNAC-K participants as of June 2008. We used logistic and Cox models to compare prevalence and survival, controlling for major confounders. We inferred incidence of dementia according to its relationship with prevalence and survival.Results: At baseline, 225 subjects in KP and 298 in SNAC-K were diagnosed with dementia. The age- and sex-standardized prevalence of dementia was 17.5% (12.8% in men; 19.2% in women) in KP and 17.9% (10.8% in men; 20.5% in women) in SNAC-K. The adjusted odds ratio of dementia in SNAC-K vs KP was 1.17 (95% confidence interval 0.95-1.46). The multiadjusted hazard ratio of death in SNAC-K vs KP was 0.71 (0.57-0.88) in subjects with dementia, 0.68 (0.59-0.79) in those without dementia, and 0.66 (0.59-0.74) in all participants.Conclusions: Prevalence of dementia was stable from the late 1980s to the early 2000s in central Stockholm, Sweden, whereas survival of patients with dementia increased. These results suggest that incidence of dementia may have decreased during this period.(C)2013 American Academy of Neurology

In the past, the cortex has for the most part been considered to be the site of seizure origin in the different forms of epilepsy. Findings from histopathologic, electrophysiologic, and brain imaging studies now provide ample evidence demonstrating that like normal cerebral function, epileptic seizures involve widespread network interactions between cortical and subcortical structures. These studies show that different forms of generalized and focal epileptiform discharges and seizures engage various subcortical structures in varying ways. This interaction has been the subject of many reviews and is not the focus of the current work. The aim of this review is to examine the evidence suggesting the possibility for some of the subcortical structures to initiate seizures independently and the clinical implications of this.(C)2013 American Academy of Neurology