Journal of neurology
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Journal of neurology · Feb 2016
Case ReportsNEFL N98S mutation: another cause of dominant intermediate Charcot-Marie-Tooth disease with heterogeneous early-onset phenotype.
The purpose of this study was to describe a pedigree with NEFL N98S mutation associated with a dominant intermediate Charcot-Marie-Tooth disease (DI-CMT) and heterogeneous early-onset phenotype. The pedigree comprised two patients, the proband and her son, aged 38 and 5 years. The proband, evaluated at age 31, showed delayed motor milestones that, as of the second decade, evolved into severe phenotype consisting of sensorimotor neuropathy, pes cavus, clawing hands, gait and kinetic cerebellar ataxia, nystagmus and dysarthria, she being wheelchair bound. ⋯ Electrophysiology in both patients showed nerve conduction slowing in the intermediate range, both in proximal and distal nerve segments, but where compound muscle action potentials exhibited severe attenuation there was conduction slowing down to the demyelinating range. In the proband, cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography disclosed active denervation in tibialis anterior, and MRI of lower-limb musculature demonstrated widespread and distally accentuated muscle fatty atrophy; furthermore, on water sensitive MRI sequences there was edema of calf muscles. We conclude that the NEFL N98S mutation is associated with a DI-CMT phenotype characterized by early-onset sensorimotor neuropathy delaying motor milestones, which may evolve into a severe and complex clinical picture including cerebellar ataxia.
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Journal of neurology · Feb 2016
Randomized Controlled TrialBrief intervention by general practitioners for medication-overuse headache, follow-up after 6 months: a pragmatic cluster-randomised controlled trial.
Medication-overuse headache (MOH) is a common health problem. Withdrawal of the overused medication is the treatment of choice. We investigated the long-term effectiveness of brief intervention (BI) for MOH patients in primary care. The BI for MOH in primary care study was a blinded, pragmatic, cluster-randomised controlled trial. 25,486 patients (age 18-50) from 50 general practitioners (GPs) were screened for MOH. GPs defined clusters and 23 GPs were randomised to receive BI training and 27 GPs to continue business as usual (BAU). The GPs assessed their MOH patients with the Severity of Dependence Scale, gave individual feedback about the risk of MOH and advice to reduce headache medication. Primary outcomes, assessed 6 months after the intervention, were reduction in headache and medication days/month. 42% were screening responders. 2.4% had self-reported MOH. A random selection of 104 patients with self-reported MOH were invited, 75 were randomised out of which 60 with a physician-defined MOH diagnosis were included. None were lost to follow-up. BI was significantly better than BAU regarding primary outcomes (p < 0.001-0.018). Headache and medication days were reduced by 5.9 (95% CI 1.1-10.8) and 6.2 (1.1-11.3) more days/month in BI than BAU group. Chronic headache resolved in 63 and 11% in the BI and the BAU group (p < 0.001). Headache-related disability was lower among those who detoxified. In conclusion, BI is an effective treatment in primary care with lasting effect 6 months after the intervention for MOH.
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Frontotemporal dementia (FTD) encompasses the syndromes of behavioural variant FTD (bvFTD) and primary progressive aphasia (PPA) and refers to those neurodegenerative diseases characterised by predominant pathological involvement of the frontal and temporal lobes. Recent years have witnessed major advances in the clinical characterisation of FTD, reflected in the publication of updated diagnostic criteria for bvFTD and PPA, and the discovery of new pathogenic mutations has added to the understanding of genotype-phenotype interactions and of disease mechanisms. Emerging results from longitudinal studies of familial FTD show that imaging and cognitive changes occur years before symptom onset and such studies may yield biomarkers of early disease that in turn will facilitate earlier diagnosis. The hope and (guarded) expectation is that these advances may together herald the beginning of the end of the chapter in which FTD is considered an inexorably progressive and untreatable condition.
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Journal of neurology · Dec 2015
Safety profile of intracranial electrode implantation for video-EEG recordings in drug-resistant focal epilepsy.
Invasive electroencephalography recordings with depth or subdural electrodes are necessary to identify the ictogenic area in some drug-resistant focal epilepsies. We aimed to analyze the safety profile of intracranial electrode implantation in a tertiary center and the factors associated with its complications. We retrospectively examined complications in 163 intracranial procedures performed in adult patients. ⋯ We believe that intracranial electrode implantation has a favorable safety profile, without permanent deficit. These risks should be balanced with the benefits of invasive exploration prior to surgery. Furthermore, this study provides preliminary evidence regarding the safety of micro-macroelectrodes.
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Most stroke is multifactorial with multiple polygenic risk factors each conferring small increases in risk interacting with environmental risk factors, but it can also arise from mutations in a single gene. This review covers single-gene disorders which lead to stroke as a major phenotype, with a focus on those which cause cerebral small vessel disease (SVD), an area where there has been significant recent progress with findings that may inform us about the pathogenesis of SVD more broadly. We also discuss the impact that next generation sequencing technology (NGST) is likely to have on clinical practice in this area. ⋯ These monogenic forms of SVD, with overlapping clinical phenotypes, are beginning to provide insights into how the small arteries in the brain can be damaged and some of the mechanisms identified may also be relevant to more common sporadic SVD. Despite the discovery of these disorders, it is often challenging to clinically and radiologically distinguish between syndromes, while screening multiple genes for causative mutations that can be costly and time-consuming. The rapidly falling cost of NGST may allow quicker diagnosis of these rare causes of SVD, and can also identify previously unknown disease-causing variants.