Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · May 2021
ReviewUnravelling the clinical spectrum and the role of repeat length in C9ORF72 repeat expansions.
Since the discovery of the C9orf72 repeat expansion as the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis, it has increasingly been associated with a wider spectrum of phenotypes, including other types of dementia, movement disorders, psychiatric symptoms and slowly progressive FTD. Prompt recognition of patients with C9orf72-associated diseases is essential in light of upcoming clinical trials. The striking clinical heterogeneity associated with C9orf72 repeat expansions remains largely unexplained. ⋯ The exact threshold at which repeat expansions lead to neurodegeneration is unknown, and discordant cut-offs between laboratories pose a challenge for genetic counselling. Accurate and large-scale measurement of repeat expansions has been severely hindered by technical difficulties in sizing long expansions and by variable repeat lengths across and within tissues. Novel long-read sequencing approaches have produced promising results and open up avenues to further investigate this enthralling repeat expansion, elucidating whether its length, purity, and methylation pattern might modulate clinical features of C9orf72-related diseases.
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J. Neurol. Neurosurg. Psychiatr. · May 2021
Effect of lateral therapy switches to oral moderate-efficacy drugs in multiple sclerosis: a nationwide cohort study.
Switching between first-line disease-modifying therapies in patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) due to reasons other than disease activity is frequent, but evidence on the effect of this practice is limited. We investigated the effect of switching patients with stable RRMS on occurrences of disability accumulation, relapses and future treatment discontinuation. ⋯ Switching from injectable platform therapies to oral first-line therapies in patients with clinically stable RRMS does not increase the risk of disability accumulation. While the postswitch risk of relapses trended towards marginally higher on TFL, this trend was eliminated by adjustment for time-variant confounders.
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J. Neurol. Neurosurg. Psychiatr. · May 2021
Editorial CommentFashion focus: neurosurgery for tremor.