Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Oct 2024
Multicenter StudyClinical value of plasma ALZpath pTau217 immunoassay for assessing mild cognitive impairment.
Among plasma biomarkers for Alzheimer's disease (AD), pTau181 and pTau217 are the most promising. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors. ⋯ Plasma pTau217 and pTau181 both correlate with AD, but the fold change in pTau217 makes it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia.
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J. Neurol. Neurosurg. Psychiatr. · Oct 2024
A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI.
Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI). Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce burden by shortening the treatment course, but the safety, feasibility, and acceptability of iTBS have not been established in MCI. ⋯ Our findings support the safety, feasibility, and acceptability of accelerated iTBS in aMCI. In addition, we provide evidence of target engagement in the form of improved cognition following treatment. These promising results directly inform future trials aimed at optimizing treatment parameters.
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Parkinson's disease (PD) is an incurable and progressive neurological disorder leading to deleterious motor and non-motor consequences. Presently, no pharmacological agents can prevent PD evolution or progression, while pharmacological symptomatic treatments have limited effects in certain domains and cause side effects. ⋯ In PD, the existing knowledge base supports exercise as (1) a protective lifestyle factor preventing the disease (ie, primary prevention), (2) a potential disease-modifying therapy (ie, secondary prevention) and (3) an effective symptomatic treatment (ie, tertiary prevention). Based on current evidence, a paradigm shift is proposed, stating that exercise should be individually prescribed as medicine to persons with PD at an early disease stage, alongside conventional medical treatment.
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J. Neurol. Neurosurg. Psychiatr. · Oct 2024
ReviewGenetics of inherited peripheral neuropathies and the next frontier: looking backwards to progress forwards.
Inherited peripheral neuropathies (IPNs) encompass a clinically and genetically heterogeneous group of disorders causing length-dependent degeneration of peripheral autonomic, motor and/or sensory nerves. Despite gold-standard diagnostic testing for pathogenic variants in over 100 known associated genes, many patients with IPN remain genetically unsolved. Providing patients with a diagnosis is critical for reducing their 'diagnostic odyssey', improving clinical care, and for informed genetic counselling. ⋯ However, the scarcity of additional families and functional data supporting variants in potential novel genes is prolonging patient diagnostic uncertainty and contributing to the missing heritability of IPNs. We review the last decade of IPN disease gene discovery to highlight novel genes, structural variation and short tandem repeat expansions contributing to IPN pathogenesis. From the lessons learnt, we provide our vision for IPN research as we anticipate the future, providing examples of emerging technologies, resources and tools that we propose that will expedite the genetic diagnosis of unsolved IPN families.
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J. Neurol. Neurosurg. Psychiatr. · Oct 2024
Pathogenesis of multiple sclerosis: genetic, environmental and random mechanisms.
The pathogenesis of multiple sclerosis (MS) requires both genetic factors and environmental events. The question remains, however, whether these factors and events completely describe the MS disease process. This question was addressed using the Canadian MS data, which includes 29 478 individuals, estimated to represent 65-83% of all Canadian patients with MS. ⋯ This analysis explicitly includes all of those genetic factors and environmental events (including their interactions), which are necessary for MS pathogenesis, regardless of whether these factors, events and interactions are known, suspected or as yet unrecognised. Nevertheless, in addition, a 'truly' random mechanism also seems to play a critical role in disease pathogenesis. This observation provides empirical evidence, which undermines the widely-held deterministic view of nature. Moreover, both sexes seem to share a similar genetic and environmental disease basis. If so, then it is this random mechanism, which is primarily responsible for the currently-observed differences in MS disease expression between susceptible women and susceptible men.