Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Nov 2023
Evoked mid-frontal activity predicts cognitive dysfunction in Parkinson's disease.
Cognitive dysfunction is a major feature of Parkinson's disease (PD), but the pathophysiology remains unknown. One potential mechanism is abnormal low-frequency cortical rhythms which engage cognitive functions and are deficient in PD. We tested the hypothesis that mid-frontal delta/theta rhythms predict cognitive dysfunction in PD. ⋯ These data demonstrate that cue-evoked mid-frontal delta/theta rhythms directly relate to cognition in PD. Our results provide insight into the nature of low-frequency frontal rhythms and suggest that PD-related cognitive dysfunction results from decreased delta/theta activity. These findings could facilitate the development of new biomarkers and targeted therapies for cognitive symptoms of PD.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2023
Systematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer's disease.
Alzheimer's disease (AD) is the leading cause of dementia. Currently, there are no effective disease-modifying treatments for AD. Mendelian randomisation (MR) has been widely used to repurpose licensed drugs and discover novel therapeutic targets. Thus, we aimed to identify novel therapeutic targets for AD and analyse their pathophysiological mechanisms and potential side effects. ⋯ This study provides genetic evidence supporting the potential therapeutic benefits of targeting the three druggable genes for AD treatment, which will be useful for prioritising AD drug development.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2023
Diffusion-based structural connectivity patterns of multiple sclerosis phenotypes.
We aimed to describe the severity of the changes in brain diffusion-based connectivity as multiple sclerosis (MS) progresses and the microstructural characteristics of these networks that are associated with distinct MS phenotypes. ⋯ In conclusion, brain connectivity is disrupted in MS and has differential patterns according to the phenotype. Secondary progressive is associated with more widespread changes in connectivity. Additionally, classification tasks can distinguish between MS types, with subcortical connections being the most important factor.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2023
Gait-combined closed-loop brain stimulation can improve walking dynamics in Parkinsonian gait disturbances: a randomised-control trial.
Gait disturbance lowers activities of daily living in patients with Parkinson's disease (PD) and related disorders. However, the effectiveness of pharmacological, surgical and rehabilitative treatments is limited. We recently developed a novel neuromodulation approach using gait-combined closed-loop transcranial electrical stimulation (tES) for healthy volunteers and patients who are post-stroke, and achieved significant entrainment of gait rhythm and an increase in gait speed. Here, we tested the efficacy of this intervention in patients with Parkinsonian gait disturbances. ⋯ These findings showed that gait-combined closed-loop tES over the cerebellum improved Parkinsonian gait disturbances, possibly through the modulation of brain networks generating gait rhythms. This new non-pharmacological and non-invasive intervention could be a breakthrough in restoring gait function in patients with PD and related disorders.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2023
Risk-conferring HLA variants in an epilepsy cohort: benefits of multifaceted use of whole genome sequencing in clinical practice.
Whole genome sequencing is increasingly used in healthcare, particularly for diagnostics. However, its clinically multifaceted potential for individually customised diagnostic and therapeutic care remains largely unexploited. We used existing whole genome sequencing data to screen for pharmacogenomic risk factors related to antiseizure medication-induced cutaneous adverse drug reactions (cADRs), such as human leucocyte antigen HLA-B*15:02, HLA-A*31:01 variants. ⋯ Comprehensive utilisation of genetic data spreads beyond the search for causal variants alone and can be extended to additional clinical benefits such as identifying pharmacogenomic biomarkers, which can guide pharmacotherapy for genetically-susceptible individuals.