Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Nov 2020
ReviewData-driven evolution of neurosurgical gene therapy delivery in Parkinson's disease.
Loss of nigrostriatal dopaminergic projection neurons is a key pathology in Parkinson's disease, leading to abnormal function of basal ganglia motor circuits and the accompanying characteristic motor features. A number of intraparenchymally delivered gene therapies designed to modify underlying disease and/or improve clinical symptoms have shown promise in preclinical studies and subsequently were evaluated in clinical trials. Here we review the challenges with surgical delivery of gene therapy vectors that limited therapeutic outcomes in these trials, particularly the lack of real-time monitoring of vector administration. ⋯ The preclinical development of these techniques are described in relation to recent clinical translation in an adeno-associated virus serotype 2-mediated human aromatic L-amino acid decarboxylase gene therapy development programme. This new paradigm allows visualisation of the accuracy and adequacy of viral vector delivery within target structures, enabling intertrial modifications in surgical approaches, cannula design, vector volumes and dosing. The rapid, data-driven evolution of these procedures is unique and has led to improved vector delivery.
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J. Neurol. Neurosurg. Psychiatr. · Oct 2020
Anti-Aβ agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis.
To assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer's disease. ⋯ From current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.
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J. Neurol. Neurosurg. Psychiatr. · Oct 2020
Serum IgG anti-GD1a antibody and mEGOS predict outcome in Guillain-Barré syndrome.
Approximately 15%-20% of patients with Guillain-Barré syndrome (GBS) are unable to walk independently at 6 months from the onset of neurological symptom. The modified Erasmus GBS outcome score (mEGOS) has been reported as a prognostic tool.Herein we investigated the association between a poor outcome, inability to walk independently at 6 months and presence of antiganglioside antibodies. ⋯ The combination of serum IgG anti-GD1a antibodies and a high mEGOS could help in making a more accurate prognosis of patients than mEGOS alone, especially for predicting poor outcomes.
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J. Neurol. Neurosurg. Psychiatr. · Oct 2020
ReviewDiffusion imaging in Huntington's disease: comprehensive review.
Huntington's disease (HD) is a monogenic disorder with 100% penetrance. With the advent of genetic testing in adults, disease-related, structural brain changes can be investigated from the earliest, premorbid stages of HD. While examining macrostructural change characterises global neuronal damage, investigating microstructural alterations provides information regarding brain organisation and its underlying biological properties. ⋯ Multiple approaches, including voxelwise, region of interest and tractography, have been used in HD cohorts, showing a centrifugal pattern of white matter (WM) degeneration starting from deep brain areas, which is consistent with neuropathological studies. The corpus callosum, longer WM tracts and areas that are more densely connected, in particular the sensorimotor network, also tend to be affected early during premanifest stages. Recent evidence supports the routine inclusion of diffusion analyses within clinical trials principally as an additional measure to improve understanding of treatment effects, while the advent of novel techniques such as multitissue compartment models and connectomics can help characterise the underpinnings of progressive functional decline in HD.
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J. Neurol. Neurosurg. Psychiatr. · Oct 2020
Deep brain stimulation of the subthalamic nucleus in obsessive-compulsives disorders: long-term follow-up of an open, prospective, observational cohort.
Obsessive-compulsive disorder (OCD) is a major cause of disability in western country and responsible for severe impairment of quality of life. About 10% of patients present with severe OCD symptoms and require innovative treatment such as deep brain stimulation (DBS). Among possible targets, the non-motor subthalamic nucleus (STN) is a key node of the basal ganglia circuitry, strongly connected to limbic cortical areas known to be involved in OCD. ⋯ Chronic DBS of the non-motor STN is an effective and relatively safe procedure to treat severe OCD resistant to conventional management.