Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Nov 2020
Serum neurofilament light chain predicts long-term prognosis in Guillain-Barré syndrome patients.
To study baseline serum neurofilament light chain (sNfL) levels as a prognostic biomarker in Guillain-Barré syndrome (GBS). ⋯ Baseline sNfL levels are increased in patients with GBS, are associated with disease severity and axonal variants and have an independent prognostic value in patients with GBS.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2020
Associations of APOE e2 genotype with cerebrovascular pathology: a postmortem study of 1275 brains.
We assessed the association of apolipoprotein E (APOE) genotype with cerebrovascular disease (CVD) in a large neuropathological database maintained by the National Alzheimer's Coordinating Center (NACC). Such a comprehensive investigation of APOE and CVD pathology has not heretofore been conducted. We focused on APOE e2, an established neuroprotective genetic variant against Alzheimer's disease. ⋯ In this, the largest study of APOE e2 effects on pathologically verified CVD, e2 was not protective against any CVD pathology compared with e3 homozygotes, including CAA. Regarding the latter pathology, e4 was associated with increases in its severity. Furthermore, and perhaps unexpectedly, e2 significantly increased risk of acute/subacute gross haemorrhage in the presence of CAA. Thus, there were limits to e2 neuroprotection against amyloidosis, despite its known and large protective effects against diffuse and neuritic amyloid plaques compared with e3/e3 and e4 carriers in this very collection.
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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.