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. · Nov 2020
MM2-type sporadic Creutzfeldt-Jakob disease: new diagnostic criteria for MM2-cortical type.
To clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity and specificity. ⋯ MM2C-sCJD can be diagnosed at earlier stage using the new criteria with high sensitivity and specificity, although it is still difficult to diagnose MM2T-sCJD clinically.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2020
Multicenter StudyEarly brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study.
Traumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not. ⋯ Although this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2020
Comparative StudyComparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease.
To compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes. ⋯ Plasma markers have lower diagnostic accuracy than CSF biomarkers. Plasma tau and NfL and CSF t-tau are significantly associated with survival in prion disease in a subtype-specific manner and can be used to improve clinical trial stratification and clinical care.