Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Nov 2019
Multicenter StudyPrognostic patterns and predictors in epilepsy: a multicentre study (PRO-LONG).
To describe the long-term prognosis of epilepsy and prognostic patterns in a large cohort of newly diagnosed patients and identify prognostic factors. ⋯ Few seizures at diagnosis, generalised epilepsy and no psychiatric comorbidity predict early or late seizure freedom in epilepsy. Achieving remission at any time after the diagnosis does not exclude further relapses.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2019
ReviewDrug repurposing in neurological diseases: an integrated approach to reduce trial and error.
Identifying effective disease-modifying therapies for neurological diseases remains an important challenge in drug discovery and development. Drug repurposing attempts to determine new indications for pre-existing compounds and represents a major opportunity to address this clinically unmet need. It is potentially more cost-effective and time-efficient than de novo drug development and has yielded notable successes in neurological disorders. ⋯ We provide an overview of the current approach to early-stage drug repurposing and consider the issues contributing to inconclusive, or possibly falsely negative, Phase II and III trial outcomes in neurological diseases by highlighting examples that illustrate the limitations of empirical evidence generation without a strong scientific basis for the dose rationale. We conclude with a framework suggesting a translational, iterative approach, that integrates pharmacological, pharmaceutical and clinical expertise, towards preclinical and early clinical drug development. This ensures appropriate dosing regimen, route of administration and/or formulation are selected for the new indication before their evaluation in prospective clinical trials.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2019
ReviewOrthostatic hypotension and REM sleep behaviour disorder: impact on clinical outcomes in α-synucleinopathies.
Review the effect of orthostatic hypotension (OH) and rapid-eye-movement sleep behavioural disorder (RBD) on survival, cognitive impairment and postural stability, and discuss pathogenic mechanisms involved in the association of these two common non-motor features with relevant clinical outcomes in α-synucleinopathies. ⋯ OH and RBD yielded individual and combined negative effects on disability in α-synucleinopathies, reflecting a 'malignant' phenotype of PD with early cognitive impairment and postural instability. Underlying mechanisms may include involvement of selected brainstem cholinergic and noradrenergic nuclei.
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J. Neurol. Neurosurg. Psychiatr. · Nov 2019
Meta AnalysisLatitude continues to be significantly associated with the prevalence of multiple sclerosis: an updated meta-analysis.
Previous studies have demonstrated a strong latitudinal gradient in multiple sclerosis (MS) prevalence. Herein, we present a meta-analysis of the latitudinal gradient of MS prevalence including studies published since our 2011 review, seeking to assess the latitudinal gradient and whether it has changed since our previous analysis. ⋯ This new meta-analysis confirms that MS prevalence is still strongly positively associated with increasing latitude and that the gradient is increasing, suggesting that potentially modifiable environmental factors, such as sun exposure, are still strongly associated with MS risk.