Journal of neurology, neurosurgery, and psychiatry
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J. Neurol. Neurosurg. Psychiatr. · Feb 2021
Randomized Controlled TrialClinical staging in amyotrophic lateral sclerosis: analysis of Edaravone Study 19.
This was a post hoc analysis of the Edaravone Phase III Study MCI186-19 ('Study 19') to examine the utility of clinical staging systems as end points in clinical trials in amyotrophic lateral sclerosis (ALS). ⋯ The King's and MiToS staging systems provided utility in assessing clinical progression in Edaravone Study 19. These findings may support the use of staging systems as end points in ALS clinical trials and to understand the timing of benefit as measured by these scales.
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Investigators acknowledge the limitations of rodent or non-human primate stroke models, hundreds of putative neuroprotectants have been evaluated in preclinical models, but not one has entered the clinical realm. Initial studies focused on the neuron, but in recent years the focus has widened to also include other neural cells including astrocytes, pericytes and endothelial cells, which together form the neurovascular unit. Some new developments raise renewed hope for neuroprotection: the appearance of new compounds with multiple mechanisms of action, or the promulgation of new standards for a rigorous preclinical testing. ⋯ In addition, otaplimastat, 3K3A-activated protein C (APC), intra-arterial verapamil and intra-arterial hypothermia were also assessed in combination with reperfusion therapy, but in RCTs that only included feasibility or safety outcomes. Some of these compounds yielded promising results which are discussed in this review. Altogether, a deeper knowledge of the mechanisms involved in the ischaemic death process at the neurovascular unit, an improved preselection and evaluation of drugs at the preclinical stage and the testing of putative neuroprotectants in enriched clinical studies of patients receiving reperfusion therapies, might prove more effective than in the past to reverse a dismal situation that has lasted already too long.
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J. Neurol. Neurosurg. Psychiatr. · Feb 2021
Meta AnalysisSuggestibility in functional neurological disorder: a meta-analysis.
Responsiveness to direct verbal suggestions (suggestibility) has long been hypothesised to represent a predisposing factor for functional neurological disorder (FND) but previous research has yielded conflicting results. The aim of this study was to quantitatively evaluate whether patients with FND display elevated suggestibility relative to controls via meta-analysis. ⋯ These results corroborate the hypothesis that FND is characterised by heightened responsiveness to verbal suggestion. Atypical suggestibility may confer risk for FND and be a cognitive marker that can inform diagnosis and treatment of this condition.
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J. Neurol. Neurosurg. Psychiatr. · Feb 2021
Cumulative health deficits, APOE genotype, and risk for later-life mild cognitive impairment and dementia.
To determine whether health-deficit accumulation is associated with the risks of mild cognitive impairment (MCI) and dementia independently of APOE genotype. ⋯ Among older Americans, health-deficit accumulation affects the likelihood of progressive cognitive impairment and the likelihood of cognitive improvement independently of a strong genetic risk factor for dementia. Frailty represents an important risk factor for cognitive dysfunction and a marker of potential prognostic value.
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J. Neurol. Neurosurg. Psychiatr. · Feb 2021
Observational StudyLocation of intracranial aneurysms is the main factor associated with rupture in the ICAN population.
The ever-growing availability of imaging led to increasing incidentally discovered unruptured intracranial aneurysms (UIAs). We leveraged machine-learning techniques and advanced statistical methods to provide new insights into rupture intracranial aneurysm (RIA) risks. ⋯ The location of IA is the most consistent parameter associated with RIA. The use of 'artificial intelligence' RF helps to re-evaluate the contribution and selection of each risk factor in the multivariate model.