Lancet neurology
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Randomized Controlled Trial Multicenter Study Clinical Trial
Donepezil in patients with subcortical vascular cognitive impairment: a randomised double-blind trial in CADASIL.
Cholinergic deficits might contribute to vascular cognitive impairment. Trials of cholinesterase inhibitors in patients with vascular dementia are difficult because of heterogeneous disease mechanisms and overlap between vascular and Alzheimer's disease (AD) pathology in the age-group recruited. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a genetic form of subcortical ischaemic vascular dementia. It represents a homogeneous disease process, and because of CADASIL's early onset, comorbid AD pathology is rare. We did a multicentre, 18-week, placebo-controlled, double-blind, randomised parallel-group trial to determine whether the cholinesterase inhibitor donepezil improves cognition in patients with CADASIL. ⋯ Donepezil had no effect on the primary endpoint, the V-ADAS-cog score in CADASIL patients with cognitive impairment. Improvements were noted on several measures of executive function, but the clinical relevance of these findings is not clear. Our findings may have implications for future trial design in subcortical vascular cognitive impairment.
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Randomized Controlled Trial
Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.
Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). ⋯ Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.
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Major advances in the management of paraneoplastic neurologic disorders (PND) include the detection of new antineuronal antibodies, the improved characterisation of known syndromes, the discovery of new syndromes, and the use of CT and PET to reveal the associated tumours at an early stage. In addition, the definition of useful clinical criteria has facilitated the early recognition and treatment of these disorders. In this article, we review some classic concepts about PND and recent clinical and immunological developments, focusing on paraneoplastic cerebellar degeneration, opsoclonus-myoclonus, and encephalitides affecting the limbic system.
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The burden associated with headache is a major public health problem, the true magnitude of which has not been fully acknowledged until now. Globally, the percentage of the adult population with an active headache disorder is 47% for headache in general, 10% for migraine, 38% for tension-type headache, and 3% for chronic headache that lasts for more than 15 days per month. ⋯ Most of the burden of headache is carried by a minority who have substantial and complicating comorbidities. Renewed recognition of the burden of headache and increased scientific interest have led to a better understanding of the risk factors and greater insight into the pathogenic mechanisms, which might lead to improved prevention strategies and the early identification of patients who are at risk.
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The decision about whether to treat an unruptured brain arteriovenous malformation (AVM) depends on a comparison of the estimated lifetime risk of intracranial haemorrhage with the risks of interventional treatment. We aimed to test whether outcome differs between adults who had interventional AVM treatment and those who did not. ⋯ Greater AVM size and interventional treatment were associated with worse short-term functional outcome for unruptured AVMs, but the longer-term effects of intervention are unclear.