Lancet neurology
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Cerebral vasospasm is a recognised but poorly understood complication for many patients who have aneurysmal subarachnoid haemorrhage and can lead to delayed ischaemic neurological deficit (stroke). Morbidity and mortality rates for vasospasm are high despite improvements in management. ⋯ Hypervolaemia, hypertension, and haemodilution (triple-H) therapy in an intensive-care setting has been shown in some studies to improve outcome and is an accepted means of treatment, although a randomised controlled trial has never been undertaken. In this review, the rationale for this approach will be discussed, alongside new thoughts and future prospects for the management of this complex disorder.
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Activity-dependent long-term potentiation (LTP) of excitatory neurotransmission underlies specific forms of associative learning and memory. A brief period of energy deprivation induces LTP in specific subsets of neurons; this synaptic plasticity might contribute to the delayed effects of brain ischaemia. ⋯ On the basis of recent studies, we propose that pathological plasticity induced by energy deprivation can play a part in delayed neuronal death in the hippocampus and the striatum after global ischaemia and in the conversion of ischaemic penumbra to infarct core after focal ischaemia. We discuss evidence that ischaemia could also induce protective and reparative forms of neuronal plasticity that may play a part in ischaemic tolerance and poststroke recovery.
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Metaphor has an important role in the discussion of scientific discovery because it enables researchers to talk about things of which their understanding is incomplete. Alzheimer's disease (AD) can be seen as a journey down a path, which becomes steadily less pleasant and ends in a wholly undesirable destination. To further the metaphor, treatments can be seen as attempts to help the patient return to the starting point, to slow the journey, or to stop at some point on the path. ⋯ This metaphor has practical implications for clinical trials. It highlights the importance of individualised outcome measures that incorporate patients' preferences and should encourage us to develop better means of enabling the recovery of self. To understand how there can be treatment success short of cure, without knowing at the outset what form that success may take, will require systematic observation and careful description of patients' experiences.
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Review
Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry?
Dopamine replacement therapy (DRT) is the most effective treatment for Parkinson's disease (PD); it provides substantial benefit for most patients, extends independence, and increases survival. A few patients with PD, however, take increasing quantities of medication far beyond those required to treat their motor disabilities. These patients demand rapid drug escalation and continue to request more DRT despite the emergence of increasingly severe drug-induced motor complications and harmful behavioural consequences. In this article we detail the features of compulsive DRT-seeking and intake in PD, in relation to theories of compulsive drug use.
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Early diagnosis of Alzheimer's disease (AD) is needed to initiate symptomatic treatment with acetylcholinesterase inhibitors, and will be of even greater significance if drugs aimed at slowing down the degenerative process, such as vaccination regimes and beta-secretase and gamma-secretase inhibitors, prove to affect AD pathology and to have clinical effect. However, there is no clinical method to determine in which patients mild cognitive impairment (MCI) will progress to AD with dementia, and in which patients MCI is benign. Hence, there is a great clinical need for biomarkers to identify incipient AD in patients with MCI. The CSF biomarkers total tau protein, phosphorylated tau protein, and the 42 amino-acid residue form of amyloid-beta may, if put in the right clinical context, prove to have high enough diagnostic accuracy to meet this challenge.