Lancet neurology
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Levodopa-induced motor complications are a common source of disability for patients with Parkinson's disease. Evidence suggests that motor complications are associated with non-physiological, pulsatile stimulation of dopamine receptors. In healthy brains, dopamine neurons fire continuously, striatal dopamine concentrations are relatively constant, and there is continuous activation of dopamine receptors. ⋯ The concept of continuous dopaminergic stimulation proposes that continuous delivery of a dopaminergic drug will prevent pulsatile stimulation and avoid motor complications. In monkeys treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and patients with Parkinson's disease, long-acting or continuous infusion of a dopaminergic drug reduces the risk of motor complications. The current challenge is to develop a long-acting oral formulation of levodopa that provides clinical benefits but avoids motor complications.
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Thunderclap headache (TCH) is head pain that begins suddenly and is severe at onset. TCH might be the first sign of subarachnoid haemorrhage, unruptured intracranial aneurysm, cerebral venous sinus thrombosis, cervical artery dissection, acute hypertensive crisis, spontaneous intracranial hypotension, ischaemic stroke, retroclival haematoma, pituitary apoplexy, third ventricle colloid cyst, and intracranial infection. ⋯ Herein, we discuss the differential diagnosis of TCH, diagnostic criteria for the primary disorder, and proper assessment of patients. We also offer pathophysiological considerations for primary TCH.
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The causes of Parkinson's disease (PD), the second most common neurodegenerative disorder, are still largely unknown. Current thinking is that major gene mutations cause only a small proportion of all cases and that in most cases, non-genetic factors play a part, probably in interaction with susceptibility genes. ⋯ Larger, well-designed prospective cohort studies have only recently reached a stage at which they have enough incident patients and person-years of follow-up to investigate possible risk factors and their interactions. In this article, we review what is known about the prevalence, incidence, risk factors, and prognosis of PD from epidemiological studies.
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Sickle-cell anaemia is the most common cause of stroke in children, and stroke is one of the most devastating complications of sickle-cell disease. Overt strokes are typically due to large-artery vasculopathy affecting the intracranial internal carotid arteries and proximal middle cerebral arteries, whereas silent strokes typically occur in the territory of penetrating arteries. ⋯ Therefore, interventions directed towards the potential mechanisms that promote vasculopathy and occlusion in sickle-cell anaemia should be investigated. Here we review the epidemiology, clinical spectrum, and pathophysiology of stroke in sickle-cell disease to identify potential therapeutic targets.
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Neoplastic meningitis is a complication of the CNS that occurs in 3-5% of patients with cancer and is characterised by multifocal neurological signs and symptoms. Diagnosis is problematic because the disease is commonly the result of pleomorphic manifestations of neoplastic meningitis and co-occurrence of disease at other sites. Useful tests to establish diagnosis and guide treatment include MRI of the brain and spine, cerebrospinal fluid (CSF) cytology, and radioisotope CSF flow studies. ⋯ Because neoplastic meningitis affects the entire neuraxis, chemotherapy treatment can include intra-CSF fluid (either intraventricular or intralumbar) or systemic therapy. Most patients (>70%) with neoplastic meningitis have progressive systemic disease and consequently treatment is palliative and tumour response is of restricted durability. Furthermore, as there is no compelling evidence of a survival advantage with aggressive multimodal treatment, future trials need be done to determine the effect of treatment on quality of life and control of neurological symptoms.