Lancet neurology
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Autosomal dominant cerebellar ataxias are hereditary neurodegenerative disorders that are known as spinocerebellar ataxias (SCA) in genetic nomenclature. In the pregenomic era, ataxias were some of the most poorly understood neurological disorders; the unravelling of their molecular basis enabled precise diagnosis in vivo and explained many clinical phenomena such as anticipation and variable phenotypes even within one family. ⋯ The identification of ataxia genes raises hope that essential pathogenetic mechanisms causing SCA will become more and more apparent. Elucidation of the pathogenesis of SCA hopefully will enable the development of rational therapies for this group of disorders, which currently can only be treated symptomatically.
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Warfarin has been in routine clinical use for more than 50 years; however, it was not proven to be of benefit in both primary and secondary prevention of stroke for patients with non-valvular atrial fibrillation (AF) until about a decade ago. Despite its efficacy in reducing the risk of stroke in patients with AF by about 60%, with an absolute reduction of about 3% per year, there have always been barriers to its use. These barriers have included the need for monitoring the degree of anticoagulation with blood tests to measure the international normalised ratio, frequent dose adjustments to maintain this ratio within quite a narrow therapeutic range, and the risk of bleeding should the upper limits of this range be exceeded. Aspirin has also been used but is less effective. ⋯ New oral drugs are being tested; these may be as effective at reducing stroke risk as warfarin in patients with AF. Direct thrombin inhibitors such as ximelagatran are not inferior to warfarin and, based on results from the SPORTIF III and V trials, are perhaps safer, with no need for long-term monitoring and dose adjustment. However, the side-effect of raised amounts of the liver enzyme alanine amino-transferase in 6% of patients needs to be resolved. In the ACTIVE trial, the efficacy of a combination of antiplatelet drugs (aspirin plus clopidogrel) is being tested against dose-adjusted warfarin; and in AMADEUS, the factor-Xa inhibitor and pentasaccharide idraparinux is being assessed in a similar way. Several surgical procedures and devices are also being developed to control AF rhythm and prevent stroke. WHERE NEXT?: The place of these new drugs in the management of AF needs to be established. In the short term, it seems that ximelagatran will replace warfarin in patients for whom there is evidence of a favourable risk-to-benefit ratio. The SPORTIF population consists of patients with AF plus at least one risk factor. More information about the effect of raised liver enzymes will probably not be available until phase IV studies are completed. Combination antiplatelet drugs need to be tested further--perhaps even triple therapy with aspirin, clopidogrel, and dipyridamole--if the results of ACTIVE are encouraging. The place of surgical procedures and devices to control rhythm and prevent stroke is unclear. Whatever happens, there is a high probability that the days of warfarin are numbered.
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Headache syndromes can be associated with focal neurological symptoms or signs. Good knowledge of primary headaches, a detailed history and a thorough clinical examination are prerequisites for their differential diagnosis. ⋯ However, structural lesions, such as vascular malformations, can produce similar symptoms to migraine with aura, which highlights that paraclinical investigations are necessary in most patients with headache and focal neurological symptoms. In this review, we provide an overview of the differential diagnosis of the most common headache disorders with focal neurological symptoms or signs to refresh the practising neurologist's differential diagnostic knowledge for the clinical situation and to aid the teaching of neurology residents.
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The retinal microcirculation can be viewed non-invasively to give a unique perspective of the cerebral microcirculation in vivo. Studying pathological changes of retinal blood vessels (microaneurysms, retinal haemorrhages, and retinal arteriolar narrowing) may help to understand the causes of various cerebrovascular disorders. Retinal photography provides such an opportunity. ⋯ Several recent studies have shown that retinal microvascular changes are reliably documented by retinal photographs. These retinopathy changes seem to be fairly common in the general population, even in people without hypertension or diabetes. Retinopathy is related to incident clinical stroke and stroke mortality and to MRI-defined subclinical cerebral white-matter lesions and cerebral atrophy, independent of blood pressure, diabetes, and other cerebrovascular risk factors. WHERE NEXT?: Retinal microvascular abnormalities seem to be markers of concomitant cerebral microangiopathy, and retinal photography may be useful for the investigation of microvascular disorders of the brain in clinical and epidemiological settings. Future research should be aimed at the development of standardised photographic methods for the assessment of retinal microvascular changes, the replication of these findings in other populations and in people with other cerebrovascular disorders, and the examination of the increased accuracy of stoke-risk stratification given by retinal photography