Nature reviews. Neurology
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Nature reviews. Neurology · Jun 2018
ReviewCGRP as the target of new migraine therapies - successful translation from bench to clinic.
Treatment of migraine is on the cusp of a new era with the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are expected to receive approval for use in migraine headache in 2018 and 2019. CGRP-related therapies offer considerable improvements over existing drugs as they are the first to be designed specifically to act on the trigeminal pain system, they are more specific and they seem to have few or no adverse effects. ⋯ We describe the biology of CGRP signalling, summarize key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatment, and synthesize what is known about the role of CGRP in the trigeminovascular system. Finally, we consider how the latest findings provide new insight into the central role of the trigeminal ganglion in the pathophysiology of migraine.
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The leukodystrophies are a group of inherited white matter disorders with a heterogeneous genetic background, considerable phenotypic variability and disease onset at all ages. This Review focuses on leukodystrophies with major prevalence or primary onset in adulthood. We summarize 20 leukodystrophies with adult presentations, providing information on the underlying genetic mutations and on biochemical assays that aid diagnosis, where available. ⋯ We highlight the distinction between adult-onset leukodystrophies and other inherited disorders with white matter involvement, and we propose a diagnostic pathway for timely recognition of adulthood leukodystrophies in a routine clinical setting. In addition, we provide detailed clinical information on selected adult-onset leukodystrophies, including X-linked adrenoleukodystrophy, metachromatic leukodystrophy, cerebrotendinous xanthomatosis, hereditary diffuse leukoencephalopathy with axonal spheroids, autosomal dominant adult-onset demyelinating leukodystrophy, adult polyglucosan body disease, and leukoencephalopathy with vanishing white matter. Ultimately, this Review aims to provide helpful suggestions to identify treatable adulthood leukodystrophies at an early stage in the disease course.
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Nature reviews. Neurology · Jan 2018
ReviewIdiopathic REM sleep behaviour disorder and neurodegeneration - an update.
So-called idiopathic rapid eye movement (REM) sleep behaviour disorder (RBD), formerly seen as a rare parasomnia, is now recognized as the prodromal stage of an α-synucleinopathy. Given the very high risk that patients with idiopathic RBD have of developing α-synucleinopathies, such as Parkinson disease (PD), PD dementia, dementia with Lewy bodies or multiple system atrophy, and the outstandingly high specificity and very long interval between the onset of idiopathic RBD and the clinical manifestations of α-synucleinopathies, the prodromal phase of this disorder represents a unique opportunity for potentially disease-modifying intervention. ⋯ The role of video polysomnography in providing quantifiable and potentially treatment-responsive biomarkers of neurodegeneration is highlighted. In light of all these advances, and the now understood role of idiopathic RBD as an early manifestation of α-synuclein disease, we call for idiopathic RBD to be reconceptualized as isolated RBD.
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Nature reviews. Neurology · Dec 2017
ReviewHuman models of migraine - short-term pain for long-term gain.
Migraine is a complex disorder characterized by recurrent episodes of headache, and is one of the most prevalent and disabling neurological disorders. A key feature of migraine is that various factors can trigger an attack, and this phenomenon provides a unique opportunity to investigate disease mechanisms by experimentally inducing migraine attacks. ⋯ We describe the development and use of these models in the discovery of molecular pathways that are responsible for initiation of migraine attacks. Combining experimental human models with advanced imaging techniques might help to identify biomarkers of migraine, and in the ongoing search for new and better migraine treatments, human models will have a key role in the discovery of future targets for more-specific and more-effective mechanism-based antimigraine drugs.
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Nature reviews. Neurology · Dec 2017
ReviewMigrainomics - identifying brain and genetic markers of migraine.
Migraine is one of the world's most prevalent and disabling disorders and imposes an enormous socioeconomic burden. The exact causes of migraine are unknown, and no recognizable diagnostic pathological changes have been identified. Specific identifiable markers of migraine would aid diagnosis and could provide insight into the pathogenesis of the condition, with the potential to direct development of new therapeutics. ⋯ In total, 44 independent single-nucleotide polymorphism loci have been robustly associated with the risk of migraine and provide new evidence for the involvement of vascular mechanisms. Both imaging and genetics, therefore, have excellent potential as markers of migraine. In this Review, we provide a summary of results regarding current and potential neuroimaging and genetic markers of migraine, consider what conclusions can be drawn from these markers about migraine mechanisms and discuss the potential of combining imaging and genetics.