Rev Neurol France
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Approximately 20% of patients with the neurodegenerative disorder frontotemporal dementia (FTD) have an autosomal dominant pattern of inheritance. Genetic FTD is caused by mutations in three genes in most cases (progranulin, microtubule-associated protein tau and chromosome 9 open reading frame 72) although a number of other genes are rare causes. ⋯ Lastly, neuropsychometric tests become abnormal in proximity to the onset of symptoms. Such studies have been relatively small until now but research centres with an expertise in genetic FTD are now forming consortia such as the Genetic Frontotemporal Dementia Initiative (GenFI) to create larger cohorts that can form the basis of future clinical trials.
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Review Comparative Study
Frontotemporal lobar degeneration and amyotrophic lateral sclerosis: molecular similarities and differences.
In the last years, new disease proteins and genes have been identified in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), leading to a dramatic shift in our understanding of the molecular mechanisms underlying both conditions. The vast majority of FTLD and ALS are characterized by the abnormal accumulation of TDP-43, including genetic forms associated with mutations in the genes C9ORF72, GRN, TARDBP and VCP. The overlap in pathology and of genetic factors, particularly C9ORF72 as common cause of ALS and FTLD, provides molecular evidence that both conditions represent a spectrum of diseases sharing similar pathomechanisms. ⋯ However, here some striking differences have been identified. All members of the FET family (FUS, EWS, TAF15) are co-accumulating with their nuclear import receptor Transportin in FTLD-FUS which is usually not associated with FUS mutations, whilst ALS-FUS is almost always associated with FUS mutations and reveals only FUS aggregates. Together with recent data demonstrating differences in the arginine methylation status of FUS in FTLD-FUS and ALS-FUS, these findings strongly imply at least partially distinct underlying disease mechanisms in these molecular subtypes of ALS and FTLD.
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Centronuclear myopathies (CNM) are rare inherited disorders characterized by nuclei placed in rows in the central part of the muscle fibres. Three CNM-causing genes have been identified, with MTM1 mutations provoking X-linked myotubular myopathy, DNM2 mutations provoking autosomal dominant (AD) CNM, and BIN1 mutations provoking autosomal recessive (AR) CNM. ⋯ Adult CNM is a slowly progressive distal myopathy with normal CK levels sometimes associated with cognitive impairment, axonal polyneuropathy, and ophthalmoparesis and ptosis. DNM2 mutations were found in eight patients, including AD and sporadic cases, and represent the major cause of CNM in this adult cohort. In contrast, no MTM1 and BIN1 mutations were observed in our series, leaving six patients with no molecular diagnosis. As these six patients presented with AD (3 cases), AR (2 cases), and sporadic (1 case) CNM, it is likely that several CNM-causing genes remain to be discovered.
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This review summarizes the history of migraine imaging and key findings of studies on functional neuroimaging in migraine and describes how these data have changed our view of the disorder. Functional neuroimaging during migraine attacks and also interictally has initiated the description of "the migraine brain". These studies have led to the demonstration of cortical spreading depression in migraine with aura, the crucial role for the brainstem during migraine attacks, and cortical hypersensitivity in migraineurs modulated by the trigeminal pathway, explaining sensory sensitization such as photophobia and osmophobia.
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The second edition of the International Classification of Headache Disorders revised in 2006 (ICHD-2R) gives a definition which requires 15 or more headache days per month over the past 3months with at least eight headache days per month that meet criteria for migraine without aura or that responds to migraine specific treatment. Approximately 2% of the global population suffers of chronic migraine (CM). ⋯ There is a high frequency of medication overuse. The treatment depends on evaluation with education, lifestyle modifications, and trigger management, behavioral and pharmacologic therapies.