Pre-symptomatic diagnosis in ALS.

Pre-symptomatic diagnosis in ALS. Rev Neurol (Paris). 2020 Jan 10;: Authors: Corcia P, Lumbroso S, Cazeneuve C, Mouzat K, Camu W, Vourc'h P, on Behalf the FILSLAN network Abstract Pathophysiology of amyotrophic lateral sclerosis (ALS) remains partially understood even though it is accepted worldwide that motor neuron death results from a pluri-factorial process with a variable role of genetic factors. Although not distinguishable from a clinical point of view, familial forms of ALS (fALS, 10% of cases) and sporadic forms (sALS, 90% of cases) can be described. Since the identification of superoxide dismutase 1 gene (SOD1) mutations, more than 30 genes have been linked to fALS. Among these genes, five (C9ORF72, SOD1, TARDBP, FUS, TBK1) seem predominant with mutation frequencies of 40%, 20%, 5%,
Source: Revue Neurologique - Category: Neurology Tags: Rev Neurol (Paris) Source Type: research

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We appreciate the criticism raised by Dr. Matsuura questioning the genetic evaluation for NOP56 gene of Asidan (spinocerebellar ataxia 36) showing clinical anticipation. Asidan is an autosomal dominant neurodegenerative disorder caused by a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene, showing cerebellar ataxia, motor neuron disease phenotype, hearing loss and frontal cognitive impairment [1 –3]. The NOP56 genetic mutation in Asidan is similar to the hexanucleotide GGGGCC repeat expansion in intron 1 of the C9orf72 gene observed in familial amyotrophic lateral sclerosis/frontotemporal dementia...
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
Purpose of review The current review provides an up to date overview of the nature and progression of the cognitive and behavioural impairment in amyotrophic lateral sclerosis (ALS). Understanding these symptoms has implications for the management of the disease and the design of clinical trials, in addition to the support of patient and caregiver regarding mental capacity and end of life decision-making. Recent findings Cognitive and behavioural change in ALS are best characterized as the consequence of extensive network dysfunction. 35–45% of ALS patients present with mild–moderate cognitive impairment a...
Source: Current Opinion in Neurology - Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Jinsy A. Andrews Source Type: research
AbstractAmyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP) are motor neuron diseases sharing clinical, pathological, and genetic similarities. While biallelicSPG7 mutations are known to cause recessively inherited HSP, heterozygousSPG7 mutations have repeatedly been identified in HSP and recently also in ALS cases. However, the frequency and clinical impact of rareSPG7 variants have not been studied in a larger ALS cohort. Here, whole-exome (WES) or targetedSPG7 sequencing was done in a cohort of 214 European ALS patients. The consequences of a splice site variant were analyzed on the mRNA level. T...
Source: Journal of Neurology - Category: Neurology Source Type: research
Primary lateral sclerosis (PLS) is a rare type of motor neuron disease (MND) characterized by the loss of upper motor neurons without lower motor neuron involvement [1]. In contrast, amyotrophic lateral sclerosis (ALS) is a common type of MND that is occasionally complicated by frontotemporal dementia (FTD) as the TDP-43 proteinopathy. However, there are few studies on the relationship of PLS with ALS, FTD and TDP-43 proteinopathy because of the rarity of autopsy cases. Here, we report a 68-year-old woman who exhibited typical clinical symptoms of PLS at onset, which then progressed to FTD, although her pathological diagno...
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
;dérique R Abstract Amyotrophic lateral sclerosis and frontotemporal dementia are two neurodegenerative diseases with currently no cure. These two diseases share a clinical continuum with overlapping genetic causes. Mutations in the CHMP2B gene are found in patients with ALS, FTD and ALS-FTD. To highlight deregulated mechanisms occurring in ALS-FTD linked to the CHMP2B gene, we performed a whole transcriptomic study on lumbar spinal cord from CHMP2Bintron5 mice, a model that develops progressive motor alterations associated with dementia symptoms reminiscent of both ALS and FTD. To gain insight into the tra...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 149Author(s): James B. RoweAbstractFrontotemporal dementia is a clinically and pathologically heterogeneous group of neurodegenerative disorders, with progressive impairment of behavior and language. They can be closely related to amyotrophic lateral sclerosis, clinically and through shared genetics and similar pathology. Approximately 40% of people with frontotemporal dementia report a family history of dementia, motor neuron disease or parkinsonism, and half of these familial cases are attributed to mutations in three genes (C9orf72, MAPT and PGRN...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Publication date: Available online 21 November 2019Source: International Review of NeurobiologyAuthor(s): James B. RoweAbstractFrontotemporal dementia is a clinically and pathologically heterogeneous group of neurodegenerative disorders, with progressive impairment of behavior and language. They can be closely related to amyotrophic lateral sclerosis, clinically and through shared genetics and similar pathology. Approximately 40% of people with frontotemporal dementia report a family history of dementia, motor neuron disease or parkinsonism, and half of these familial cases are attributed to mutations in three genes (C9orf...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
The primary role of magnetic resonance imaging (MRI) in routine diagnostic work-up of motor neuron disease patients is currently still largely limited to exclusion of relevant non-degenerative pathologies. We here present an illustrative case of a 63-year-old woman with early stage Frontotemporal-Dementia-Amyotrophic-Lateral-Sclerosis (FTD-ALS) spectrum disorder showing a striking hypointense signal of the cortical band along the precentral gyrus, termed “Motor Band Sign” (MBS). Based on this finding, we analysed the frequency of the MBS in clinical routine MRIs in a large consecutive series of ALS patients (MR...
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Source Type: research
Purpose of review The fatal motoneuron disease amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a high contribution of genetic factors to pathogenesis, in probably both familial and sporadic ALS cases. State-of-the art sequencing techniques continue to reveal novel monogenic causes for ALS, risk factors and modifiers. This leads to an improved genotype/phenotype correlation and is becoming increasingly relevant for genetic diagnosis, counseling and therapy. The first gene-specific therapies are being tested in ongoing clinical trials. Consequently, this review aims to summarize the most important ...
Source: Current Opinion in Neurology - Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert C. Ludolph Source Type: research
Abstract Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. A strong genetic component has been shown in PDB, and variants in several genes, such as SQSTM1, VCP, and OPTN, have been associated with the disease. Mutations in the same genes have also been reported in patients with frontotemporal dementia and amyotrophic lateral sclerosis. Hexanucleotide repeat expansions in the C9ORF72 gene have been shown to be responsible for both familial and sporadic frontotemporal dementia/amyotrophic lateral sclerosis. Thence, we evaluated the frequency of the C9ORF72 hexanucleotide repe...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research
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