Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The association of Pick's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) as a familial syndrome is reported for the first time. Four members in two generations of the investigated family suffered from this syndrome, allowing the hypothesis of a dominant mode of inheritance. PD is primary, with onset at 58 to 67 years: loss of interests, depression, aggressivity, perseveration , stereotypies, reduction of speech until total mutism; a few months later appear ALS signs: fasciculations and/or pyramidal symptoms. The total evolution is 3 to 5 years. The brain showed a fronto-temporal atrophy spreading to the precentral gyrus with cortical and white matter gliosis, neuronal loss, atrophic neurons and some ballooned cells, but without senile plaques (SP), neurofibrillary tangles (NFT) or cortical spongiosis; the spinal cord and the medulla oblongata showed typical ALS lesions; mild lesions in the basal nuclei, particularly in the substantia nigra and the pallidum. The differential diagnosis is discussed with: Alzheimer's Disease + ALS (SP + NFT); the Guam syndrome (NFT); Creutzfeldt-Jakob's Disease (cortical microspongiosis); ALS + dementia (primary ALS); Mitsuyama's syndrome (primary dementia and secondary ALS, but with cortical spongiosis and without familial incidence).
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PMID:[A familial syndrome: a combination of Pick's disease and amyotrophic lateral sclerosis]. 332 1

We wished to determine whether patients with amyotrophic lateral sclerosis (ALS) show behavioural changes similar to those of frontotemporal dementia (FTD). There is accumulating evidence to suggest a link between ALS and FTD, yet there has been little systematic exploration of behaviour in ALS. An informant based semi-structured behavioural interview, sensitive to the behavioural changes of FTD, was administered to carers of 16 consecutive patients attending a motor neuron disease clinic. Findings varied across the group. At one extreme informants reported no behavioural change, whereas at the other they reported a spectrum of behaviours similar to those seen in FTD. Changes in affect and social behaviour were most common, although some patients also showed altered response to sensory stimuli, gluttony and indiscriminate eating, behavioural stereotypies and compulsions. Behavioural changes were mirrored by SPECT abnormalities in the frontal and/or temporal lobes. Thus, behavioural changes of the type seen in FTD may be present even in a small consecutive cohort of ALS patients. Detection of behavioural change is crucial for optimal management.
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PMID:Behaviour in amyotrophic lateral sclerosis. 1842 98

Corticobasal syndrome (CBS) is a neurodegenerative disease characterized by progressive asymmetrical rigidity and apraxia, cortical sensory loss, myoclonus, dystonia, and cognitive impairment. CBS is usually sporadic and associated with tau pathology but there are reports of TDP-43 pathology. We screened 39 CBS cases to determine if any of the cases could be explained by a G4C2-repeat expansion in a noncoding region of C9orf72 gene, the most common genetic cause of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. One patient with CBS had a large (>50 repeats) expansion in C9orf72. Our case features a 63-year-old right-handed woman who developed mild apathy 9 years before presentation, which progressed to include behavioral symptoms, oral stereotypies, significant language impairment, parkinsonism and apraxia. A magnetic resonance imaging acquired at age 60 years, that is, 6 years after disease onset revealed significant asymmetric left > right frontotemporal atrophy, including orbitofrontal and parietal areas. Her father developed a behavioral syndrome and died at an early age. This case highlights the importance of genetic screening for C9orf72 in patients with CBS.
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PMID:Mutation analysis of C9orf72 in patients with corticobasal syndrome. 2616 5

Mutations in the charged multivesicular body protein 2B (CHMP2B) are associated with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and with a mixed ALS-FTD syndrome. To model this syndrome, we generated a transgenic mouse line expressing the human CHMP2Bintron5 mutant in a neuron-specific manner. These mice developed a dose-dependent disease phenotype. A longitudinal study revealed progressive gait abnormalities, reduced muscle strength and decreased motor coordination. CHMP2Bintron5 mice died due to generalized paralysis. When paralyzed, signs of denervation were present as attested by altered electromyographic profiles, by decreased number of fully innervated neuromuscular junctions, by reduction in size of motor endplates and by a decrease of sciatic nerve axons area. However, spinal motor neurons cell bodies were preserved until death. In addition to the motor dysfunctions, CHMP2Bintron5 mice progressively developed FTD-relevant behavioural modifications such as disinhibition, stereotypies, decrease in social interactions, compulsivity and change in dietary preferences. Furthermore, neurons in the affected spinal cord and brain regions showed accumulation of p62-positive cytoplasmic inclusions associated or not with ubiquitin and CHMP2Bintron5 As observed in FTD3 patients, these inclusions were negative for TDP-43 and FUS. Moreover, astrogliosis and microgliosis developed with age. Altogether, these data indicate that the neuronal expression of human CHMP2Bintron5 in areas involved in motor and cognitive functions induces progressive motor alterations associated with dementia symptoms and with histopathological hallmarks reminiscent of both ALS and FTD.
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PMID:A transgenic mouse expressing CHMP2Bintron5 mutant in neurons develops histological and behavioural features of amyotrophic lateral sclerosis and frontotemporal dementia. 2732 63