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)

During a 16-year period 672 patients were admitted to the Columbia Presbyterian Medical Center with spastic paraplegia-paraparesis (SPP) as a prominent finding. Group I. 520 patients (77.3%) had either a familial disorder, sensory findings, other neurological signs, or a diagnosis obvious on admission by history, examination or plain spine roentgenograms. Group II. In 108 patients (16.2%) diagnosis was reached after more extensive investigation. In 78 of these a cause other than multiple sclerosis was found including spinal cord tumor, arteriovenous malformation and cervical spondylotic myelopathy. Thirteen patients had probable multiple sclerosis on the basis of additional signs emerging, and 17 were considered to have possible multiple sclerosis on the basis of elevated CSF gamma-globulin. Group III. In 44 patients (6.5%) no cause for SPP could be found. Diagnostic considerations for this group included amyotrophic lateral sclerosis, multiple sclerosis, unappreciated structural lesions, hereditary disease, and "primary lateral sclerosis".
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PMID:Spastic paraplegia-paraparesis. A reappraisal. 615 77

Amyotrophic lateral sclerosis is one of the most common neurodegenerative disorders, with an incidence of about 1/100,000. One of the typical features of this progressive, lethal disease, occurring both sporadically and as a familial disorder, is degeneration of cortical and spinal motor neurones. Present evidence indicates that loss of neurones in patients results from a complex interplay among oxidative injury, excitotoxic stimulation, dysfunction of critical proteins and genetic factors. This review focuses on existing evidence that oxidative stress is a major culprit in the pathogenesis of amyotrophic lateral sclerosis. An increase in reactive oxygen species and in products of oxidation has been observed both in post-mortem samples and in experimental models for ALS. This increase may be consequent to altered metabolism of copper and iron ions, that share the property to undergo redox cycling and generate reactive oxygen species. Metal-mediated oxidative stress would lead to several intracellular alterations and contribute to the induction of cell death pathways.
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PMID:Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals. 1290 79

Work done over the past decade has led to a molecular understanding of frontotemporal lobar degeneration (FTLD), a deadly disease that afflicts patients in mid-life. It is a common cause of dementia, second only to Alzheimer's disease in the population below 65 years of age. Neuroanatomical and neurobiological substrates have been identified for the three major subtypes of FTLD and these discoveries have broadened the FTLD spectrum to include amyotrophic lateral sclerosis (ALS). Mutations in MAPT were found to cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), a familial disorder with filamentous tau inclusions in nerve cells and glial cells. FTDP-17 can result in clinical syndromes that closely resemble progressive supranuclear palsy, corticobasal degeneration and Pick's disease. More recently, mutations in three genes (VCP, CHMP2B and PGRN) have been found to cause FTLD with ubiquitin-positive, tau-negative neuronal inclusions (FTLD-U). They explain a large proportion of inherited FTLD-U. It remains to be seen whether dementia lacking distinctive histopathology (DLDH) constitutes a third disease category, as many of these cases are now being reclassified as FTLD-U. Recently, TAR DNA-binding protein-43 (TDP-43) has been identified as a key protein of the ubiquitin inclusions of FTLD-U and ALS. Thus, for familial forms of FTLD and related disorders, we now know the primary etiologies and accumulating proteins. These findings are pivotal for dissecting the pathways by which different etiologies lead to the varied clinicopathological presentations of FTLD.
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PMID:Frontotemporal lobar degeneration: current concepts in the light of recent advances. 1749 44

Amyotrophic lateral sclerosis (ALS) is a late-onset, progressive motor neuronal degenerative disease occurring as sporadically and as a familial disorder. The patients with ALS typically become progressively paralyzed and develop respiratory failure that eventually leads to death within 3-5years. For this disease, there is no effective diagnostic method and also drug. This report describes a simple and useful diagnostic biomarker for ALS. Our findings suggest that the combination analysis of a metabolite of prostaglandin D2, 11,15-dioxo-9-hydroxy-,2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor PGDM and tPGDM) with creatinine is the diagnostic approach for ALS with high accuracy. tPGDM has the potential to be an important diagnostic tool in the pre-symptomatic stages and progression evaluation of ALS, and also to be a biomarker for the evaluation of drug effect.
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PMID:Tetranor PGDM analyses for the amyotrophic lateral sclerosis: positive and simple diagnosis and evaluation of drug effect. 2202 43

Numerous kindreds with familial frontotemporal dementia and/or amyotrophic lateral sclerosis have been linked to chromosome 9, and an expansion of the GGGGCC hexanucleotide repeat in the non-coding region of chromosome 9 open reading frame 72 has recently been identified as the pathogenic mechanism. We describe the key characteristics in the probands and their affected relatives who have been evaluated at Mayo Clinic Rochester or Mayo Clinic Florida in whom the hexanucleotide repeat expansion were found. Forty-three probands and 10 of their affected relatives with DNA available (total 53 subjects) were shown to carry the hexanucleotide repeat expansion. Thirty-six (84%) of the 43 probands had a familial disorder, whereas seven (16%) appeared to be sporadic. Among examined subjects from the 43 families (n = 63), the age of onset ranged from 33 to 72 years (median 52 years) and survival ranged from 1 to 17 years, with the age of onset <40 years in six (10%) and >60 in 19 (30%). Clinical diagnoses among examined subjects included behavioural variant frontotemporal dementia with or without parkinsonism (n = 30), amyotrophic lateral sclerosis (n = 18), frontotemporal dementia/amyotrophic lateral sclerosis with or without parkinsonism (n = 12), and other various syndromes (n = 3). Parkinsonism was present in 35% of examined subjects, all of whom had behavioural variant frontotemporal dementia or frontotemporal dementia/amyotrophic lateral sclerosis as the dominant clinical phenotype. No subject with a diagnosis of primary progressive aphasia was identified with this mutation. Incomplete penetrance was suggested in two kindreds, and the youngest generation had significantly earlier age of onset (>10 years) compared with the next oldest generation in 11 kindreds. Neuropsychological testing showed a profile of slowed processing speed, complex attention/executive dysfunction, and impairment in rapid word retrieval. Neuroimaging studies showed bilateral frontal abnormalities most consistently, with more variable degrees of parietal with or without temporal changes; no case had strikingly focal or asymmetric findings. Neuropathological examination of 14 patients revealed a range of transactive response DNA binding protein molecular weight 43 pathology (10 type A and four type B), as well as ubiquitin-positive cerebellar granular neuron inclusions in all but one case. Motor neuron degeneration was detected in nine patients, including five patients without ante-mortem signs of motor neuron disease. While variability exists, most cases with this mutation have a characteristic spectrum of demographic, clinical, neuropsychological, neuroimaging and especially neuropathological findings.
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PMID:Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. 2236 93

A hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 (C9ORF72) gene was recently discovered as the cause underlying frontotemporal degeneration (FTD) and/or amyotrophic lateral sclerosis (ALS) linked to chromosome 9 (c9FTD/ALS). In this atypical case of c9FTD/ALS, the proband presented with amnestic mild cognitive impairment which evolved into Alzheimer's disease (AD)-type dementia and later developed ALS. Fluorodeoxyglucose-positron emission tomography of the brain demonstrated mild hypometabolism involving the medial frontal and lateral temporal lobes, left more so than right, which progressed over time. He was subsequently confirmed to have the C9ORF72 expansion. This report highlights the need to consider mutations in the FTD-associated genes when a familial disorder is suggested and neuroimaging studies reveal findings atypical of an AD pathophysiological process despite the typical anterograde amnestic syndrome.
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PMID:The GGGGCC repeat expansion in C9ORF72 in a case with discordant clinical and FDG-PET findings: PET trumps syndrome. 2319 40