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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A retrospective study of endogenous and exogenous risk factors in amyotrophic lateral sclerosis (ALS) was conducted in 35 ALS patients and 35 healthy controls, using guided questioning. No significant correlation was detected between the disease and most of the environmental factors explored. A significant difference (p less than 0.05) was found between patients and controls in only two parameters: 1) occurrence of injuries during the year that preceded the diagnosis of ALS (usually localized to the limbs), and 2) regular practice of sports in adulthood. It appeared that injuries often revealed but could not be considered as a possible cause of the disease. Analysis of the sport activities was not sufficient for a definite conclusion. On the other hand, 11 p. 100 of ALS patients had a family history of ALS, and 25 p. 100 (as against 8 p. 100 of controls) had a history of degenerative disease of the nervous system. These results should lead to a reconsideration of genetic factors or to a search for exposure of several members of the same family to toxic or infectious environmental factors.
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PMID:[Risk factors in amyotrophic lateral sclerosis. Initial results apropos of 35 cases]. 177 24

Widespread astrogliosis exists in the subcortical white matter in amyotrophic lateral sclerosis (ALS). As revealed by glial fibrillary acidic protein (GFAP) immunostaining, the gliosis has the morphological properties of an active process. It is present in the midfrontal, inferior parietal, temporal, cingulate, and occipital cortices, as well as in the motor cortex. Compared to matched regions from other neurological diseases, the gliosis in ALS does not appear to be the nonspecific result of a progressive, degenerative disease. In cell number and apparent cell size, the gliosis is comparable to that present in neurological diseases known to have white matter gliosis. Cytologically, the gliosis most closely resembles that present in cases of cerebral infarction. The basis for this similarity is unknown.
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PMID:Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain. 177 89

Three aspects of neuropsychological functioning in patients with ALS are examined. Contrary to previous research, a new psychometric study of psychological adjustment suggested significant depression-distress in this population and related psychological disturbance differentially to signs of upper versus lower motor neuron involvement and to respiratory failure. An association between ALS and impaired neuropsychological functioning is discussed through an examination of the clinical and pathologic literatures. ALS appears to be a multisystem degenerative disease with a variety of expressions that may frequently include loss of cognitive-behavioral competency with progressive involvement of the prefrontal cortex and, in a few instances, profound dementia. Finally, the article describes an analysis of trends in psychological adjustment and in the perception of physical capability over the course of a pilot clinical trial.
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PMID:Neuropsychological perspectives in amyotrophic lateral sclerosis. 310 53

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of the motor system in adults that occurs in sporadic, familial, and Western Pacific forms. Involvement of non-motor pathways has been increasingly recognized, both clinically and pathologically. Although the usual course is relentlessly progressive with death in half the cases within three years from onset, it can sometimes be protracted. Degeneration and loss of large motor neurons in the cerebral cortex, brainstem, and cervical and lumbar spinal cord are characteristic. Marked reduction in the number of large myelinated fibers is notable in the cervical and lumbar ventral roots. Peripheral nerves show reduced numbers of large myelinated fibers, acute axonal degeneration at all levels, and distal axonal atrophy. Motor end-plates reveal small or absent nerve terminals. Subclinical non-motor system involvement includes neuronal loss in Clarke's nucleus and dorsal root ganglia, degeneration of non-motor tracts in the spinal cord, loss of receptors in the dorsal horns of the spinal cord, and myelinated fiber loss with segmental demyelination in sensory and mixed nerves. The serious implications of the diagnosis of ALS make it mandatory to exclude similar potentially treatable disorders. Management should be multidisciplinary, and discussions with the patient and family members should be frank and frequent. Discussions about ventilatory support should take place early in the disease so that death from respiratory failure can be prevented, when that is desired, and conversely to obviate the discontent and anger that accompany involuntary life on a ventilator.
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PMID:Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management. 405 56

To determine if immune function differed in normal Guamanian Chamorros at various ages we measured the percentage and total numbers of lymphocytes and T-lymphocytes, their response to phytohemagglutinin (PHA), and serum levels of immunoglobulin A, G, and M in subjects 20 to 83 years of age. Regression analysis showed highly significant negative correlations for total lymphocytes and T-cells with age and a less significant negative correlation for PHA response with age in this population. Serum IgA levels increased with age, IgM levels declined, and IgG levels were unchanged. These findings are similar to, but less marked than, immunologic aberrations previously observed in Guamanians with amyotrophic lateral sclerosis or Parkinsonism-dementia. The occurrence of prominent differences in immune functions between younger and older individuals in a population where neurofibrillary degeneration in brain occurs at an early age and neurodegenerative and other age-related diseases are highly prevalent suggests the possibility that immunity and age-associated degenerative disease may be linked etiologically in this population.
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PMID:Immune function among normal Guamanians of different age. 660 28

Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons, characterized by depositions of neurofilaments in the perikarya and proximal axons. The pathogenesis of ALS remains poorly understood, but two lines of evidence suggest that neurofilament accumulation may play a causal role. First, transgenic mice that overexpress neurofilament proteins show motor neuron degeneration and, second, variant alleles of the neurofilament heavy-subunit gene (NF-H) have been found in some human ALS patients. To investigate how disorganized neurofilaments might cause neurodegeneration, we examined axonal transport of newly synthesized proteins in mice that overexpress the human NF-H gene. We observed dramatic defects of axonal transport, not only of neurofilament proteins but also of other proteins, including tubulin and actin. Ultrastructural analysis revealed a paucity of cytoskeletal elements, smooth endoplasmic reticulum and especially mitochondria in the degenerating axons. We therefore propose that the neurofilament accumulations observed in these mice cause axonal degeneration by impeding the transport of components required for axonal maintenance, and that a similar mechanism may account for the pathogenesis of ALS in human patients.
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PMID:Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. 753 96

An autopsy case of dementia beginning with right hand muscle atrophy was reported. A 42-year-old woman with no family history of neurologic disease developed weakness of the right hand at age 30, and was diagnosed as having amyotrophic lateral sclerosis (ALS). The weakness and atrophy spread to the four extremities subsequently. At age 36, she could not walk without assistance. At age 38, she was first noted as having dementia with forced crying, and she also showed generalized muscle weakness and atrophy. She rapidly developed akinetic mutism, and died of respiratory failure at age 42, 12 years after the onset of the symptoms. Macroscopically, the brain showed fronto-temporal atrophy. Microscopic examination revealed numerous intracytoplasmic inclusions throughout the central nervous system (CNS) including anterior horn of the spinal cord. The inclusions were stained moderate to dark brown with silver stain. Electron microscopically, they consisted of fibrils covered along most of the length with granular and fuzzy materials. This case was thought to be difficult to categorize in any known neuro-degenerative diseases. We proposed the case to be "atypical Pick's disease" with ALS features. This case might be a new entity of neuro-degenerative disease.
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PMID:Dementia with ALS features and diffuse Pick body-like inclusions (atypical Pick's disease?). 772 73

The recent molecular cloning of BDNF and CNTF based on traditional protein purification and protein sequencing and the identification and cloning of NT-3 and NT-4 by homology cloning strategies has led to a tremendous flurry of interest in the biology of these proteins and initiation of studies to assess their potential utility in neurological disorders ranging through degenerative disease, stroke and ischemia, trauma and peripheral neuropathies. Tissue culture studies have been very useful in identifying neuronal specificities of the neurotrophins and CNTF and in combination with localization studies of these growth factors and their receptors have provided the basis for in vivo studies. Initial animal studies with BDNF indicate efficacy of BDNF in models of Alzheimer's and Parkinson's disease and small fiber sensory neuropathy. Studies with CNTF have similarly progressed from in vitro findings, especially the discovery that CNTF is a growth factor for motor neurons, to in vivo findings where CNTF has been shown to be effective in slowing symptoms of motor neuron dysfunction in three genetic models. Based on these positive animal data, CNTF is currently in clinical trials for the potential treatment of motor neuron disease or amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.
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PMID:Neurotrophic growth factors and neurodegenerative diseases: therapeutic potential of the neurotrophins and ciliary neurotrophic factor. 783 3

Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis possess immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti-voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore-forming alpha 1 subunit of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel alpha 1 subunit-directed monoclonal antibody, which itself mimics the effects of ALS IgG on skeletal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel-binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both alpha 1 and beta subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.
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PMID:Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel alpha 1 subunit. 810 94

Human manganese superoxide dismutase (MnSOD) is a homotetrameric enzyme which protects mitochondria against oxygen-mediated free radical damage. Within each subunit, both the N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands to the catalytic manganese site. Two identical four-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form a novel tetrameric interface that stabilizes the active sites. The 2.5 A crystallographic structure of the naturally occurring polymorphic variant Ile58Thr MnSOD reveals that the helical hairpin mutation Thr58 causes two packing defects in each of the two four-helix bundles of the tetrameric interface. Similar mutations, expected to cause packing defects in the Cu,ZnSOD dimer interface, are associated with the degenerative disease amyotrophic lateral sclerosis. Ile58Thr MnSOD is primarily dimeric in solution and is significantly less thermostable than the normal enzyme, with decreases of 15 degrees C in the main melting temperature and 20 degrees C in the heat-inactivation temperature. Consequently, this mutant MnSOD is compromised at normal body temperatures: thermal inactivation, predicted from the decrease in thermal stability, occurs with a theoretical half-life of only 3.2 h at 37 degrees C (1.4 h at 41 degrees C), compared with 3.1 years for native MnSOD. This prediction is supported by direct measurements: incubation at 41.7 degrees C for 3 h has no effect on the activity of native MnSOD but completely inactivates mutant MnSOD. Rapid inactivation of Ile58Thr MnSOD at the elevated temperatures associated with fever and inflammation could provide an early advantage by killing infected cells, but also would increase superoxide-mediated oxidative damage and perhaps contribute to late-onset diseases.
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PMID:Human mitochondrial manganese superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface. 860 77


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