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)

At the present time, it seems unlikely that progressive neurodegenerative diseases, such as ALS, Parkinson's disease, and dementia of the Alzheimer type, are triggered by environmental agents with excitotoxic potential. These include excitotoxic agents that behave as glutamate agonists or disrupt energy metabolism: both types elicit permanent but self-limiting neuronal diseases with patterns of neuronal deficit that reflect selective chemical exposure (MPP+ and parkinsonism), differential susceptibility to energy dysmetabolism (NPA and dystonia), or the distribution of glutamate-receptors (domoic acid and memory loss). If environmental agents play an etiologic role in progressive neurodegenerative diseases, they are likely to target a critical, irreplaceable neuronal molecule that is required to maintain long-term neuronal integrity.
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PMID:Are human neurodegenerative disorders linked to environmental chemicals with excitotoxic properties? 132 79

Increasing numbers of patients are being recognized with neurological abnormalities associated with the immunochemical changes of plasma cell disease. To illustrate the wide spectrum of clinical disorders that can be found, I discuss in detail 5 patients: 2 with neuropathy, 3 with amyotrophic lateral sclerosis (ALS), all of whom had serum monoclonal paraproteinemia. In addition, I report in tabular form 6 patients with paraproteinemia and the following clinical presentations: 1) systemic lupus with polyneuropathy and severe cerebritis, 2) myasthenia gravis with thymoma, 3) polymyositis, 4) polymyositis, arthritis and Grave's disease, 5) relapsing polyneuritis (one of the original patients diagnosed by Austin) and 6) ALS, dystonia and parkinsonism. Major improvements in clinical condition occurred sometimes, but not always, coincident with reductions in the levels of the paraprotein using prednisone, cyclophosphamide, chlorambucil and plasma exchange treatments even in some of the patients who had the clinical appearance of ALS. Patients with neuromuscular diseases should be routinely screened with serum immunoelectrophoresis for monoclonal gammopathy. If a monoclonal gammopathy is found and if the disease is serious, then those patients should be treated as if they had an autoimmune disorder.
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PMID:Neuropathy and motor neuron syndromes associated with plasma cell disease. 647 86

Hexosaminidase deficiency diseases or GM2-gangliosidoses were originally described as infantile encephalopathies. Recently, hexosaminidase deficiencies have been found with different phenotypes, including juvenile and adult encephalopathies, cerebellar ataxias, and motor neuron diseases. Individual cases have resembled Ramsey-Hunt syndrome, olivopontocerebellar ataxia, Friedreich ataxia, amyotrophic lateral sclerosis, Kugelberg-Welander disease, Fazio-Londe disease, and Charcot-Marie-Tooth disease. Tremor, dystonia, spastic paresis, and psychosis have been seen. Since few diagnosable causes for these system atrophies are known, these patients should be tested for hexosaminidase deficiency. These recessive disorders fit a multiple loci/multiple alleles genetic scheme, and a clinical genetic classification is presented.
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PMID:The clinical spectrum of hexosaminidase deficiency diseases. 719 92

Epidemics of neurotoxic disease in developing regions of the world are often associated with dietary dependence on plant components with inherent toxic potential or which have spoiled and become contaminated with mycotoxins. Diseases triggered by plant toxins include lathyrism and cassavism, types of irreversible spastic parapareses associated with staple diets of grass pea and bitter cassava root, respectively. Mildewed sugarcane poisoning, an encephalopathy and tardive dystonia, illustrates the neurotoxic effects of a widely distributed plant and fungal toxin. Food and medicinal use of the neurotoxic cycad plant is thought to have a role in the etiology of western Pacific amyotrophic lateral sclerosis and parkinsonism-dementia. Plant-associated neurotoxicity is a significant and preventable cause of morbidity in certain regions of Africa, Asia, and Oceania.
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PMID:Neurologic diseases associated with use of plant components with toxic potential. 832 56

The natural history of cervical dystonia (spasmodic torticollis) was investigated in a population-based study in Rochester, Minnesota. Eleven new cases were identified with onset during the 20-year period 1960-1979. The overall incidence rate was 1.2 per 100,000 person-years (95% confidence interval 0.5-1.9) with a female:male ratio of age-adjusted incidence rates of 3.6:1. A unitary etiology was not apparent: injury antedated onset in four of the 11 patients, whereas six had documented thyroid disease and four had diabetes. A family history of movement disorder was recorded for only one subject. Only one of the cases would have been classified as moderate in severity; the others were mild. In follow-up through 1993, progressive disability was noted in only two patients, and two others went into remission. Three cases of intracranial aneurysm were confirmed, two of which produced fatal subarachnoid hemorrahage. A third death was due to amyotrophic lateral sclerosis.
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PMID:Epidemiology and outcome of cervical dystonia (spasmodic torticollis) in Rochester, Minnesota. 855 13

A neurogenetic disorder is defined as a clinical disease caused by a defect in one or more genes which affect the differentiation and function of the neuroectoderm and its derivatives. Genetic findings in various neurogenetic disorders are discussed. Huntington disease, spinobulbar muscular atrophy, and the autosomal dominant cerebellar ataxias are examples of autosomal dominant disorders caused by the expansion of trinucleotides (CAG) within disease genes. The CAG expansions appear to result in a gain of gene function. Prenatal, presymptomatic, and differential diagnostic tests are based on the detection of the repeat expansions. Point mutations within disease genes result in many additional neurogenetic disorders. An autosomal dominant form of amyotrophic lateral sclerosis and various types of craniosynostotic syndromes are described. The mutations in the disease genes also appear to result in a gain of gene function. Molecular diagnosis in these disorders is based on the direct examination of the mutated gene by methods such as single-strand conformation polymorphism analysis, denaturing gradient gel electrophoresis, and direct DNA sequencing. In many neurogenetic disorders the disease gene has not yet been identified. Here molecular diagnosis relies on indirect approaches based on methods such as the analysis of linkage and of allelic association. Hereditary forms of dystonia are presented as examples. Common sporadic neurological disorders such as Alzheimer and Parkinson diseases frequently have multifactorial causes. Investigations into the molecular basis and the development of diagnostic tests in these two important diseases are discussed. At present no curative therapies exist in neurogenetic disorders. Gene therapeutic approaches, however, provide promise for a cure in at least some of these diseases. Basic principles of gene therapy are explained and attempts at gene therapy in Alzheimer and Parkinson diseases are described. Finally, some of the many obstacles are summarized that must be overcome before gene therapy becomes feasible in most monogenic neurological diseases.
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PMID:Neurogenetic diseases: molecular diagnosis and therapeutic approaches. 882 Apr 2

Riluzole has been shown recently to increase life expectancy in patients with amyotrophic lateral sclerosis. A number of experimental studies also suggest that this compound may be a neuroprotectant. We have investigated in baboons whether riluzole would protect striatal neurons from a prolonged 3-nitropropionic acid (3NP) treatment and ameliorate the associated motor symptoms. In animals receiving 3NP and the solvent of riluzole, 12 weeks of high-dose 3NP treatment resulted in the appearance of persistent leg dystonia and significant increases in the incidence of three categories of abnormal movements and in the dyskinesia index in the apomorphine test (0.5 mg/kg i.m.). Quantitative assessment of these behavioral deficits using a video movement analysis system demonstrated a significant decrease in locomotor activity and peak tangential velocity in 3NP-treated animals compared to controls. Histological analysis showed the presence of severe, bilateral, striatal lesions, localized in both caudate and putamen. Cotreatment with riluzole (4 mg/kg i.p., twice daily) significantly reduced the dyskinesia index (-35%, P < 0.02) in the apomorphine test. In the quantitative behavioral analysis, riluzole significantly ameliorated the decrease in peak tangential velocity (P < 0.02) but not the decrease in locomotor activity observed after 3NP. Comparative histological analysis of the two groups of treated animals did not demonstrate a clear neuroprotective effect of riluzole. The present study suggests that one potential therapeutic interest for riluzole in neurodegenerative disorders may reside in the reduction of motor symptoms associated with striatal lesions.
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PMID:Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration. 922 46

Neurofilaments are a major component of the axonal cytoskeleton and their abnormal accumulation is a prominent feature of the cytopathology encountered in several neurodegenerative diseases. Thus, an attractive and widely held model of pathogenesis involves the participation of disrupted neurofilaments as a common toxic intermediate. Here, in direct contrast to this hypothesis, we show that two neurodegenerative disease models in the mouse, dystonia musculorum (dt) and a superoxide dismutase 1 (SOD1)-mediated form of human motor neuron disease (amyotrophic lateral sclerosis, ALS), progress with little or no abatement on a transgenic background in which neurofilaments are withheld from the axonal compartment. By specifically excluding a necessary role for axonal neurofilaments, our observations redefine the components of the pathogenic pathway leading to axon disruption in these two degenerative diseases.
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PMID:Pathogenesis of two axonopathies does not require axonal neurofilaments. 946 35

In the last decade, a new electrophysiological tool has become available since the development of painless magnetic stimulators able to activate the primary motor cortex and the motor roots in conscious man. Therefore, it became possible to measure the conduction time within fast-conducting central motor pathways by substracting from the total latency of muscle responses elicited by cortical stimuli the conduction time in peripheral nerves. This technique proved sensitive enough to illustrate early abnormalities of central motor conduction in various neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, cervical spondylotic myelopathy, degenerative ataxias or hereditary spastic paraplegias. When recorded early after stroke, motor evoked potentials are also a valuable tool to predict functional outcome. They can also illustrate subtle pathophysiological disturbances in diseases where there is no direct involvement of central motor pathways such as Parkinson's disease, dystonia or epilepsy. Magnetic cortical stimulation also offers unique opportunities to explore intracerebral inhibitory and excitatory circuits and mechanisms of brain plasticity. The recent development of rapid rate stimulators also enables functional studies of non-motor cerebral regions such as visual or frontal cortices. Moreover, rapid rate stimulation seems useful in the treatment of drug-resistant depression but the safety of this procedure, particularly with regard to the production of seizures or kindling, remains to be fully documented.
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PMID:[Applications of cortical magnetic stimulation]. 956 96

In addition to the traditional preoccupation for accurate localization of lesions, a new trend in our discipline emphasizes therapeutic approaches to various neurological disorders. This review summarizes the result of multi-center trials that we personally participated during the past decade to present an overview of the current thought in the area of our interest. The disorders in question include dystonia, chronic inflammatory demeyelinating polyneuropathy, myoclonic epilepsy, diabetic polyneuropathy, amyotrophic lateral sclerosis, and experimental allergic neuritis. These results and other equally encouraging data suggest that we are not necessarily fighting a loosing battle in dealing with these incapacitating diseases, even though our effort often falls short of achieving a complete cure. In formulating a list of differential diagnosis, we must always entertain the possibility of remedy as the eventual goal of our clinical practice.
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PMID:[Therapy oriented neurology from repair to remedy]. 1034 32


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