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)

Seventy-one Japanese cases of presenile dementia with motor neuron disease were reviewed. The clinico-pathological features were: (1) progressive dementia with insidious onset, mostly in the presenile period: (2) neurogenic muscular wasting in the course of illness (ALS- or SPMA-like symptoms); (3) duration from the onset of the illness to death: 2-5 years (average 30.6 months); (4) extrapyramidal symptoms and definite sensory deficits are less commonly present; (5) no characteristic abnormalities in the CSF or EEG; (6) no known consanguinity or familial occurrence; (7) non-specific mild to moderate degenerative changes in the fronto-temporal cerebral cortex, hypoglossal nuclei and spinal cord, and frequently in the substantia nigra. The author was interested in discovering whether the frequency and topology of lesions in the brain of patients with presenile dementia and motor neuron disease differed characteristically from the distribution found in cases of Alzheimer's disease, Pick's disease, Creutzfeldt-Jakob disease or progressive subcortical gliosis. Presenile dementia with motor neuron disease might be a new disease entity.
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PMID:Presenile dementia with motor neuron disease. 840 81

This is the report of a case of a 41-year-old male patient with a rapidly progressing amyotrophic lateral sclerosis (ALS) combined with a severe presenile dementia. Screening for antibody binding on fresh-frozen human brain sections, we found that the patient's cerebrospinal fluid contained antibodies against microglia, the dominant and potentially cytotoxic immuneffector cell of the brain. This finding extends previous observations of CSF autoantibodies against microglia in neurodegenerative diseases. It demonstrates that in addition to antigens of neuronal origin (e.g. anti-Purkinje cell antibodies in paraneoplastic cerebellar dysfunction), glial antigens also appear to be under the surveillance of the CNS and/or the peripheral immune system. Our data provide evidence for a close link between neurodegeneration and the activation of microglia; a possible local antigen production against microglia/brain macrophages, which might regulate the concomitant glial activation in neurodegenerative diseases; and the presence of microglia-binding cerebrospinal antibodies as a marker for the acuity of the disease process underlying the acute deterioration of the neurological and cognitive performance in patients with, e.g., ALS. Future therapeutic strategies could therefore include the modulation of the possibly disease-promoting activation of microglia/brain macrophages.
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PMID:Antibodies against microglia/brain macrophages in the cerebrospinal fluid of a patient with acute amyotrophic lateral sclerosis and presenile dementia. 852 21

The role of immune factors in the pathogenesis of ALS is taken into account and, in view of this, it was decided to study the role of interleukins (IL) taking IL-6 as an example. Its concentration was determined in blood and CSF with Amersham RIA kits. The study was carried out on 16 ALS patients and 16 patients with low back pain who served as controls. The IL-6 level in blood and CSF did not vary between these groups statistically significantly. Then from the ALS group the cases with only bulbar symptoms or with predominance of bulbar symptoms were isolated. This subgroup comprised 6 patients, their mean age was higher, and disease duration was shorter. The IL-6 level in the CSF was 27.1 +/- 8.6 nmol/ml and was statistically significantly higher than in the remaining cases. The specificity of this finding is discussed.
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PMID:[The level of Interleukin-6 in patients with amyotrophic lateral sclerosis]. 854 32

There is evidence of oxidative injury in postmortem brain, spinal cord, and CSF of patients with sporadic amyotrophic lateral sclerosis (SALS patients). We investigated the oxidative metabolism and calcium homeostasis in peripheral blood lymphocytes from such patients and did not find statistical differences in the basal oxygen consumption rate (QO2), cytochrome c oxidase activity, catalase activity, and lactate production. However the increase in QO2, induced by an uncoupler of oxidative phosphorylation, was depressed and the basal (resting) level of free cytosolic calcium ([Ca2+]in) was higher in lymphocytes from SALS patients (p < 0.01). Further increase in free [Ca2+]in challenged by a K+ channel blocker or by an uncoupler of oxidative phosphorylation was similar in SALS and control lymphocytes. The results show that systemic changes consistent with the presence of mitochondrial and of calcium metabolism dysfunction are present in SALS.
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PMID:Amyotrophic lateral sclerosis: oxidative energy metabolism and calcium homeostasis in peripheral blood lymphocytes. 885 45

In the present study we describe an ELISA to quantify the light subunit of the neurofilament triplet protein (NFL) in CSF. The method was validated by measuring CSF NFL concentrations in healthy individuals and in two well-characterized groups of patients with amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). The levels were increased in ALS (1,743 +/- 1,661 ng/L; mean +/- SD) and AD (346 +/- 176 ng/L) compared with controls (138 +/- 31 ng/L; p < 0.0001 for both). Within the ALS group, patients with lower motor neuron signs only had lower NFL levels (360 +/- 237 ng/L) than those with signs of upper motor neuron disease (2,435 +/- 1,633 ng/L) (p < 0.05). In a second study patients with miscellaneous neurodegenerative diseases were investigated (vascular dementia, olivopontocerebellar atrophy, normal pressure hydrocephalus, cerebral infarctions, and multiple sclerosis), and the CSF NFL level was found to be increased (665 +/- 385 ng/L; p < 0.0001). NFL is a main structural protein of axons, and we suggest that CSF NFL can be used to monitor neurodegeneration in general, but particularly in ALS with involvement of the pyramidal tract.
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PMID:Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF. 886 8

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterized by upper and lower motoneurone degeneration. Excitotoxicity and oxidative stress have been proposed as possible aetiological factors. We measured the neuronal death induced in rat cortical cell cultures by CSF taken from seven ALS patient and seven control subjects with lumbar radiculopathies. Cultures were exposed to CSF for 48 h at a dilution of 1:4. Some cultures were also exposed to antioxidant drugs, the free radical scavenger vitamin E (250 microM) and the xanthine oxidase inhibitor allopurinol (50 microM), alone or combined. The mean neuronal death rate was 31.8 +/- 3.4% in cultures exposed to ALS CSF and 10.9 +/- 1.8% in cultures exposed to control CSF. The cytotoxicity of ALS CSF was partially blocked by vitamin E (21.6 +/- 3%) or by allopurinol (18.6 +/- 2.7%). The combination of these two antioxidants reduced the toxicity from 31.8 +/- 3.4% to 10.6 +/- 1.7%. The present work suggests that neurotoxicity induced by CSF from patients with ALS indirectly involves free radicals. A combination of allopurinol and vitamin E may be useful in ALS therapy.
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PMID:Antioxidant drugs block in vitro the neurotoxicity of CSF from patients with amyotrophic lateral sclerosis. 890 5

The excitotoxic hypothesis of neurodegeneration has stimulated much interest in the possibility of using compounds that will block excitotoxic processes to treat neurologic disorders. Riluzole is a neuroprotective drug that blocks glutamatergic neurotransmission in the CNS. Riluzole inhibits the release of glutamic acid from cultured neurons, from brain slices, and from corticostriatal neurons in vivo. It is thought these effects may be partly due to inactivation of voltage-dependent sodium channels on glutamatergic nerve terminals, as well as activation of a G-protein-dependent signal transduction process. Riluzole also blocks some of the postsynaptic effects of glutamic acid by noncompetitive blockade of N-methyl-D-aspartate (NMDA) receptors. In vivo, riluzole has neuroprotective, anticonvulsant, and sedative properties. In a rodent model of transient global cerebral ischemia, a complete suppression of the ischemia-evoked surge in glutamic acid release has been observed. In vitro, riluzole protects cultured neurons from anoxic damage, from the toxic effects of glutamic-acid-uptake inhibitors, and from the toxic factor in the CSF of patients with amyotrophic lateral sclerosis.
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PMID:The pharmacology and mechanism of action of riluzole. 895 95

A 68-year-old female had been well until the age of 52 when she noticed weakness and atrophy of her right small hand muscles. She began to have gait disturbance at the age of 63. On admission, neurological examinations revealed atrophy and weakness of the small hand muscles on both sides as well as spastic paraparesis. As the antibody titer for human T-lymphotropic virus type I (HTLV-I) was elevated both in the serum and CSF, a diagnosis of HTLV-I associated myelopathy (HAM) was made. Electrophysiological studies showed neurogenic changes and suggested anterior horn cell involvement. After oral administration of prednisolone, her spasticity and gait disturbance improved slightly. Small hand muscle atrophy can be one of the initial signs of HAM, and may mimic amyotrophic lateral sclerosis and cervical spondylosis.
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PMID:[Small hand muscle atrophy as an initial sign in HTLV-I associated myelopathy]. 914 73

To reconcile the autoimmune and excitotoxic hypotheses regarding the etiology of amyotrophic lateral sclerosis (ALS), we injected rats intraperitoneally with ALS immunoglobulins and monitored CSF glutamate, aspartate, glutamine, and glutathione. CSF glutamate was significantly increased at 24 and 72 hours compared with both basal levels and disease control injected rats. CSF aspartate was increased at 72 hours. Glutamine and glutathione were unchanged. These data suggest that ALS immunoglobulins may enhance CSF glutamate and aspartate levels and contribute to motoneuron injury.
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PMID:Increased CSF glutamate following injection of ALS immunoglobulins. 915 55

The aim of the present study was to report the levels of ascorbic acid in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) and the effectiveness of ascorbic acid homeostasis in the central nervous system. Plasma and CSF ascorbic acid levels were measured by high performance liquid chromatography in 19 ALS patients, 17 AD patients and 15 controls. No statistically significant difference was found between patients and controls. However, wide fluctuations of plasma concentrations were found to result in relatively stable CSF levels, by appropriate adjustments of CSF/plasma ratio. It appears that in normal subjects and in the disease under study, this ratio reflects the activity of the choroid plexus ascorbate transporter.
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PMID:Ascorbate in healthy subjects, amyotrophic lateral sclerosis and Alzheimer's disease. 927 83


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