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)

We report an 80-year-old woman with progressive muscular atrophy predominantly involving her right lower extremity. She was well until 1992 (75 years of age) when she noted an onset of weakness in her right leg which had got progressively worse. She was admitted to our service in July 1994. On admission, general physical examination was unremarkable. She was alert and well oriented without dementia. Higher cerebral functions were normal. Cranial nerves also appeared intact. She dragged her right leg in walking. Mild to moderate weakness (2/5 to 4/5) was noted in muscles in her right lower extremity more in the distal part. Deep tendon reflexes were within normal limits, and the plantar response was flexor bilaterally. Sensation was intact. Laboratory examinations were also unremarkable except for slight increase in CK which was 470 IU/l. CSF was also normal. EMG revealed neurogenic changes in the lower extremities. She was admitted to Aoki Hospital on October 21, 1994, by that time, her weakness in the right lower extremity had gotten worse in that the muscle strength of the right extensor hallucis longus was 0 and tibialis anterior 2; muscle atrophy was also prominent in her right leg; the right ankle jerk could not be elicited. In the subsequent course, weakness and atrophy appeared in her left lower extremity, however, upper extremities and cranial nerves had never been affected. Babinski sign was always negative. In February 1996, she developed delusional ideation of self persecution, and showed difficulty in communication with medical staffs. She developed fever of 38.7 degrees C on June 13, 1996 expired on the next day. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had a form of spinal muscular atrophy. Opinions were divided between ALS and spinal muscular atrophy. Post-mortem examination revealed marked loss of anterior horn neurons in the lumbar area with astrogliosis. Bunina bodies were seen in some of the remaining neurons. No myelin pallor was noted in the pyramidal tracts, however, atrophy and loss of Betz cells were noted in the motor cortex. Other cortical areas were unremarkable. The neuropathologist arrived at the conclusion that the patient had ALS. This patient was unique in that she had asymmetric atrophy and weakness limited to the lower extremities. This is quite unusual as ALS of four years duration. In addition, the patient developed some mental change which was thought to represent dementia by some participants. But no clear morphologic changes were seen to account for her mental change.
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PMID:[Neurological CPC.57. An 80-year-old woman with four years history of muscle atrophy involving lower extremities predominantly on the right side]. 931 Oct 7

Although human retroviruses seem plausible agents of motor neuron diseases, there are only few reports of patients infected by the human immunodeficiency virus, with documented motor neuron disorder. That retroviral infections may cause motor neuron pathology by various mechanisms in animals and humans is known. Neurological symptoms potentially attributed to damage of lower motor neurons are often described during the course of HIV-1 infection and AIDS, however, it is often difficult to establish whether the disorder is primarily affecting the perikarya of lower motor neurons, or whether it is due to a focal proximal axonopathy, or to a dying-back process. We report a 30-year-old heroin abuser, HIV-1 positive, who presented a rapidly progressive limb weakness, muscle wasting, and bulbar signs, in absence of sensory loss of cerebellar and pyramidal signs. Imaging studies were negative. CSF showed increased protein content, negative cytology, and no oligoclonal bands. Serum protein electrophoresis, urinary heavy metal, and viral researches were negative. CD4 cells were counted 340 mm3 with a CD4-CD8 ratio equal to 0.4. Electrophysiology showed acute and chronic neurogenic changes, confirmed by muscle biopsy. Conduction studies along motor and sensory nerves fell within normal range. Biopsy of sural nerve revealed mild myelinated and unmyelinated fiber loss, occasional degeneration and regeneration, unremarkable inflammation. Despite treatment with AZT, zalcitabine, and steroids, the patient died after 3-month illness. Neuropathology showed normal cortical cell Betz's, and hemispheric white matter. Brain stem motor nuclei (inferior olival, dorsal motor of the vagus, hypoglossal) showed atrophy and intracytoplasmatic lipofuscin accumulation. Vacuolization, central chromatolysis, and neuronophagia were rarely seen. As associated pathology, in the fourth ventricle there were two small subependymal foci of demyelination, with reactive astrocytes and vascular proliferation. A possible crucial role of the HIV-1 infection in the development and progression of our patient's illness is considered in view of the known altered immunity proved in MND and ALS cases.
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PMID:Motor neuron disease and HIV-1 infection in a 30-year-old HIV-positive heroin abuser: a causal relationship? 962 4

We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 30 patients with sporadic amyotrophic lateral sclerosis (SALS) and 78 matched controls. The mean CSF and serum vitamin E levels did not differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal versus bulbar) of SALS. CSF alpha-tocopherol levels did not correlate with age, age at onset, and duration of the disease. These results suggest that CSF and serum alpha-tocopherol concentrations are unrelated with the risk for ALS.
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PMID:Cerebrospinal fluid levels of alpha-tocopherol in amyotrophic lateral sclerosis. 982 12

In 13 subjects with ALS, we studied the safety and pharmacokinetic properties of Procysteine, a cysteine prodrug that increases levels of intracellular glutathione. We found that oral administration of Procysteine was safe. Procysteine enters CSF after both IV and oral dosing and accumulates to significant levels in CSF. We also observed that CSF levels of glutathione fall dramatically with aging.
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PMID:The pharmacokinetics and pharmaco-dynamics of Procysteine in amyotrophic lateral sclerosis. 1022 42

By means of a randomized, controlled and open study the authors wanted to find out if cerebrospinal (CSF)-filtration was of substantial benefit to patients with sporadic amyotrophic lateral sclerosis (SALS). Five SALS patients, aged 51-75 years, being treated with riluzole underwent CSF-filtration daily over five days (group A). Five other SALS patients, aged 52-70 years, were treated only with riluzole (group B). Although all five patients in the first group reported a subjective benefit following CSF- filtration, the Norris score, the Frenchay score, the vital capacity, the ulnar nerve F-wave persistence and the peak-ratio of the brachial biceps and anterior tibial muscles did not change significantly after five days of therapy, either in group A or in group B. In conclusion, filtration of 200-250 ml CSF daily, over five days, does not seem to have a substantial therapeutic effect in patients with SALS.
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PMID:Cerebrospinal fluid filtration in amyotrophic lateral sclerosis. 1045 94

Although the essential requirements for diagnosis of amyotrophic lateral sclerosis (ALS) are clearly defined by the El Escorial criteria, many physicians, including neurologists, still miss the diagnosis. Physician misdiagnosis of ALS relates to lack of knowledge about ALS and skill and to diagnostic difficulty. The differential diagnosis must exclude nonmotor neuron diseases and other adult-onset motor neuron diseases with restricted presentations, e.g., progressive bulbar palsy (pure bulbar), progressive muscular atrophy (pure lower motor neuron) and primary lateral sclerosis (pure upper motor neuron), ALS-like syndromes and ALS variants, and adult-onset spinal muscular atrophies. Although the diagnosis of ALS remains a clinical one, laboratory testing can be used to exclude other diseases and to confirm the diagnosis. Such tests include EMG and nerve conduction studies, MRI and CT of the spine and brain, identification of biochemical markers in blood and CSF, and muscle or nerve biopsy. Genetic testing can identify gene defects in some types of familial ALS and in certain other inherited motor neuron diseases that mimic ALS. At present there is no widely accepted protocol for laboratory testing in cases of suspected ALS, but it is hoped that laboratory tests will improve in the future to facilitate earlier confirmation of a diagnosis of ALS. However, correct and early diagnosis of ALS can only be achieved when the first, second, or third physician who sees the patient knows about ALS and includes it in a differential diagnosis.
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PMID:Diagnostic challenges in ALS. 1056 Jun 34

Cerebrospinal fluid from 15 patients with ALS and 11 controls without neurological disease were analysed for levels of the neurotrophic factors BDNF and GDNF. Analyses were performed using a sensitive sandwich immunoassay (ELISA). There was no significant difference in BDNF levels between the ALS patients and the control subjects studied. Measurable levels of GDNF were found in 12 out of 15 ALS samples. GDNF was not detected in CSF from any of the control subjects. The finding of increased CSF levels of GDNF in ALS compared to controls, together with earlier findings of increased expression of GDNF mRNA in muscle in ALS, indicates that the capacity to synthesize GDNF is enhanced in this disorder.
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PMID:GDNF but not BDNF is increased in cerebrospinal fluid in amyotrophic lateral sclerosis. 1085 44

Mutations in CuZn-superoxide dismutase (CuZn-SOD) have been linked to familial amyotrophic lateral sclerosis (ALS), and motor neurone death is caused by the gain of a toxic property of the mutant protein. Here we determined amounts, activity and molecular forms of CuZn-SOD in CSF from ALS patients carrying the D90A and other CuZn-SOD mutations and patients without such mutations. There were no differences in amount of protein and enzymic activities of CuZn-SOD between 37 neurological controls, 54 sporadic and 12 familial ALS cases, and 10 cases homozygous for the D90A mutation. Three cases heterozygous for the A89V, S105L and G114A CuZn-SOD mutations showed low amounts of CuZn-SOD. There was no evidence for accumulation of inactive protein in any of the groups. Immunoblots showed no evidence for the presence of any precipitates or other molecular forms of CuZn-SOD with higher molecular weight in the groups. About 25% of the CuZn-SOD subunits in CSF from controls shows an N-terminal truncation. This truncated portion does not differ between controls and ALS groups not carrying CuZn-SOD mutations, but is 70% larger in samples from D90A homozygous ALS patients. The findings suggest an essentially normal amount and activity of D90A mutant CuZn-SOD in CNS tissues of ALS cases. The increased occurrence of N-terminally truncated mutant subunits may indicate a difference in degradation routes compared with the wild-type enzyme, resistance against subsequent proteolytic steps and/or a compromised downstream proteolytic machinery. Molecular fragments accumulated to a greater extent from the D90A mutant enzyme might contribute to the motor neurone degeneration. We also determined the other SOD isoenzymes: in the controls, CuZn-SOD contributed 75%, extracellular SOD 25% and Mn-SOD <5% of the total SOD activity. There was no difference in the amount of extracellular SOD between any of the groups.
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PMID:Superoxide dismutase in CSF from amyotrophic lateral sclerosis patients with and without CuZn-superoxide dismutase mutations. 1140 40

A 32-year-old woman presenting with a rapidly progressive ALS-like syndrome was found to be HIV positive with a CD4 count of 44/mm(3). The patient recovered completely during 1 year after treatment with nelfinavir, zidovudine, and lamivudine, and recovery is sustained nearly 4 years later. Recovery was accompanied by HIV RNA becoming undetectable in plasma and CSF.
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PMID:An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy. 1217 98

Some cases of familial amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding cytosolic, copper-zinc superoxide dismutase (SOD1). We report here that rats that express a human SOD1 transgene with two different ALS-associated mutations (G93A and H46R) develop striking motor neuron degeneration and paralysis. As in the human disease and transgenic ALS mice, pathological analysis demonstrates selective loss of motor neurons in the spinal cords of these transgenic rats. In spinal cord tissues, this is accompanied by activation of apoptotic genes known to be activated by mutant SOD1 protein in vitro and in vivo. These animals provide additional support for the proposition that motor neuron death in SOD1-related ALS reflects one or more acquired, neurotoxic properties of the mutant SOD1 protein. The larger size of this rat model as compared with the ALS mice will facilitate studies involving manipulations of spinal fluid (implantation of intrathecal catheters for chronic therapeutic studies; CSF sampling) and spinal cord (e.g., direct administration of viral- and cell-mediated therapies).
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PMID:Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease. 1171 58


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