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)

This paper reports the results obtained on using guanidine hydrochloride in the treatment of patients with amyotrophic lateral sclerosis, degenerative diseases of the spinocerebellar system or the peripheral nervous system and dystrophic muscle diseases. A long-term effect of the substance was a diminution in the rate of progression of the diseases, with the exception of the group with dystrophic muscle diseases. Initial clinical improvement occurred in certain patients of both groups. The substance seems to be more effective in less-advanced cases than on administration in the later stages of the disease. The therapeutic dosage was 20 to 40 mg/kg/day. The most frequent side-effect was paraesthesia and sometimes gastric disturbance was reported. Therapy had to be discontinued in 3 patients due to leucopenia. In these patients the symptoms rapidly increased in severity after discontinuation of treatment. This supports the assumption that guanidine hydrochloride treatment slows down the progress of the disease.
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PMID:[The application of guanidine hydrochloride to the treatment of degenerative nervous and muscular diseases. I. Clinical results (author's transl)]. 20 24

Electrical stimulation was applied to the spinal cord of 75 patients who had demyelinating and degenerative diseases of the central nervous system, and 3 patients who had sustained spinal cord injuries. The electrical energy was delivered to the central nervous system by the percutaneous technique. The amount of electrical energy required to produce the perception of paresthesias was measured in 11 patients. The minimum power necessary was 76.89 muW, the maximum was 868 muW, and the average was 448.8 muW. The patients were evaluated by 4 examiners by means of routine neurologic examination, videotape movies, and measurement of urinary bladder function. Continued improvement in neurological status, which allowed the patient to live a better lifestyle, occurred in 30 of the 61 patients with multiple sclerosis, and 6 of the 10 patients with ataxia. The patient with transverse Myelitis, the patient with primary lateral sclerosis, and 1 patient with olivopontocerebellar atrophy; also noted similar enhancement of neurological function. The patients with amyotrophic lateral sclerosis and spinal cord injuries had no changes of significance. Thirty-two out of 44 patients who were ambulatory had significant improvement, whereas 10 of the 19 patients who were not ambulatory had improvement. There was no evidence that electrical stimulation of the spinal cord, when applied via dorsally placed percutaneous electrodes and when carried only to the perception of a paresthesias, has any adverse effect on neurological function. It is hypothecated that the electrical current alters neurotransmitters to enhance the transmission along nervous and neurochemical pathways. The exact mechanisms are unknown at the present time.
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PMID:Treatment of demyelinating and degenerative diseases by electro stimulation of the spinal cord. 31 May 8

Among 10 patients with amyotrophic lateral sclerosis who had combined biopsy of muscle and cutaneous nerves, two had a history of paresthesia that suggested involvement of peripheral afferent neurons. Of four patients without paresthesia, two had unequivocal abnormalities of touch-pressure sensation of the toe. On morphometric evaluations of lateral fascicles of deep peroneal nerve, one nerve had an abnormally low myelinated fiber density and seven of 10 had abnormally high frequencies of teased-fiber abnormalities. Teased fibers in which myelin was degenerating into linear rows of myelin ovoids and balls occurred in 10.5 percent of fibers in amyotrophic lateral sclerosis nerves as compared with 1.7 percent in control nerves (0.01 less than p less than 0.025). Estimates of density of myelinated fibers were less sensitive than estimates of the frequency of various changes in teased fibers for detecting abnormality.
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PMID:Frequency of nerve fiber degeneration of peripheral motor and sensory neurons in amyotrophic lateral sclerosis. Morphometry of deep and superficial peroneal nerves. 117 12

All identified Israeli patients with amyotrophic lateral sclerosis (ALS) with onset of the disease from 1959 through 1975 (n = 318) were evaluated clinically. Most of our patients (63%) presented with weakness; only 10% presented with atrophy and 3% with fasciculations. In 31% of the cases, the onset of the disease was focal and 22% of the patients presented with bulbar signs, but only 6 patients presented with emotional lability (pseudo-bulbar). Twelve per cent of the patients presented with muscle cramps, pain or paraesthesia. Atypical signs such as motor cranial nerve lesion, dementia, sphincter disturbance and deep sensation loss are discussed. A relatively high proportion of our patients suffered from malignant tumour, but with no association with any specific tumour. The median survival time was 3 years. Patients with onset of their disease with bulbar signs had a shorter life expectancy (2.2 years): Twenty nine per cent of our patients survived for more than 5 years and 16% for more than 10 years.
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PMID:Amyotrophic lateral sclerosis. A study of its presentation and prognosis. 405 36

A 63-year-old woman had suffered from progressive weakness and wasting of the right lower limb for seven years. In the lower limbs, there were profound muscular atrophy and weakness on the right, and mild weakness with spasticity on the left. Muscle strength of the upper limbs was normal. Sensory examination was normal except for paresthesias below the right knee. Anti-HTLV-I antibody titer was raised both in serum and in the CSF. Motor nerve conduction studies of the lower limbs showed small compound muscle action potentials and somewhat slow conduction velocities, more evident in the right side. F-wave was evoked only in the left tibial nerve and its latency was increased. Sensory nerve conduction studies were normal in the lower limbs. Somatosensory evoked potentials (SEPs) after tibial nerve stimulation at the ankles showed increased interpeak latencies between lumbar N20 and scalp P37. Nerve conduction studies in the upper limb were normal. Single fiber electromyography suggested anterior horn involvement not only in the lumbosacral cord but also in the cervical cord. Weakness and spasticity improved after oral administration of prednisolone. The SEPs findings and a favorable response to prednisolone excluded the possibility of amyotrophic lateral sclerosis. This case is a clinical variant of HTLV-I-associated myelopathy presenting profound atrophy of unilateral lower limb.
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PMID:[HTLV-I associated myelopathy presenting with profound atrophy of unilateral lower limb]. 825 34

Riluzole, a benzothiazole, affects neurons by 3 mechanisms: by inhibiting excitatory amino acid release, inhibiting events following stimulation of excitatory amino acid receptors and stabilising the inactivated state of voltage-dependent sodium channels. It has demonstrated neuroprotective activity in vivo and in vitro. Results from 2 randomised double-blind placebo-controlled trials in patients with amyotrophic lateral sclerosis (ALS; motor neuron disease) have demonstrated that riluzole can extend survival and/or time to tracheostomy. After 18 months, the relative risk of death or tracheostomy with riluzole 100 mg/day was reduced by 21%. Although riluzole slowed the rate of deterioration in muscle strength in the first trial, this was not confirmed in the second, larger trial. Riluzole had no effect on any other functional or secondary variable. Gastrointestinal effects, anorexia, asthenia, circumoral paraesthesia and dizziness were reported more frequently with riluzole than placebo. Elevated alanine aminotransferase levels were observed in 10.6 versus 3.8% of patients treated with riluzole 100 mg/day versus placebo, leading to treatment withdrawal in 3.8 versus 2.1% of patients. In conclusion, riluzole is the first drug that has been shown to have an effect on survival in patients with ALS. Although the effect of riluzole was modest, it has allowed some insight into the pathogenesis of ALS from which future gains may be made.
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PMID:Riluzole. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in amyotrophic lateral sclerosis. 889 67

Compared with control subjects, patients with amyotrophic lateral sclerosis (ALS) have been reported to experience less or no paresthesias during and after release of ischemic compression of the upper arm for 10 min. This is reminiscent of the resistance to ischemia of diabetic patients, in whom sensory and motor axons undergo less ischemic depolarization and less postischemic hyperpolarization than in control subjects. The present study compared the changes in axonal excitability produced by ischemia for 10 min in 21 patients with ALS and 14 age-matched control subjects. Fewer patients reported intraischemic or postischemic paresthesias and the intensity of paresthesias was less, but this was significant only for postischemic paresthesias. There were quantitatively similar changes in refractoriness, supernormality, and strength-duration time constant during ischemic compression, but the increase in excitability of motor axons was less during the second half of ischemia in the patients. After release of ischemia the postischemic hyperpolarization was greater in the ALS patients, the opposite of what occurs in diabetes. These changes could reflect reduced intraneural K+ accumulation due to loss of motor axons or an alteration in nerve metabolism or membrane properties. Either way, the present study has failed to confirm previous reports of "ischemic resistance" in ALS, and indicates that the changes in axonal properties in ALS are not analogous to those in diabetes mellitus.
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PMID:Ischemic resistance of cutaneous afferents and motor axons in patients with amyotrophic lateral sclerosis. 984 71

Familial amyotrophic lateral sclerosis (fALS) is a well-recognised condition that accounts for almost 10% of all cases of ALS. Most cases are now known to be transmitted by an autosomal dominant trait. When fALS is compared clinically to sporadic ALS, 20% of cases manifest atypical features such as pain, paraesthesia or urgency micturition. Moreover, a disease duration of over 10 years, with very slow progression, appears to occur almost exclusively in cases of fALS. Studies of superoxide dismutase (SOD1) mutations in fALS have shown that the disease may be multidegenerative, with oculomotor or cerebellar involvement. Molecular genetics has also demonstrated that not all SOD1 mutations have a dominant influence, and the detailed description of the Scandinavian D90A homozygous mutation is very informative in this regard. Misdiagnosis of fALS can be attributed to one of the following situations: (i) atypical phenotype ALS with a multidegenerative profile; (ii) unusually long lasting ALS with mild motor neuron involvement; (iii) significant clinical heterogeneity between affected family members; (iv) low reliability of family history; (v) existence of an unknown or unexpected mode of transmission; and (vi) other multidegenerative disorders with motor neuron involvement. Pedigrees and fALS cases corresponding to these situations are presented.
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PMID:Genetics of familial ALS and consequences for diagnosis. French ALS Research Group. 1044 77

The Cu,Zn superoxide dismutase (Cu,Zn SOD) mutations described in amyotrophic lateral sclerosis (ALS) have, for the most part, a dominant influence. However, while a few cases with a heterozygous D90A mutation have been described in different countries, D90A has been recently proven to be recessively inherited with a common founder effect in Scandinavia. We screened French ALS families for Cu,Zn SOD mutations. The presence of the D90A allele was found in two index-cases, and their families were subsequently studied. In the first family the ALS patients were homozygotes for D90A, while in the second, all ALS patients were heterozygotes. In both families the disease was found to initially involve the lower limbs with slower progression than in sporadic cases, and frequent atypical signs such as paresthesia and urgency of micturition. We determined the D90A allele frequency in controls (n = 200) and sporadic ALS patients (n = 408). No D90A allele was found. This is the first report of coexistence of dominant and recessive families with the D90A Cu,Zn SOD mutation within the same country.
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PMID:Coexistence of dominant and recessive familial amyotrophic lateral sclerosis with the D90A Cu,Zn superoxide dismutase mutation within the same country. 1080 43

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with the fatal evolution. Recent studies in knowledge of the pathogenic mechanisms underlying ALS showed that the excitotoxicity has an important role in the neurodegeneration. The riluzole, an antagonist of glutamate, is the first drug approved by FDA for the treatment of patients with ALS. The efficacy of riluzole (dose recommended 50 mg twice a day) in prolonging the survival of patients with ALS has been demostrated in two principal controlled clinical trials. The most frequent adverse events related to riluzole treatment were: nausea, vomiting, anorexia, diarrhea, asthenia, somnolence, vertigo, circumoral paresthesia, abdominal pain and dizziness. Some events tend to be related to the dose: vertigo, diarrhea, nausea, circumoral paresthesia and anorexia appear more frequently with 200 mg/die that with lower dose. Generally with tree months from the beginning of the treatment with riluzole, an increase serum transaminase levels has been noted; mostly transient and regressing after two-sex months of treatment. A monitoring of serum transaminase levels is suggested during the first year of treatment with riluzole The clinical studies shows that the adverse events produced by riluzole are mostly reversible and dose-dependent, this demostrates a satifying profile of tolerability of the drug. Anyway, a deeper knowledge of its tolerability may lead us to a better use of riluzole, avoiding in this way the interruption of treatment.
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PMID:[Tolerability of riluzole: a review of the literature]. 1514 78


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