Showing papers on "Amyotrophic lateral sclerosis published in 1984"
TL;DR: When behavioral patterns were assessed, patients with MS demonstrated a significantly higher rate of depressed affective disorders than patients with the other two diseases, suggesting multiple sclerosis may present a neurologic model for mood disturbance.
Abstract: • Certain CNS diseases can produce specific behavioral abnormalities. We used a computer search technique to identify all inpatients at Strong Memorial Hospital, Rochester, NY, who had received diagnoses of multiple sclerosis (MS), temporal lobe epilepsy (TLE), and amyotrophic lateral sclerosis (ALS) between 1965 and 1978. We found 368 patients with MS, 402 patients with TLE, and 124 patients with ALS. These groups were matched against the Monroe County (New York) Psychiatric Register to determine patterns of behavioral pathology. Prevalence rates for psychiatric contact were not significantly different between MS and TLE (19.3% v 22.9%), but both were higher than the prevalence rate for ALS (4.8%). When behavioral patterns were assessed, patients with MS demonstrated a significantly higher rate of depressed affective disorders (61.97% of register matches) than patients with the other two diseases. Multiple sclerosis may present a neurologic model for mood disturbance.
183 citations
TL;DR: Axonal swelling on lower motor neurons appears to be a significant feature of the pathology of ALS, and its implications in terms of etiology are unknown.
166 citations
TL;DR: If the demonstrated deposition of metals, particularly calcium and aluminum, in central nervous system tissues of Guamanians with these two conditions is a cause of the diseases and of the early appearance of neurofibrillary tangles in neurons, the accumulation has apparently occurred long before onset of symptoms, and detectable abnormalities of calcium and vitamin D metabolism may already have been corrected.
Abstract: We evaluated 16 Guamanian Chamorros with amyotrophic lateral sclerosis and 33 patients with parkinsonism-dementia for disturbances of calcium and vitamin D metabolism. The serum immunoreactive parathyroid hormone level was mildly elevated in 6 patients with amyotrophic lateral sclerosis and in 5 patients with parkinsonism-dementia. There were significant positive correlations between serum immunoreactive parathyroid levels and duration of illness in male patients with motor neuron disease, but not in female patients or in patients with parkinsonism-dementia. Intestinal absorption of calcium, as assessed by serum and urinary activity of calcium 47 following oral administration, was decreased in 2 patients with amyotrophic lateral sclerosis and in 4 patients with parkinsonism-dementia, all of whom had low levels of serum 1,25-dihydroxyvitamin D. Reductions in cortical bone mass were striking in patients with motor neuron disease. A significant negative correlation was found between the percentage of cortical area of the second metacarpal bone and muscle atrophy and weakness, and significant positive correlations were found between degree of immobility and ratio of urinary hydroxyproline to creatinine in patients with amyotrophic lateral sclerosis and parkinsonism-dementia. In general, abnormalities in calcium metabolism were subtle. Thus, if the demonstrated deposition of metals, particularly calcium and aluminum, in central nervous system tissues of Guamanians with these two conditions is a cause of the diseases and of the early appearance of neurofibrillary tangles in neurons, the accumulation has apparently occurred long before onset of symptoms, and detectable abnormalities of calcium and vitamin D metabolism may already have been corrected.
115 citations
TL;DR: In three patients dementia without neurofibrillary tangles or Pick bodies antedated amyotrophy by several years, the disease in these patients may represent a subset of motor neuron disease or a multisystem atrophy.
Abstract: In three patients dementia without neurofibrillary tangles or Pick bodies antedated amyotrophy by several years. The motor neuron disorder in two patients was characterized by terminal bulbar symptoms; in one it was similar to classic amyotrophic lateral sclerosis. In two patients, quantitative studies of selected regions of the cortex using a computerized image analyzer disclosed, as in patients with senile dementia of Alzheimer type, a marked reduction in the number of neurons, especially those larger than 90 mu 2. The findings differed from those in Alzheimer dementia, however, in that the cells in the substantia innominata were not reduced and the levels of choline acetyltransferase and somatostatin-like immunoreactivity, determined in one patient, were within normal limits. A variable degree of sponginess of the upper layers of the cortex was attributed to attrition of pyramidal cell dendrites, observed in the one patient in whom Golgi study was successful. Because of severe degeneration of the substantia nigra in all three, the disease in these patients may represent a subset of motor neuron disease or a multisystem atrophy.
115 citations
TL;DR: Deposits of IgG and complement were demonstrated by direct immunofluorescent techniques with sections of motor cortex and spinal cord from amyotrophic lateral sclerosis patients and were found in the CNS in disease states associated with possible immune or infectious etiologies and in normal controls.
109 citations
TL;DR: The results demonstrate that the insulin resistance in this disorder cannot be explained by a decrease in glucose-receptor space and suggest a primary carbohydrate aberration in the disease process itself.
88 citations
TL;DR: It is indicated that new motor-neuron disease can occur in patients with prior poliomyelitis and that immunopathologic mechanisms may play a role.
Abstract: Seventeen relatively young patients, ages 31-65 years (average, 45) with prior poliomyelitis, who after a number of years of stability had experienced new neuromuscular symptoms, were studied. Seven patients had deterioration of functional capacity and then stabilization without new muscular weakness. The other 10 had late postpoliomyelitis muscular atrophy (late PPMA) characterized by focal progressive muscle weakness, wasting, fasciculations, and muscle pains affecting previously spared muscles or muscles previously affected but recovered. Four patients with late PPMA had lymphorrhages or lymphocytic infiltrates in their biopsied muscle; three of three patients had oligoclonal IgG bands in their spinal fluid, and five had variable peripheral T lymphocyte-subset ratios. In one patient with late PPMA, antibodies to poliovirus were specifically elevated in the cerebrospinal fluid. Our findings indicate that new motor-neuron disease can occur in patients with prior poliomyelitis and that immunopathologic mechanisms may play a role. Some patients with a history of acute paralytic poliomyelitis experience not only residual muscle weakness from the initial illness, but they also develop new neuromuscular symptoms later in life. These symptoms may vary in form and severity from simple decline of musculoskeletal function to the development of new progressive muscle weakness and typical cases of amyotrophic lateral sclerosis [1-7]. The cause and frequency of these symptoms are unknown. Some of the proposed explanations include reactivation of poliovirus and normal aging process in previously affected muscle groups collaterally innervated by an already de
88 citations
TL;DR: An antibody in the serum of patients with amyotrophic lateral sclerosis is detected that inhibits sprouting of neurons and subsequent reinnervation of skeletal muscle, and may provide reagents for studies of the trophic communications between muscle and motor neurons.
Abstract: To investigate the pathogenesis of amyotrophic lateral sclerosis, we compared the effect of serum from patients with this disease on the regenerative sprouting of terminal axons in botuiinum-treated mouse gluteus muscle with the effects of serum from controls and from patients with diabetic peripheral neuropathy. Serum from 9 of 19 patients with the sporadic form of amyotrophic lateral sclerosis and from 2 of 6 patients with the familial form caused a reduction in the proportion of sprouting terminal axons, as compared with that found in muscles treated with serum from controls or diabetic patients. Immuno-globulin from patients with amyotrophic lateral sclerosis, when tested on immunoblots, recognized a 56-kilodalton protein secreted by denervated rat diaphragm muscle; rabbit antiserum raised against this protein also suppressed terminal axonal sprouting. Thus, we have detected an antibody in the serum of patients with amyotrophic lateral sclerosis that inhibits sprouting of neurons and subseque...
87 citations
TL;DR: Findings support the hypothesis that blood-brain barrier damage occurs in ALS and the finding of a higher mononuclear cell count in young ALS patients is briefly discussed in the light of the hypothesis of an exogenous agent of some relevance in pathogenesis.
Abstract: The cerebrospinal fluid (CSF) was examined in 90 amyotrophic lateral sclerosis (ALS) patients and in 50 age-matched normal controls. Total protein concentration was significantly higher in ALS patients than in normal controls. CSF IgG and albumin, quantitatively determined by single radial immunodiffusion, were significantly increased in ALS. No difference in serum concentrations was observed between ALS patients and normal controls. On isoelectric focusing a clearcut "fingerprint" pattern was observed in 11 of 12 cases. These findings support the hypothesis that blood-brain barrier damage occurs in ALS. The finding of a higher mononuclear cell count in young ALS patients is briefly discussed in the light of the hypothesis that an exogenous agent might be of some relevance in pathogenesis. An alteration of at least one of the CSF parameters considered was found in 45.5% of ALS cases.
69 citations
TL;DR: A pathological slowing of conduction along the central sensory pathways in amyotrophic lateral sclerosis is suggested.
Abstract: Forty five patients with amyotrophic lateral sclerosis were investigated, by means of somatosensory evoked potentials, in order to detect the presence of subclinical sensory changes. Cervical SEPs from the median nerve and cortical SEPs from the median and tibial nerve were recorded, showing a delay of N13 and subsequent components; the latency of the first constant cortical potential was also increased in many patients. Only the SEPs from the tibial nerve showed a decrease of amplitude. These results suggest a pathological slowing of conduction along the central sensory pathways in amyotrophic lateral sclerosis.
66 citations
TL;DR: Subsequent spectrophotometric analysis of the medium disclosed a significantly higher degree of haemolysis in samples from ALS‐patients than from controls, giving further evidence for the existence of an abnormality of the red cells in the disease.
Abstract: — Erythrocytes from patients with amyotrophic lateral sclerosis (ALS) and controls were suspended in an electrolyte-substrate medium and subjected to mechanical stress by centrifugation under standardized conditions. Subsequent spectrophotometric analysis of the medium disclosed a significantly higher degree of haemolysis in samples from ALS-patients than from controls. The observation gives further evidence for the existence of an abnormality of the red cells in the disease. The nature and possible significance of this abnormality in relation to the pathogenesis of ALS is as yet unknown, but notably there was no significant correlation between the degree of cell abnormality as manifested by haemolysis and the duration of the disease in the individual patient.
TL;DR: No statistically significant beneficial effect of the drug was demonstrated, but the large coefficient of variation for each item indicated that a sample size of several hundred patients would have been necessary to exclude the possibility that the drug produced a 25% slowing of progression of the disease.
Abstract: We conducted a double-blind controlled study of the effect of brain gangliosides in amyotrophic lateral sclerosis. Nineteen patients received intramuscular gangliosides (40 mg/d) for 6 months, and 21 received placebo. The deterioration rates for approximately 120 clinical and electrophysiologic parameters of neuromuscular function were analyzed, but no statistically significant beneficial effect of the drug was demonstrated. However, the large coefficient of variation for each item indicated that a sample size of several hundred patients would have been necessary to exclude the possibility that the drug produced a 25% slowing of progression of the disease.
Journal Article•
TL;DR: A population based survival analysis of all incident cases of motor neuron disease in the province of Turin, Italy, during the period 1966-1980 showed both life-tables showed a similar pattern with a rapidly fatal outcome in the first 3 years after diagnosis and a slower death rate in the following years.
TL;DR: Investigation of the patient's pedigree back to the 17th century revealed nine additional family members who had exhibited signs of amyotrophic lateral sclerosis or parkinsonism‐dementia or both, which suggests that a recessive trait with genetic epistasis is responsible for the disorder.
Abstract: We report here on a 59-year-old man from southwest Germany who died after a 14-year course of an illness characterized by progressive dementia, parkinsonism, and amyotrophic lateral sclerosis. Postmortem examination revealed Alzheimer's neurofibrillary tangles in the substantia nigra, innominata, locus ceruleus, parahippocampal gyrus, and less frequently in the hippocampus and the cerebral cortex. Investigation of the patient's pedigree back to the 17th century revealed nine additional family members who had exhibited signs of amyotrophic lateral sclerosis or parkinsonism-dementia or both. The pedigree suggests that a recessive trait with genetic epistasis is responsible for the disorder.
TL;DR: Daily intramuscular injections of 40 mg of brain gangliosides for 6 months had no beneficial effect in ALS and no significant difference between the two groups in the progression of weakness.
Abstract: A 6-month double-blind study of bovine brain gangliosides was carried out in 40 patients with ALS. Thirty-two patients completed the study; 18 were treated with gangliosides and 14 with placebo. Using 10 different objective tests of muscle strength, we failed to show a significant difference between the two groups in the progression of weakness. Daily intramuscular injections of 40 mg of brain gangliosides for 6 months had no beneficial effect in ALS.
Journal Article•
TL;DR: Fourteen cases of amyotrophic lateral sclerosis were investigated neuropathologically, emphazising the sacral spinal cord which contains Onuf's nucleus X, which innervates the pelvic sphincters and indicates that a characteristic morphology of the nucleus X-innervated muscles exists.
Abstract: Fourteen cases of amyotrophic lateral sclerosis (ALS) were investigated neuropathologically, emphazising the sacral spinal cord which contains Onuf's nucleus X. The nucleus innervates the pelvic sphincters. In two cases, small striated pelvic muscles were studied. No changes characteristic of ALS were observed in Onuf's nucleus X, not even in 8 cases in which other caudal motoneuron nuclei presented a severe loss of neurons. The striated sphincters proper demonstrated no signs of neurogenic atrophy in contrast to muscles in the limbs. The bulbo- and ischiocavernosus muscles, also supposedly innervated by Onuf's nucleus, were without pathological changes. Moreover, the latter two muscles were found to have a composition very similar to that of the sphincters. This indicates that a characteristic morphology of the nucleus X-innervated muscles exists. A review of the clinical records of all the cases revealed, that although 8 demonstrated severe involvement of the lower extremities, only one presented vesico-rectal dysfunction which could be ascribed to ALS. But even in this case, the pelvic closure mechanisms appeared to be intact. The preservation of continence in ALS is related to the neuropathological findings, and the observations are compared with previous neuropathological studies concerning Onuf's nucleus X as well with experimental studies including this nucleus. It is pointed out that structural and biochemical differences must exist between nucleus X neurons and other motoneurons.
TL;DR: Two sibling cases of familial ALS revealed degerneration usually associated with other systemic degenerative disorders, suggesting that familial ALS may be a multisystemic degenerative disorder, frequently involving the spinocerebellar tracts, but occasionally involving other systems as well.
Abstract: Two sibling cases of familial amyotrophic lateral sclerosis (ALS) revealed degerneration usually associated with other systemic degenerative disorders. The changes in the 41-year-old sister were compatible with those reported in other familial ALS cases affecting the upper and lower motor neurons, posterior columns, and spinocerebellar tracts. The 45-year-old sister revealed more wide-spread degenerative changes involving not only motor neuron systems, but also proprioceptive, general somatic afferent and spinocerebellar afferent systems. Intracytoplasmic hyaline inclusions were observed in the oculomotor nuclei. Clinical manifestations of urinary disturbance and oculomotor imparirment seldom seen in sporadic ALS were interpreted to be due to the unusual distribution of the morbid process. These pathologic findings suggest that familial ALS may be a multisystemic degenerative disorder, frequently involving the spinocerebellar tracts, but occasionally involving other systems as well.
TL;DR: The use and rationale for plasma exchange in neurologic disorders including myasthenia gravis, demyelinative neuropathies, inflammatory myopathies, Eaton-Lambert syndrome, multiple sclerosis, and amyotrophic lateral sclerosis are reviewed.
Abstract: Plasma exchange has become increasingly popular as a mode of therapy in putative immunopathologic diseases of man, including several disorders of interest to neurologists. Among these are myasthenia gravis (MG), demyelinative neuropathies (acute, relapsing, and chronic progressive), inflammatory myopathies, Eaton-Lambert syndrome (ELS), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). Despite, or perhaps because of, the intense interest in and enthusiasm for this form of therapy, firm evidence of therapeutic efficacy in neurologic diseases is limited to MG. In this article, I will review the use and rationale for plasma exchange in these neurologic disorders and outline my personal view of the current role and use of plasma exchange in these diseases. MG Myasthenia gravis can be considered a prototype antibody-mediated autoimmune disease in which the pathogenesis of neuromuscular weakness can be attributed to a decrease in available nicotinic receptors for acetylcholine at the muscle end-plate. 1-4 This decrease is
TL;DR: In 515 cases of motor neuron disease followed until death, multivariate analysis disclosed that duration is shorter in ALS when age at onset was older, and when bulbar muscles or left limbs were initially affected, and in SPMA when age is older, dysphagia was present.
Abstract: In 515 cases of motor neuron disease followed until death, (1) the proportion of three subtypes of motor neuron disease (MND): amyotrophic lateral sclerosis (ALS), progressive bulbar paralysis (PBP), spinal progressive muscular atrophies (SPMA) was 78.3, 1.9, 19.8; (2) sex ratios were 1.41 in ALS, nearly one in PBP and 1.59 in SPMA, the ratio being high in cases initially involving the upper limbs; (3) age at onset was smoothly unimodal and identical in three subtypes; (4) bulbar symptoms appeared either at the initial stage or towards the fatal end; (5) duration was compatible with a compound Weibull distribution; (6) survival rates showed a reverted J type distribution and was more favorable in SPMA than ALS; (7) life expectancies decreased first but increased about 46 months after onset; (8) multivariate analysis disclosed that duration is shorter in ALS when age at onset was older, and when bulbar muscles or left limbs were initially affected, and in SPMA when age at onset was older, dysphagia was present, and probably in those patients who had a history of trauma.
TL;DR: In the past few years there have been advances in understanding toxic, viral, genetic and immunological syndromes that involve motor neurons, and better comprehension of these disorders may give clues about ALS itself.
TL;DR: No overall difference in lipofuscin level was found between the normal and the ALS material, but some neurons of intermediate size did show increased amounts of lip ofuscin, which is attributed to shrinkage during degeneration by larger cells having proportionately more lipofuskin originally.
Abstract: • Lipofuscin has been reported to accumulate in abnormal amounts in motor neurons of patients with amyotrophic lateral sclerosis (ALS). Microdensitometry was used to quantitate such lipid masses in spinal motor neurons in normal subjects compared with spinal motor neurons in ALS cases. No overall difference in lipofuscin level was found between the normal and the ALS material. Some neurons of intermediate size did show increased amounts of lipofuscin, which is attributed to shrinkage during degeneration by larger cells having proportionately more lipofuscin originally.
TL;DR: The folate cycle hypothesis offers a unified explanation of the reduction of RNA and the elevation of taurine in nervous tissue of this disease.
Abstract: The folate cycle, which has a close correlation with nucleic acid synthesis as well as with sulfur amino acid metabolism, may have some bearing on the pathogenesis of amyotrophic lateral sclerosis. The folate cycle hypothesis offers a unified explanation of the reduction of RNA and the elevation of taurine in nervous tissue of this disease.
Patent•
30 Mar 1984TL;DR: A treatment for the amelioration of symptoms of amyotrophic lateral sclerosis and other conditions which result from dysfunction of lower or upper motor neurons by the administration of doses of thyrotropin-releasing hormone by intravenous infusion or subcutaneous injection.
Abstract: A treatment is provided for the amelioration of symptoms of amyotrophic lateral sclerosis and other conditions which result from dysfunction of lower or upper motor neurons by the administration of doses of thyrotropin-releasing hormone by intravenous infusion or subcutaneous injection.
Journal Article•
TL;DR: The authors studied 102 clinical observations of patients presenting the symptoms of amyotrophic lateral sclerosis (Charcot's disease). Two distinct groups were discerned from an analysis of the ages of onset: the first group, comprising 20 patients, represents the juvenile form, with onset before the age of 30, and the second group (82 patients) represents the classic form of Charcot's disease.
TL;DR: In this paper, the peroxidase-antiperiperoxideidase technique for glial fibrillary acidic protein (GFAP) was used to examine the spinal nerve roots in 86 autopsy cases with various spinal lesions.
Abstract: Glial bundles (GBs) in spinal nerve roots in 86 autopsy cases with various spinal lesions were examined using the peroxidase-antiperoxidase technique for glial fibrillary acidic protein (GFAP). In 19 of 22 cases of Werding-Hoffmann disease (WHD), GBs were present in the anterior roots (ARs) but absent in the youngest age group (age<1.5 months at death). GBs were numerous in classical cases (age 3–24 months), accompanying severe damage of the anterior horns and roots, but were less prominent in most cases of protracted course (age 2–8.5 years). Thus, development of GBs in the ARs of motor neuron disease at a young age seems to depend on the clinical type (age at onset and disease duration) and degree of damage to motor neurons and ARs. Varying numbers of GBs were found also in the posterior roots (PRs) of 12 cases of WHD. In 13 patients with amyotrophic lateral sclerosis (ALS), few GBs were observed in the ARs of two and PRs of five cases without apparent relation to other clinicopathologic data. GBs in the PRs of both WHD and ALS might indicate spreading of the degenerative process to sensory neurons despite the absence of pathology detectable by routine histological stains. Numerous GBs were found also in adults affected with polymyelitis in childhood. Varying numbers of GBs were present, however, in many different diseases, such as Friedreich ataxia, Guillain-Barre syndrome, various polyneuropathies, cervical spondylosis, ataxia telangiectasia, metachromatic leukodystrophy, and Leigh syndrome. It is concluded that GBs are a characteristic but nonspecific reaction of the central-peripheral transition zone of the nervous system, which develops prominently in response to early damage of the myelinated fibres in the nerve roots. However, their absence in many cases of severe damage of the spinal roots renders their exact pathogenesis and significance still obscure.