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Showing papers on "Amyotrophic lateral sclerosis published in 1986"


Journal ArticleDOI
TL;DR: Clinical and laboratory examinations of all three forms of MND were similar in clinical course and findings, but there were minor variations in age at onset, sex ratio, survival, and the frequency with which onset occurred in the lower extremities.
Abstract: We analyzed the medical records of 103 patients with familial adult motor neuron disease (MND). In the 72 families, 329 members were known to be affected. Observations were compared with the sporadic and Mariana forms of MND. Clinical and laboratory examinations of all three forms were similar in clinical course and findings, but there were minor variations in age at onset, sex ratio, survival, and the frequency with which onset occurred in the lower extremities. Recognition of the familial form still depends on diagnosis of the disease in more than one member of a family.

392 citations


Journal ArticleDOI
TL;DR: New post-polio muscle weakness is not a life-threatening form of motor-neuron deterioration, but that it is due to a dysfunction of the surviving motor neurons that causes a slow disintegration of the terminals of individual nerve axons.
Abstract: A "post-polio" syndrome characterized by new neuromuscular symptoms, including muscle weakness, may develop years after recovery from acute paralytic poliomyelitis. We studied 27 patients (mean age, 50.6 years) in whom new muscle weakness developed a mean of 28.8 years after recovery from acute polio. We reevaluated these patients during a mean follow-up period of 8.2 years (range, 4.5 to 20) after they were originally studied at the National Institutes of Health. The total mean follow-up period after the onset of new weakness was 12.2 years (range, 6 to 29). The patients were assessed with quantitative muscle testing, muscle biopsy, electromyography, and virologic and immunologic examination of the cerebrospinal fluid. Muscle strength had declined in all patients. The rate of decline averaged 1 percent per year. The decrease was irregular, with subjective plateau periods that ranged from 1 to 10 years. None of the patients had amyotrophic lateral sclerosis. Oligoclonal bands (IgG) were found in the cerebrospinal fluid of 7 of 13 patients studied, but no specific elevation of antibodies to poliovirus was observed in the cerebrospinal fluid. The newly affected muscles that were evaluated longitudinally with follow-up muscle biopsies and electromyography showed signs of chronic and new denervation. Groups of atrophic muscle fibers (group atrophy) and "neurogenic jitter" were not present. New post-polio muscle weakness is not a life-threatening form of motor-neuron deterioration. It appears that this weakness is not due to a loss of whole motor neurons, as in amyotrophic lateral sclerosis, but that it is due to a dysfunction of the surviving motor neurons that causes a slow disintegration of the terminals of individual nerve axons.

331 citations


Journal ArticleDOI
TL;DR: This study emphasizes the worth of having a muscle proton map of patients with muscle dysfunction to assure that meaningful phosphorus spectroscopic information is obtained from a volume of tissue limited to an appropriate muscle.
Abstract: Lower extremity skeletal muscle of 22 individuals (five normal volunteers and 17 patients with muscular or neuromuscular diseases) was studied with magnetic resonance imaging. Axial images generated with spin-echo pulse sequences using short repetition times (500-900 msec TR) and short echo times (30-60 msec TE) provided excellent contrast between fat (high signal intensity) and muscle (intermediate signal intensity). Seventeen patients with clinically verified muscle disorders were evaluated in a manner similar to the normal volunteers. Conditions studied include Duchenne muscular dystrophy (three patients), limb-girdle muscular dystrophy (five), facioscapulohumeral dystrophy (three), and spinal muscular atrophy, amyotrophic lateral sclerosis, hereditary sensorimotor neuropathy, cerebral palsy, poliomyelitis, and Kearn-Sayre mitochondrial muscle disease (one each). General patterns of muscle abnormality were common among the diseases and included decreased or increased muscle size and a spectrum of muscl...

157 citations


Journal ArticleDOI
TL;DR: There were no major temporal changes in the frequencies of physical findings or histopathologic features, but in the past three decades, an increase in age at onset was observed for both ALS and PD.
Abstract: We reviewed the records of 279 Guamanian Chamorro patients with amyotrophic lateral sclerosis (ALS) and 293 patients with parkinsonism-dementia (PD), who had onset of symptoms between 1950 and 1979, to determine if there were changes in the clinical and neuropathologic features that might clarify the declining incidence rates in the past decade. There were no major temporal changes in the frequencies of physical findings or histopathologic features, but in the past three decades, an increase in age at onset was observed for both ALS and PD. There was also a shorter duration of illness in ALS and a longer duration in PD. Good correlation was found between the clinical and pathologic findings for both ALS and PD throughout this period.

125 citations


Journal ArticleDOI
TL;DR: The T-cell phenotypes and functions were comparable in the ALS and control groups, with the exception of the presence of Ia antigen, and data support involvement of autoimmune mechanisms in ALS.
Abstract: • We examined the family history and associated diseases in 58 patients with amyotrophic lateral sclerosis (ALS), as well as the T-cell phenotypes and functions in 46 consecutive patients with this disorder. A family history of thyroid disease was present in 19%, and an additional 21% of patients described family members with other possible autoimmune disorders. In 19% of the patients with ALS either past or present thyroid disease was documented. Eleven of 47 additional patients with ALS had significant elevations of microsomal and/or thyroglobulin antibody levels. The T-cell phenotypes and functions were comparable in the ALS and control groups, with the exception of the presence of Ia antigen. In patients with ALS, 11.9% of the T cells were positive for the Ia antigen, while in both a normal control population and a non-ALS neurologic disease population, only 6.4% of T cells have this antigenic determinant. These data support involvement of autoimmune mechanisms in ALS.

101 citations


Journal ArticleDOI
TL;DR: The results imply that these two disorders distinguished by different clinical manifestations share a common loss of somatic motor and parasympathetic motor neurons at least in the sacral cord.

100 citations


Journal ArticleDOI
TL;DR: A late-onset neurological disease has been identified in a substrain of C57Bl/6 mice, characterized by hindlimb weakness and ataxia starting at 5-11 months of age, progressing to severe spastic paralysis of all limbs, with premature death.
Abstract: A late-onset neurological disease has been identified in a substrain of C57Bl/6 mice. The disorder is characterized by hindlimb weakness and ataxia starting at 5-11 months of age, progressing to severe spastic paralysis of all limbs, with premature death. Histopathology reveals degeneration of upper and lower motoneurons. Both sexes are affected; the mice are fertile, although breeding efficiency is reduced. In outcrosses to wild-type, symptoms have been observed in all obligate heterozygotes, with a similar age range for onset to that of homozygotes. We have designated this autosomal dominant disorder Motor neuron degeneration (Mnd).

89 citations


Journal ArticleDOI
TL;DR: No association was found between heavy metal exposure and the pathogenesis of ALS in this patient population and Demographic factors, fracture history, immunizations, travel and other variables were similar in ALS patients and controls.
Abstract: A retrospective case-control study of occupational heavy metal exposure was conducted using 66 amyotrophic lateral sclerosis (ALS) patients and 66 age- and sex-matched controls. Cases were ascertained

76 citations


Journal ArticleDOI
TL;DR: S sensory evoked potential evidence of CNS sensory dysfunction in ALS is more frequent than that noted clinically or pathologically and offers further support to previous observations of sensory system involvement in ALS.
Abstract: We have reviewed sensory evoked potential (EP) findings in 17 patients with amyotrophic lateral sclerosis (ALS). Somatosensory EPs were abnormal in 7 of 16 patients after lower-extremity stimulation and in 2 of 16 patients after upper-extremity stimulation. Brainstem auditory EP abnormalities were found in 2 of 12 patients. No abnormalities were noted on pattern reversal visual EPs in 12 patients. Overall, 47% of all ALS patients studied had at least one EP abnormality. EP evidence of CNS sensory dysfunction in ALS is more frequent than that noted clinically or pathologically and offers further support to previous observations of sensory system involvement in ALS.

75 citations


Journal ArticleDOI
TL;DR: A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted, and the investigators believed the effects were of any marked clinical significance.
Abstract: A double-blind controlled trial of thyrotropin releasing hormone (TRH) 150 mg IM daily in 30 patients with amyotrophic lateral sclerosis is reported. The drug/placebo was administered for 2 months, followed by a 2-month “wash-out.” Evaluation of strength, functional ability, and respiratory functions was performed. A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance. The course of the illness was not altered.

70 citations



Journal ArticleDOI
TL;DR: Six patients with ALS were treated with a ten- to 14-day course of intensive immunosuppression with cyclophosphamide in a pilot study and it is concluded that this form of immunOSuppression does not alter the course of ALS.
Abstract: • Amyotrophic lateral sclerosis (ALS) is a progressive disorder of the nervous system for which there is no known treatment. Because recent studies have suggested that there may be abnormalities of the immune function in patients with ALS and since we have found a beneficial effect from a short course of intensive immunosuppression with cyclophosphamide in progressive multiple sclerosis, we treated six patients with ALS with a ten- to 14-day course of intensive immunosuppression in a pilot study. At 18 months following therapy, all patients showed a continued progression of the disease; four of the six patients died. We conclude that this form of immunosuppression does not alter the course of ALS.

Journal ArticleDOI
TL;DR: The increased risk among spouses of patients and the lack of increase among their offspring, together with recent histochemical findings, support the contention that exogenous factors are strong contributors to the etiology of amyotrophic lateral sclerosis and parkinsonism-dementia.
Abstract: Familial and genetic studies of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia among the Chamorro people of Guam were initiated in 1958 with the establishment of a prospective case-control registry. The major objective of this registry was to determine if first-degree relatives and spouses of patients with amyotrophic lateral sclerosis or parkinsonism-dementia had an increased risk of developing disease compared with relatives of nonaffected controls individually matched for age, sex, and village. At the time of its closing in 1963, the registry included 126 patients (77 with amyotrophic lateral sclerosis, 42 with parkinsonism-dementia, and seven with both amyotrophic lateral sclerosis and parkinsonism-dementia) and an equal number of controls; 994 living first-degree relatives (parents, siblings, and offspring) of patients and 1,218 of controls; and 88 living spouses of patients and 101 of controls. The present analysis of the 25-year follow-up study (1958-1983) demonstrated a significantly increased risk of developing amyotrophic lateral sclerosis or parkinsonism-dementia among parents, siblings, and spouses of patients, but not among relatives of controls. Offspring of both patients and controls showed no significantly increased risk of developing disease. The increased risk among spouses of patients and the lack of increase among their offspring, together with recent histochemical findings, support the contention that exogenous factors are strong contributors to the etiology of amyotrophic lateral sclerosis and parkinsonism-dementia. The present results also demonstrate a declining incidence of both diseases.

Journal ArticleDOI
TL;DR: A total of 23 patients with motor neuron disease (MND), encompassing 17 cases of amyotrophic lateral sclerosis, 4 of progressive muscular atrophy and 2 of progressive bulbar palsy, was diagnosed in Benghazi, north-eastern Libya, between 1980 and 1985.
Abstract: A total of 23 patients with motor neuron disease (MND), encompassing 17 cases of amyotrophic lateral sclerosis, 4 of progressive muscular atrophy and 2 of progressive bulbar palsy, was diagnosed in Be

Journal ArticleDOI
TL;DR: Morphometric and biochemical studies implied a disease process that affected small, possibly somatostatinergic, cortical neurons, and the lobar distribution of cortical atrophy were consistent with Pick's disease, but Pick bodies and ballooned neurons were not present.
Abstract: We studied a patient with amyotrophic lateral sclerosis and the Kluver-Bucy syndrome. At autopsy there was extensive degeneration of the limbic system with the brunt of the changes in the medial temporal lobe, especially the entorhinal cortex and subiculum. Degenerative changes were also seen in the substantia nigra and lower motor neurons. Morphometric and biochemical studies implied a disease process that affected small, possibly somatostatinergic, cortical neurons. These latter findings and the lobar distribution of cortical atrophy were consistent with Pick9s disease, but Pick bodies and ballooned neurons were not present.

Journal ArticleDOI
TL;DR: A method has been developed to determine quantitatively the level of the anti-neurofilament antibodies in the blood of patients affected with different neurological diseases, which showed increases in patients with Parkinson dementia and amyotrophic lateral sclerosis who originated from Guam.
Abstract: A method has been developed to determine quantitatively the level of the anti-neurofilament antibodies in the blood of patients affected with different neurological diseases. In 7 out of the 52 patients, taken as controls and in 33 out of the 208 patients affected with neurological diseases, the antibody levels were increased. The increases were greater in 43 patients with Parkinson dementia and amyotrophic lateral sclerosis who originated from Guam. On the other hand, the levels were very low in 10 patients affected with subacute sclerosing panencephalitis and in 11 cases with Chagaz' disease. In 24 cases with dementia of Alzheimer type, the levels were normal.

Journal ArticleDOI
TL;DR: A case of sporadic amyotrophic lateral sclerosis characterized by a marked accumulation of neurofilaments in the cytoplasm of neurons, identified by immunohistochemical and electron microscopic studies shed light on the pathogenesis of ALS.
Abstract: We report a case of sporadic amyotrophic lateral sclerosis (ALS) characterized by a marked accumulation of neurofilaments in the cytoplasm of neurons. The neurofilament was identified by immunohistochemical and electron microscopic studies. The distribution of the accumulation in this case was unique, not only in the motoneurons of the anterior horn but also in the neurons of the other areas of the spinal gray matter, some nuclei in the brain stem, pontine reticular formation, substantia nigra, dentate nucleus in the cerebellum and pyramidal cells in the motor cortex. These observations shed light on the pathogenesis of ALS.

Journal ArticleDOI
TL;DR: Observation of the spinal cord of a patient with generalized motor deficits revealed changes in the anterior horns characterized by the selective loss of large motor neurons, gliosis and the abnormal accumulation of 10 nm filaments which appeared as argyrophilic spheroids in the perikarya and axons of motor neurons.
Abstract: Morphologic study of the spinal cord of a patient with generalized motor deficits revealed changes in the anterior horns characterized by the selective loss of large motor neurons, gliosis and the abnormal accumulation of 10 nm filaments which appeared as argyrophilic spheroids in the perikarya and axons of motor neurons. The ventral roots were predominantly affected and showed a variable loss of axons. The remaining axons displayed prominent onion-bulb formations, frequent axonal sprouting and occasionally evidence of active demyelination. The coexistence of a demyelinating motor radiculopathy and anterior horn changes simulating those of amyotrophic lateral sclerosis (ALS) may contribute to our understanding of the unresolved question of whether the neuronal perikaryon or its axon is the primary target in the pathogenesis of ALS. These observations also indicate that a rigid separation of pathogenetic mechanisms into neuronopathy, axonopathy and myelinopathy may not be always possible.

Journal ArticleDOI
TL;DR: The autopsy confirmed characteristic “burned out” plaques of multiple sclerosis and anterior horn cell and axonal degeneration of amyotrophic lateral sclerosis.
Abstract: We report the clinical and pathological findings of the unusual combination of two idiopathic central nervous system diseases, multiple sclerosis and amyotrophic lateral sclerosis in a 56 year old physician with a twenty-seven year history of a disease initially characterized by relapses and remissions, followed by an eight year quiescent period. During the last year of life there was rapid deterioration with development of generalized weakness, atrophy, weight loss and fasciculations of body and tongue, and associated difficulty with swallowing and sudden respiratory failure. The autopsy confirmed characteristic "burned out" plaques of multiple sclerosis and anterior horn cell and axonal degeneration of amyotrophic lateral sclerosis.


Journal ArticleDOI
TL;DR: A man with an incurable, degenerative motor neuron disease, which progressively destroys the muscles in the extremities and trunk, who lives with his wife, Paula, on the first floor of a comfortable two-family house on the outskirts of a large Eastern city.
Abstract: Maurice Baker * * lives with his wife, Paula, on die first floor of a comfortable two-family house on the outskirts of a large Eastern city. Mr. Baker, who is seventy-seven years old, and his wife, who is seventy-diree, are part-owners of the house. They have been married for fifty-two years. The Bakers were bom and married in England, arriving in the United States in 1948. Their son lives in the Midwest, and visits his parents every two or three months. Mr. Baker worked as an insurance agent until his illness forced him to stop at the end of 1979. Mr. Baker's illness is amyotrophic lateral sclerosis (ALS). This is an incurable, degenerative motor neuron disease, which progressively destroys the muscles in the extremities and trunk. It is marked by increasing weakness and paralysis, although sensory nerves are not affected. Though its progress can be erratic, with periods of rapid deterioration of strength and function interspersed with periods of stability, functions that are lost cannot be restored.


Journal ArticleDOI
TL;DR: In most of the ALS biopsies examined, ultrastructural‐cytochemical analysis revealed large reductions in AChE reaction product of both synaptic infoldings and sarcoplasmic reticulum of the muscles' motor endplate regions, compatible with the view that alterations observed in A ChE forms from ALS muscles are related to disturbances in the normal “trophic” interactions between nerve and muscle.
Abstract: Acetylcholinesterase (AChE) molecular forms in muscle biopsies from control and amyotrophic lateral sclerosis (ALS) patients were extracted under low (G: globular forms) and high (A: asymmetric forms) ionic strength conditions and were evaluated by velocity sedimentation analysis. Total AChE activity in endplate-containing ALS muscle sections was reduced by an average of 65% of control muscle levels. This decrement resulted from an almost complete disappearance of 9.5S (G4) and 8.0S (A4) AChE and significant decreases in the 3.8S (G1), 12.1S (A8), and 15.8S (A12) forms (66%, 9%, and 25% of control, respectively). In most of the ALS biopsies examined, ultrastructural-cytochemical analysis revealed large reductions in AChE reaction product of both synaptic infoldings (extracellular) and sarcoplasmic reticulum (intracellular) of the muscles' motor endplate regions. These data are compatible with the view that alterations observed in AChE forms from ALS muscles are related to disturbances in the normal "trophic" interactions between nerve and muscle.

Journal ArticleDOI
TL;DR: Serum from patients with amyotrophic lateral sclerosis was tested by immunoblotting for reactivity against three muscle-derived preparations: denervated chick leg muscle extracts, media conditioned by denervate rat hemidiaphragms, and a human muscle extract; results fail to confirm a recent report suggesting that anti-56K reactivity is characteristic of ALS.
Abstract: Serum from patients with amyotrophic lateral sclerosis (ALS) was tested by immunoblotting for reactivity against three muscle-derived preparations: denervated chick leg muscle extracts, media conditioned by denervated rat hemidiaphragms, and a human muscle extract. For each preparation, multiple bands were present using serum from all patients and controls, and no band was unique to ALS. Against rat muscle-conditioned medium, bands in the 56,000 (56K) molecular weight range were present to an equal degree in ALS and in controls; in addition, different bands near 56K were recognized by serum from different ALS patients. These results fail to confirm a recent report suggesting that anti-56K reactivity is characteristic of ALS.

Journal ArticleDOI
TL;DR: This may be the first autopsy case of spinocerebellar degeneration with severe concurrent involvement of the motor neuron system, and an unusual combination of system degenerations has on rare occasions been reported in the heredofamilial cerebellar disorders.
Abstract: A sporadic case of spinocerebellar degeneration with prominent involvement of the motor neuron system is reported. A Japanese male without contributing family history, developed cerebellar ataxia at the age of 52, followed by generalized amyotrophy and ophthalmoplegia, and died aged 58. The clinical findings were pathologically verified as degeneration of the spino-ponto-cerebellar system and the motor neuron system, the latter almost identical to those of amyotrophic lateral sclerosis. Additional subclinical changes were found in the dentate nucleus and substantia nigra. Brain-stem nuclei subserving eye movements were well preserved, suggesting a supranuclear basis for the ophthalmoplegia. This unusual combination of system degenerations has on rare occasions been reported in the heredofamilial cerebellar disorders. As a sporadic case, however, this may be the first autopsy case of spinocerebellar degeneration with severe concurrent involvement of the motor neuron system.

Journal ArticleDOI
TL;DR: Octacosanol was tried in amyotrophic lateral sclerosis in a double-blind, placebo-controlled, crossover design and neurologic and pulmonary function evaluations showed no benefit.
Abstract: Octacosanol was tried in amyotrophic lateral sclerosis in a double-blind, placebo-controlled, crossover design. Neurologic and pulmonary function evaluations showed no benefit.

Journal ArticleDOI
TL;DR: Compared with cultures grown in the presence of serum from healthy controls or patients with other neurologic disorders, ALS serum lowered the level of neurofilament proteins, and effects were similar with or without muscle-derived neurotrophic factors; there was no specificity for motor neurons.
Abstract: We used a quantitative immunoassay to examine the effects of human serum and immunoglobulins on neurofilament protein expression in cultures of chick spinal neurons Compared with cultures grown in the presence of serum from healthy controls or patients with other neurologic disorders, ALS serum lowered the level of neurofilament proteins Effects were similar with or without muscle-derived neurotrophic factors; there was no specificity for motor neurons No neurotoxic activity was found in immunoglobulin fractions, and there was no evidence of circulating antibodies that might neutralize muscle-derived neurotrophic factors or induce cytolysis of spinal neurons

Journal Article
TL;DR: Significant improvement was noted in muscle strength in the 9 patients treated by sequential intravenous administration of 240 mg of TRH over one hour every two weeks and the psychological improvement noted in some patients after an even transient improvement in motor performance.

Journal ArticleDOI
TL;DR: A 51-year-old man with primary amyloidosis, with typical amyloids neuropathy and signs of motor neuron disease, including widespread fasciculation in limb muscles, tongue atrophy and fasciculations, swallowing and chewing difficulty, symmetric hyperreflexia, and bilateral Hoffmann's signs is related to the motor neuron Disease of plasma cell dyscrasias.
Abstract: A 51-year-old man had primary amyloidosis, with typical amyloid neuropathy and signs of motor neuron disease, including widespread fasciculation in limb muscles, tongue atrophy and fasciculation, swallowing and chewing difficulty, symmetric hyperreflexia, and bilateral Hoffmann's signs. Fasciculations, fibrillations, and positive sharp waves were found in electromyography of all muscles tested. Motor nerve conduction velocities were moderately slow. Lambda chains were detected in serum and CSF. Amyloid was found in sural nerve biopsy. This combination of amyloid neuropathy and features of amyotrophic lateral sclerosis is related to the motor neuron disease of plasma cell dyscrasias.

Journal ArticleDOI
TL;DR: Results suggests that CRF may be related in the pathophysiology of ALS, and this value was significantly lower in the patients with ALS than in controls.
Abstract: Corticotropin-releasing factor (CRF) is widely distributed within the brain and spinal cord and may have direct extrahypophysiotrophic effects, independent of its pituitary action. The CRF level was measured using, the RIA method in cerebrospinal fluid (CSF) from 5 patients with amyotrophic lateral sclerosis (ALS), and in CSF from 10 patients with discopathy, treated as a controlled group. The median values of CRF level in the patients with ALS was 27.5 pg/ml, and this value was significantly lower than in controls, 53.5 pg/ml (P less than 0.05). These results suggests that CRF may be related in the pathophysiology of ALS.