Showing papers on "Amyotrophic lateral sclerosis published in 1987"

Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin

Abstract: The decline in the high incidence of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer-type dementia among the Chamorro population of the western Pacific islands of Guam and Rota, coupled with the absence of demonstrable viral and hereditable factors in this disease, suggests the gradual disappearance of an environmental factor selectively associated with this culture. One candidate is seed of the neurotoxic plant Cycas circinalis L., a traditional source of food and medicine which has been used less with the Americanization of the Chamorro people after World War II. Macaques were fed the Cycas amino acid beta-N-methylamino-L-alanine, a low-potency convulsant that has excitotoxic activity in mouse brain, which is attenuated by N-methyl-D-aspartate receptor antagonists. These animals developed corticomoto-neuronal dysfunction, parkinsonian features, and behavioral anomalies, with chromatolytic and degenerative changes of motor neurons in cerebral cortex and spinal cord. In concert with existing epidemiological and animal data, these findings support the hypothesis that cycad exposure plays an important role in the etiology of the Guam disease.

Abnormal glutamate metabolism in amyotrophic lateral sclerosis.

Abstract: Glutamate levels were determined in the fasting plasma of 22 patients with early-stage primary amyotrophic lateral sclerosis (ALS) and compared to those of healthy and diseased controls. There was a significant increase (by approximately 100%, p less than 0.0005) in the plasma glutamate of the ALS patients as compared with the controls. Oral glutamate loading (60 mg of monosodium glutamate per kilogram of body weight, taken orally after overnight fasting) resulted in significantly greater elevations in the plasma glutamate and aspartate levels in the ALS patients than in the controls. Glutamate, a potentially neuroexcitotoxic compound, is thought to be the transmitter of the corticospinal tracts and certain spinal cord interneurons. A systemic defect in the metabolism of this amino acid may underlie primary ALS.

Lowered cerebral glucose utilization in amyotrophic lateral sclerosis

Abstract: Regional cerebral metabolic rates for glucose (rCMRGlc) were analyzed in 19 studies of 12 patients with amyotrophic lateral sclerosis (ALS) by positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose In the 8 ALS patients with upper motor neuron signs, the mean cortical rCMRGlc was significantly lower than in 11 age-matched control subjects (p less than 001) The degree of hypometabolism correlated with the duration of the clinical signs and extended throughout the cortex and basal ganglia, but not to the cerebellum Of the 4 such patients who had repeat PET scans, 3 demonstrated significant subsequent reduction in the rCMRGlc, corresponding to the worsening of the clinical picture In contrast, 4 ALS patients with disease confined to lower motor neurons and 3 patients with lower motor neuron disease from old paralytic poliomyelitis had normal or near-normal rCMRGlc throughout the brain Because histological evidence shows no generalized neuronal cell loss in the cortex of ALS patients, including in some cases the primary motor regions, the demonstration of severe generalized hypometabolism in structurally normal cortex indicates that some cortical neurons exist in a state of neuronal nonfunction, rather than cell death, and that anatomoclinical correlations may be more complex The data also indicate that ALS with upper motor neuron involvement extends beyond the corticospinal tracts and differs in cortical function from the ALS confined to lower motor neurons or the other lower motor neuron disorders

Central motor conduction is abnormal in motor neuron disease.

Abstract: Conduction in the central motor pathways of the brain and spinal cord was studied in 12 patients with motor neuron disease. Six healthy volunteers served as controls. Transcutaneous electrical stimulation of the cortex, cervical cord, thoracic cord and conus medullaris was used to determine motor latencies to the biceps brachii, thenar eminence and tibialis anterior muscles. Prominent, and often asymmetrical, slowing of central motor conduction was demonstrated in seven of the 12 patients; these findings were most marked in the spinal cord and in most cases correlated with clinical features of corticospinal involvement. In general it was more difficult to excite motor pathways in the central nervous system in the patients with motor neuron disease than in control subjects. Evidence of subclinical involvement of central motor pathways was found in five patients. The central lesion in motor neuron disease may thus contribute more significantly to the clinical deficit than has been realised, since the clinical signs of the upper motor neuron lesion are often masked by the more obvious lower motor neuron features.

Brain glutamate deficiency in amyotrophic lateral sclerosis.

Abstract: Amino acid contents were measured in autopsied brains of eight patients with the sporadic form of amyotrophic lateral sclerosis (ALS) and in brains of control subjects dying without neurologic or psychiatric disease. Glutamic acid content was reduced in most brain regions and in the cervical cord in the ALS patients, while glutamine contents were normal. Taurine contents were increased, and γ-aminobutyric acid contents were decreased in some brain regions in the ALS patients. The brain glutamate deficiency in ALS is unexplained, but insufficient production or release of this excitatory neurotransmitter might have important secondary effects on motor neurons.

Mechanisms of nervous propagation along central motor pathways: noninvasive evaluation in healthy subjects and in patients with neurological disease.

Abstract: Motor evoked potentials (MEPs) to scalp stimulation have been obtained in 45 control patients and in 70 patients with neurological diseases. Optimal responses were obtained through a pericranial cathode consisting of 6 to 12 regularly spaced, interconnected pericranial cathodal discs whose resistance was carefully balanced with that of a stimulating anodal disc placed on the appropriate scalp region. The foci of maximal response for proximal and distal upper limb muscles as well as for lower limb muscles were localized. The scalp to cervical cord central conduction time (CCT) along motor tracts governing the hand muscles was 5.21 +/- 0.42 ms. This index was highly correlated with the subject's height and stable in time when repeatedly tested. Collision between orthodromically and antidromically propagated motor impulses was obtained. Response facilitation was achieved by means of prestimulus voluntary contraction of the target muscle, continuous vibration of its tendon, or scalp stimulation with paired shocks. The presence of a premovement facilitation of MEPs was also demonstrated, as was the presumed presence of transcallosal facilitation. An efferent volley secondary to scalp stimulation was recorded from the nerve trunk. Abnormalities in MEP characteristics as well as in CCTs were found in patients with multiple sclerosis, amyotrophic lateral sclerosis, cord compression, and degenerative diseases of the central nervous system.

A cohort study of amyotrophic lateral sclerosis and parkinsonism-dementia on Guam and Rota.

Abstract: A prospective study of the incidence of new cases of amyotrophic lateral sclerosis and parkinsonism-dementia was conducted by follow-up of 899 Chamorros in the Mariana Islands who participated in a baseline medical examination and interview in 1968. During a 15-year follow-up period, 28 new neurologically confirmed cases occurred, including 23 with parkinsonism-dementia and five with amyotrophic lateral sclerosis. The low incidence of amyotrophic lateral sclerosis was consistent with the reported disappearance of this disease from the Mariana Islands. However, the continuing high incidence of parkinsonism-dementia was not in agreement with a similarly reported disappearance nor with the hypothesis of a common cause of both diseases. Of 23 selected baseline examination variables, only the preference for traditional Chamorro food was significantly associated with an increased risk of parkinsonism-dementia. A review of the accumulated epidemiologic data on these neurologic diseases in the Mariana Islands did not support the current hypothesis that a chronic nutritional deficiency of calcium is a cause of both amyotrophic lateral sclerosis and parkinsonism-dementia.

Histopathology of the late-onset motor neuron degeneration (Mnd) mutant in the mouse

Abstract: The motor neuron degeneration (Mnd) is characterized by a progressive deterioration of motor function (stiff-legged gait, abnormal limb placements and grasping, and finally paralysis; moving from rear to forelimbs). There is a dramatic degeneration of spinal cord motor neurons, more severe in the lumbosacral than in the other regions, as well as variable pathology in the lower cranial nerves. Upper motor neurons of the red nucleus, reticular formation of the pons and medulla, and restricted areas of the cerebral cortex are also affected. Degenerating motor neurons share many characteristics seen in the human disease amyotropic lateral sclerosis, including loss of Nissl substance, increases in lipofuscin and abnormal cytoplasmic inclusions. Additionally, Mnd, like ALS, is a disease of later life.

Central motor conduction in motor neuron disease

Abstract: Central motor conduction was assessed in 13 patients with motor neuron disease and in 15 control subjects. All patients with motor neuron disease, even those without clinical pyramidal signs, had slowed central motor conduction, and in some the delays were asymmetrical. Evoked motor potentials represent a new and reliable method to detect physiological abnormalities of central motor pathways early in the course of motor neuron disease.

Trauma and amyotrophic lateral sclerosis: A report of 78 patients

Abstract: This was a controlled study to assess the possible role of mechanical trauma in the pathogenesis of some cases of amyotrophic lateral sclerosis (ALS). Questionnaires were sent to 181 patients with ALS who had developed the disease before age 45. Among the 135 respondents 78 (58%) reported having sustained injuries severe enough to have required medical attention prior to the onset of their motor neuron illness. Fifty nine (76%) of the ALS patients reporting an earlier trauma had incurred an injury to the head, neck, shoulder and/or arm. For controls, we used the 85 patients with multiple sclerosis who responded to the questionnaires sent them. The findings of this investigation add further evidence that a former injury may be important in the etiology of some cases of ALS developing early in life.

Recent views on amyotrophic lateral sclerosis with emphasis on electrophysiological studies

Abstract: Peripheral electrophysiological studies are of particular value of elucidating the anatomy and pathophysiology of neuromuscular diseases, but they can also help in providing clues to the etiology of the disease. Recent studies of the motor units in chronic denervating conditions including amyotrophic lateral sclerosis (ALS) are reviewed. These indicate that reinnervation is a relatively active process which compensates for the progressive loss of motoneurons in ALS until more than 50% of the motoneurons have died. There seems to be no predilection for death of motoneurons of any particular size in ALS. Fasciculations may arise both proximally and distally. The dying-back change is not a major feature of ALS. These and other data cast doubt on the etiological theories that ALS arises from premature aging of motoneurons, deficiency of motoneuron trophic factors, or an inhibitor of a motoneuronal sprouting factor, and point to the need to study metabolic changes intrinsic to the motoneuron in ALS.

A distinctive distribution of reactive astroglia in the precentral cortex in amyotrophic lateral sclerosis.

Abstract: Morphological changes in astrocytes have been studied in the primary motor cortex of persons dying with or without amyotrophic lateral sclerosis (ALS). Glial fibrillary acidic protein (GFAP) and S-100 protein were used as immunohistochemical markers for reactive astroglia. In 12 brains of individuals without neurological disease glial cells showing moderate immunoreactivity for both GFAP and S-100 protein were uniformly distributed in the primary motor cortex in the upper regions of layer I and layer II. In 8 of 11 ALS cases, intensely immunoreactive cells were additionally found to occur and were scattered irregularly, mostly in layers II and III, but occasionally in layers IV and V. Clusters of these intensely positive cells occurred in patches about 200–400 μm in diameter, each containing about 6 to >20 such cells. GFAP-positive astrocytes were seen in some of the 36 brains from persons with neurological problems other than ALS but the pattern was different. The abnormal appearance of clusters of positive astrocytes of the primary motor cortex may be intimately associated with the ALS disease process.

Motor neuron disease in the United States, 1971 and 1973–1978 Patterns of mortality and associated conditions at the time of death

Abstract: Mortality rates for deaths “due to” and “with” motor neuron disease are presented for the first time. Age-specific mortality rates increase with age until 70 to 74 years and then decline. There appear to be no major differences by race in the age-adjusted mortality rates, but these rates are higher for males both white and nonwhite. A case-control study of all deaths with amyotrophic lateral sclerosis (ALS) was conducted for deaths due to ALS in the year 1971. Conditions associated with ALS at the time of death include pneumonia and bronchopneumonia, symptoms referable to respiratory system, superficial injury to shoulder and upper arm, essential benign hypertension, chronic skin ulcer, and malnutrition. No association was found between ALS and malignancies, Parkinson9s disease, or dementia.

Observations about amyotrophic lateral sclerosis and the parkinsonism-dementia complex of Guam with regard to epidemiology and etiology.

Abstract: For more than 150 years, Chamorro natives of the Mariana Islands in the Western Pacific Ocean, have developed fatal paralysis in middle and later life, which we term amyotrophic lateral sclerosis/parkinsonism-dementia (ALS/PD). The cause of the disease might be exposure to seeds of the indigenous cycad. Motor system disease is induced in cynomolgus monkeys by feeding them beta-N-methylamino-L-alanine (BMAA), an amino acid present in cycad seeds. We believe that the cycad seeds which usually cause no immediate adverse symptoms when prepared and eaten as flour, or applied topically as medicine, can give rise to widespread and severe nerve cell degeneration after a latency of many decades. Furthermore, it may be that only a single exposure to this potent but silent toxin(s) can result in fatal neurological disease years later.

Antineural antibodies in the serum of patients with amyotrophic lateral sclerosis

Abstract: Sera from 12 patients with amyotrophic lateral sclerosis (ALS) and 18 controls were screened for antineural antibodies using immunoblotting. No consistent differences were detected between ALS patients and controls, although antibodies to 52,000- and 70,000-dalton proteins in mouse spinal cord were somewhat more common in ALS sera. Antibodies to a protein of approximately 150,000 to 200,000 daltons were also evident. The 70,000- and 52,000-dalton proteins were detected in brain, cerebellum, and liver as well as spinal cord. Immunohistochemistry suggested antibody activity was directed at least in part to neurofilaments. While the antibodies to the 52,000- and 70,000-dalton proteins were more common in ALS than control sera ( p

Nerve cell death in degenerative diseases of the central nervous system: clinical aspects.

Abstract: The origin of degenerative diseases of the central nervous system lies in genetic and acquired disorders. Analysis of the clinical characteristics of diseases affecting specific neuronal systems may help us to understand their pathogenesis. The stereotyped symptomatology characteristic of most degenerative diseases results from neuronal death in specific pathways: pyramidal tract and motor neurons in amyotrophic lateral sclerosis, nigrostriatal dopamine system in Parkinson's disease, posterior and lateral columns of the spinal cord in Friedreich's ataxia, etc. This suggests that these neurons are sensitive to pathological processes that are still unknown. Progression of the disease, whether linear or not, is slow, but it is more rapid than similar effects due to ageing. This indicates either that the environmental cause of degeneration (if it exists) is continuously present or that a vital process has been once and for all disrupted, perhaps at the level of the genome, causing insufficient production of essential proteins, or accumulation of eventually toxic metabolites. Symptoms generally appear during adulthood, i.e. after normal differentiation has taken place, and after a considerable number of neurons have already been damaged. The initiation of neuronal death precedes the appearance of the first symptoms.

Amyotrophic lateral sclerosis in finland

Abstract: The epidemiology of amyotrophic lateral sclerosis (ALS) has been studied in Finland since 1963. The country is suitable for epidemiological investigations because of its stable population structure and accurate population registers.

Amyotrophic Lateral Sclerosis: Concepts in Pathogenesis and Etiology

Abstract: The ALS symposium in Vancouver was the first of its kind in Canada and was a contribution from both American and Canadian investigators. The main points presented were (1) a definition of what is truly ALS, in the clinical and pathological sense, based on what is called "classical" ALS: (2) how neurons may be cultured to provide a valuable experimental tool; (3) the significance of lipid abnormalities in ALS and the characterization of the ALS-like syndromes produced by hexosaminidase A deficiency; (4) the possible role of autoimmune disease as it may accompany classical ALS and nerve growth factor derived from skeletal muscle; (5) the western Pacific form of ALS as it has been intensely studied and has given rise to two hypotheses on pathogenesis: mineral toxicity caused by secondary hyperparathyroidism and poisoning through ingestion of the cycad seed, and (6) the possible abiotropic interaction of one or many environmental toxins over a lifetime with the aging nervous system, depleting it of its frail reserve of neurons.

Infantile neurodegenerative disease with neuronal accumulation of phosphorylated neurofilaments.

Abstract: A caucasian male with a history of mental retardation and intractable epilepsy since birth, developed progressive wasting and weakness of skeletal muscles, leading to death at 4 years of age. A biopsy of gastrocnemius muscle at 2 years of age revealed severe neurogenic atrophy. Sural nerve biopsies at 2 and 3 years showed progressive atrophy and loss of large myelinated nerve fibers with a paucity of neurofilaments in remaining nerve fibers. Postmortem immunohistochemical and ultrastructural examination showed that neurons were markedly distended by phosphorylated neurofilaments. Whereas large lower motor neurons were most severely involved, dorsal root ganglia and neurons in the cerebral cortex and deep gray nuclei were also affected. It is suggested that this disease is caused by a disorder of neurofilament phosphorylation and transport.

Serum insulin-like growth factor-I levels in amyotrophic lateral sclerosis.

Abstract: The serum concentrations of the myotrophic hormone insulin-like growth factor-I (IGF-I) in 23 patients with amyotrophic lateral sclerosis were not significantly different from those found in the sera of 13 control patients. There was no difference in binding of 125I-IGF-I by serum from patients with amyotrophic lateral sclerosis in comparison with that found in the controls. These results indicate that immunoreactive IGF-I concentrations are normal in patients with amyotrophic lateral sclerosis and that such patients do not have significant antibodies binding their endogenous IGF-I.

Amyotrophic lateral sclerosis and history of skeletal fracture: A case‐control study

Abstract: A retrospective case-control study was conducted, using 66 amyotrophic lateral sclerosis (ALS) patients and 66 closely matched controls. Cases were ascertained primarily through a neurology clinic. A self-administered questionnaire probed for history of skeletal fractures. Using McNemar9s test, no association was found between history of skeletal fracture and pathogenesis of ALS. No predilection for the head, neck, or spine was demonstrated. The extremities accounted for most fracture sites in cases and controls. Among cases, 68% of the fractures occurred before diagnosis, 58% occurring more than 10 years before diagnosis of ALS.

Sympathetic cholinergic dysfunction in amyotrophic lateral sclerosis

Abstract: — The results of evaluation of the autonomic nervous system of a patient with amyotrophic lateral sclerosis are presented As previously reported, parasympathetic function and sympathetic adrenergic function were normal as assessed by cardiovascular reflexes However, a disturbance in sympathetic cholinergic function as measured by the sympathetic skin response was demonstrated We suggest that the latter test be included in all electrophysiological evaluations of autonomic function in amyotrophic lateral sclerosis

Phenotypic and genotypic heterogeneity of dominantly inherited amyotrophic lateral sclerosis.

Abstract: — Twenty-seven cases of hereditary amyotrophic lateral sclerosis (ALS), belonging to 8 families, are reported. The analysis of the pedigrees suggests an autosomal dominant transmission, apparently with incomplete penetration. The mean age at onset of symptoms was 50.3 (SD 12.4) years. The mean duration of the disease was 31.2 (SD 20.4) months, ranging from 9 to 86. The median survival time was 24 months. The degree of variation of some quantitative characters, both within and among families, was statistically analyzed. The results support the hypothesis of a phenotypic and genetic heterogeneity of autosomal dominant transmitted ALS.