Showing papers on "Amyotrophic lateral sclerosis published in 1990"
TL;DR: It is concluded that excitatory amino acid metabolism is altered in patients with ALS and these changes may play a role in motor neuron loss in ALS.
Abstract: Recently, the excitatory amino acid neurotransmitter glutamate was implicated in the pathogenesis of a variety of chronic degenerative neurological diseases in humans and animals. This report describes abnormalities in excitatory amino acids in the central nervous system of 18 patients with amyotrophic lateral sclerosis (ALS). The concentration of the excitatory amino acids glutamate and aspartate in the cerebrospinal fluid were increased significantly (p less than 0.01) by 100 to 200% in patients with ALS. Similarly, the concentrations of the excitatory neuropeptide N-acetyl-aspartyl glutamate and its metabolite, N-acetyl-aspartate, were elevated twofold to threefold in the cerebrospinal fluid from the patients. There was no relationship between amino acid concentrations and duration of disease, clinical impairment, or patient age. In the ventral horns of the cervical region of the spinal cord, the level of N-acetyl-aspartyl glutamate and N-acetyl-aspartate was decreased by 60% (p less than 0.05) and 40% (p less than 0.05), respectively, in 8 patients with ALS. Choline acetyltransferase activity was also diminished by 35% in the ventral horn consistent with motor neuron loss. We conclude that excitatory amino acid metabolism is altered in patients with ALS. Based on neurodegenerative disease models, these changes may play a role in motor neuron loss in ALS.
653 citations
TL;DR: The accumulation of IgG in motoneurons and the presence of immunologically active macrophages provide additional evidence for the participation of immunologic factors in the pathogenesis of ALS.
Abstract: • The spinal cord and motor cortex of patients with amyotrophic lateral sclerosis (ALS) were examined with immunohistochemical methods for the presence of IgG. In 13 of 15 spinal cords, a population of motoneurons stained positively for IgG in a granular pattern, characteristic of binding to the rough endoplasmic reticulum. In 6 of 11 motor cortices, a proportion of pyramidal cells also stained positively for IgG. No such reactivity was noted in motoneurons of control human tissues, although positive IgG staining was present in astrocytes of ALS and control specimens. Reactive microglia and/or macrophages were detected in the territory of degenerating pyramidal tracts and ventral horns. The surface of most of these cells stained positively for IgG, and 50% stained positively for HLA-DR. The accumulation of IgG in motoneurons and the presence of immunologically active macrophages provide additional evidence for the participation of immunologic factors in the pathogenesis of ALS.
220 citations
TL;DR: Present data support the hypothesis that altered presynaptic glutamatergic mechanisms may be responsible for a neuroexcitotoxic cell loss in patients with amyotrophic lateral sclerosis, and high local concentrations of glycine released from glycinergic terminals may disrupt adaptive processes contributing to abnormal potentiation of excitatory transmission.
Abstract: Recent studies provided evidence for a generalized defect in glutamate metabolism in patients with amyotrophic lateral sclerosis, associated with widespread alterations in the central nervous system levels of this excitatory amino acid putative transmitter. Present data support the hypothesis that altered presynaptic glutamatergic mechanisms may be responsible for a neuroexcitotoxic cell loss in this disorder. High local concentrations of glycine, released from glycinergic terminals, may disrupt adaptive processes contributing to abnormal potentiation of excitatory transmission mediated by glutamate receptors and resultant selective degeneration of motor neurons. These considerations offer new therapeutic strategies for amyotrophic lateral sclerosis.
182 citations
TL;DR: The findings do not lend support to the hypothesis that the sporadic form of ALS results from overexcitation of motor neurons by excitatory amino acids, and concentrations of glutamate, aspartate, and glycine were normal in the CSF of all 17 patients examined.
Abstract: Concentrations of glutamic acid have been reported to be elevated in fasting plasma and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS); glycine concentrations have also been reported to be increased in the CSF of such patients. Autopsy studies have shown glutamate contents to be significantly decreased in brain and spinal cord in ALS. These observations suggested that a systemic abnormality of glutamate metabolism might underlie the pathogenesis of ALS. We report here the findings of our studies of amino acid concentrations in patients with the sporadic form of ALS. Glutamate concentrations were normal in the fasting plasma of a great majority of the patients with ALS. Concentrations of glutamate, aspartate, and glycine were normal in the CSF of all 17 patients examined. beta-N-Methylamino-L-alanine, a plant neurotoxin possibly responsible for causing the Guamanian form of ALS, was not detectable in the plasma or CSF of any of our patients. Our findings do not lend support to the hypothesis that the sporadic form of ALS results from overexcitation of motor neurons by excitatory amino acids.
164 citations
TL;DR: Patients with hereditary motor system diseases belonging to 17 families with clinical features of a bilateral pyramidal syndrome, weakness with atrophy and fasciculation of the hands and/or the legs, with or without a bulbar or a pseudobulbar syndrome were studied.
Abstract: Forty-three patients with hereditary motor system diseases belonging to 17 families were studied. The clinical features consisted of a bilateral pyramidal syndrome, weakness with atrophy and fasciculation of the hands and/or the legs, with or without a bulbar or a pseudobulbar syndrome and without sensory disturbance. Electromyography in 31 cases (including all index cases) showed evidence of denervation. Motor and sensory nerve conduction velocity was normal; sensory nerve action potential amplitudes, examined in 11 cases, were also normal. Nerve and muscle biopsies taken in 29 cases (including all index cases) showed neurogenic atrophy in the peroneus brevis muscle and minor changes only in the superficial peroneal nerve. The mean age of onset was 12.06 (range 3-25 years), and progression was very slow. Inheritance appeared to be autosomal recessive. Depending on the clinical presentation, the patients were subdivided into three groups comprising (1) upper limb and sometimes bulbar amyotrophy with a bilateral pyramidal syndrome (17 patients: 11 familial and 6 isolated); (2) spastic paraplegia with peroneal muscular atrophy (14 patients: 11 familial and 3 isolated); and (3) a spastic pseudobulbar form (12 patients in a large kinship). These entities are discussed and compared with other cases reported in the literature.
161 citations
TL;DR: Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis, Werdnig-Hoffmann's disease, X-linked recessive bulbospinal neuronopathy and multiple system atrophy were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments.
Abstract: Lower motor neurons of the spinal cord of patients with amyotrophic lateral sclerosis (ALS), Werdnig-Hoffmann's disease (WH), X-linked recessive bulbospinal neuronopathy (X-BSNP) and multiple system atrophy (MSA), all of which were known to involve the lower motor neurons, were immunohistochemically examined by using a monoclonal antibody (Ta-51) specific to phosphorylated epitopes of high molecular weight subunits of neurofilaments. The incidence of Ta-51-positive neurons was significantly increased in ALS, WH and MSA, but not in X-BSNP. Ta-51-positive neurons showed a wide variety of morphological appearances, including neurons with normal appearance, central chromatolysis, simple atrophy and neurons containing massive neurofilamentous accumulation. In aged-control cases, similar Ta-51-positive neurons were observed, although to a much lesser extent. In ALS, spheroids and globules, which were strongly positive for Ta-51, were also significantly increased. Ta-51-positive motor neurons, spheroids and globules appeared in proportional to the number of remaining large motor neurons in ALS.
128 citations
TL;DR: There is an inordinately high occurrence of paraproteinemia in MND; some of these patients may have lymphoma; and IFE on agarose is more sensitive than electrophoresis on cellulose acetate in detecting paraproteins.
Abstract: From 1984 to 1988, 11 of 120 patients (9%) with motor neuron disease (MND) had paraproteins detected by serum immunofixation electrophoresis (IFE), compared with 4 (3%) by cellulose acetate gels: 1 patient had progressive spinal muscular atrophy, 5 patients had amyotrophic lateral sclerosis (ALS), and 5 patients had ALS with probable upper motor neuron signs. Four of 5 patients (80%) with cerebrospinal fluid (CSF) protein content above 75 mg/dl had paraproteins, as did 6 of 30 with values above 50 mg/dl. Four of 14 patients with cerebrospinal oligoclonal bands (OCB) also had paraproteins. Two patients with ALS, CSF protein content above 75 mg/dl, and paraproteinemia had lymphoma. We conclude the following about patients with MND: high CSF protein content (especially above 75 mg/dl) or CSF OCB makes paraproteinemia more likely; some of these patients may have lymphoma; there is an inordinately high occurrence of paraproteinemia in MND; and IFE on agarose is more sensitive than electrophoresis on cellulose acetate in detecting paraproteins. Syndromes of paraproteinemia and high CSF protein are not restricted to the lower motor neuron but qualify as "ALS" with coexisting upper motor neuron signs.
118 citations
TL;DR: Physical trauma, the frequent consumption of freshly caught Lake Michigan fish, and a family history of cancer were reported more often by case patients than control subjects, and the causative role of diet should be further explored.
Abstract: • From 1975 to 1983, six cases of amyotrophic lateral sclerosis (ALS) were diagnosed in long-term residents of Two Rivers, Wis; the probability that this occurred due to chance was less than.05. To investigate potential risk factors for ALS, we conducted a case-control study using two control subjects matched to each case patient for age, gender, and duration of residence in Two Rivers. Physical trauma, the frequent consumption of freshly caught Lake Michigan fish, and a family history of cancer were reported more often by case patients than control subjects. These findings support previous studies proposing a role for trauma in ALS pathogenesis and suggest that the causative role of diet should be further explored. Continued surveillance for and epidemiologic investigation of ALS clusters with subsequent retrospective analysis may provide clues concerning the cause of ALS.
86 citations
TL;DR: For each clinical category, the annual death rate remained constant throughout the observation period, indicating the effects of a steadily progressing degenerative disorder.
Abstract: We investigated the survival of patients with amyotrophic lateral sclerosis (ALS) in a follow-up study of all patients hospitalized with the disease in 2 Danish counties during the period 1974 to 1986. There were 186 patients, with a mean age at diagnosis of 64.3 years. The median survival time was 12 months from diagnosis, the 3-year survival rate was 12%, and the 5-year survival rate 4%. (The corresponding figures from onset were 23 months, 26%, and 7%). Old age and bulbar findings at onset were negative prognostic factors. For each clinical category, the annual death rate remained constant throughout the observation period, indicating the effects of a steadily progressing degenerative disorder. We found no evidence of the existence of a separate variety of ALS, associated with long survival.
80 citations
TL;DR: A 74-year-old man with a paraneoplastic motor neuron disease mimicking amyotrophic lateral sclerosis had an elevated erythrocyte sedimentation rate, other laboratory abnormalities, and a previously undiagnosed renal cell carcinoma and four months after nephrectomy.
Abstract: A 74-year-old man had a paraneoplastic motor neuron disease mimicking amyotrophic lateral sclerosis. He had an elevated erythrocyte sedimentation rate, other laboratory abnormalities, and a previously undiagnosed renal cell carcinoma. Four months after nephrectomy, his strength had improved and he had no fasciculations. Seven other patients with cancer and motor neuron disease improved or stabilized after tumor treatment. Even though it is rare, paraneoplastic motor neuron disease is important to diagnose because it may be treatable.
79 citations
Journal Article•
TL;DR: In this paper, a spontaneous motor neuron disease or neuronopathy was identified in 10 horses from the northeastern United States, showing signs of generalized weakness, muscle fasciculations, muscle atrophy and weight loss.
Abstract: A spontaneous motor neuron disease or neuronopathy was identified in 10 horses from the northeastern United States. Signs of generalized weakness, muscle fasciculations, muscle atrophy and weight loss progressed over 1 to several months in young and old horses of various breeds. Pathologic studies revealed that degeneration and loss of motor neurons in the spinal cord and brain stem resulted in axonal degeneration in the ventral roots and peripheral and cranial nerves and denervation atrophy of skeletal muscle. Many spinal neurons were swollen, chromatolytic and contained neurofilamentous accumulations. Other cell bodies were shrunken and undergoing neuronophagia and some were lost and replaced by glia. This fatal equine motor neuron disease has not been reported previously and its cause has not been determined. The progressive weakness and wasting and the neuronal degenerative changes in these horses were similar to those described in people with sporadic amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.
TL;DR: Most likely causes of misdiagnosis were physicians' failure to consider the diagnosis and lack of familiarity with the common clinical presentations of amyotrophic lateral sclerosis.
Abstract: • To confirm our impression that a high percentage of patients with amyotrophic lateral sclerosis are initially misdiagnosed, we reviewed records of 33 patients with a definitive diagnosis of amyotrophic lateral sclerosis seen over 10 years. Fourteen patients (43%) were initially misdiagnosed. Mean time to correct diagnosis was significantly greater for the misdiagnosed group (16.0 ± 9.3 months) than for the rest of the patients (7.6 ± 4.1 months). Two of three patients with an initial symptom of dyspnea were misdiagnosed. Three patients underwent laminectomies because of misdiagnosis. Age, stage of disease, and unusual presenting symptoms were not identified as causes of misdiagnosis. Most likely causes were physicians' failure to consider the diagnosis and lack of familiarity with the common clinical presentations of amyotrophic lateral sclerosis. Earlier diagnosis of amyotrophic lateral sclerosis may help prevent medical mismanagement and may benefit patients both medically and psychologically. (Arch Intern Med.1990;150:2301-2305)
TL;DR: There appears to be a statistically significant association between ALS and immunoreactivity to B burgdorferi, at least among men living in hyperendemic areas.
Abstract: • Of 19 unselected patients with the diagnosis of amyotrophic lateral sclerosis (ALS) living in Suffolk County, New York (an area of high Lyme disease prevalence), 9 had serologic evidence of exposure to Borrelia burgdorferi ; 4 of 38 matched controls were seropositive. Eight of 9 sero-positive patients were male (8 of 12 male patients vs 2 of 24 controls). Rates of seropositivity were lower among patients with ALS from nonendemic areas. All patients had typical ALS; none had typical Lyme disease. Cerebrospinal fluid was examined in 24 ALS patients—3 (all with severe bulbar involvement) appeared to have intrathecal synthesis of anti- B burgdorferi antibody. Following therapy with antibiotics, 3 patients with predominantly lower motor neuron abnormalities appeared to improve, 3 with severe bulbar dysfunction deteriorated rapidly, and all others appeared unaffected. There appears to be a statistically significant association between ALS and immunoreactivity to B burgdorferi , at least among men living in hyperendemic areas.
TL;DR: Pelvic floor muscles play a fundamental role in signaling arrival of feces to the perineum and other mechanisms such as the anorectal angle and anal cushions are also of relevance, although emphasis has been put on motor factors.
TL;DR: A case report of a 51-year-old patient with sporadic ALS who developed progressive external ophthalmoplegia 3 years after he remained on a respirator and died 5 years later, 13 years after the onset of his illness, indicates that long-term use of respirators may make some patients with this illness prone to developing atypical clinical and neuropathologic features which are not observed during the natural course of ALS.
TL;DR: The nigrostriatal lesions in the subjects with amyotrophic lateral sclerosis and the Guamanian normal subjects are examples of subclinical neuronal damage demonstrable in living subjects with positron emission tomography.
Abstract: • We performed positron emission tomography using18F-6-fluorodopa on four Guamanians with an amyotrophic lateral sclerosis syndrome, eight Guamanians with parkinsonism, and seven clinically normal Guamanians; the results were compared with those of nine Vancouver control subjects. The Guamanian subjects had all been exposed to similar Chamorro life-styles. The scans were analyzed using a graphic method that calculates a constant for whole striatal18F-6-fluorodopa uptake. The parkinsonian subjects all had significantly reduced striatal18F-6-fluorodopa uptake. The group with amyotrophic lateral sclerosis had significantly reduced uptake that was intermediate between that of the control group and the parkinsonian group. Two Guamanian normal subjects had reduced striatal18F-6-fluorodopa uptake. The nigrostriatal dopaminergic lesion in Guamanian parkinsonism is similar to that found in idiopathic parkinsonism. The nigrostriatal lesions in the subjects with amyotrophic lateral sclerosis and the Guamanian normal subjects are examples of subclinical neuronal damage demonstrable in living subjects with positron emission tomography.
TL;DR: Findings support the role of some antecedent events in causing ALS but show that they have little influence on clinical features and disease evolution.
Abstract: Risk factors for amyotrophic lateral sclerosis (ALS) such as country of residence, hard labour, intense athletic activities, heavy metal and pet exposure, skeletal trauma, surgical procedures, malignancies, and recurrent infectious disease were investigated in 77 patients and 80 controls, matching the cases for selected parameters, hard work occurred more frequently in ALS patients than in controls; hard labour, skeletal trauma and exposure to heavy metals showed a high relative risk. Some differences were detected in the clinical evolution of ALS, as defined using the Norris scale. These findings support the role of some antecedent events in causing ALS but show that they have little influence on clinical features and disease evolution.
Patent•
12 Sep 1990
TL;DR: In this article, the extracellular concentrations of adenosine in and around the neural tissue are increased to prevent tissue damage caused by excitotoxicity due to increased release of excitatory amino acids.
Abstract: Methods of preventing neural tissue damage caused by excitotoxicity due to increased release of excitatory amino acids by increasing extracellular concentrations of adenosine in and around the neural tissue are provided. These methods are especially useful in treating neurodegenerative diseases such as Parkinson's Disease, Alzheimer's Disease, Amyotrophic Lateral Sclerosis or Huntington's Disease.
TL;DR: Bilateral increased signal areas of various sizes in the centrum semiovale, corona radiata, internal capsule, pedunculi of midbrain, pons, medulla and even in the frontal lobe, topographically related with the corticospinal tract, were found in patients with motor neuron disease and controls.
Abstract: Magnetic resonance imaging (MRI) of the brain was evaluated in 20 patients with motor neuron disease (MND) and in a control group of 11 healthy people. Bilateral increased signal areas of various sizes in the centrum semiovale, corona radiata, internal capsule, pedunculi of midbrain, pons, medulla and even in the frontal lobe, topographically related with the corticospinal tract, were found in 8 out of 20 patients. Three out of 4 patients with progressive bulbar paralisis and 5 out of 11 cases of amyotrophic lateral sclerosis had abnormal MRI. Such MRI abnormalities have neither been found in patients with progressive muscular atrophy nor in controls, suggesting that they may be the hallmark of pyramidal tract degeneration in motor neuron disease.
TL;DR: The data support the notion of a generalized defect in glutamate metabolism in ALS rather than a selective defect in nezlronal glutamate transport, metabolism, storage, release, or receptors, and the observation that persons develop selective upper and lower motor neuron disorders after exposure to the glutamatergic neurotoxins is supported.
Abstract: In this issue, one review and two original articles appear that address the potential role of excitatory amino acids in the pathogenesis of amyotrophic lateral sclerosis (ALS) 11-31. The hypothesis, as put forward by Plaitakis 1 11, is that a generalized defect in excitatory amino acid metabolism in ALS may render select groups of neurons vulnerable to excitatory amino acid-induced neurotoxic damage because of their unique neuronal properties and the neurochemical character of their connections. Several studies are cited as providing evidence for increased plasma and cere-brospinal fluid (CSF) glutamate concentrations in patients with ALS, and also decreased concentrations of brain glutamate and decreased spinal cord glutamate, aspartate, N-acetylaspartate (NAA), and N-acetyl-aspartyl glutamate (NAAG). Plaitakis concludes that the data support the notion of a generalized defect in glutamate metabolism in ALS rather than a selective defect in nezlronal glutamate transport, metabolism, storage, release, or receptors. Why, then, is ALS characterized by such regionally specific pathological find-ings? Would not other regions of the nervous system be affected in ALS if glutamate (which is a neuro-transmitter and a potential neurotoxin throughout brain) is metabolized abnormally? Plaitakis argues that the selective vulnerability may reside in the particular properties of motor neuron innervation or factors that could abnormally potentiate this innervation, or both. H e suggests that one such potentiator could be gly-cine. Glycine is an inhibitory neurotransmitter of inter-neurons in spinal cord and brainstem and is uniquely present in high concentrations in these regions. It is also a positive modulator of one subtype of glutamate receptor, the N-methyl-D-aspartate (NMDA) receptor. The NMDA receptor is thought to play a crucial role in glutamate-induced neurotoxicity 143. Glycine enhances glutamate's excitatory actions at the NMDA receptor and promotes recovery of NMDA receptors after glutamate-induced desensitization. Thus, many nervous system regions may be able to compensate for high extracellular glutamate concentrations except in spinal cord and brainstem where glycine enhances glutamate's actions. In support of Plaitakis' hypothesis is the observation that persons develop selective upper and lower motor neuron disorders after exposure to the glutamatergic neurotoxins in Lathyrzls sutizu and Cycus circinalir 151. The data of Rothstein and coworkers 131 support Plaitakis' hypothesis by demonstrating 100 to 2009% increases in glutamate and aspartate concentrations in CSF of patients with ALS. CSF NAA and NAAG are also shown to be increased several-fold. In spinal cord of patients with ALS, NAA and NAAG concentrations are reportedly decreased. In contrast, …
Journal Article•
TL;DR: Changes observed in Hg and Se levels in ALS tissues deserve special attention and the significance of these alterations in trace element levels in relation to the pathogenesis of ALS is discussed.
Abstract: Concentrations of 15 elements were determined by instrumental neutron activation analysis in brain, spinal cord, blood cells, serum and nails of Amyotrophic Lateral Sclerosis (ALS) patients and appropriately matched control subjects. Several significant imbalances were detected in trace element levels in ALS samples compared to control samples. Some of these changes are probably secondary to the loss of tissue mass, especially in spinal cord. However the widespread changes observed in Hg and Se levels in ALS tissues deserve special attention. The significance of these alterations in trace element levels in relation to the pathogenesis of ALS is discussed.
TL;DR: Investigation of the selective involvement of spinocerebellar neurons in sporadic amyotrophic lateral sclerosis was investigated using two monoclonal antibodies that have neuronal subset specificity in human spinal cord, and some surface molecules are modified during the degenerative process are suggested.
Abstract: The selective involvement of spinocerebellar neurons in sporadic amyotrophic lateral sclerosis was investigated using two monoclonal antibodies that have neuronal subset specificity in human spinal cord. In normal control subjects, monoclonal antibody 6A2 showed specificity for neurons of the dorsal nucleus of Clarke, the cells of origin of the dorsal spinocerebellar tract. Immunoreactive neurons were also observed in locations corresponding to the central cervical nucleus and spinal border region, containing neurons of the cervicospinocerebellar and ventral spinocerebellar tracts, respectively. The latter two neuronal subsets are indistinguishable from surrounding neurons when conventional histological stains are used. Antigen 6A2 was distributed on surfaces of neuronal somas and proximal neurites and extended into the extracellular space. A second antibody, monoclonal antibody 44.1, labeled the cytoplasm of neuronal somas and neurites, including all monoclonal antibody 6A2-reactive cells and alpha motoneurons. In spinal cords of all 5 patients with amyotrophic lateral sclerosis, monoclonal antibody 6A2 reactivity in the majority of spinocerebellar neurons was absent or localized to the somal cytoplasm, which still stained with monoclonal antibody 44.1. In more severely involved tissues, there was loss of some spinocerebellar neurons and a corresponding loss of monoclonal antibody 44.1 reactivity. These findings confirm involvement of the spinal cord components of the spinocerebellar system at all levels in sporadic amyotrophic lateral sclerosis and suggest that some surface molecules are modified during the degenerative process.
TL;DR: Familiarity studies have shown that influenza A is an optimal candidate among other RNA viruses for delayed nervous system infection as a possible cause of ALS/PD.
Abstract: Guamanian amyotrophic lateral sclerosis with parkinsonism-dementia (ALS/PD) has been the subject of intensive study since its discovery in 1947 because of its extraordinarily high incidence in a small ethnic group (Chamorros) whose dietary lack and customs have suggested possible causes. As yet, these and other suspected causes have eluded proof. Because of marked similarities between Guamanian ALS/PD and late onset post-encephalitic (encephalitis lethargica) parkinsonism and ALS it is suggested that they have a common cause. The parkinsonism and ALS in the two disorders are clinically very similar and neuropathological studies have shown a very similar distribution of neurofibrillary tangles in neurons. Some clinical differences, such as ocular features in the post-encephalitic cases and dementia in Guamanian ALS/PD, can be explained by differences in the severity of infection and the interval between the encephalitis and onset of sequelae. Although unproven, influenza A (HswilN1 strain) has long been suspected as the cause of encephalitis lethargica because of simultaneous pandemics of the two diseases in the 1920s. Because influenza A can persistently infect cells and has a marked propensity to mutate it is an optimal candidate among other RNA viruses for delayed nervous system infection as a possible cause of ALS/PD.
TL;DR: The common appearance of BBs, although the number is small, in the medullary reticular formation (MRF) in ALS is demonstrated, indicating that pathological processes that undermine the lower motor neurons in ALS in some way also affect neurons other thanMotor neurons in this condition.
Abstract: To determine how often Bunina bodies (BBs) appear in the medullary reticular formation (MRF) in amyotrophic lateral sclerosis (ALS), we microscopically examined 20 serial sections of MRFs from each of nine autopsied ALS cases, which had BBs in the lower motor neurons, including those of cranial motor nuclei. In 1 of them, the pontine tegmentum was examined in the same way. In 8 cases one to several BB-containing neurons in the MRF were seen. The case in which the pontine tegmentum was also investigated exhibited several neurons with BBs in this region. Some of the BBs in the MRFs were confirmed by electron microscopy. Thus, this study demonstrates the common appearance of BBs, although the number is small, in the MRF, indicating that pathological processes that undermine the lower motor neurons in ALS in some way also affect neurons other than motor neurons in this condition.
TL;DR: The clinical symptoms were predominantly those of initial shoulder girdle and ultimate partial bulbar muscle involvement and neuropathological findings included, next to classical features, degeneration of various spinal tracts and Purkinje cells loss.
TL;DR: There was a significant negative correlation between upper motor neuron symptoms and MMS, as well as memory tests, which revealed that more sensitive neuropsychological measurements might reveal cerebral dysfunction in ALS patients who are not presenting evident dementia.
Abstract: A study was undertaken to elucidate the existence of cognitive and memory impairments in patients with amyotrophic lateral sclerosis (ALS) by comparing a group of ALS patients with both nonneurological medical controls (MC) and healthy controls (HC) on neuropsychological tests. We also examined the relationship between the severity of motor disabilities and intellectual impairment. Twenty-two ALS patients, 18 MCs and 17 HCs participated. The tests used were the Mini-mental state examination (MMS) and the immediate and delayed memory tests. The mean MMS score of the ALS patients was lower than the mean scores of both control groups. In the memory tests, there were significant differences between the ALS group and the two control groups. Correlation analyses of several motor symptoms and neuropsychological results revealed that there was a significant negative correlation between upper motor neuron symptoms and MMS, as well as memory tests. The evidence for multisystem degeneration in ALS has prompted specu...
TL;DR: The accumulating epidemiological, genetic and environmental evidence, as well as the development of new and promising experimental animal models, support the hypothesis that a basic metabolic defect lead to increased intestinal absorption of toxic metals and the co-deposition of calcium, aluminium and silicon in neurons of patients with ALS and PD.
Abstract: Amyotrophic lateral sclerosis (ALS) on Guam previously attained incidence rates 50 to 100 times that of the continental United States and Europe and accounted for one in five deaths among Chamorros over age 25. A second neurological disorder in high incidence, parkinsonism-dementia (PD), and the early appearance in those populations of neurofibrillary tangles such as are seen in Alzheimer's disease and normal ageing have also been noted. Incidence and mortality rates of both diseases have declined dramatically during the past 30 years, and today, the risk of developing either disease among Guamanian Chamorros is only several times higher than in non-Guamanian populations. The decline is most likely a consequence of increased acculturation over the past three decades, with a concomitant decrease in isolation, changes in dietary habits and local water supplies, and much less dependence on locally grown foodstuffs. Similar declines are evident in the remaining two Pacific foci of high- incidence ALS, namely the Kii Peninsula focus in Japan and southern West New Guinea where western contact and introduction of new foodstuffs have occurred.The accumulating epidemiological, genetic and environmental evidence, as well as the development of new and promising experimental animal models, support the hypothesis that a basic metabolic defect, provoked by chronic nutritional deficiencies of calcium, lead to increased intestinal absorption of toxic metals and the co-deposition of calcium, aluminium and silicon in neurons of patients with ALS and PD. This elemental deposition is thought to result in aberrant microtubule assembly and/or abnormal post-translational modification of the amyloid precursor protein leading to widespread formation of neurofibrillary tangles, the hallmark pathological features in these disorders. The naturalistic paradigms of these foci in the Western Pacific have provided insights to understanding not only ALS and PD but other neurological disorders, such as classical ALS, Parkinson's disease, Alzheimer's disease and early neuronal ageing.
TL;DR: The possibility that the neuromuscular dysfunction in schizophrenia may predispose to ALS and provide an explanation for the association of these two disorders is discussed.
TL;DR: In agreement with recentviews regarding the sources of the early anterior cortical responses, neuronal loss in the motor cortex may be considered as affecting the generator sites of these potentials.
Abstract: We examined median somatosensory evoked potentials (SEPs) in 26 patients with sporadic motor neuron disease (MND). SEPs were recorded with multiple scalp derivations, using both the midfront and the earlobe as references for each subject. Central conduction time (CCT) was abnormal in three patients, but only when using the midfront reference. Moreover, an exclusive alteration of the early prerolandic potentials (absent or delayed P20 and/or P22) was noted using the earlobe reference in amyotrophic lateral sclerosis and in progressive bulbar palsy (54% and 50% of patients, respectively) but not in progressive muscular atrophy. These findings correlated with clinical evidence of upper motor neuron signs and with the severity of the disease. In agreement with recent views regarding the sources of the early anterior cortical responses, neuronal loss in the motor cortex may be considered as affecting the generator sites of these potentials.
TL;DR: The clinical and pathologic features of a patient with fragile X syndrome who developed amyotrophic lateral sclerosis (ALS) at a relatively young age are reported and the development of ALS in this patient might be related to the chromosomal aberration of fragile X Syndrome.
Abstract: Fragile X syndrome is a common cause of mental retardation. We report the clinical and pathologic features of a patient with fragile X syndrome who developed amyotrophic lateral sclerosis (ALS) at a relatively young age. Although the occurrence of these 2 diseases could be a mere coincidence, the development of ALS in this patient might be related to the chromosomal aberration of fragile X syndrome.