Showing papers on "Amyotrophic lateral sclerosis published in 1988"
TL;DR: 2 patients with a treatable, immune‐mediated motor polyneuropathy associated with antibodies to defined neural antigens, initially diagnosed as having lower motor neuron forms of amyotrophic lateral sclerosis are reported.
Abstract: We report 2 patients with a treatable, immune-mediated motor polyneuropathy associated with antibodies to defined neural antigens. In these patients asymmetrical weakness developed in one arm and progressed over 2 to 3 years to involve the other arm, legs, and trunk. Both patients were initially diagnosed as having lower motor neuron forms of amyotrophic lateral sclerosis. However, repeated electrophysiological testing eventually showed multifocal conduction blocks in motor but not sensory fibers compatible with patchy selective demyelination. Serum testing by thin-layer chromatography and enzyme-linked immunosorbent assay revealed that both patients had high titers of antibody directed against GM1 and other gangliosides. Initial therapeutic trials of prednisone (100 mg daily for 4 to 6 months) and plasmapheresis were unsuccessful. Treatment with cyclophosphamide, however, was followed by Marchked improvement in strength in both patients.
588 citations
TL;DR: The data suggest the presence of a generalized defect that may affect the neurotransmitter and metabolic pool of glutamate in amyotrophic lateral sclerosis and the possibility that distribution of glutamate between the intracellular and extracellular pool may be altered in ALS and may mediate the neurodegeneration.
Abstract: Because recent studies showed a systemic defect in glutamate metabolism in amyotrophic lateral sclerosis (ALS), we measured the levels of free amino acids in frontal and cerebellar cortex and two areas of spinal cord obtained at autopsy from 22 patients who died of this disease. Glutamate levels were significantly decreased (by 21 to 40% of control values) in all areas investigated; cervical and lumbar spinal cord showed the greatest change. Aspartate levels were also significantly reduced (by 32 to 35%) in the spinal cord only. A positive correlation was shown between the changes of glutamate and aspartate as well as a significant alteration in the glutamate to glutamine ratio in the spinal cord of patients with ALS. Although we cannot exclude the possibility that these abnormalities may partly result from neuronal cell loss, the data suggest the presence of a generalized defect that may affect the neurotransmitter and metabolic pool of glutamate. The defect may be expressed more severely in the spinal cord than in other central nervous system areas. These results, taken together with the previously shown systemic abnormality, raise the possibility that distribution of glutamate between the intracellular and extracellular pool may be altered in ALS and may mediate the neurodegeneration.
217 citations
TL;DR: It is proposed that phosphorylation of NF in ALS occurs prematurely and that it is more likely to be associated with an impairment of NF transport than to be part of a chromatolytic reaction of lower motor neurons.
Abstract: We used a library of monoclonal antibodies (Mab) that distinguish phosphorylated (P+) and non-phosphorylated (P-) neurofilament (NF) epitopes to examine phosphorylation of NF in lower motor neurons of patients with amyotrophic lateral sclerosis (ALS), of neurologically normal controls of different ages, and of patients with central chromatolysis due to injuries to motor root axons. Monoclonal antibodies directed to P+ NF immunostained five to ten times more neuronal perikarya in ALS than in age-matched controls. Spheroids, which are NF containing axonal enlargements, found in significantly greater number in proximal axons in ALS, were also intensely immunostained with Mab to P+ NF. Moreover, anterior root axons in five of eleven cases of ALS reacted only with the Mab to P+ NF, while both P- and P+ NF were present in motor roots from controls. In control groups, the number of neuronal perikarya and spheroids that immunoreacted with the Mab to P+ NF increased moderately with age. Chromatolytic lower motor neurons were recognized by Mab to P+ NF. Our results show that the process of phosphorylation is altered in ALS. We propose that phosphorylation of NF in ALS occurs prematurely and that it is more likely to be associated with an impairment of NF transport than to be part of a chromatolytic reaction of lower motor neurons.
203 citations
TL;DR: All measures indicated that the tongue muscles were most severely affected, even in patients who initially had symptoms in the extremities.
Abstract: Facial, trigeminal, and hypoglossal motoneuron involvement was quantified in 25 amyotrophic lateral sclerosis patients and in normal controls. Measures included (1) maximum voluntary contraction of the lower lip, mandible, and tongue using custom-designed force transducers, (2) clinical functions of each muscle group, and in some patients (3) orofacial mobility using videofluoroscopy. All measures indicated that the tongue muscles were most severely affected, even in patients who initially had symptoms in the extremities.
153 citations
TL;DR: Male cynomolgus monkeys developed cortico-neuronal dysfunction, parkinsonian features and behavioral changes with chromatolysis and degeneration of motor neurons following daily oral doses of β-N-methylamino-l-alanine (BMAA), a ‘free excitatory' neurotoxic amino acid present in the seeds of Cycas circinalis.
147 citations
TL;DR: The presence of serum antibodies directed against GM1 ganglioside, a defined neural antigen, in many patients with amyotrophic lateral sclerosis (ALS) was reported and the anti-GM1 antibodies in these patients tended to differ from those in ALS based on an analysis of their light chain types.
Abstract: We report the presence of serum antibodies directed against GM1 ganglioside, a defined neural antigen, in many patients with amyotrophic lateral sclerosis (ALS). We examined serum from a series of patients with well-documented clinical diagnoses. Serum antibodies to GM1 ganglioside were measured using ELISA assays. Our results showed that polyclonal IgM anti-GM1 antibodies were present at dilutions of 1:25 to 1:2,000 in 42 of 74 (57%) patients with ALS. The anti-GM1 antibodies were especially frequent in patients with prominent lower motor neuron signs (41/59; 69%). Few normal controls (2/23) and motor-sensory neuropathy patients (3/27) had similar antibodies. Anti-GM1 antibodies did occur in patients with nonneural autoimmune disorders. However, the anti-GM1 antibodies in these patients tended to differ from those in ALS based on an analysis of their light chain types. Further examination of the role and spectrum of serum antiganglioside antibody activity in motor neuron syndromes is warranted.
145 citations
TL;DR: Two patients had symmetrical areas of increased signal intensity seen on MRI extending from the cortex, through the corona radiata, posterior limb of the internal capsule, and cerebral peduncles into the pons, presumably relate to the pathological changes observed by others in the central white matter of patients with amyotrophic lateral sclerosis.
Abstract: Magnetic resonance imaging (MRI) was used in 5 patients with clinically definite amyotrophic lateral sclerosis to determine the frequency of central white matter abnormalities. Two patients had symmetrical areas of increased signal intensity seen on MRI extending from the cortex, through the corona radiata, posterior limb of the internal capsule, and cerebral peduncles into the pons. These MRI abnormalities presumably relate to the pathological changes observed by others in the central white matter of patients with amyotrophic lateral sclerosis.
144 citations
TL;DR: The Tufts Quantitative Neuromuscular Exam (TQNE) consists of 28 items that were designed to measure voluntary motor deficit in amyotrophic lateral sclerosis (ALS) and related diseases and should enhance the usefulness of testing in therapeutic trials and in analyzing the natural history of ALS andrelated diseases.
Abstract: The Tufts Quantitative Neuromuscular Exam (TQNE) consists of 28 items that were designed to measure voluntary motor deficit in amyotrophic lateral sclerosis (ALS) and related diseases. Individual raw data were converted to Z scores for standardization and then grouped into five megascores with statistical and clinical relevance. The derived megascores were Mega 1, pulmonary function; Mega 2, bulbar function; Mega 3, timed hand activities; Mega 4, isometric arm strength; and Mega 5, isometric leg strength. Megascores should enhance the usefulness of testing in therapeutic trials and in analyzing the natural history of ALS and related diseases.
131 citations
TL;DR: This work studied six living patients in whom PLS was diagnosed clinically after comprehensive evaluations that excluded the alternative diagnoses, and two patients with this syndrome of PLS and antibodies to human immunodeficiency virus seropositivity that clinically resembled PLS.
Abstract: • Adults with slowly progressive non-inherited gait disorders may show no abnormalities on examination other than signs implicating the corticospinal tracts. That is the syndrome of "primary lateral sclerosis" (PLS), a clinical diagnosis that has been avoided because it is a diagnosis of exclusion, proven only at autopsy. Now, modern technology can exclude other disorders that can cause the syndrome with an accuracy of about 95%. That serves to eliminate the following: compressive lesions at the foramen magnum or cervical spinal cord, multiple sclerosis, amyotrophic lateral sclerosis, Chiari malformation, syringomyelia, biochemical abnormality, and persistent infection with human immunodeficiency virus or human T-lymphotrophic virus type I. We studied three autopsy-proved cases of PLS; six living patients in whom PLS was diagnosed clinically after comprehensive evaluations that excluded the alternative diagnoses; and two patients with this syndrome of PLS and antibodies to human immunodeficiency virus seropositivity that clinically resembled PLS. Primary lateral sclerosis is now a respectable and permissible diagnosis.
121 citations
TL;DR: Although the observed motor-sensory deficit in ALS is consistent with histopathological findings, the more generalized hypometabolism and the asymmetry suggest more widespread effects.
Abstract: We previously reported generalized cerebral glucose hypometabolism in amyotrophic lateral sclerosis (ALS) patients with upper motor neuron disease, using positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose. The present article presents a more detailed regional analysis of the hypometabolism, including measurements of the motor-sensory cortex at higher levels than used earlier. The analysis is based on 19 PET studies of 12 patients with ALS, four of whom had only lower motor neuron involvement, and 11 studies of age-matched control subjects. A brain size correction was included to eliminate differences in metabolism related to brain size but not to pathology. The eight ALS patients with both upper and lower motor neuron disease showed generalized hypometabolism, compared with the normal control subjects, that was greatest in the motor-sensory cortex and putamen. The motor-sensory deficit was strongly correlated with length of disease, and a marked sequential reduction was seen in repeat studies on four of the patients. There was also significant right-left asymmetry in these scans. No cerebral hypometabolism was seen in the four ALS patients without upper motor neuron involvement. Although the observed motor-sensory deficit in ALS is consistent with histopathological findings, the more generalized hypometabolism and the asymmetry suggest more widespread effects.
107 citations
TL;DR: The current status of pathogenesis and therapeutic trials in amyotrophic lateral sclerosis (ALS) is reviewed, and several rare but definable causes for apparent ALS are identified.
Abstract: • We reviewed the current status of pathogenesis and therapeutic trials in amyotrophic lateral sclerosis (ALS). Clinical studies have identified several rare but definable causes for apparent ALS. Certain clinical features previously considered unlikely to occur in ALS are found on careful examination. Epidemiologic surveillance and recent studies of neurotoxic plant seeds used in Guam have shed light on the pathogenesis of endemic ALS. Extensive analyses of biochemical, metabolic, immunologic, viral, and toxic factors have provided provocative results requiring further studies. Reflecting on some of these hypotheses, therapeutic trials have been performed more vigorously than ever. Amyotrophic lateral sclerosis is now investigated at the molecular genetic level. Human autopsy and experimental animal studies have expanded our understanding of basic mechanisms involving motoneuronal degeneration. In the future, we must continue a relentless search for the pathogenesis of ALS, prospective clinical studies to define the limits of ALS, and well-designed, controlled therapeutic trials.
TL;DR: Because the thoracic paraspinal muscles are frequently affected in ALS and spared in spondylotic amyotrophy, their assessment provides a practical strategy in differentiating ALS from other motor syndromes.
Abstract: The distribution of muscle involvement, assessed clinically and electromyographically, was analyzed prospectively in 55 consecutive amyotrophic lateral sclerosis (ALS) patients and in 54 patients with other predominantly motor syndromes, some of whom were referred with suspected ALS. In ALS patients, distal limb muscles and thoracic paraspinal muscles were affected most frequently, more so than proximal limb and cranial muscles. The incidence of bulbar symptoms in ALS was greater in women than in men. These patterns suggest selective vulnerability of specific neuronal populations. The vulnerability of truncal muscles, illustrated by thoracic paraspinal wasting or head and shoulder drooping, was a helpful differential sign in diagnosing ALS. Thoracic paraspinal electromyography was especially valuable in distinguishing ALS from other disorders, such as combined cervical and lumbar spondylotic amyotrophy or polymyositis, which may masquerade as ALS. The finding of denervation atrophy on biopsy of thoracic paraspinal muscles was diagnostic in difficult cases. Because the thoracic paraspinal muscles are frequently affected in ALS and spared in spondylotic amyotrophy, their assessment provides a practical strategy in differentiating ALS from other motor syndromes.
TL;DR: MEPs and SEP recording revealed central propagation abnormalities coupled to a severe clinical picture of the peripheral nerve involvement (as in the case of SCD) and combining SEP records enhanced the diagnostic yield in this field.
TL;DR: In this article, the spinal cord segments from all patients who had had poliomyelitis showed loss or atrophy of motor neurons, severe reactive gliosis (disproportional to the neuronal loss), and a surprising mild to moderate perivascular and interparenchymal inflammation.
Abstract: • In a retrospective study, we reviewed sections from the spinal cords from eight patients, aged 36 to 61 years, who had had poliomyelitis and who died of nonneurologic diseases nine months to 44 years (mean, 20.7 years) after the acute poliomyelitis infection. Five patients had stable postpoliomyelitis deficits without new symptoms, and three patients had new slowly progressive muscle weakness defined as postpoliomyelitis progressive muscular atrophy (PPMA). Representative spinal cord sections matched the patients' clinical involvement in both groups. Control tissues from ten patients with amyotrophic lateral sclerosis and five with spinocerebellar degeneration were examined simultaneously. The spinal cord segments from all patients who had had poliomyelitis showed loss or atrophy of motor neurons, severe reactive gliosis (disproportional to the neuronal loss), and a surprising mild to moderate perivascular and interparenchymal inflammation. There was no difference in these pathologic changes between the patients with stable postpoliomyelitis deficits and those with PPMA. Additional findings were axonal spheroids (dystrophic axons) and occasional chromatolytic neurons in the spinal cord of patients with PPMA. Corticospinal tracts were spared.
TL;DR: A decrease in the number of motor units in the tibialis anterior muscle with increasing age in normal subjects is suggested, and in myasthenic patients the motor unit count was within the normal range for their age group.
Abstract: The technique of the macro-EMG was used to estimate the number of motor units in the tibialis anterior muscles of healthy subjects in a wide range of ages, and of patients with myasthenia gravis and patients with amyotrophic lateral sclerosis or spinal muscular atrophy. The results obtained suggest a decrease in the number of motor units in the tibialis anterior muscle with increasing age in normal subjects. In myasthenic patients the motor unit count was within the normal range for their age group. Patients with motor neuron disorders on the average had a very low number of motor units.
TL;DR: Findings suggest that the presynaptic terminal of the motor neuron may be an early target and that immunological factors may play an important role in the disease process.
Abstract: Amyotrophic lateral sclerosis (ALS) is an incapacitating neuromuscular disease of unknown etiology. Although laboratory evidence is lacking, circumstantial evidence supports the importance of immune factors in the pathogenesis of ALS. In the present study immunoglobulins from 4 of 8 ALS patients induced a significant increase in spontaneous quantal transmitter release as monitored by miniature end-plate potential (MEPP) frequency in mouse phrenic nerve-diaphragm preparations at 23 degrees C, whereas immunoglobulins from normal individuals and from patients with other neuromuscular diseases had no effect. At 32 degrees C neither normal nor disease control immunoglobulins influenced MEPP frequency, but 8 of 11 ALS immunoglobulin samples produced a significant increase in spontaneous quantal transmitter release. The enhancing effect could be prevented by 10 mM Mg2+. No effects were noted on MEPP amplitude and muscle resting potential. These findings suggest that the presynaptic terminal of the motor neuron may be an early target and that immunological factors may play an important role in the disease process.
TL;DR: It was concluded that there are three forms of degenerative diseases of the principal motor pathways: one involving both central and peripheral neurons, ie, amyotrophic lateral sclerosis; one involving only peripheral neurons; one featuring only spinal amyotrophy; and one involvingonly central motor neurons, i.e, PLS.
Abstract: • Although it was first described over a century ago (by Charcot in 1865; by Erb in 1875), the concept of primary lateral sclerosis (PLS) is still not universally accepted. Despite this skepticism, several well-documented cases of isolated degeneration with varying degrees of involvement of corticospinal pyramidal pathways have been reported in the literature. The clinical manifestations in these cases can take one of two forms, ie, isolated spasmodic paraplegia or tetraplegia on the one hand or spasmodic tetraplegia associated with a pseudobulbar syndrome featuring severe spastic dysarthria (chronic progressive bilateral spinobulbar spasticity) on the other hand. Obviously, without firm pathologic data, PLS is a hazardous diagnosis for isolated paraplegia or tetraplegia. Conversely, for bilateral spinobulbar spasticity, it would appear to be the only diagnosis possible once investigative findings have eliminated the other possibilities, such as a pyramidal form of amyotrophic lateral sclerosis or a spinal form of multiple sclerosis. To underscore this point, in this report, five cases of chronic progressive bilateral spinobulbar spasticity developed over 5, 10, 12, 10, and 28 years, respectively, for which the only possible diagnosis was PLS. It was concluded that there are three forms of degenerative diseases of the principal motor pathways: one involving both central and peripheral neurons, ie, amyotrophic lateral sclerosis; one involving only peripheral neurons, ie, spinal amyotrophy; and one involving only central motor neurons, ie, PLS.
TL;DR: Although severe motor unit losses were seen in many ALS cases, in most there were clear indications of increases in innervation densities, linked potentials, and blocking.
Abstract: A newly developed technique for estimating the number of motor units in the biceps-brachialis muscles and for studying the innervation patterns of motor units in the same muscles has been applied to the study of 17 patients with amyotrophic lateral sclerosis (ALS). Although severe motor unit losses were seen in many ALS cases, in most there were clear indications of increases in innervation densities, linked potentials, and blocking. This technique provides a powerful new tool for quantitatively assessing the extent of motor unit losses and the accompanying changes in innervation patterns in ALS.
TL;DR: The findings seem to support the conclusion that the immune alterations in idiopathic ALS patients are related to the mechanisms of the disease and not to complications of its evolution.
Abstract: Serum and CSF from 32 patients with idiopathic ALS, 30 agematched controls and 30 MS patients were investigated regarding immunoglobulin concentration and virus-specific antibodies, the lymphocytes in the peripheral blood and lymphocyte subsets were also investigated. ALS patients’ results were compared with findings in MS and controls. The ALS patients had significantly higher IgG concentration in serum than the controls, marked lymphopenia, reduction of CD2, CD8 and Leu 7 positive cells and increase of the CD4/CD8 ratio and of SIg-positive lymphocytes. Compared with the MS patients, the ALS patients showed similarity in T-subset distribution with a lower standard deviation. No HTLV-I and HIV antibodies were found in any group and no significant differences in antibody distribution to Toxoplasma G, herpes simples, cytomegalovirus, measles and mumps viruses were evident. All ALS patients were investigated at an early disease stage, therefore, our findings seem to support the conclusion that the immune alterations are related to the mechanisms of the disease and not to complications of its evolution.
TL;DR: It is the hypothesis that for each of the neural systems involved in the degenerative neurologic diseases Alzheimer's disease, parkinsonism, and amyotrophic lateral sclerosis, there is both a primary insult and a secondary effect that is the result of retrograde degeneration.
Abstract: The causes of some of the most common and devastating diseases of the human nervous system remain unknown. Prominent on this list are amyotrophic lateral sclerosis (ALS), parkinsonism, and Alzheimer’s disease. Each of these conditions is presently considered to be a degenerative disorder of unknown origin. In each, there may be a variable clinical expression reflecting different etiologies in different patients. A specific inherited metabolic disorder may account for a small percentage of cases, while immunological, viral, or other etiologies may be responsible for the remainder.
Abstract: Ultrastructural features of chromatolytic neurons observed in a sporadic case with amyotrophic lateral sclerosis (ALS) are reported. A 70-year-old woman died of weakness and atrophy of the four limbs, bulbar and facial muscles, and hyperreflexia, of 3 1/2 years' duration. Neuronal loss was marked in the anterior horn of the spinal cord, with degeneration of the pyramidal tracts. Most of the remaining neurons showed chromatolysis. Some of the chromatolytic neurons contained faintly eosinophilic inclusions with a halo. Few spheroids were observed. Hypoglossal nuclei, nucleus ambiguus, motor nuclei of N.VII and N.V were well populated, but contained several chromatolytic neurons. Ultrastructurally, the chromatolytic neurons contained aggregates of fibrils thicker than the 10-nm neurofilaments. These fibrils were arranged randomly, and were closely associated with granular materials as well as rough endoplasmic reticulum. Neurofilamentous accumulations reported to be common in sporadic ALS were rare in this case. No Bunina body was observed.
TL;DR: Examination of specimens of skin overlying the sacral region from patients with amyotrophic lateral sclerosis and controls found that in ALS patients, collagen fibrils had a greater density and became more tightly packed with the duration of illness, suggesting that the increased density of collagenfibrils may protect the skin of ALS patients from pressure ischemia.
TL;DR: It is concluded that the new technique of examining motor conduction along the corticospinal tract may be useful to detect a subclinical lesion in the corto-cervical tract.
Abstract: Conduction in the central motor pathways was studied in 9 patients with cerebrovascular disease (CVD), 13 with amyotrophic lateral sclerosis (ALS) and 3 with spinal progressive muscular atrophy (SPMA). Motor responses evoked in the limb by cortical, cervical and lumbar stimulations were recorded. The central conduction time (CCT) was calculated for each muscle. In patients with CVD, responses to cortical stimulation were unobtainable or delayed in the paretic limb muscles. In patients with ALS the abnormality of central motor conduction had significant correlation with the extensor plantar response. The CCTs were normal in patients with SPMA. This technique demonstrated a subclinical lesion in some patients. We conclude that the new technique of examining motor conduction along the corticospinal tract may be useful to detect a subclinical lesion in the corticospinal tract.
Journal Article•
TL;DR: This hypothesis could explain the preferential vulnerability of the spinal, corticospinal and cortico-bulbar neurons to damage and death in ALS because only these neurons contain conspicuous bundles of neurofilaments in dendrites.
TL;DR: Fibre density and amplitudes of macro-EMG motor unit potentials were studied and compared with conventional EMG in the anterior tibial muscles from 51 patients with amyotrophic lateral sclerosis and the fibre density was increased in 46 muscles.
Abstract: Fibre density and amplitudes of macro-EMG motor unit potentials were studied and compared with conventional EMG in the anterior tibial muscles from 51 patients with amyotrophic lateral sclerosis. The fibre density was increased in 46 muscles. Increased amplitudes of macro-EMG motor unit action potentials were found in 46 muscles, while the mean duration of motor unit potentials recorded with a concentric needle electrode was prolonged in only 26 muscles. Changes in the packing density of muscle fibres of surviving motor units are thought to influence the different electrophysiological parameters in different ways.
TL;DR: No significant alterations of single or total AA concentrations were found in patients with Amyotrophic Lateral Sclerosis compared with healthy controls, which contrast with data published in a previous study.
Abstract: — The concentrations of 23 amino acids (AA) were measured in CSF of patients with Amyotrophic Lateral Sclerosis (ALS). A micro-method with picomole sensitivity was used. Compared with healthy controls no significant alterations of single or total AA concentrations were found. These results contrast with data published in a previous study and will be discussed in detail.
Journal Article•
TL;DR: Hex A deficiency apparently is an unusual etiology of typical or atypical ALS but is of medical and genetic importance in individual families.
Abstract: Abnormalities of GM2 ganglioside metabolism owing to hexosaminidase A (Hex A) deficiency have been associated with ALS phenotypes. The clinical features described in these ALS patients with Hex A deficiency include early onset, positive family history, and/or long disease duration. In an attempt to determine prospectively the incidence of Hex A deficiency within an ALS population, the records of The Mount Sinai Medical Center ALS Clinic were reviewed to select those patients with "atypical" ALS (total N = 52), i.e. onset before age 35, positive family history, and/or disease duration greater than 90 months. The control group (total N = 50), "typical" ALS patients, did not fulfill any of these historical criteria. Hex A activity determined in isolated peripheral blood leukocytes was normal in all typical ALS patients (mean 67.3%). Hex A deficiency was not found in any atypical ALS patients. Thus, Hex A deficiency apparently is an unusual etiology of typical or atypical ALS but is of medical and genetic importance in individual families.
TL;DR: The subsequent development of tongue fasciculations and the lack of response to treatment made a diagnosis of amyotrophic lateral sclerosis more likely despite the presence of conjugate gaze paresis and the absence of many of the typical clinical and electromyographic findings seen in this condition.
Abstract: The initial presentation and clinical course of this 60-year old woman suggested a diagnosis of myasthenia gravis. The subsequent development of tongue fasciculations and the lack of response to treatment made a diagnosis of amyotrophic lateral sclerosis (ALS) more likely despite the presence of conjugate gaze paresis and the absence of many of the typical clinical and electromyographic (EMG) findings seen in this condition. The pathological findings were consistent with either a motor neuronopathy or an unusual variant of ALS. We review the clinical and pathological features of this unusual case in this report.