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At least 19 recordsLinked to original sources
PubMed1979

Changes in motor unit populations in motor neurone disease.

In motor neurone disease changes in the functional properties of motor units, including the surface voltage, latency, conduction velocity, and response to repetitive stimulation, were investigated. Progression was marked by motor unit loss, increase in the proportion of larger motor unit potentials, and inclusion of motor unit potentials larger than normal in the remaining motor unit population. Even late in the disease, motor unit potentials with a low surface voltage persisted. The relationship between motor unit potentials, surface voltage, and latency, present in control subjects, broke down in motor neurone disease, large motor unit potentials having abnormally long latencies and small motor unit potentials unexpectedly short latencies. Amplitude decrements were more frequent and severe in motor unit potentials at later stages in the disease, particularly in those units with lower surface voltages. In one surviving motor unit potential there was evidence suggestive of functional recovery. The observations point to complex changes in the functional properties of motor units in motor neurone disease.

Cell Count↗
PubMed1978

A quantitative electrophysiological study of motor neurone disease.

Thirty-two patients with motor neurone disease were investigated using quantitative electrophysiological techniques. Estimates of the number of surviving motor units in the extensor digitorum brevis muscle and measurements of the electrophysiological parameters of these units are present along with the values for motor nerve conduction velocities. The results indicate that reinnervation in motor neurone disease is sufficient to compensate completely for the loss of up to 50% of the motor neurone pool supplying the muscle. The capacity for reinnervation is greater than we have found in a number of neuropathies but the efficiency of reinnervation decreases as the number of surviving motor units falls. Reinnervation appears to cease when 5% or less of the motor units remain viable. There is no electrophysiological evidence of a preferential loss of fast conducting axons, of pathological slowing of conduction nor of a dying-back process affecting the motor axon. Comparison of the electrophysiological parameters in progressive muscular atrophy and amyotrophic lateral sclerosis shows no significant differences. The underlying pathophysiological mechanisms are discussed in terms of the results.

Adult↗
PubMed2025

Whole blood transcriptome profile identifies motor neurone disease RNA biomarker signatures.

Blood-based biomarkers for motor neuron disease are needed for better diagnosis, progression prediction, and clinical trial monitoring. We used whole blood-derived total RNA and performed whole transcriptome analysis to compare the gene expression profiles in (motor neurone disease) MND patients to the control subjects. We compared 42 MND patients to 42 aged and sex-matched healthy controls and described the whole transcriptome profile characteristic for MND. In addition to the formal differential analysis, we performed functional annotation of the genomics data and identified the molecular pathways that are differentially regulated in MND patients. We identified 12,972 genes differentially expressed in the blood of MND patients compared to age and sex-matched controls. Functional genomic annotation identified activation of the pathways related to neurodegeneration, RNA transcription, RNA splicing and extracellular matrix reorganisation. Blood-based whole transcriptomic analysis can reliably differentiate MND patients from controls and can provide useful information for the clinical management of the disease and clinical trials.

Humans↗
PubMed1977

Changing mortality patterns of motor neuron disease in Japan.

The age-adjusted female death rate from motor neuron disease in Japan was noted to rise after 1952 and to fall rapidly since about 1960. A similar trend was also noticed in the males. Further study will show whether this was a part of a cyclical change or whether the mortality of the disease has entered a period of prolonged decline in that country. Death rates for neurological diseases in various countries were reported previously for 1953-58. Updating this study for 1966-71, a rising trend of deaths from motor neuron disease was identified in European countries, but the rate has been stationary in the United States. The rapidly changing patterns of the mortality seemed incompatible with a purely genetic causation of the disease. This indicates the need for extensive epidemiological studies to identify the extrinsic factors which induced such a trend, and were thus possibly the cause of the disease. In view of the results of the re-evaluation of the diagnosis in death certificates, mortality figures of motor neuron disease in females appeared reasonably reliable for an epidemiological study.

Adolescent↗
PubMedDate not supplied

Motor neuron diseases in man and animals.

Aspects of motor neuron diseases in man are described and compared with a series of animal models for these disorders. Such models provide new approaches to understanding many features of abnormalities of the central and peripheral nervous system.

Amyotrophic Lateral Sclerosis↗
PubMed1978

Oculocutaneous albinism associated with motor neuron disease.

The patient described is a 14-year-old girl who suffered from an oculocutaneous albinism. The developmental milestones were reached with some delay. Gradually she experienced fatiques, and wasting of the pelvic girdle muscles and weakness appeared. In suralis nerve biopsy sections no abnormalities were found. In muscle biopsy sections the characteristic findings of a primary central neuronal muscular atrophy were seen. Based on clinical and histopathological findings it may be stated that the patient is suffering from a motor neuron disease. The chance of the combined occurrence of oculocutaneous albinism and motor neuron disease can be estimated to be one out of 750 X 10(6), unless an incestuous relation is supposed.

Adolescent↗
PubMed1979

Metals in spinal cord tissue of patients dying of motor neuron disease.

To evaluate the role of toxic metals in causing motor neuron disease (MND), we used a photon-excited, energy-dispersive x-ray analytical system to measure the metal content of spinal ventral horn tissue. Specimens were taken from the cervical and lumbar enlargements of 7 patients who died of MND and the results compared with those found in 12 control patients. Anterior horn lead levels were elevated in MND patients compared to controls (mean, 40.7 micrograms/gm versus 14.6 micrograms/gm; p less than 0.05) and lead levels correlated with the duration of illness (r = +0.84, p less than 0.05). Only 2 MND patients had detectable manganese levels (72.3 and 132.2 micrograms/gm) whereas 1 control had detectable manganese (14.3 micrograms/gm). One MND patient had 244 micrograms/gm selenium, but 3 controls had levels of 180, 58, and 62. Patients with the histories of greatest environmental exposure to metals during life exhibited the highest tissue levels of metals after death; despite chelation therapy for about a year, high lead levels remained in their tissue.

Aged↗
PubMed1977

An autoradiographic study of muscular dystrophy, motor neuron disease and Charcot-Marie-Tooth disease.

The autoradiographic findings using tritiated leucine are described in muscle biopsy material from five patients with progressive muscular dystrophy (P.M.D.), three with motor neuron disease (M.N.D.) and four with Charcot-Marie-Tooth disease (C.M.T.). In progressive muscular dystrophy there is a marked increase in uptake of leucine into cytoplasmic proteins and precursors, and reduced incorporation into structural protein. In Charcot-Marie Tooth disease muscle there is a significantly increased uptake into cytoplasmic elements and a normal uptake into structural protein. In motor neuron disease the uptake into cytoplasmic elements appears normal but is reduced into structural proteins. The abnormal uptake in C.M.T. could be explained as a product of regenerative efforts associated with reinnervation. However, the abnormal uptake may represent the primary effects of gene action in the muscle, as seems probable in progressive muscular dystrophy.

Charcot-Marie-Tooth Disease↗
PubMed2026

Revisiting somatosensory evoked potentials in motor neuron diseases: neurophysiological insights from a large cohort.

OBJECTIVE: To systematically investigate Somatosensory Evoked Potential (SEP) abnormalities in a large cohort of patients with Motor Neuron Disease (MND), and to explore their relationship with Motor Evoked Potentials (MEPs) and clinical phenotypes. METHODS: We retrospectively analyzed 267 patients with confirmed MND who underwent standardized SEPs and transcranial magnetic stimulation. Patients were divided into pure/predominant Upper Motor Neuron (UMN) and pure/predominant Lower Motor Neuron/Amyotrophic Lateral Sclerosis (LMN/ALS) groups. SEP abnormalities were assessed using internal normative data, including prolonged latencies, reduced amplitudes, and increased N20-P25 amplitudes. MEPs were classified semi-quantitatively as normal or abnormal by independent raters. RESULTS: At least one SEP abnormality was detected in 75&#xa0;% of patients, with no significant differences between the UMN and LMN/ALS groups. Increased N20-P25 amplitudes were observed in both phenotypes, suggesting widespread sensory cortical hyperexcitability across the MND spectrum. In contrast, abnormal MEPs were significantly more frequent in UMN patients (p&#xa0;<&#xa0;0.001). No significant association was found between SEP abnormalities and MEP findings. Upper- and lower-limb SEP latencies were strongly correlated (all p&#xa0;<&#xa0;0.001), whereas increased SEP amplitudes did not correlate with latency abnormalities. CONCLUSIONS: SEP abnormalities are highly prevalent in MND and appear largely independent from corticospinal dysfunction. Increased SEP amplitudes likely reflect primary cortical sensory hyperexcitability rather than impaired sensory conduction. SIGNIFICANCE: These findings support the concept of MND as a multisystem network disorder that involves sensory cortical circuits and highlight the role of SEPs in the diagnostic workup.

Humans↗
PubMed1978

Histochemical study of the muscle spindles in parkinsonism, motor neuron disease and myasthenia. An examination of the pathological fusimotor endings by the acetylcholinesterase technic.

Pathological changes of the fusimotor endings in parkinsonism, motor neuron disease and myasthenia were examined by the acetylcholinesterase technic on serial sections. In parkinsonism, the diffuse endings, which are thought to be supplied by the static gamma nerve fibers, showed remarkable enlargement, while en plaque and en grappe endings were atrophic. In motor neuron disease, en plaque and en grappe endings, which are thought to be innervated by the beta nerve fibers and dynamic gamma nerve fibers respectively, revealed marked atrophy. However the diffuse endings were normal. In myasthenia gravis and myasthenic syndrome (Eaton-Lambert syndrome), en plaque and en grappe endings were atrophic, though only the diffuse endings were spared. The significance of these changes in the fusimotor endings is discussed.

Acetylcholinesterase↗
PubMed2026

Base editing rescues a hereditary motor neuron disease in mouse and patient-derived iPSC organoid models.

In hereditary motor neuron diseases (MNDs), including forms of amyotrophic lateral sclerosis (ALS) caused by single-nucleotide variants, effective therapeutic strategies need to address both gain- and loss-of-function mechanisms. Genome editing-based gene therapy represents a promising approach for simultaneously targeting these mechanisms. To establish proof-of-concept for base editing in a hereditary MND, we targeted the P285L variant in the TRK-fused gene (TFG), which causes hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P), a disorder that shares clinical and histopathological features with ALS. We identified the optimal adenine base editor by comparing candidate editors in HMSN-P patient-derived induced pluripotent stem cells (iPSCs). We then generated a transgenic mouse model expressing human TFG P285L and evaluated the selected editor by subpial delivery of adeno-associated virus (AAV) vectors to the spinal cord. AAV-mediated base editing prolonged survival, preserved motor neurons, and attenuated axon loss in ventral nerve roots. Treatment with the selected base editing vector reduced TFG aggregation and suppressed neuronal death in HMSN-P iPSC-derived neuromuscular organoids. Collectively, these findings support the therapeutic potential of base editing for hereditary MNDs.

AAV↗
PubMed1979

Exercise effect on creatine phosphokinase elevation in motor neuron disease.

Creatine phosphokinase (CPK) is usually elevated in inflammatory and degenerative muscle disease but is usually reported as normal in neuropathic diseases. A review of the literature indicates, however, that it is elevated in 50 to 75% of patients who have motor neuron diseases, and that these elevations are usually 5 to 6 times normal. The effect of bedrest and moderate exercise on serial CPK values in a patient with motor neuron disease is assessed. Bedrest for 24 hours decreased his CPK to 0.58 of the baseline value; 5 hours following moderate exercise it increased to 1.71 of the basal value. This phenomenon appears to be a response to exercise stimuli rather than to the disease process itself. CPK values up O 1000 IU/L are compatible with the diagnosis of amyotrophic lateral sclerosis (ALS). In patients whose CPK values seem atypical, it is best to have them rest 48 hours before repeating the test.

Amyotrophic Lateral Sclerosis↗
PubMed1977

Motor neurone disease and multiple sclerosis among immigrants to Britain.

Hospital discharge rates for various immigrant groups resident in Greater London and the West Midlands were studied to compare the incidence of two diseases of the nervous system-motor neurone disease (MND) and multiple sclerosis (MS). For both these conditions immigrants from Europe, Ireland, America and from the old commonwealth countries of Canada, Australia, and New Zealand had discharge rates that were similar to those for people born in the United Kingdom. In contrast, immigrants from the new commonwealth countries of Asia, Africa, America (including the West Indies), and Europe (Gibraltar, Malta, and Gozo) had a greatly reduced risk of MS but a very similar risk of MND compared with those born in the United Kingdom. MS but not MND was rare among immigrants of Asian or African ethnic origin and uncommon among immigrants from the West Indies. Deaths attributed to MS and MND have also been studied. During a three-year period there were no deaths reported for MS among immigrants of Asian and African ethnic origin and 14 were expected. There were two deaths from MND among these immigrants and five were expected. Among the immigrants from the West Indies two deaths were attributed to MS and 13 were expected, and there were three deaths attributed to MND and four were expected. The contrast between MND and MS in hospital morbidity and mortality confirms that MS among immigrants to Britain is rare in those of Asian and African ethnic origin.

Adolescent↗
PubMed1977

Motor neuron disease in Australia (State of New South Wales).

The case histories of 70 patients with typical motor neuron disease (MND) have been analysed to ascertain the natural history of the disease in Australia. The place of birth and residence during life of each patient has been sought to determine whether there is any 'clustering' of patients in the State of New South Wales. The mean age of onset was 55 years and mean duration of life from onset was 3 years 5 months. These figures are comparable with those from the USA and UK and Japan although the onset in Australia was later and the duration longer. The case history of 1 patient who is still living 38 years after the onset of the disease is described as there is no longer survival time recorded in the literature to our knowledge. Attention is drawn to muscle aches and cramps mentioned spontaneously by 27 of the 70 patients. These symptoms occurred at the onset of MND and often correlated with the site of onset of weakness. Weight loss averaged 1.6lb (0.7kg) per month in those patients in whom weight was recorded. The CSF protein was greater than 45mg/100ml, ranging up to 110mg/100ml, in 9 of 37 patients. The place of residence of patients bore no relation to known areas of increased manganese in the soil, and there was no evidence of 'clustering' of cases.

Adolescent↗
PubMed1979

Histologic findings in motor neuron disease. Relation to clinically determined activity, duration, and severity of disease.

Correlation of 18 histologic variables with age and sex of 24 patients with motor neuron disease (MND), and the duration, severity, and activity of their disease, showed that high density of atrophic fibers correlated with degree of muscle weakness and the worst prognosis and that type I grouping correlated with the best prognosis. Although both type I and type II fibers are involved in the majority of patients with MND, the data suggest that involvement of type I fibers is more important in relation to activity of the disease.

Adult↗