The central nervous system in motor neurone disease

Forty-five necropsied cases with primary degeneration of lower motor neurones are described and discussed. Of these, 36 are considered to be `typical' cases of motor neurone disease, eight of which showed no upper motor neurone lesions. The relation of the nine `atypical' cases to the remainder is discussed. It is concluded that motor neurone disease constitutes an ill-defined band in a broad spectrum of multiple system atrophies. The authors have found no evidence suggesting a causal relation between motor neurone disease and either vascular or malignant diseases. They point out suggestive analogies with various subacute encephalomyelopathies in man and other animals.     

Lower motor neurone disease in dogs

Summary This paper describes nine cases of a parenchymatous peripheral neuropathy in dogs, characterized clinically by posterior ataxia and paralysis, and pathologically by widespread myelin and axon destruction in ventral spinal and peripheral nerves, together with disappearance of ventral horn neurones. It is discussed in relation to nutritional and other peripheral neuropathies seen in man and animals.

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Zusammenfassung Diese Arbeit behandelt neun Fälle einer parenchymatösen peripheren Neuropathie bei Hunden, die klinisch durch Hinterstrangsataxie und Lähmung, pathologisch durch weitverbreitete Markscheiden- und Axonzerstörung in den vorderen Wurzeln und in den peripheren Nerven mit Verlust von Vorderhornganglienzellen charakterisiert ist.Die Beziehungen zu ernährungsbedingten und anderen bei Menschen und Tieren vorkommenden Neuropathien werden erörtert.

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Intramuscular nerves in motor neurone disease

Summary The ultrastructure of human intramuscular nerves at biopsy has been compared in motor neurone disease with that in other neuromuscular disease including muscular dystrophy and in controls. Myelinated axons appeared to be lost in control patients aged over 50 years, but this varied both between and within nerve fascicles. Even in two boys aged 31/2 and 9 years, but with Duchenne's dystrophy, examples were found of nerve fascicles with few or no axons. In motor neurone disease additional nerve fibres were lost, but there was little change in the size distributions of axons and myelin sheaths within the muscle. In both preterminal and terminal fascicles there was an increase of Schwann cell cytoplasm in association with unmyelinated axons, which was compatible with nerve sprouting. It is concluded that intramuscular nerves are likely to be lost with age as well as motor neurone disease. The results are discussed in relation to the stage of the disease process at biopsy.     

Incidence and prevalence of motor neuron disease in two Danish counties

A total of 186 cases of motor neuron disease (MND) was identified in two Danish counties during the period 1974-1986. The average annual incidence rate was 1.4/100,000 population, and the male:female ratio of incidence rates was 1.5. Mean age at diagnosis was 64.3 +/- 10.0 years. The incidence rates increased significantly with advancing age and reached a maximum at age 60-79 years, followed by a nonsignificant decrease. The average point prevalence was 3.1/100,000 population. Bulbar symptoms were part of the initial symptoms in 65% of cases, and patients with bulbar onset were older than patients with spinal onset. Age- and sex-specific incidence rates indicated a marked male preponderance amongst the youngest patients, in contrast to a female preponderance in patients above 60 years with bulbar onset of MND. Familial MND accounted for 2.7% of cases.     

Ocular fixation instabilities in motor neurone disease

Objective   Eye movements are classically felt to be spared in motor neurone disease (MND). Although a range of ocular motor disorders have been reported, no consistent pattern has been established. Disturbances of ocular fixation have been noted in MND; however, fixation has not yet been formally examined. With the recent characterization of ocular fixation using saccadic intrusion amplitude and fixation periods, we performed a cross-sectional study to examine for abnormalities of ocular fixation in non-dementing patients with MND. Methods   A total of 44 patients and 45 controls were recruited. Fixation was examined using infra-red oculography and all subjects then underwent a neuropsychological evaluation. Results   Saccadic intrusion amplitude was found to be greater in patients compared to controls and in particular, spinal-onset patients. Saccadic intrusion amplitude in patients correlated with neuropsychological measures sensitive to lesions of the frontal lobes. Conclusions   This is the first study to identify abnormalities of fixation in MND and these results indicate that ocular fixation instabilities may be a marker of the sub-clinical frontal lobe dysfunction in MND. A longitudinal study to examine if saccadic intrusion amplitude deteriorates with time would be of interest as this could provide a quantifiable objective marker of disease progression.     

Slow saccades in bulbar-onset motor neurone disease

Historical studies of eye movements in motor neurone disease (MND) have been conflicting although current findings suggest that eye movement abnormalities relate to frontal lobe impairment. Numerous case reports, however, describe slow saccades and supranuclear gaze palsies in patients with MND often associated with bulbar-onset disease. We performed a study of saccades and smooth pursuit in a large group of patients with MND to examine for any differences between bulbar-onset and spinal-onset patients. Forty-four patients (14 bulbar-onset and 30 spinal-onset patients) and 45 controls were recruited. Reflexive saccades, antisaccades and smooth pursuit were examined using infra-red oculography and all subjects then underwent neuropsychological evaluation. Reflexive saccades were found to be slower in bulbar-onset compared to spinal-onset patients and controls (p = 0.03, p = 0.05). Antisaccade latency (p = 0.01) and antisaccade type 1 errors (p = 0.03, p = 0.04) were increased in patients compared to controls. ‘Proportion of time spent in smooth pursuit’ and smooth pursuit ‘velocity gain’ were reduced in patients compared to controls (p = 0.000, p = 0.001). Antisaccade errors and velocity gain correlated with neuropsychological measures sensitive to lesions of the frontal lobes. This is the first study to highlight the presence of slow saccades in bulbar-onset MND. These findings suggest that slow saccades may be due to increased brainstem pathology in bulbar-onset disease that involves burst cell neurons. Furthermore these observations highlight the potential for overlap between bulbar-onset MND and progressive supranuclear palsy (PSP) as both can have a bulbar palsy and slowed saccades.     

Cricopharyngeal myotomy in motor neurone disease.

Twenty-five patients with dysphagia caused by neurological disorders, mainly motor heurone disease, underwent cricopharyngeal myotomy. Nineteen patients showed slight to dramatic improvement of swallowing for variable periods of time. There were five postoperative deaths. The results indicate that this simple procedure is of benefit to a substantial proportion of patients with neurological causes of dysphagia.     

Carbohydrate metabolism in motor neurone disease.

Eight patients with classical motor neurone disease, and eight control patients with neurological disease and matched for degree of wasting, were studied. Both groups had abnormal glucose tolerance, but the patients with motor neurone disease had a significantly lower insulin response both to oral glucose loading and to intravenous tolbutamide. These results suggest that in patients with motor neurone disease there is an impaired synthesis or release of insulin due to islet cell damage. Blood pyruvate and lactate, and cerebrospinal fluid pyruvate, lactate, and citrate, did not differ significantly from the control group. Blood citrate levels were significantly higher in patients with motor neurone disease compared with the controls. Triglyceride levels were raised in patients with motor neurone disease compared to the control patients. This may be secondary to the increased citrate levels.     

The changing mortality from motor neurone disease and multiple sclerosis in England and Wales and the Republic of Ireland.

A study has been undertaken to ascertain the changes in mortality from motor neurone disease (MND) and from multiple sclerosis (MS) in England and Wales and in the Republic of Ireland. During the 20 years 1968-1987, 16,077 deaths were reported as being primarily due to MND in England and Wales with a male/female ratio of 1.22. There has been an increase in MND deaths from 3,185 in 1968-1972 to 5,241 in 1983-1987. The increase occurred in the death rates in both sexes and in all age groups, but particularly over the age of 65. In contrast, there was no increase in MS deaths and the MS death rates fell below the age of 55 but increased over this age, evidence that MS patients are living longer. A similar but more marked increase in MND mortality, and a considerable fall in MS mortality, occurred in the Republic of Ireland. The increase in MND mortality is not due to an increase in the number of neurologists, as there has been little increase in their numbers. The highest MND mortality was in Social Class IIIN males - skilled non-manual workers.     

The prevalence of motor neurone disease in the Province of Alberta.

Using data from the Alberta Health Care Insurance Plan, the prevalence of motor neurone disease (MND) was estimated for the Province of Alberta, Canada. Between January 1, 1994 and December 31, 1995, 208 cases of MND (125 males, 83 females) were identified from physician billing records giving a period prevalence of 7.38 (8.9 for males, 5.9 for females) per 100,000 population. On prevalence day, July 1, 1995, there were 171 cases (103 males, 68 females) of MND giving a point prevalence estimate of 6.07 (7.3 for males, 4.8 for females) per 100,000 population. Males were more likely to be diagnosed (OR = 1.52, 95% CI 1.1, 2.1) with MND and there was an increased risk of receiving a diagnosis with increasing age (chi 2trend = 281, p < 0.001). The mean age of the cases was 59.2 years (58.5 for males, 60.3 for females) and did not differ significantly between the sexes. Geographically, there was no statistically significant difference in the prevalence across regions of the Province. During the study period, 28% of the cases had died (30% of males, 25% of females). The prevalence of MND in Alberta, is among the highest reported in the literature and requires additional investigation to verify these estimates and identify possible causative factors.     

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.     

Pattern of motor neurone disease in eastern India

A clinical study about the pattern of motor neurone disease in eastern India was carried out from July 1993 to June 1995 at Bangur Institute of Neurology, Calcutta and SSKM Hospital, Calcutta. A total of 110 cases were studied and they constituted 0.11 % of all neurological cases seen in the general OPD. Of 110 cases, amyotropic lateral sclerosis (ALS) constituted 43.6%, progressive muscular atrophy (PMA) 10.9%, post-polio progressive muscular atrophy (PPMA) 1.8%, spinal muscular atrophy (SMA) 20%, atypical form Madras pattern of MND (MMND) 0.9% and monomelic amyotrophy (MM A) 22.7% of cases. Disease is more common in males than females and average duration of symptoms before presentation varied from 1 to 12 months. Most of the patients were either agricultural labourers or manual workers in ALS variety whereas MMA variety was evenly distributed in both hard labourers and sedentary workers. Most of the patients in MMA and SMA groups presented before 30 years of age whereas ALS and PMA group presented after 30 years. Trauma was the commonest antecedent event in ALS and MMA followed by electrocution in the same two groups. Family history was found to be absent in SMA group though the disease is considered as a hereditary one. Weakness of the limbs and wasting of the muscles were common presenting symptoms and signs. Bulbar symptoms and signs were found only in the ALS group. EMG showed neurogenic pattern and mixed pattern in most of the patients in all groups. Only a few patients showed myopathic pattern. Neuroimaging study helped in exclusion of compressive lesion excepting two cases of MMA where lacetal hypertrophy was present. Monomelic amyotrophy, a special variety of motor neurone disease, is not rare in this part as compared to other parts of India and Asia.     

A histochemical study of motor neurone disease

Summary Enzymes functioning in the major metabolic pathways of the central nervous system have been examined in 5 cases of motor neurone disease.Surviving motor nerve cells exhibited a normal response to all enzymes except ATPase and 5-nucleotidase. Nerve cells exhibiting partial degeneration showed a stronger activity of some enzymes (AChE, NADH₂ diaphorase, G6-PDH) than others (ATPase, 5-nucleotidase, monoamine oxidase). Complete enzymic loss was evident in some anterior horn motor nerve cells.Striking alterations in NADH₂ diaphorase, G6-PDH, acid phosphatase and thiamine pyrophosphatase activities were observed in swollen astrocytes in the internal capsule, the lateral corticospinal tract and frequently in the anterior corticospinal tract. PAS-positive material was depleted in these areas. The findings are discussed biochemically and in relation to other disorders of the central nervous system.

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Zusammenfassung Das Verhalten der Enzyme der wichtigsten Stoffwechselkreise des Zentralnervensystems wurde in fünf Fällen von Erkrankungen des motorischen Neurons untersucht.Die überlebenden Motoneurone zeigten normales Enzymverhalten mit Ausnahme der ATPase und 5-Nucleotidase. In Nervenzellen im Zustand partieller Degeneration zeigten einige Enzyme (AChE, NADH₂-Diaphorase, G6-PDH) stärkere Aktivität als andere (ATPase, 5-Nucleotidase, Monoaminooxydase). In einigen motorischen Vorderhornzellen bestand ein kompletter Enzymverlust.Auffallende Änderung der NADH₂ Diaphorase-, G6-PDH-, der sauren Phosphatase — sowie der Thiamin-Pyrophosphataseaktivität wurde in hyperplastischen Astrocyten in der inneren Kapsel, im lateralen Pyramidenstrang und häufig auch im ventralen Pyramidenstrang erhoben. PAS-positives Material lag in diesen Gebieten vor. Die Befunde werden vom biochemischen Standpunkt diskutiert und mit anderen Störungen des ZNS in Beziehung zu setzen versucht.

     

The distribution and frequency of spontaneous fasciculations in motor neurone disease

A system of recording spontaneous fasciculations in patients with motor neurone disease is described. The detection of fasciculations is more effective than that achieved by clinical examination. Estimates have been made of the mean and median frequencies of discharge. The relationship of the results of the study to other electrodiagnostic features of motor neurone disease is briefly discussed.