Diagnosis Of Motor Neuron Disease Research Articles

A Case of Invasive Thymoma

A 52 year-old man with a past medical history of an isolated seizure presented to the Veterans Affairs hospital complaining of weakness which was most prominent in the face and upper extremities. About 6 months prior to this admission he developed intermittent episodes of weakness when chewing and swallowing. He would often have to use his hands to close his jaw when eating or talking. He noticed that his voice had developed a nasal quality but he did not have slurred speech. He denied drooling, ptosis, cramping or muscle twitches. He was seen 6 months ago at another VA hospital where a neurologic workup was done. This included a cranial nerve EMG positive for denervation of cranial nerves, R arm and T- and L-spine. MRI and CT scans could not be done because the patient aspirated when supine. He was given a presumptive diagnosis of motor neuron disease, specifically bulbar ALS. At that time he was told he would need a PEG-feeding tube placed due to significant weight loss. The patient refused the feeding tube and did not follow up until 6 months later when the symptoms had worsened.

Outcome of ventilatory support for acute respiratory failure in motor neurone disease

Objectives: To review the outcome of acute ventilatory support in patients presenting acutely with respiratory failure, either with an established diagnosis of motor neurone disease (MND) or with a clinical...

Pitfalls in the diagnosis of motor neurone disease.

Motor neurone disease is characterized by progressive degeneration of upper and lower motor neurones with preservation of cognition. Recognition of classical motor neurone disease is not difficult, but during the early stages both false positive and false negative diagnoses are common. Careful examination, frequent follow-up and ancillary tests are necessary to avoid erroneous diagnoses.

Electrophysiological diagnosis of motor neuron disease and pure motor neuropathy.

Motor neuron disease (MND) is a group of disorders in which there is degeneration of upper and lower motor neurons to a variable degree. Amyotrophic lateral sclerosis is the most frequent form of the disease, presenting with both upper and lower motor neuron involvement. Frequently, especially in the early stages of the disease, only lower motor neuron signs are present. In these conditions, some pure motor neuropathies may resemble MND. The diagnosis is of importance because some of these motor neuropathies are "dysimmune" disorders and may respond to immune therapies. In such diseases the multifocal motor neuropathy with conduction block appears to be the more frequent. In MND and pure motor neuropathies, the electrophysiological examination is the most decisive test. In MND, it is of diagnostic importance. In addition, it is useful in the assessment of disease severity and progression, in the evaluation of therapeutic trials and in the understanding of etiopathogenesis of the disease. In pure motor neuropathies, the presence of conduction block leads to immune treatment with good response in more than 50% of the cases.

Electrodiagnostic studies in clinical trials for motor neuron disease.

Motor neuron disease (MND) is a group of neurodegenerative disorders characterized by death of upper motor neurons (UMN) and lower motor neurons (LMN). Clinical study of UMN loss is limited, but electrodiagnostic studies can be used readily to assess the functional state of LMN. Electrodiagnostic studies are regularly used in making the diagnosis of amyotrophic lateral sclerosis (ALS) and other forms of MND. They can also be used to follow disease progression and serve as end point measures in drug trials. In this role, electrodiagnostic studies can provide specific information not readily available from measurement of muscle strength or clinical functional scales. This article emphasizes the primary pathologic and secondary physiologic changes that take place after LMN loss and how they can be assessed by electrodiagnostic studies. It reviews the uses of routine electrodiagnostic studies for the diagnosis of MND but focuses on how special electrodiagnostic studies can be used as end point measures in drug trials.

Genetic transfer of the wobbler gene to a C57BL/6J x NZB hybrid stock: natural history of the motor neuron disease and response to CNTF and BDNF cotreatment.

Preclinical diagnosis of motor neuron disease (MND) in the wobbler mouse (wr/wr) has been impossible until recently. However, with the development of a new hybrid, the C57BL/6J x New Zealand Black (B6NZB) wr/wr mouse, the polymerase chain reaction (PCR) can be used to establish the preclinical diagnosis. We compared the clinical and histological features of MND and the effects of neurotrophic factor cotreatment between the hybrid B6NZB-wr/wr and the congenic C57BL/6J-wr/wr mice. Clinical assessments of body weight, grip strength, running speed, paw position, and walking pattern were made weekly from age 2 weeks through 8 weeks (n = 10, B6NZB-wr/wr; n = 15, C57BL/6J-wr/wr). Survival was analyzed (n = 7, each strain) as was C5 and C6 spinal cord motoneuron morphology and ventral root histometry (n = 7, each strain). For cotreatment, 8 B6NZB-wr/wr and 7 C57BL/6J-wr/wr mice received subcutaneous ciliary neurotrophic factor (1 mg/kg) and brain-derived neurotrophic factor (5 mg/kg) on alternate days, 6 days/week for 4 weeks. B6NZB-wr/wr mice could be distinguished from C57BL/6J-wr/wr mice at age 3 weeks by a more abnormal paw position (P < 0.01) and walking pattern (P < 0.05) and lower grip strength (P < 0.001) and running speed (P < 0.001). After 3 weeks, the changes continued to be greater in B6NZB-wr/wr mice. Although B6NZB-wr/wr mice were more severely affected early in the disease, their survival was comparable to C57BL/6J-wr/wr mice. Anterior horn cell vacuolar degeneration and myelinated fiber histometry were similar in both strains. The clinical response to CNTF/BDNF cotreatment was marked in both groups although it was weaker in B6NZB-wr/wr mice. Thus, the hybrid B6NZB-wr/wr mice have a more severe clinical phenotype and offer a unique opportunity to study the mechanisms of presymptomatic motor neuron degeneration and the effects of therapeutic agents for human MND.

British motor neuron disease twin study.

OBJECTIVES: To investigate the cause of sporadic motor neuron disease (MND) by twin study, so allowing (1) estimation of the genetic contribution, and (2) collection of matched pairs for a...

Sensitivity of motor unit potential and turns-amplltude analysis in early diagnosis of motor neuron disease

The interaction among the recurrent discharge of motor units is studied in surface recorded composite F-response. In the first experiment, 200 serially elicited polyphasic F-responses from foot muscles of patients with different lower motor neurone (LMN) disorders were rearranged to understand the behaviour of individual negative and positive peaks. These peaks were considered on the basis of simultaneous recording with a single fibre EMG needle, to be the partial expression of either a single motor unit potential (MUP) or more than one MUP generated simultaneously. In another experiment, two serially averaged F-responses (50 each) were superimposed over each other to look for their similarities at 15 min intervals 6 times. Result analysis indicated interaction of MUPs by in-phase summation and out-of-phase subtraction. Less affected MUPs recurred as negative or positive peaks in morphologically different F-responses. Certain peaks were observed more frequently than the others. Two serially averaged F-responses were nearly identical on superimposition over each other but their morphologies differed at different time intervals. The study suggests more frequent generation of F-response in a specific group of alpha motoneurones at one point of time, which is replaced by another group at another point of time. The characteristic variation in F parameters is, however, mainly due to the interaction of these frequently generated F-response MUPs with other sporadically generated ones. This interaction can be appreciated on visual screening of F-responses in patients with lower motor neurone disorders, perhaps because of a reduction in the number of participating MUPs.

Communicating the diagnosis of motor neurone disease.

Communication of the diagnosis of motor neurone disease (MND) is a particularly difficult task for doctors in view of the poor prognosis and the lack of significant treatment. This study examined patients' views of being given the diagnosis and of how it was communicated. Fifty people who had been diagnosed with MND more than six months previously were interviewed about their experience of the diagnosis. The majority reported positive aspects of being told, especially having a label for their condition. The most frequently mentioned critical aspect of how they were told was the directness and clarity with which they were given the information. Patients were more critical if the diagnosis was worse than expected (as it was for most patients) and more satisfied if they felt they had been able to ask questions. There was no evidence that unsatisfactory communications were associated with later mood disturbance. A longitudinal study is recommended to overcome limitations in this cross-sectional design.

Neuroprotective effect of basic fibroblast growth factor on wobbler mouse motor neuron disease

Basic fibroblast growth factor (bFGF) possesses neuroprotective effects on a variety of neurons. Here we report that it delays progression of motor neuron disease (MND) in the wobbler mouse. After initial diagnosis of MND at post-natal age 3-4 weeks, wobbler mice receive either recombinant human bFGF (1 mg kg-1, n = 10) or vehicle (n = 10), daily for weeks by subcutaneous injection in a blind fashion. We performed symptomatic and neuropathological assessments in both groups. The treatment was fulfilled at 7-8 weeks of age. In comparison with vehicle, bFGF treatment potentiated grip strength (p < 0.008), attenuated forelimb contracture (p < 0.003), and increased weight of the biceps muscle (p < 0.008). bFGF-treated mice retarded denervation muscle atrophy (p < 0.001) and degeneration of spinal motoneurons (p < 0.001). Our study shows that bFGF treatment is beneficial in a murine MND model. We provide a rationale that bFGF may have therapeutic potential in peripheral motor neuropathy or MND.

Receiving the diagnosis of motor neurone disease

ABSTRACT It has been asserted that the impact of illness can best be understood in terms of the perception of the patient (identity of the illness, cause, time‐line, consequence and cure) rather than the disability resulting from the disease. This study was set up to examine patients' perceptions of illness before and after diagnosis and to assess, firstly, whether their perceptions determined the emotional impact of the diagnosis and, secondly, the coping strategies employed to cope with the diagnosis. This was a longitudinal study of 38 patients with suspected motor neurone disease (MND), seen before and after diagnosis in three centres in the UK, using standardised measures and theoretically derived questions. The standardised measures included disability rating scales and tests of emotional outcome. Patients' perceptions: identity. The mean number of symptoms did not alter before and after diagnosis. About 20% of patients identified their illness as MND before going to hospital for investigations; their anxiety and depression decreased after diagnosis, presumably as a result of being ‘prepared’. As expected, significantly more subjects (64%, Sign test, p = 0.0018) gave the MND label after diagnosis. For these people, anxiety and depression increased after diagnosis. Most saw something positive in getting the diagnosis. Patients who did not have the correct label before diagnosis became significantly more disabled over time. Patients' perceptions: cause. About half the subjects attributed their MND to a cause, even though there is no accepted cause of MND. They had significantly higher wellbeing scores; of these about 40% attributed it to their own behaviour and were found to be significantly less disabled (t = 2.84, df = 16, p = 0.012). Patients' perceptions: time‐line and cure. Before the diagnosis, only 24% of patients expected a cure, 24% expected to be better, and 26% expected to be worse. After diagnosis, 20% still expected a cure but none expected to be better. No significant relationship was found with severity of disability. Patients' perceptions: consequences. At both times, patients ranked their illness as being serious. This was not related to the severity of disability. In this study most of the subjects took coping action. This was associated with a reduction in anxiety and depression. It is important to note that seeking alternative remedies was associated with anxiety. This study has important implications for managing patients with MND.

Multifocal motor neuropathy with conduction block: a study of 24 patients.

Twenty four patients with pure motor neuropathy are reported. The chronic motor involvement associated with fasciculations and cramps, mainly in the arms, led, in most patients, to an initial diagnosis of motor neuron disease. In some patients (nine of 24), there was no appreciable muscle atrophy. Tendon reflexes were often absent or weak. The finding of persistent multifocal conduction block confined to motor nerve fibres raises questions about the nature and the importance of this syndrome. Segmental reduction of motor conduction velocity occurred at the site of the block, but significant slowing of motor nerve conduction was not found outside this site. The response to intravenous IVIg treatment seems to be correlated with the absence of amyotrophy. Patients with little or no amyotrophy had an initial and sustained response to IVIg, and did not develop amyotrophy during the follow up study. They could be considered to have a variant of chronic inflammatory demyelinating polyneuropathy. Patients with pronounced amyotrophy independent of the disease duration did not respond as well to IVIg treatment, suggesting the existence of a distinct entity. Among the patients treated about two thirds who had an initial good response to IVIg had high or significant antiganglioside GM1 (anti-GM1) antibody titres, but there was no correlation between the high titres before treatment and long lasting response to IVIg treatment.

Utility of Scottish morbidity and mortality data for epidemiological studies of motor neuron disease.

To determine the accuracy of (1) hospital discharge data and (2) death certificates, coded as motor neuron disease (MND). Comparison of data from The Scottish Motor Neuron Disease Register (SMNDR) with routinely collected Scottish Hospital In-Patient Statistics (SHIPS) and death certificate coding. Scotland UK. 1) 379 adults (> 15 years) discharged for the first time from a Scottish hospital in 1989-90 and (2) 281 deaths in the same period assigned to the International Classification of Diseases (ICD)-9, category 335 (MND). The sensitivity and positive predictive value of a diagnosis of MND as retrieved by (1) the Information and Statistics Division of the Common Services Agency for the Scottish Health Service for morbidity data and (2) the Registrar General's office for mortality data, using the SMNDR as the 'gold standard'. (1) Thirty per cent of adult patients identified as having MND by SHIPS did not have this disease and 23% of patients with MND did not appear on SHIPS. The sensitivity of a diagnosis of MND, as retrieved by SHIPS, was 84% and the positive predictive value was 70% overall. Miscoding of patients with pseudobulbar palsy caused by cerebrovascular disease was the major source of false positive error. The incidence of adult onset sporadic MND was over estimated by SHIPS by a factor of 1.6. (2) Mortality data were more accurate, with a false negative rate of 6% and a positive predictive value of 90%. Coded hospital discharge data are an inaccurate record of a diagnosis of MND and cannot, in their present form, be used as a reliable measure of disease incidence in Scotland. Greater care is required in the preparation of discharge summaries and coding if these data are to be useful for health care planning and epidemiological research. SHIPS is, however, an important source of information to achieve a complete sample of patients with MND. There is also a problematic false positive rate for mortality data but this source more closely approximates true incidence.

Limbic encephalopathy-case report and review of the literature

A 60 year old male with a long history of low -grade depression and a 12 month history of dysarthria, dysphasia, weakness and altered cognitive function was admitted to Bethlehem Hospital for terminal care. A preadmission diagnosis of Motor Neuron Disease had been made by a private neurologist. He was treated with due care but died of clinical bronchopneumonia 1 month after admission. At autopsy the brain was heavy (1400 gm) and macroscoplcally unremarkable. The lungs showed evidence of congestive cardiac failure but no bronchopneumonia. The left kidney was of small size, showed reduced cortical thickness, dilated pelvicalyceal system and had three cortical masses between 5 and 35 mm in diameter. A fourth Intra-cortical area of yellowish discolouration 3 mm in length was also present. These areas represent renal cortical neoplasms of the proximal tubules which are histologically and macroscopically at the boundary between benign and malignant neoplasms of the renal cortex. No evidence of metatstatic disease was noted. The brain showed sponginess and gliosis of the medial temporal cortex bllaterally. There was also some mild loss of motor neurons in the spinal cord. Only two other cases of renal carcinomas and limbic encephalopathy were found in the last 16 years, one of which was also associated with an oat cell carcinoma of lung. Limbic encephalopathy is a para-neoplastic syndrome, which in its pure form as seen In this case, is exceedingly uncommon. It Is usually in association with bulbar, cord and posterior root ganglia lesions and Is most commonly seen in cases of primary lung carcinomafoat cell carcinoma).

Surface EMG in the recording of fasciculations.

The usefulness of multichannel surface recording of fasciculations was evaluated by a retrospective study of 116 patients with various neurological disorders. Eight channels of a conventional electroencephalograph were used with plate electrode recordings from the upper arms and legs. Wide-spread fasciculations (defined as five or more of the eight muscle groups) were recorded in 48 of 54 patients with motor neuron disease, spinal muscular atrophy or postpolio syndrome, but noted on routine clinical examination at presentation in only 6. Eleven of 23 patients with peripheral neuropathy or myelopathy had fasciculations in five or more leads compared to one clinically, and 3 of 39 with other neurological diseases had fasciculations electrically but in only one were they clinically observed. The method is a noninvasive and sensitive adjunct to clinical examination for detecting fasciculations. Its diagnostic value is limited by the relatively high incidence of fasciculations in neuropathies and myelopathies. However, this study suggests that "false negatives" are rare and that the diagnosis of motor neuron disease should be reconsidered when less than five leads shows fasciculations.

Diagnosis of motor neuron disease by neurologists: a study in three countries.

Ninety four neurologists in the United Kingdom, China, and West Germany responded to two structured questionnaires. The first assessed the diagnostic weighting assigned to a number of symptoms, signs, and clinical investigations ascertained from classical descriptions and case notes of patients with motor neuron disease (MND). The second tested the likelihood and consistency of diagnosis in a series of case summaries representing the clinical data of 10 patients with clinically and pathologically documented motor neuron disease. There was a wide measure of agreement concerning the common clinical features of the disease, especially regarding fasciculation of the tongue, fasciculation associated with weakness seen in more than one limb, and dysphagia. In the case summaries, however, there was clear variation in the ranked likelihood of the diagnosis of MND and in the consistency of diagnostic behaviour in the different groups of neurologists. These findings support the need for internationally agreed criteria in the diagnosis of MND. Any such criteria will need to be tested against a standardised data set to establish their validity.

HIV‐related neuromuscular syndrome simulating motor neuron disease

A young homosexual man presented with slowly progressive weakness and diffuse fasciculations. Muscle biopsy was compatible with clinical diagnosis of motor neuron disease. The patient died from opportunistic infections related to acquired immunodeficiency syndrome. Autopsy revealed evidence of myelopathy, patchy fiber loss from anterior nerve roots, marked demyelination within intramuscular twigs of peripheral nerves, and primary myopathic features superimposed on advanced neurogenic atrophy of the skeletal muscles.

A filamentous inclusion body within anterior horn neurones in motor neurone disease defined by immunocytochemical localisation of ubiquitin.

Using an immunocytochemical method to localise antibodies to ubiquitin, filamentous inclusion bodies were seen in spinal anterior horn neurones in cases of motor neurone disease (MND) but not in any control cases. These inclusion bodies appeared to be closely associated with classical Bunina bodies and immuno-electron microscopy suggested that they were based on arrays of straight 10-15 nm filaments together with some granular material. These observations link the protein ubiquitin with a chronic neurodegenerative disease and extend previous observations of a close association between filamentous inclusion bodies and ubiquitin. Ubiquitin-filament inclusions should be regarded as a new hallmark in the histological diagnosis of MND.

ENIGMATIC DYSPNOEA: AN UNUSUAL PRESENTATION OF MOTOR-NEURONE DISEASE

Although dyspnoea is common in advanced motor-neurone disease (MND), it is rare as the presenting disorder. Three patients in whom dyspnoea was the first symptom of MND are reported to alert physicians to this possibility so that delay in diagnosis of MND can be avoided.