Hemicrania continua: side alternation and response to topiramate.
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Adult↗
Biomedical subjects
M Swash
Publications and source records attributed to M Swash.
The onset of amyotrophic lateral sclerosis.
Two patients in whom both the neurological examination and electromyography (EMG) were normal prior to the onset of amyotrophic lateral sclerosis (ALS) are reported. In each patient, the onset of ALS some 18 months later was clearly defined clinically and confirmed by subsequent EMG studies. These unique observations show that ALS commences at a defined time, and that there is early generalisation with an initial phase of rapid progression.
Aged↗
Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.
BACKGROUND: Minicore myopathy (multi-minicore disease [MmD]) is a congenital myopathy characterized by multifocal areas with loss of oxidative activity on muscle biopsy. MmD is clinically heterogeneous and distinct phenotypes have been associated with recessive mutations in either the selenoprotein N (SEPN1) or the skeletal muscle ryanodine receptor (RYR1) gene, also implicated in central core disease and malignant hyperthermia. External ophthalmoplegia is an additional finding in a subset of patients with MmD. OBJECTIVE: To clinically and genetically examine families with MmD and external ophthalmoplegia. METHODS: The authors investigated 11 affected individuals from 5 unrelated families. Clinical, histopathologic, and imaging studies were performed and RYR1 haplotyping and mutational analysis were carried out. RESULTS: All patients had multiple cores involving the entire fiber diameter on longitudinal sections. Weakness and wasting in the shoulder girdle, scoliosis, moderate respiratory impairment, and feeding difficulties were prominent. In contrast to SEPN1-related myopathies, soleus was more severely affected than gastrocnemius on muscle MRI. Haplotyping suggested linkage to the RYR1 locus in informative families and mutational screening revealed four novel RYR1 mutations in three unrelated families; in addition, functional haploinsufficiency was found in one allele of two recessive cases. CONCLUSION: These findings expand the phenotypic spectrum associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. Recessive mutations of domains commonly affected in malignant hyperthermia appear to be particularly prevalent in multi-minicore disease with external ophthalmoplegia and might suggest a different pathomechanism from that involved in central core disease.
Adolescent↗
Contribution of the pudendal nerve to sensation of the distal rectum.
BACKGROUND: Anal and rectal sensory mechanisms and pudendal nerve function are important in the control of faecal continence. The contribution of the pudendal nerve to sensation of the distal rectum was investigated. METHODS: Heat thresholds in the anal canal, distal and mid rectum were measured using a specially designed thermoprobe. Rectal sensory threshold volumes were measured using the balloon distension method. Needle electrodes were inserted into the external anal sphincter. Pudendal nerve block was performed through a perineal approach, and completeness assessed by loss of electromyographic activity. Heat and rectal volume thresholds were measured again following unilateral and bilateral pudendal nerve block. RESULTS: The technique was successful in four of six volunteers. Bilateral pudendal nerve block produced complete anaesthesia to heat in the anal canal (P = 0.029), but had no effect on heat thresholds in the distal or mid rectum. Rectal sensory threshold volumes were also unaffected by pudendal nerve anaesthesia. CONCLUSION: Anal canal sensation is subserved by the pudendal nerve, but this nerve is not essential to nociceptive sensory mechanisms in the distal or mid rectum. The transition between visceral control mechanisms in the lower rectum and somatic mechanisms in the anal canal may have functional importance in the initiation of defaecation and the maintenance of continence.
Adult↗
The anal reflex elicited by cough and sniff: validation of a neglected clinical sign.
BACKGROUND: It is unclear whether contraction of the external anal sphincter (EAS) following a voluntary cough is an integral component of the cough response itself, or a reflex response to the abdominal and pelvic floor dynamics induced by the cough. Clinical experience suggests a reflex origin for this response. OBJECTIVE: To compare motor latencies for intercostal, abdominal, and EAS muscle contraction after transcranial magnetic stimulation with those following voluntary coughing and sniffing. METHODS: A needle electrode inserted into the EAS measured responses, which were confirmed by tonic electromyographic recording. Direct motor latencies from the cerebral cortex to the intercostal, rectus abdominis and EAS muscles were obtained using transcranial magnetic stimulation. Sniff and cough induced responses were also recorded in these muscles. RESULTS: The results suggest that EAS responses following a voluntary cough or sniff represent a polysynaptic reflex. CONCLUSIONS: As the cough induced anal reflex response is consistent and easily elicited, its use in clinical neurological examination is appropriate.
Adult↗
Reproducibility of neurophysiological and myometric measurement in the ulnar nerve-abductor digiti minimi system.
Reliability in strength and neurophysiological measurements is important in evaluating progression of neuromuscular diseases. No data are available on the variability of neurophysiological parameters as compared with maximal voluntary isometric contraction (MVIC) in the same muscles, in healthy subjects. A control population of 26 healthy subjects was studied twice on different days. We evaluated the reliability of neurophysiological parameters obtained from bilateral ulnar nerve stimulation, recording the response over the abductor digiti minimi (ADM) muscle, including distal motor latency, compound muscle potential amplitude and area, F-wave frequency and mean F-wave latency, and the derived neurophysiological index that we have described previously. MVIC force was measured in each session in both ADM muscles. The variances between the grouped data obtained in the two recording sessions were identical, indicating a low intrinsic variability with this experimental methodology. Comparison of the mean values obtained in the two sessions revealed no statistically significant differences. The reliability of these neurophysiological and strength measurements in the same nerve/muscle system suggests they may be useful in comparing the dynamics of weakness and neurophysiological change in neuromuscular disease.
Adult↗
Clinical neurophysiology of ALS.
The neurophysiology of amyotrophic lateral sclerosis is important not only in relation to diagnosis, but also in the development of methods to follow progress, and the effects of putative therapies, in the disease. Quantitative techniques can be applied to the measurement of reinnervation using needle electromyogram. The methodology of motor unit number estimation may be useful in measuring loss of functioning motor units in groups of patients but variability in the measurement using current methods limits its sensitivity in the evaluation of individual patients. Conventional neurophysiological measurements, expressed as a multimetric index, may be useful in assessing progress. The cortical and upper motor neuron system can be assessed using transcortical magnetic stimulation protocols, and cortical excitability may be measured by the peristimulus histogram method. In this review the advantages, limitations and promise of these various methods is discussed, in order to indicate the direction for further neurophysiological studies in this disorder.
Action Potentials↗
ALS and motor neuron disorders today and tomorrow.
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Amyotrophic Lateral Sclerosis↗
Measuring mental health in amyotrophic lateral sclerosis (ALS): a comparison of the SF-36 Mental Health Index with the Psychological General Well-Being Index.
OBJECT: The purpose of this study was to compare the performance of the five-item mental health dimension of SF-36 (the Mental Health Index, MHI-5) with that of the 22-item Psychological General Well-Being Index (PGWB) in patients presenting with amyotrophic lateral sclerosis/motor neuron disease, using tests of reliability and validity. DESIGN: A questionnaire-based survey of patients diagnosed with ALS across 15 European countries. SAMPLE: Patients presenting at neurological clinics for treatment of their ALS were asked to join the survey. RESULTS: 1048 patients with ALS have been recruited, of whom 861 (82.2%) have returned baseline questionnaires. There was evidence supporting the internal consistency of both instruments, and for their construct validity in distinguishing between groups, in terms of gender and age. The scores on the two instruments were highly correlated (Spearman rank correlation 0.85). CONCLUSION: Both the MHI-5 and the PGWB showed high levels of construct validity and internal reliability in this patient group. The MHI-5 has comparable psychometric performance to the PGWB, and can be used to measure and compare mental health in defined populations.
Adult↗
ALS--future directions.
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Amyotrophic Lateral Sclerosis↗
Amyotrophic lateral sclerosis: current understanding.
Amyotrophic lateral sclerosis (ALS), or motor neuron disease (MND) as it is usually termed in the United Kingdom, is a fatal degenerative disease resulting in progressive weakness and wasting of voluntary muscles. The disease is caused by degeneration of upper motor neurons in the motor cortex and of lower motor neurons in the brainstem and spinal cord. This combined loss of function causes spastic paralysis, flaccid muscle weakness, wasting, and fasciculations. The disease process spares the sensory, autonomic, and oculomotor neurons. ALS is the most common of the MND syndromes in adults. Although the cause of ALS is unknown, there is evidence that the excitatory neurotransmitter glutamate plays an important role in neuronal cell death in the disease. Several risk factors, such as exposure to welding and soldering, inhalation of lead vapor, exposure to chemicals, and electrical trauma are postulated as contributing to the pathogenesis of ALS. About 90% of all ALS patients have the sporadic form. Approximately 20% of all familial ALS cases are associated with mutations of the copper/zinc superoxide dismutase-1 gene. What is not clear is what factors contribute to the causation of the more common sporadic cases. The drug riluzole has neuroprotective effects in ALS and is the only disease-specific treatment available to date. Riluzole has been approved by the National Institute for Clinical Excellence for use in the National Health Service of the United Kingdom. Other treatments are aimed at managing the devastating symptoms of ALS.
Drug Approval↗
ALS 2000: the past points to the future.
In this introductory review a number of issues concerning the direction of future research in ALS are addressed in relation to current understanding of this disorder and its treatment. The importance of understanding the pathways leading to motor neuron dysfunction and death is emphasized. Contemporary epidemiology, understandably focussed on genetic markers for familial ALS, needs to be widened to include as yet undocumented susceptibility-related genetic traits. Potential avenues for therapy are considered, and the fundamental contemporary issue of clinical measurement is discussed. Neglected aspects of contemporary research, including disturbed axoplasmic flow, are brought to attention. The role of experiment derived from clinical observation, and vice versa, is described by reference to a number of past and recent contributions to the understanding of ALS.
Amyotrophic Lateral Sclerosis↗
Diagnostic delay in amyotrophic lateral sclerosis: what scope for improvement?
The average time taken from symptom onset to diagnosis in motor neuron disease is many months and has shown no sign of improving despite the introduction of riluzole therapy. We performed a retrospective analysis of the time to diagnosis in 57 patients using a structured interview with the patients and/or their carers. In this cohort, studied in England and Wales, the mean time from onset to diagnosis was 16.2 months. An initial incorrect diagnosis, refusal to consider the diagnosis when it was suggested by the informed patient, failure to consider a neurological cause for the patient's symptoms, and failure to make early referral to a neurologist were the major factors leading to delayed diagnosis. Bulbar symptoms were more likely to lead to correct diagnosis than limb-onset features. Ten of our patients made the diagnosis by consulting reference books or the Internet before they were informed of it by their physician.
Amyotrophic Lateral Sclerosis↗
The effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in multiple sclerosis.
We investigated the effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in patients with multiple sclerosis. Following a double blind trial designed to compare the effect of oral and intravenous methylprednisolone treatment on promoting recovery from acute relapses of multiple sclerosis, 80 patients were followed for two years with six-monthly assessments during which all subsequent relapses were recorded. The annual relapse rate was slightly higher in the oral compared with the intravenous methylprednisolone-treated patients (1.06 vs. 0.78), but the adjusted difference between the two groups was not statistically significant (0.18; 95% CI -0.19 to 0.55, P=0.3). The time to onset and the severity of the first relapse after treatment, the number of relapse free patients at the end of the follow-up period, and the severity of the relapses during the follow-up period were similar in the two groups. This trial did not show a statistically significant difference in relapse rate during the first two years following oral compared with intravenous methylprednisolone treatment.
Administration, Oral↗
Nerve conduction studies in amyotrophic lateral sclerosis.
We studied 137 ulnar nerves and abductor digiti minimi (ADM) muscles in 70 patients with amyotrophic lateral sclerosis (ALS), and correlated the results with ADM strength graded on the Medical Research Council (MRC) scale, to address the potential value of a standardized neurophysiological assessment of this nerve-muscle system. The ulnar nerves of 35 normal subjects matched for age, gender, and height served as controls. Reduced compound muscle action potential (CMAP) amplitude and area in the ADM muscle recordings correlated strongly with weakness. Distal motor latency, proximal conduction time, and F-wave frequency were abnormal with minimally detectable weakness. In weaker ADM muscles, conduction velocities and F-wave latencies were also abnormal. Conduction block was never observed and sensory potentials were normal. An "ALS neurophysiological index" was derived from these ulnar nerve studies and consisted of the expression: (CMAP amplitude/DML) x F frequency -, where F frequency was expressed as the number of F responses recorded in 20 trials. This index was strongly correlated with ADM weakness (r = 0.74, P < 0.001). Neurophysiological studies restricted to a single nerve-muscle system, the ulnar nerve/ADM, appear potentially useful in objectively assessing change in ALS.
Adult↗
The ALS Health Profile Study: quality of life of amyotrophic lateral sclerosis patients and carers in Europe.
The measurement of functioning and well-being from the perspective of the patient has in recent years become central to the assessment of health and the evaluation of treatment regimes. The past decade has seen an enormous growth in the application of measures designed to assess quality of life in a vast array of medical specialties. However, the use of such measures in neurology has been relatively limited, and this has certainly been the case in amyotrophic lateral sclerosis (ALS). The European ALS Health Profile Study is a longitudinal survey of patients diagnosed with ALS or other motor neurone diseases in which patients are asked to complete questionnaires concerning their subjective health status. Data from clinical assessments are also collected. It is intended that the information collected will provide more systematic and detailed evidence of the impact of the disease from the perspective of the patient. This contribution documents results from baseline assessment obtained from data supplied by clinicians, carers and patients themselves. Three outcome measures are assessed in this paper: the SF-36, a generic measure of well being and functioning, the ALS Functional Rating Scale and the Carer Strain Index. The evidence presented here suggests that these measures provide a meaningful and valid picture of the impact of the disease. The data indicate that ALS has substantial adverse effects both upon the functioning and well being of patients and carers, as well as an association between the emotional health status of patients and carers, and between the physical health status of patients and carers.
Adult↗
El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis.
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Diagnosis, Differential↗
Motor neuron disease: classification and nomenclature.
The classification and nomenclature of motor neuron disease, whether sporadic or familial, is confused. For example, both the sporadic and familial motor neuron diseases are phenotypically heterogeneous and, in familial ALS, phenotypic heterogeneity correlates only weakly with different underlying mutations in the SOD1 gene. We propose a classification which is based on underlying causative mechanisms, where these are known, but which also recognizes different clinical phenotypes when the cause is unknown. This classification is flexible, and allows reattribution of clinical syndromes when their causation is understood. Currently uncertain associations--for example, a possible association of ALS with cancer--are given tentative recognition in this classification. In addition, this new classification recognizes geographical clustering and descriptions of unusual motor neuron disorder phenotypes of unknown origin in different parts of the world.
Amyotrophic Lateral Sclerosis↗