Biomedical subjects

P R Fawcett

Publications and source records attributed to P R Fawcett.

At least 19 recordsLinked to original sources

PubMed2001

A novel autosomal dominant distal myopathy with early respiratory failure: clinico-pathologic characteristics and exclusion of linkage to candidate genetic loci.

We describe a novel autosomal dominant myopathy presenting in mid-adult life with tibialis anterior weakness. We carried out a detailed clinical assessment of 24 individuals spanning three generations, documenting pathologic features of the muscles in 7 of the 11 affected individuals, including an autopsy study on one case. The second generation of affected individuals presented at an earlier age, and the disease progressed more rapidly than in the first generation. Lung function tests revealed progressive global respiratory muscle weakness detectable from the time of presentation, with preferential diaphragmatic involvement in some cases. Hip girdle and shoulder girdle weakness appeared later in the disease course. We observed a striking correlation between the clinical and pathological features. Clinically unaffected muscles had minimal pathologic change. Fiber splitting, eosinophilic inclusions, and vacuoles with basophilic rims were seen in moderately affected muscles, and fat and fibrous connective tissue replaced muscle fibers in the severely involved muscles. The inclusions were Congophilic and reacted with antibodies to desmin, beta-amyloid, and phosphorylated tau protein. The disease was not linked to any of the known loci associated with distal myopathies, confirming that the disorder in this family is both genetically and phenotypically distinct.

Adult↗

PubMed1999

Variation in diagnostic strategy of the EMG examination--a multicentre study.

OBJECTIVES: In order to improve the universal quality of the EMG examination, knowledge about the variation among physicians is needed. METHODS: The variation among physicians in diagnostic strategy or criteria for diagnosing was analysed from a multicentre database with 940 EMG examinations sampled by seven physicians from six laboratories in Europe. RESULTS: For the whole group of patients as well as for the subgroup of patients with polyneuropathy, variation among physicians in examination techniques, number of examined structures per patient and number of abnormal structures per patient required for a diagnosis was found. Some of the variation may be explained by use of different techniques, which showed differences in sensitivity, while some of the variation may be due to differences in diagnostic strategy and criteria for diagnosing. CONCLUSIONS: The study indicates a need for development and revision of international guidelines for EMG practice although implementation of standards requires caution.

Decision Making↗

PubMed1997

Electromyography in myopathy.

Electromyography (EMG) is the most common procedure for screening patients with myopathies and remains the most important technique for assessing the course of the disease over time. Fibrillation potentials, positive sharp waves, myotonic or complex repetitive discharge, as well as polyphasic potentials are non specific and can occur in both myopathic and neurogenic lesions. The most sensitive and specific parameter for myopathy in conventional EMG is the decreased duration of motor unit potentials (MUP), but this can also be seen in disorders of the terminal motor fibers or the neuromuscular junction. More advanced techniques such as single fiber EMG, macro EMG, scanning EMG and turns/amplitude analysis have opened additional possibilities for analysis of the motor unit and the interference pattern, by which both the sensitivity to early changes and specificity for myopathic alterations is increased. The importance of combining different techniques to improve diagnostic yield and specificity is stressed.

Electromyography↗

PubMed1997

Utrophin abundance is reduced at neuromuscular junctions of patients with both inherited and acquired acetylcholine receptor deficiencies.

Congenital myasthenic syndromes are a heterogeneous group of conditions in which muscle weakness resulting from impaired neuromuscular transmission is often present from infancy. One form of congenital myasthenic syndrome is due to a reduction of the number of acetylcholine receptors (AChRs) at the neuromuscular junction. We describe four new cases of AChR deficiency, characterized by a reduction in both miniature endplate potential amplitude and AChR abundance accompanied by elongation of the neuromuscular junction and some decrease in postsynaptic folding. A number of cytoplasmic proteins are normally associated with the postsynaptic membrane and may contribute to the clustering of AChRs at the neuromuscular junction. We therefore investigated the expression of several of these proteins in these AChR-deficiency patients. In each patient, immunolabelling of the neuromuscular junction for rapsyn, dystrophin, beta-dystroglycan and a form of beta-spectrin was strong but that for utrophin was markedly reduced or absent. This suggested that a defect in utrophin expression might underlie the congenital AChR deficiency. However, a reduction in utrophin labelling was also seen in three patients with adult acquired autoimmune myasthenia gravis in whom AChR loss results directly from the extracellular binding of autoantibodies. We conclude that the loss of AChRs in AChR deficiency does not result from the absence of rapsyn or beta-dystroglycan and that reduction of utrophin is probably secondary to the loss of AChRs. The possible role of AChRs and/or utrophin in determining the extent of postsynaptic folding is discussed.

Action Potentials↗

PubMed1995

Neuromuscular effects of Papuan Taipan snake venom.

Snakebite is a cause of significant morbidity in Central Province, Papua New Guinea. Three adult patients with clinical evidence of neurotoxicity following envenomation by the Papuan taipan had serial neurophysiological examinations over the course of their subsequent hospitalization. All required artificial ventilation for 2.5 to 5 days. The compound muscle action potential (CMAP) amplitudes declined over the first 2 to 4 days after envenoming and then gradually increased in parallel with clinical recovery. Repetitive stimulation studies revealed a distinctive pattern of abnormality. Activation resulted in brief potentiation of the CMAP followed by significantly greater decrement than observed at rest. This effect lasted up to 30 minutes and was not altered after intravenous edrophonium. Single-fiber electromyographic recordings during the recovery phase of the illness were abnormal with marked blocking and increased jitter. All patients were able to return home.

Adult↗

PubMed1993

KANDID--an EMG decision support system--evaluated in a European multicenter trial.

KANDID is an advanced EMG decision support system dedicated to the support of the clinical neurophysiologist during EMG examinations. It has facilities for test planning, automatized and structured data interpretation, EMG diagnosis, explanation, and reporting. In a prospective European multicenter field trial, the agreement levels between clinical neurophysiologists and KANDID's diagnostic statements were measured under ordinary clinical EMG practice. KANDID was assessed in 159 individual patient EMG examinations by nine clinical neurophysiologists at seven different EMG laboratories. The reasoning of KANDID was considered understandable for the examiners in 80-90% of cases. The agreement level for the electrophysiological states of muscles and nerves between KANDID and the individual examiners was, on average, 81%. The corresponding diagnostic agreement with KANDID was, on average, 61%. A pronounced interexaminer variation in the agreement level related to the different EMG centers was observed. All Danish and Belgian examiners agreed with KANDID in more than 50% of their cases with regard to the EMG diagnosis, while the English examiners were in agreement with KANDID in 50% or less of their cases. These differences were possibly due to differences in epidemiology, examination techniques, control material, and examination planning strategies. It is concluded that it is possible to transfer systems like KANDID out of their development sites and apply them successfully if they can be locally customized by the clinical end users via editors.

Decision Making, Computer-Assisted↗

PubMed1993

Repetitive nerve stimulation of anconeus in the assessment of neuromuscular transmission disorders.

Repetitive nerve stimulation of the anconeus muscle is described. Control studies showed the test to be reliable and well tolerated over a range of stimulus frequencies and train lengths. Sixty-one patients with primary disorders of neuromuscular transmission were tested. Repetitive nerve stimulation of anconeus was abnormal in 2 of 21 patients with ocular myasthenia, but showed a significant decrementing response in 16 of 30 patients with generalized myasthenia gravis. In comparison with other muscles, repetitive nerve stimulation of anconeus was more sensitive than abductor digiti minimi, but equally sensitive as deltoid. The test may also be used to help characterize other disorders of neuromuscular transmission such as congenital myasthenia or the Lambert-Eaton myasthenic syndrome. Compared with single fibre EMG on extensor digitorum communis, repetitive stimulation of anconeus was usually, but not always, a less sensitive method of detecting a neuromuscular transmission disorder.

Action Potentials↗

PubMed1992

Electromyographic abnormalities in the urethral and anal sphincters of women with idiopathic retention of urine.

Previous concentric needle studies of the urethral sphincter in women with idiopathic urinary retention have found evidence of denervation and reinnervation as well as abnormal patterns of muscle fibre discharge--complex repetitive discharges (CRDs). In order to test the hypothesis that these abnormalities represented a more widespread disease process of pelvic floor function, we carried out an electromyographic (EMG) study of both anal and urethral sphincters in 18 women with idiopathic urinary retention. The urethral sphincter EMG was abnormal in 15 patients. These abnormalities included polyphasic and long duration potentials. Complex repetitive discharges were identified in 8 women. However, abnormalities of the anal sphincter were found in 14 of the 15 patients with abnormal urethral sphincter EMGs, polyphasic and abnormally long duration potentials being found in the anal sphincters of all 14 patients. In addition, 7 of the 8 women who had complex repetitive discharges in the urethral sphincters had similar complex repetitive discharges in their anal sphincters. Women with complex repetitive discharges had a significantly greater proportion of abnormal potentials than women with no such repetitive discharges. These results support the previous findings of electromyographic urethral sphincter abnormalities in women with idiopathic urinary retention, but also suggest that these abnormalities reflect a widespread disease process involving the pelvic floor in such patients.

Adult↗

PubMed1992

Structure and function of neuromuscular junctions in the vastus lateralis of man. A motor point biopsy study of two groups of patients.

The properties of neuromuscular junctions (NMJs) in the vastus lateralis of man have been studied in motor point biopsy samples and compared with those reported for lower vertebrates (frogs and mice). The patients studied had no convincing evidence of a primary disturbance of neuromuscular transmission or other neurogenic component. Morphological studies were made using a variety of methods at the light- and electron-microscope levels. The size of the presynaptic nerve terminal and the area of postsynaptic specialization were smaller, relative to the size of the muscle fibres, than in the lower vertebrates. In contrast, the extent of postsynaptic folding was greater. Intracellular recordings from single muscle fibres showed that the duration of synaptic currents was longer than in most other vertebrates so far studied and that the number of transmitter 'quanta' released by a single nerve impulse, about 20, was lower, probably reflecting the small size of the presynaptic terminals. The hypothesis is discussed that in man, a relatively weak effect of transmitter on the muscle fibre surface is amplified by voltage-dependent sodium channels which have been shown in the rat to be concentrated in the depths of the synaptic folds. The implications of this hypothesis for the interpretation of pathological findings in myasthenic syndromes are also discussed.

Adolescent↗

PubMed1991

Familial infantile myasthenia: a diagnostic problem.

The authors report the diagnostic difficulties experienced with two siblings presenting with recurrent apnoeic attacks caused by the rare condition, familial infantile myasthenia. Standard repetitive nerve stimulation studies were normal in both cases, while changes typical of a subacute neurogenic condition were noted on concentric needle electromyography in one. A 14-day course of pyridostigmine did not elicit any clinical improvement in the elder sibling, in whom tracheomalacia was diagnosed by chest fluoroscopy and bronchoscopy. This infant died at the age of 11 months with hypoxic brain-damage after a severe apnoeic episode. For the second sibling, a positive decremental response was obtained in the hypothenar muscles only after two minutes continuous 10 Hz stimulation of the ulnar nerve. This child has responded well to treatment with pyridostigmine.

Chromosome Aberrations↗

PubMed1989

The quadriceps femoris muscle in 20-70-year-old subjects: relationship between knee extension torque, electrophysiological parameters, and muscle fiber characteristics.

Comparisons have been made between torque (isometric and isokinetic), electrophysiological (SFEMG, Macro EMG), and muscle fiber characteristics in the vastus lateralis muscle of both legs in healthy subjects aged between 20 and 70 years. Torque was greater in males and decreased with age in both sexes. Multifactorial analysis showed a positive correlation between torque, body surface area, and mean fiber area. These variables explained only about 30-40% of the torque changes. The electrophysiological parameters (Marco EMG amplitudes and fiber density) revealed evidence of reinnervation, indicating preceeding denervation and therefore loss of motor units. It was concluded that this fall out of motor units also contributes to the reduction in torque, when compensatory reinnervation begins to fall. Other factors, such as reduction in muscle fiber contractility, metabolic factors, and central factors, may also play a role in age-related reduction in torque.

Adult↗

PubMed1987

F-response frequency in motor neuron disease and cervical spondylosis.

During a train of 200 stimuli, F-response frequency, frequency of identical responses, and F-response shape were studied in the ulnar nerve of 17 patients with motor neuron disease (MND) and 16 patients with cervical spondylosis (CS). In MND patients, F-response frequency varied between 5% and 96% with a median of 39% which was significantly lower than controls (p less than 0.001), and showed a significant rank correlation with the M-response amplitude (r = 0.62, p less than 0.004). Identical responses occurred more frequently than in controls (median 30.8%, p less than 0.001). F-response frequency was normal in CS patients (median 76.3%, range 35% to 97%), but the frequency of identical responses (median 6.3%) was higher than normal (p less than 0.01). Reduced F-response frequency in MND was thought to reflect loss of lower motor neurons, while the presence of spasticity was probably the major factor underlying the increased frequency of identical responses in both disorders. F-response shape tended to be simpler in MND and rather more complex in CS patients than controls.

Adult↗

PubMed1987

Demyelinating neuropathy due to primary IgM kappa B cell lymphoma of peripheral nerve.

A 53-year-old man presented with a painful, demyelinating sensorimotor peripheral neuropathy with lymphomatous infiltration on sural nerve biopsy, but no evidence of systemic lymphoma. The neuropathy responded to cytotoxic therapy. Seven years later he developed generalized lymphadenopathy due to B cell lymphoplasmacytoid lymphoma, with a subpopulation of cells expressing a monoclonal pattern of IgM kappa. The lymphomatous infiltrate in the original nerve biopsy showed similar monoclonal IgM kappa reactivity. The mechanism of demyelination of the peripheral nerves may be similar to that described in patients with IgM kappa monoclonal gammopathies.

B-Lymphocytes↗

PubMed1986

F-responses in syringomyelia.

Motor and sensory nerve conduction and various F-response parameters have been examined in the median and ulnar nerves bilaterally in 22 patients with syringomyelia. Excluding those nerves with isolated peripheral lesions, motor and sensory conduction was normal in the distal nerve segments, except for one subject in whom severe wasting of the muscles was associated with slowed motor velocities. Minimum and/or maximum F-response latencies were increased in one or more nerves in 16 of the 22 cases, which was attributed to disturbed function of anterior horn cells and the intraspinal segment of the motor fibres, or mild subclinical nerve trauma. There was a tendency for F-response amplitude and duration to be increased, probably reflecting the combined effects of spasticity and enlargement of motor units due to reinnervation.

Adult↗

PubMed1986

Mitochondrial myopathies. A clinico-pathological study of cases with and without extra-ocular muscle involvement.

The clinical and pathological features of 28 patients with mitochondrial myopathy were reviewed. The cases were divided into a group with involvement of the extra-ocular muscles alone or with limb muscle involvement, and a group with a facioscapulohumeral syndrome or generalised weakness without extra-ocular muscle involvement. Cardiac and central nervous system manifestations occurred particularly in the first group which included six patients with multisystemic features and two with the complete Kearns-Sayre syndrome. Diabetes mellitus occurred in the second group only. Quantitative histology on limb muscle biopsies showed a higher proportion of fibres with abnormal mitochondrial aggregates in the second group. No one type of mitochondrial inclusion or other ultrastructural change was specific for either group of cases. The findings illustrate the clinical heterogeneity of cases of mitochondrial myopathy and the lack of specificity of any of the myopathological changes for different subgroups of patients.

Adolescent↗

PubMed1985

F-response behaviour in a control population.

Various parameters of the F-response including minimal and maximal latency, chronodispersion, amplitude (absolute and F%M) and duration have been determined for a sample of 20 responses in the median and ulnar nerves bilaterally in normal healthy subjects of both sexes aged between 12 to 81 years. Side to side comparisons revealed no significant differences in any of the parameters except for slightly longer minimum F latencies in the right median nerve. Strong correlations were found between minimal and maximal F latencies and height, while much weaker relationships were found between these parameters and age. There was a slight but significant relationship between F%M and age, but no age or sex related changes were noted for any of the remaining F-response parameters.

Adolescent↗

PubMed1985

F-responses: a study of frequency, shape and amplitude characteristics in healthy control subjects.

Characteristics of the surface recorded F-response, including frequency, occurrence of identical responses, shape and amplitude have been investigated in the ulnar nerve of control subjects. During a train of 200 stimuli, F-response frequency varied between 50% and 93% in different subjects with a mean of 79%. The vast majority of responses (96.6%) occurred only once; of those responses which repeated, 89.5% occurred between 2-5 times, 9% between 6-10 times and only 1.5% 11 or more times. F-response shape was variable, the majority containing two or more negative peaks. F-response amplitudes tended to be a relatively small proportion of the compound M-response, with median F%M values ranging from 0.8% to 4%. The data suggest that a large proportion of surface recorded F-responses following supramaximal stimulation are composed of recurrent discharges derived from more than one motor unit.

Adult↗

PubMed1983

Polyneuropathy in occult hypothyroidism.

A patient who developed symptoms and signs of a polyneuropathy was found to have hypothyroidism, though this diagnosis was not clinically suspected. Treatment with thyroxine resulted in resolution of his symptoms and restored his nerve conduction studies to normal.

Humans↗