Michael Swash

INJURY TO INNERVATION OF PELVIC FLOOR SPHINCTER MUSCULATURE IN CHILDBIRTH

71 women delivered at St Bartholomews Hospital, London, were studied by electrophysiological tests of the innervation of the external anal sphincter muscle and by manometry. The investigations were done 2-3 days after delivery and again, in 70% of these women, 2 months later. Faecal and urinary incontinence developing after vaginal delivery has been thought to be due to direct sphincter division, or muscle stretching, but the results of the study suggest that in most cases this incontinence results from damage to the innervation of the pelvic floor muscles.

Electrodiagnostic criteria for diagnosis of ALS

A consensus meeting was held to determine the best use and interpretation of electrophysiological data in the diagnosis of ALS. The utility of needle EMG and nerve conduction studies was affirmed. It is recommended that electrophysiological evidence for chronic neurogenic change should be taken as equivalent to clinical information in the recognition of involvement of individual muscles in a limb. In addition, in the context of a suspected clinical diagnosis of ALS, fasciculation potentials should be taken as equivalent to fibrillation potentials and positive sharp waves in recognising denervation. The importance of searching for instability in fasciculation potentials and in motor unit potentials in ALS is stressed. These changes in the interpretation of electrophysiological data render obsolete the category Probable Laboratory-Supported ALS in the modified El Escorial diagnostic criteria for ALS. Methods for detection of upper motor neuron abnormality appear sensitive but require further study, particularly regarding their value when clinical signs of upper motor neuron lesion are uncertain.

Controversies and priorities in amyotrophic lateral sclerosis.

Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72. This breakthrough provides an opportunity to re-evaluate longstanding concepts regarding the cause and natural history of ALS, coming soon after the pathological unification of ALS with frontotemporal dementia through a shared pathological signature of cytoplasmic inclusions of the ubiquitinated protein TDP-43. However, with profound clinical, prognostic, neuropathological, and now genetic heterogeneity, the concept of ALS as one disease appears increasingly untenable. This background calls for the development of a more sophisticated taxonomy, and an appreciation of ALS as the breakdown of a wider network rather than a discrete vulnerable population of specialised motor neurons. Identification of C9orf72 repeat expansions in patients without a family history of ALS challenges the traditional division between familial and sporadic disease. By contrast, the 90% of apparently sporadic cases and incomplete penetrance of several genes linked to familial cases suggest that at least some forms of ALS arise from the interplay of multiple genes, poorly understood developmental, environmental, and age-related factors, as well as stochastic events.

Pathogenesis of ano-rectal incontinence ☆: A histometric study of the anal sphincter musculature

Type 1 fibre predominance was found in the external anal sphincter, puborectalis and levator ani muscles of 17 control subjects, and of 16 patients with ano-rectal incontinence. In the external anal sphincter and puborectalis muscles of the control subjects the mean diameter of Type 2 fibres was slightly greater than that of Type 1 fibres, but in the levator ani muscles of control female subjects the mean diameter of Type 1 fibres was much greater than that of Type 2 fibres. In the patients with anorectal incontinence there was marked hypertrophy of fibres of both histochemical types. This was most marked in the puborectalis and external anal sphincter muscles. In 12 of the 16 incontinent patients there were histological and statistical features consistent with a neurogenic disorder. These histometric studies provide a quantitative basis for physiological and pathological studies of these muscles in incontinence and other anorectal disorders.

Effects of aging on the anorectal sphincters and their innervation

The effects of aging on the pelvic floor musculature and its innervation are described in 102 women and 19 men without colorectal or pelvic floor disease. In the women, a reduction in anorectal “squeeze” pressure was found in the fifth decade, but the resting anal pressure remained unchanged. This reduction in squeeze anal pressure was accompanied by an increase in the mean pudendal nerve terminal motor latency, indicating damage to this nerve, and increased perineal descent in the resting and straining positions. The fiber density, recorded by single fiber electromyography in the external anal sphincter muscle, a muscle innervated by the pudendal nerves, was increased in the sixth decade, indicating the later development of compensatory reinnervation in this muscle. The interrelation of aging, menopausal effects, and parity in these changes is difficult to define from currently available data, but the authors suggest, from other evidence, that menopausal effects may be relevant.

Damage to the innervation of the pelvic floor musculature in chronic constipation

Constipation and defecation straining have been implicated in the pathogenesis of anorectal incontinence. We have studied 24 women with chronic constipation and 20 age- and parity-matched control subjects. Electrophysiologic techniques were used to study the innervations of the puborectalis and external anal sphincter muscles. The results show that damage can occur to the nerve supply of both these muscles in chronic constipation, and that this probably is due to perineal descent during defecation straining.

Consensus guidelines for the design and implementation of clinical trials in ALS

BACKGROUND In 1994 consensus guidelines were developed for conducting clinical trials in ALS. With growing experience in clinical trials, it has become clear that a number of further guidelines were needed. METHODS Under the auspices of the World Federation of Neurology Committee on Research, a multinational group of neurologists, statisticians, patient advocates, representatives from the pharmaceutical industry as well as regulatory agencies developed consensus about a number of revisions to the existing guidelines during a 2 day conference in April 1998. RESULTS Expanded areas of focus include greater protection of patient rights, more detailed guidelines for outcome measures statistical analyses, disclosure of study results and improved interaction between investigators and the corporate sector. COMMENT Substantial progress has been made in standardizing and improving the quality of clinical trials in ALS through these consensus guidelines.

Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis.

BACKGROUND An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS. METHODS 42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzkes expanded disability status scale (EDSS), Hausers Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks. FINDINGS There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment. INTERPRETATION Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost.

Unifying concept of pelvic floor disorders and incontinence.

Denervation of pelvic floor sphincter muscles is a feature of pelvic floor disorders. When severe, it may be accompanied by stress incontinence of faeces, or of urine. The extent of chronic partial denervation of these pelvic floor muscles can be quantified by electromyography (EMG), and its cause identified by electrophysiological studies of the motor innervation of these striated muscles. Damage to this innervation is often initiated by childbirth, but appears to progress during a period of many years so that the functional disorder usually presents in middle life. Incontinence develops in some patients, but not in others. This can be predicted by the severity of the abnormalities found in EMG studies of the pelvic sphincter musculature and motor latency studies of its innervation. The results of such investigations in the six common types of pelvic floor disorder are presented. Recognition of the causative factors leading to damage to the innervation of the pelvic sphincter muscles implies new approaches to treatment and to prevention of pelvic floor disorders and incontinence.

Central motor conduction in multiple sclerosis: evaluation of abnormalities revealed by transcutaneous magnetic stimulation of the brain.

Magnetic stimulation of the brain and spinal column was used to assess conduction in the descending central motor pathways controlling arm and leg muscles of 20 patients with multiple sclerosis, and 10 normal subjects. The multiple sclerosis patients had relapsing and remitting disease but all were ambulant and in stable clinical remission. Increased central motor conduction times (CMCTs), up to three times normal, were frequently encountered in multiple sclerosis patients and in leg muscles these correlated closely with clinical signs of upper motor neuron disturbance; in the upper limb muscles a higher proportion of subclinical lesions was present. Weak muscles were almost invariably associated with abnormal central conduction but increased CMCTs were also found for 52 of the 104 muscles with normal strength. CMCTs for lower limb muscles were directly related (p less than 0.005) to functional motor disability (Kurtzke and Ambulatory Index Scales). No patient developed clinical evidence of relapse during follow-up of at least 8 months. Magnetic brain stimulation is easy to perform, painless, and safe, and provides clinically relevant information in the diagnosis and monitoring of multiple sclerosis patients.