Beverley A. Phillips

Gait and balance impairment in early multiple sclerosis in the absence of clinical disability

This study evaluated the gait and balance performance of two clinically distinct groups of recently diagnosed and minimally impaired multiple sclerosis (MS) patients (Expanded Disability Status Scale range 0- 2.5), compared to control subjects. Ten MS patients with mild pyramidal signs (Pyramidal Functional Systems 1.0), 10 MS patients with no pyramidal signs (Pyramidal Functional Systems 0) and 20 age- and gender-matched control subjects were assessed using laboratory-based gait analysis and clinical balance measures. Both MS groups demonstrated reduced speed and stride length (P < 0.001), and prolonged double limb support (P<0.02), compared to the control group, along with alterations in the timing of ankle muscle activity, and the pattern of ankle motion during walking, which occurred independent of gait speed. The pyramidal MS group walked with reduced speed (P=0.03) and stride length (P=0.04), and prolonged double limb support (P=0.01), compared to the non-pyramidal group. Both MS groups demonstrated concomitant balance impairment, performing poorly on the Functional Reach Test compared to the control group (P<0.05). The identification of incipient gait and balance impairment in MS patients with recent disease onset suggests that motor function may begin to deteriorate in the early stages of the disease, even in the absence of clinical signs of pyramidal dysfunction.

Idiopathic inflammatory myopathies: epidemiology, classification, and diagnostic criteria

Epidemiologic studies have helped to define the prevalence and incidence of PM, DM, and IBM and have highlighted differences in risk between men and women and in the age at onset for the different forms of myositis. Additionally, these studies have shown that there is a substantially higher risk of PM and DM in certain racial groups which is likely to be genetically determined. These differences are all likely to be fundamental in terms of the pathogenesis of these diseases but, as yet, their full significance remains uncertain. They do, however, suggest that the interplay between genetic and environmental initiating factors is different in the three disorders. Additional population-based studies in homogeneous racial groups, in parallel with studies of susceptibility genes for autoimmune disease, such as those encoding the MHC and inflammatory cytokines, are needed to throw further light on the role of genetic factors in the pathogenesis of the IIMs [47]. Because of the paucity of epidemiologic data on IBM, further studies are required to determine the degree of variation in prevalence in different populations and racial groups, as well as the consistency of the male association and age spectrum of manifestations of the disease. The particularly strong association with DR3 in this form of IIM [48] clearly points to the importance of genetic factors in pathogenesis, but further studies of DR3-associated genes in the MHC and of other candidate genes are needed to define more precisely the genes that convey susceptibility to the disease in different racial groups. Epidemiologic studies also have the potential to identify environmental factors that may play a part in disease initiation in genetically susceptible individuals. Seasonal patterns of disease onset have been reported, particularly in patients with DM [49-51] as well as seasonal variation in the frequency of relapses [52], pointing to the probable involvement of intercurrent infections, ultraviolet light exposure, or other environmental factors in disease initiation and reactivation. Further prospective studies are required to determine the contribution of environmental exposures and how they interact with genetic susceptibility factors to lead to myositis. One of the major limitations of a number of the previous epidemiologic studies is the lack of precision in the diagnostic criteria used and the classification of cases of IIM. The Bohan and Peter criteria [1] which were used in most studies after 1975, were introduced before IBM was recognized as an entity distinct from PM; most of the published incidence and prevalence figures for PM are therefore likely to be inaccurate. Multicentered, interdisciplinary, prospective studies, incorporating comprehensive clinical, laboratory, and pathologic information, are needed to develop and validate better diagnostic and classification criteria and to determine the true prevalence and incidence of the many forms of IIM.

Inflammatory myopathies : clinical, diagnostic and therapeutic aspects

The three major forms of immune‐mediated inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and inclusion‐body myositis (IBM). They each have distinctive clinical and histopathologic features that allow the clinician to reach a specific diagnosis in most cases. Magnetic resonance imaging is sometimes helpful, particularly if the diagnosis of IBM is suspected but has not been formally evaluated. Myositis‐specific antibodies are not helpful diagnostically but may be of prognostic value; most antibodies have low sensitivity. Muscle biopsy is mandatory to confirm the diagnosis of an inflammatory myopathy and to allow unusual varieties such as eosinophilic, granulomatous, and parasitic myositis, and macrophagic myofasciitis, to be recognized. The treatment of the inflammatory myopathies remains largely empirical and relies upon the use of corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all of which have nonselective effects on the immune system. Further controlled clinical trials are required to evaluate the relative efficacy of the available therapeutic modalities particularly in combinations, and of newer immunosuppressive agents (mycophenolate mofetil and tacrolimus) and cytokine‐based therapies for the treatment of resistant cases of DM, PM, and IBM. Improved understanding of the molecular mechanisms of muscle injury in the inflammatory myopathies should lead to the development of more specific forms of immunotherapy for these conditions. Muscle Nerve 27:407–425, 2003

Isometric force-related activity in sensorimotor cortex measured with functional MRI.

Abstract Isometric force-related functional magnetic resonance imaging (fMRI) signals from primary sensorimotor cortex were investigated by imaging during a sustained finger flexion task at a number of force levels related to maximum voluntary contraction. With increasing levels of force, there was an increase in the extent along the central sulcus from which a fMRI signal could be detected and an increase in the summed signal across voxels, but these parameters were related in such a way that the signal from each voxel was similar for each level of force. The results suggest that increased neuronal firing and recruitment of corticomotor cells associated with increased voluntary isometric effort are reflected in an expansion of a relatively constant fMRI signal over a greater volume of cortex, rather than an increase in the magnitude of the response in a particular circumscribed region, possibly due to perfusion of an increase in oxygen-enriched blood over a wider region of the cortex.

Reliability of pelvic floor muscle strength assessment using different test positions and tools

AIMS The aims of this study were to determine the intra-therapist reliability for digital muscle testing and vaginal manometry on maximum voluntary contraction strength and endurance. In addition, we assessed how reliability varied with different tools and different testing positions. METHODS Subjects included 20 female physiotherapists. The modified Oxford scale was used for the digital muscle testing, and the Peritron perineometer was used for the vaginal resting pressure and vaginal squeeze pressure assessments. Strength and endurance testing were performed. The highest of the maximum voluntary contraction scores was used in strength analysis, and a fatigue index value was calculated from the endurance repetitions. Bent-knee lying, supine, sitting, and standing positions were used. The time interval for between-session reliability was 2-6 weeks. RESULTS Kappa values for the between-session reliability of digital muscle testing were 0.69, 0.69, 0.86, and 0.79 for the four test positions, respectively. Intra-class correlation coefficient (ICC) values for squeeze pressure readings for the four positions were 0.95, 0.91, 0.96, and 0.92 for maximum voluntary contraction, and 0.05, 0.42, 0.13, and 0.35 for endurance testing. ICC values for resting pressure were 0.74, 0.77, 0.47, and 0.29. CONCLUSIONS Reliability of digital muscle testing was very good in sitting and good in the other three positions. vaginal resting pressure demonstrated very good reliability in all four positions for maximum voluntary contraction, but was unreliable for endurance testing. Vaginal resting pressure was not reliable in upright positions. Both measurement tools are reliable in certain positions, with manometry demonstrating higher reliability coefficients.

Physiological studies of the corticomotor projection to the hand after subcortical stroke

OBJECTIVE The mechanisms which lead to recovery of motor function after a stroke are poorly understood. Functional reorganization of cortical motor centres is thought to be one of the factors which may contribute to recovery. We have investigated the extent of reorganization which occurs at the level of the primary motor cortex after a lesion of the corticospinal pathway. METHODS Transcranial magnetic stimulation was used to map the topography of the primary corticomotor projection to the abductor pollicis brevis muscle and study changes in cortical motor thresholds and corticospinal conduction in a group of 20 subjects with subcortical infarcts of varying duration (1 week to 15 years) and varying degrees of motor deficit. RESULTS There was a broad correlation between motor evoked potential (MEP) amplitude and motor thresholds on the one hand and the severity of motor deficit and site and extent of the lesion on the other. Shifts in the cortical motor maps were found in both early and late cases, irrespective of the site of the lesion, but were more frequent in the longer standing cases. Shifts were usually along the mediolateral axis but anteroposterior shifts were found in some late cases. CONCLUSION Our findings indicate that there is functional reorganization of the corticomotor projection in subjects who regain a degree of motor control following a subcortical lesion sparing the motor cortex.

Prevalence of sporadic inclusion body myositis in Western Australia

A 10‐year retrospective review was conducted to ascertain the prevalence of inclusion body myositis (IBM) in Western Australia. Seventeen patients with sporadic IBM aged 45–90 years were identified and the prevalence of IBM was calculated to be 9.3 × 10−6. The prevalence was higher in men (10.9 × 10−6) than in women (7.7 × 10−6). The mean age of onset of IBM was 56.6 years, and the mean delay between onset of symptoms and diagnosis was 4.4 years. The age‐adjusted prevalence over the age of 50 years was 35.3 × 10−6. The results suggest a higher prevalence of IBM than has previously been reported.

Patterns of muscle involvement in inclusion body myositis: Clinical and magnetic resonance imaging study

The differential patterns of muscle involvement in the upper and lower limbs in sporadic inclusion body myositis (sIBM) were examined in 18 patients using both quantitative and manual muscle testing as well as magnetic resonance imaging (MRI) in 9 patients. Weakness of the quadriceps femoris and the forearm flexors was present in most patients, but there was considerable variability in the patterns and severity of muscle involvement. MRI disclosed preferential patterns of muscle involvement within functional groups such as the quadriceps femoris, in which there was severe involvement of the vasti with relative sparing of the rectus femoris, and the triceps surae, in which selective involvement of the medial gastrocnemius was common. Involvement of flexor digitorum profundus on MRI was found in only one third of patients. The results emphasize the variability in the clinical phenotype and differential susceptibility of muscles to the disease process in sIBM.

Treatment of inflammatory myopathies

The treatment of the immune‐mediated inflammatory myopathies remains largely empirical. Corticosteroids are usually effective in polymyositis and dermatomyositis but may need to be combined with methotrexate or azathioprine in some patients. Intravenous immunoglobulin (IVIg) is effective as add‐on therapy in some patients not adequately controlled with steroids or immunosuppressive agents, but further controlled trials of IVIg are necessary to define the indications and optimal dose regimens. Cyclophosphamide, cyclosporin, or chlorambucil may be effective in patients with refractory polymyositis or dermatomyositis. Low‐dose whole body or lymphoid irradiation is a last option in severely disabled patients resistant to all other treatments. As a small proportion of patients with inclusion body myositis respond to corticosteroid or immunosuppressive therapy, a 3–6‐month trial of such therapy is justified in this condition. More specific immunotherapy for these disorders awaits identification of the target antigens and further clarification of the immunopathogenetic mechanisms.

Sporadic inclusion body myositis: Phenotypic variability and influence of HLA-DR3 in a cohort of 57 Australian cases

Background and Aims: There have been few studies of the variability in the clinical phenotype in sporadic inclusion body myositis (sIBM) and it is not known whether the human leucocyte antigen (HLA) haplotype influences the phenotype and course of the disease. We studied a large cohort of patients with sIBM in order to determine the degree of phenotypic variability and different modes of presentation, as well as the influence of HLA haplotypes. Method: A cross-sectional study of 57 biopsy-proven sIBM cases from three Australian centres was performed. Patients were interviewed and examined by a single investigator, and had HLA typing and autoantibody studies. Results: Although the initial symptoms in the majority of cases were attributable to quadriceps weakness (79%), a proportion of patients presented due to finger weakness (12%), foot drop (7%) or dysphagia (1.8%). Although the majority had the classic combination of quadriceps and forearm muscle involvement, some patients had predominantly forearm weakness with sparing of the quadriceps, or severe involvement of the anterior tibial muscles. Asymmetrical involvement was common (82%), particularly of the forearm muscles, with the non-dominant side being more severely affected in most cases. Carriage of the HLA-DRB1*0301 (DR3) allele was associated with lower quadriceps muscle strength and a more rapid decline in strength. Conclusions: The findings emphasise the variability in the mode of presentation, patterns of muscle involvement and clinical course of sIBM in this population, and indicate that the HLA-DRB1*0301 (DR3) allele may influence the rate of progression as well as susceptibility to the disease.