The AsTex: clinimetric properties of a new tool for evaluating hand sensation following stroke.

OBJECTIVES: To investigate the clinimetric properties and clinical utility of the AsTex((R)), a new clinical tool for evaluation of hand sensation following stroke. DESIGN: The AsTex((R)) was administered on two occasions separated by a week to appraise test-retest reliability, and by three assessors on single occasion to establish inter-rater reliability. Pilot normative values were collected in an age-stratified sample. Clinical utility was evaluated based on ease of administration, ceiling and floor effects, and responsiveness to sensory recovery. PARTICIPANTS: Test-retest (n = 31) and inter-rater (n = 31) reliability and normative values (n = 95) for the AsTex((R)) were established in neurologically normal participants aged 18-85 years. Test-retest reliability was investigated in 22 individuals a mean of 46 months (range 12-125) post stroke and clinical utility was evaluated in an additional 24 subacute stroke participants a mean of 29.4 days (range 12-41) post stroke. MAIN MEASURE: The AsTex((R)). RESULTS: The AsTex((R)) demonstrated excellent test-retest (intraclass correlation coefficient (ICC) = 0.98, 95% confidence interval (95% CI) = 0.97-0.99) and inter-rater reliability (ICC = 0.81, 95% CI = 0.73-0.87) in neurologically normal participants. Test-retest reliability of the AsTex((R)) in individuals following stroke was excellent (ICC = 0.86, 95% CI = 0.68-0.94). The AsTex((R)) was simple to administer, demonstrated small standard error of measurement (0.14 mm), minimal floor and ceiling effects (12.5% and 8.3%) and excellent responsiveness (standardized response mean = 0.57) in subacute stroke participants. CONCLUSION: The AsTex((R)) is a reliable, clinically useful and responsive tool for evaluating hand sensation following stroke.

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.

Early onset chromosome 14-linked distal myopathy (Laing).

A dominantly inherited form of distal myopathy with onset in early childhood was first reported in a 4-generation Australian family in 1995. In the present report we provide further information on the clinical phenotype and natural history of this myopathy, and on the electromyogram and magnetic resonance imaging findings in affected individuals. The pattern of muscle involvement was similar to that in the 'tibial' forms of distal myopathy such as the Finnish (Udd) and Markesbery-Griggs types, with additional involvement of the finger extensors and of some more proximal limb and neck muscles. However, the age of onset was earlier than in these other myopathies and rimmed vacuoles were not found in biopsies from two affected individuals. Evidence of possible anticipation was found in one branch of the family. The gene locus for this myopathy had been mapped to 14q11.2-q13. The linkage region has been refined to a 24 cM region between D14S283 and D14S49 and mutations have been excluded in the PABP2 gene for oculopharyngeal muscular dystrophy which lies within this region.

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.

Human vitreal prostaglandin levels and proliferative diabetic retinopathy.

PURPOSE: To determine the association of prostaglandins E1 (PGE1), E2 (PGE2), and F2-alpha (PGF2-alpha) with proliferative diabetic retinopathy (PDR) in human vitreous. METHODS: We collected human vitreous samples from eyes undergoing pars plana vitrectomy for proliferative diabetic retinopathy with vitreous hemorrhage (N=13) and for other reasons including macular gliosis and Stage IV idiopathic macular holes (N=7). Vitreal prostaglandins E1, E2, and F2-alpha were measured by radioimmunoassay. RESULTS: Eyes with PDR had significantly lower vitreal levels of PGE1 (74.77 pg/ml +/- 15.70) compared to those without PDR (91.86 pg/ml +/- 13.36) (p=0.025) using t-test analysis. Eyes with PDR also had significantly lower levels of PGE2 (127.52 pg/ml +/- 70.52) compared to those eyes without PDR (194.43 pg/ml +/- 57.10) (p=0.045). In addition, eyes with PDR had significantly lower levels of PGF2-alpha (34.62 pg/ml +/- 11.56) compared to those eyes without PDR (51.43 pg/ml +/- 18.44) (p=0.021). Panretinal photocoagulation in diabetic eyes did not have an effect on vitreal concentrations of PGE1 (p=0.588). PGE2 (p=0.460) and PGF2-alpha (p=0.351), but sample size was too small. CONCLUSIONS: Diabetic eyes with PDR had significantly lower vitreal levels of PGE1, PGE2 and PGF2-alpha compared to controls consistent with decreased production of these prostaglandins by the endothelial cells of diabetic eyes. Laser treatment did not appear to have a significant effect on vitreal concentrations of these prostaglandins, but sample size was small. The lower concentration of these vasodilatory prostaglandins may reflect the vasculature's inability to produce these substances and the vasoconstrictive state of the end-stage diabetic eye with PDR.

Long-term changes in motor cortical organisation after recovery from subcortical stroke.

The present study has investigated the long-term changes in the organisation of the corticomotor projection to the hand in a group of subjects who had sustained a subcortical hemispheric stroke up to 15 years previously and had subsequently recovered normal or near-normal motor function. Transcranial magnetic cortical stimulation (TMCS) was employed to map the topography of the primary corticomotor projection to the hand and to obtain measures of cortical motor threshold, long-latency intracortical inhibition and corticospinal conduction. Changes in motor threshold and in motor-evoked potential (MEP) amplitude and latency in keeping with persisting impairment of conduction in the corticospinal pathway were still present in the majority of subjects, whereas the duration of the post-MEP silent period, reflecting the strength of long-latency intracortical inhibition, was usually normal. Topographic shifts in the corticomotor representation relative to the unaffected side were found in the majority of subjects. In some the shifts were in the mediolateral axis suggesting reorganisation within the primary motor cortex, while in the others anteroposterior shifts were present in keeping with recruitment of premotor or postcentral cortex. The present findings indicate that changes in the physiological properties of the corticomotor projection to the hand are frequently present in subjects who have recovered motor function after a subcortical stroke and may persist indefinitely. We postulate that these changes are the result of reorganisation at cortical level and that cortical reorganisation is one of the processes which contribute to motor recovery after a subcortical lesion and which may compensate for persisting impairment of conduction in the corticospinal pathway.

Exercise therapy in patients with myopathy.

Common impairments experienced by patients with myopathy include muscle weakness, reduced endurance and cardiovascular fitness. Strength-training programmes, incorporating isometric, isotonic or isokinetic exercise, have been shown to improve muscle strength in the short term, without evidence of increased muscle damage using biochemical markers. However, there is some evidence that eccentric exercise may have adverse effects in patients with myopathy. Aerobic training programmes using cycle ergometers or treadmills have demonstrated an improvement in cardiovascular fitness, muscle strength and endurance, again without evidence of increased muscle damage. Further research is needed to determine the optimum training protocols for patients with various types of myopathy, and in particular to improve the ability of patients to be active and independent in daily life.

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 x 10(-6). The prevalence was higher in men (10.9 x 10(-6)) than in women (7.7 x 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 x 10(-6). The results suggest a higher prevalence of IBM than has previously been reported.

Muscle force measured using "break" testing with a hand-held myometer in normal subjects aged 20 to 69 years.

OBJECTIVE: To measure the strength of 17 muscle groups in the upper and lower extremities in a large group of healthy subjects using "break" testing with a hand-held myometer, and to examine the intrasession and intersession reliability of the testing protocol. SUBJECTS AND INSTRUMENTATION: A convenience sample of 20 men and 20 women in each decade of age from 20 to 69 years (n = 200) was tested using a Penny & Giles hand-held myometer. RESULTS: Reliability coefficients were >.85 for both intrasession and intersession reliability, except for the ankle dorsiflexors. Men exerted a significantly greater force than women for all muscle groups. Age, weight, and side of testing were significant predictors of force in the majority of muscle groups. The fifth percentile values, as the lower limit of normal, are reported separately for gender and side of testing for each decade of age. CONCLUSION: Using the testing protocol specified in this study, data from patients with various neuromuscular diseases may be compared with the appropriate gender- and age-matched normal data to accurately identify the presence of weakness.

Novel mutation in the myelin protein zero gene in a family with intermediate hereditary motor and sensory neuropathy.

OBJECTIVES: To determine the molecular basis for autosomal dominant intermediate hereditary motor and sensory neuropathy (HMSN) in a four generation family. The gene defects in families with intermediate HMSN are not known, but it has been suggested that most have X linked HMSN. METHODS: All participating family members were examined clinically. Genomic DNA was obtained from 10 affected and seven unaffected members. Linkage analysis for the known HMSN loci was first performed. Mutations in the peripheral myelin protein zero gene (PMP0) were sought in two affected members, using one unaffected member for comparison, by amplification of the six exons of the gene followed by single strand conformation polymorphism (SSCP) analysis, dideoxy fingerprinting (ddF), and sequencing. Subsequently, the mutation was screened for in all affected and unaffected members in the family using Alu I digestion and in 100 unrelated control subjects using "snap back" SSCP analysis. Sequencing of cDNA from a sural nerve biopsy from an affected member was also performed. RESULTS: The clinical phenotype was of variable severity, with motor nerve conduction velocities in the intermediate range. Linkage to PMP0 was demonstrated. Analysis of genomic DNA and cDNA for PMP0 identified a novel codon 35 GAC to TAC mutation. The mutation produces an inferred amino acid change of aspartate to tyrosine at codon six of the processed protein (Asp6Tyr) in the extracellular domain and was present in all affected family members but not in 100 unrelated controls. CONCLUSIONS: The present findings further extend the range of phenotypes associated with PMP0 mutations and indicate that families with "intermediate" HMSN need not necessarily be X-linked as previously suggested.

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.

Differences in functional magnetic resonance imaging of sensorimotor cortex during static and dynamic finger flexion.

Functional magnetic resonance imaging (fMRI) studies of the human motor system have commonly used movement paradigms which contain a dynamic component; however, the relationship between the fMRI signal for motor tasks with and without a dynamic component is not known. We have investigated the relationship between the fMRI signal during a static finger flexion task and during dynamic finger flexion at 1-3 Hz, each at two levels of force (5% and 10% of maximum voluntary contraction). A small fMRI response could be recorded from only a few subjects during the static tasks. In contrast, a substantial fMRI response occurred during dynamic tasks in all subjects at both levels of force. The fMRI response was not significantly correlated with force or movement rate during the dynamic tasks. It is concluded that the factors responsible for generating an fMRI response are fundamentally different during steady contractions compared to those involving a dynamic component, and that the fMRI signal may be more sensitive to changes in the pattern of neural activation rather than the ongoing firing rate or extent of activation.

Frequency of relapses in patients with polymyositis and dermatomyositis.

The frequency of clinical and biochemical relapses was determined in a group of 50 patients with polymyositis (PM), dermatomyositis (DM), or overlap syndromes who were followed for periods of up to 13 years. Relapses occurred in 30 of the 50 patients (60%) during the period of follow-up. The annual relapse rate was not significantly different in the three groups of patients. Subclinical relapses occurred in each group but were less frequent in the DM than in the PM and overlap groups. Relapses could occur at any time but were more frequent during periods of stable maintenance therapy. There was no correlation between relapses and initial disease severity, delay to diagnosis and commencement of treatment, or any class I or II histocompatibility locus antigen.

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

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.

Immunoglobulin therapy in inflammatory myopathies.

A prospective open label trial of add on therapy with intravenous immunoglobulin (i.v.Ig) was carried out in 16 patients with inflammatory myopathy who had continued to deteriorate or had relapsed on conventional therapy. The response was assessed using isometric myometry, functional scales, MRC grading, and serum creatine kinase concentrations with a three month run in period before commencement of i.v.Ig. Five of seven patients with isolated dermatomyositis or polymyositis and all four patients with an overlap syndrome responded to i.v.Ig with partial or complete remission of disease and normalisation of serum creatine kinase concentrations. None of five patients with inclusion body myositis showed any functional improvement although myometry scores improved in some muscles in one case. It is concluded that i.v.Ig is an effective therapeutic option in patients with drug resistant polymyositis or dermatomyositis. However, further controlled trials are required to confirm the efficacy of this form of treatment and to establish optimal doses and administration regimes.

Pulmonary function testing: detection of invalid performance.

We surveyed physician members of the American Thoracic Society and their technicians regarding indicators of the validity of PFTs. Surveys were returned by 50 physicians and 52 technicians. Both groups felt that consistency of effort and the shape/slope of the curve were important indicators, with behavioral observations rated slightly lower. Approximately 38% of physicians and 19% of technicians felt that they detected 75% or fewer of individuals giving inadequate effort during PFTs. Twenty percent of physicians and 29% of technicians were using quantitative criteria other than those recommended by the 1979 "Snowbird" technical paper to determine acceptability of PFTs. Twenty-eight percent of physicians and 31% of technicians spontaneously indicated that patients pursuing compensation or disability claims for pulmonary disorders were most likely to give suboptimal effort. Empirical research into the impact and detection of suboptimal effort on PFTs is encouraged.

Dominantly inherited proximal myotonic myopathy and leukoencephalopathy in a family with an incidental CLCN1 mutation.

A two generation family of Greek origin with mild myotonia, predominantly proximal muscle weakness, and cataracts compatible with the syndrome of proximal myotonic myopathy, is reported. In addition, brain MRI showed a diffuse leukoencephalopathy in the propositus. Molecular genetic studies showed the R894X mutation in exon 23 of the muscle chloride channel gene in the propositus but in only one of her two clinically affected offspring, indicating that it is not the mutation causing disease in this family.

Monitoring sleep and breathing: methodology. Part I: Monitoring breathing.

There is considerable variation in monitoring techniques and definitions of sleep-disordered breathing. Work underway in the Sleep Heart Health Study may help to clarify these issues. Home and portable monitoring have the potential to improve cost and convenience of diagnosis and treatment of sleep disorders but are currently indicated only in specific instances. Detection and monitoring of pediatric sleep-disoriented breathing varies considerably from that of adults.

Serological evidence for infection with Campylobacter jejuni/coli in patients with multifocal motor neuropathy.

Campylobacter jejuni/coli (CJC) infection has been implicated in the immunopathogenesis of Guillain-Barré syndrome (GBS), acute motor axonal neuropathy (AMAN), and Miller Fisher syndrome (MFS). However, its role in chronic immune mediated neuropathies such as multifocal motor neuropathy (MMN) or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is less clear. Anti-ganglioside antibodies are associated with chronic motor neuropathies such as MMN and IgM anti-GM1, and IgM anti-asialo GM1 antibodies have been shown to cross-react with CJC lipopolysaccharides. Molecular mimicry between CJC and IgG anti-GM1 antibodies has also been suggested. Therefore we have performed a retrospective assessment of anti-CJC-specific IgG, IgM, and IgA antibodies in a cohort of seven patients with clinical and electrophysiologically definite MMN. The control group consisted of 140 healthy blood donors with no history of enteric illnesses. We found elevated titres of anti-CJC-specific IgG in 5 of 7 patients, IgM in 3 of 7 and IgA in 1 of 7. At least 1 anti-CJC antibody was elevated in 6 of 7 patients, and 3 patients had elevations of both IgG and IgM antibodies. Three patients had significantly elevated titres of anti-ganglioside antibodies without a clear relationship to the anti-CJC titres. Therefore antibodies specific for CJC were found more frequently than expected in patients with MMN. Prior or ongoing infection with CJC may play a role in the actiopathogenesis of MMN.