Delayed amantadine toxicity causing apparent progression of multiple sclerosis.

BACKGROUND: Amantadine is sometimes used to treat fatigue in multiple sclerosis. OBJECTIVES: To report a patient with secondary progressive multiple sclerosis (SPMS) who developed late-onset side effects of amantadine which were initially felt to represent a progression of her SPMS. METHODS: A single retrospective case report. RESULTS: Symptoms of cognitive deterioration, ataxia and hallucinations resolved completely on cessation of the amantadine she had been prescribed several years beforehand. CONCLUSION: Clinicians involved in the management of the symptoms of SPMS should be aware of the potential for cumulative side effects of drugs used to treat symptoms and consider their potential role in precipitating neurological deterioration.

Rehabilitation following anti-NMDA encephalitis.

BACKGROUND: Anti-NMDA (N-methyl D-Aspartate) encephalitis is an autoimmune disorder of the central nervous system which presents acutely with seizures, disturbances in consciousness and behavioural change. Although there is an increasing amount of information about the diagnosis and acute treatment strategies, little is known about rehabilitation needs and outcomes for this patient group. CASE REPORT: This study presents a 52-year old woman who initially presented with generalized seizures and drowsiness. She was admitted to hospital where autoimmune encephalitis was diagnosed based on a positive serum anti-NMDA antibody titre. When medically stabilized, she was transferred to a specialist neurorehabilitation unit for ongoing care. Her main clinical issues were around behavioural disturbance, communication, continence, mobility and cognition. A multi-disciplinary approach was taken to her problems and she was eventually discharged back to community living having made substantial improvements in all domains of functioning. The clinical challenges encountered throughout her rehabilitation and the approach to ameliorating these is described. CONCLUSION: Although having a relatively rare diagnosis, the specific rehabilitation needs of this patient were met through an existing specialist neurorehabilitation service. A broader case series is required to determine needs and effective approaches across this patient group as a whole.

Outcomes for older adults in inpatient specialist neurorehabilitation.

BACKGROUND: Inpatient specialist neurorehabilitation in the United Kingdom is based on providing a service to "working-age" adults (<65 years), with little evidence for outcomes for older adults involved with these services. OBJECTIVE: The aim of this study is to determine any difference in outcome after inpatient neurorehabilitation between younger and older adults assessed as having rehabilitation potential. METHODS: A two-centre retrospective review was performed comparing patients aged<65 and≥65 years by diagnostic group in terms of length of stay, changes in UK Functional Independence Measure+Functional Assessment Measure (UK FIM+FAM) scores and discharge destination. RESULTS: Six hundred and sixteen patients (32%≥65 years) were included. The 2 age groups did not differ in length of stay (median difference 7 days, 95% confidence interval [CI] -2 to 15, P=0.112), but both UK FIM+FAM change and efficiency were higher for the older than younger group (median difference 7, 95% CI 2-13, P=0.006 and 0.10, 0.01-0.19, P=0.031 respectively). Older age was associated with discharge to long-term care (6%<65 years; 11%≥65 years, x2=4.10, P=0.043). Results and trends were similar in patients with acquired brain injury (n=429), spinal cord injury (n=59) and peripheral neuropathy (n=34) but not progressive neurological disorders (n=70). CONCLUSION: Older adults considered to have rehabilitation potential may have greater functional gains from inpatient specialist inpatient rehabilitation than younger adults. Age alone should not exclude admission to inpatient specialist neurorehabilitation.

Predicting length of stay in specialist neurological rehabilitation.

AIMS: A retrospective case series was performed to determine which measures of complexity, dependency and function most accurately predict inpatient neurorehabilitation length of stay for individuals with post-acute neurological disorders. METHODS: Sociodemographic, medical and functional variables were extracted from data submitted to the UK Rehabilitation Outcomes Collaborative. Length of stay was calculated as the total number of inpatient days, functional status was measured using Barthel Index, rehabilitation complexity was measured using Extended Rehabilitation Complexity Scale, and nursing dependency was measured using the Northwick Park Dependency Scale. RESULTS: The mean rehabilitation length of stay was 70.9 days, with length of stay being 35.1 days higher in inpatients with acquired brain injury than inpatients with spinal cord injury. Diagnostic category, Barthel Index scores, Extended Rehabilitation Complexity Scale scores and Northwick Park Dependency Scale scores at admission independently predicted length of stay. Multiple regressions including diagnostic group, Barthel Index, Extended Rehabilitation Complexity Scale and Northwick Park Dependency Scale statistically significantly predicted 37.9% of the variability in length of stay (p < 0.005). Northwick Park Dependency Scale on admission was most closely correlated with inpatient length of stay. CONCLUSIONS: In conclusion, inpatient length of stay is predicted by diagnostic category, Extended Rehabilitation Complexity Scale, Northwick Park Dependency Scale and Barthel Index. The most influential predictor of rehabilitation length of stay was Northwick Park Dependency Scale score at admission. These results may help facilitate rehabilitation resource planning and implementation of effective commissioning plans. Implications for Rehabilitation The most accurate predicting variable for length of stay in inpatient neurological rehabilitation was nursing need as measured by the Northwick Park Dependency Scale score on admission. Service users and commissioners can be provided with more realistic predictions of length of stay derived from admission variables that can be used in planning inpatient rehabilitation. Age and gender do not seem to have an effect on the total length of stay in rehabilitation.

Brachial plexus hypertrophy in chronic inflammatory demyelinating polyradiculoneuropathy.

We present the clinical, imaging and neuropathological findings in three patients with predominant brachial plexus neuropathy. MR scanning was key to determining the brachial plexus involvement. Biopsy of the brachial plexus was performed in one patient. The appearances of the brachial plexus on MRI, in conjunction with the clinical presentations of these patients, suggest that they are unusual variants within the spectrum of chronic inflammatory demyelinating polyradiculoneuropathy.

Late and multifocal presentations of malignant peripheral nerve sheath tumours following radiotherapy.

Peripheral nerve sheath tumours are a well-recognised complication of radiotherapy. Single tumours presenting up to 10 years after initial treatment have been previously described. We report an individual with two anatomically separate nerve sheath tumours developing at different time intervals following initial treatment, after 38 and 42 years, respectively. This case illustrates the importance of maintaining vigilance for the development of complications even at an advanced stage following index radiotherapy treatment.

The academic value of rehabilitation medicine meetings.

PURPOSE: Twice-yearly meetings of The British Society of Rehabilitation Medicine (BSRM) take place at which posters and free papers are generated, as abstracts, to present novel research findings, audits and case reports. The aim of this study was to evaluate the academic value of these meetings, by determining the subsequent rate of publication in peer-reviewed journals of abstracts presented. This was compared to the publication rate of other European medical specialist society meetings. METHODS: The authors used MEDLINE, PubMed and Google Scholar search engines to look for publication of abstracts presented at BSRM meetings within peer-reviewed journals over a 7-year period (2000-2006). The abstracts were categorised into sub-groups (original study, audit, review, case report and service description) to determine which type was more likely to be published. The above databases were used also to extract studies on publication rate of other medical specialties in Europe. RESULTS: In 7 years, a total of 251 abstracts (of which 152 are original studies) have been presented as free papers or posters in a total of 13 meetings. The publication rate for the described study categories were: total 34%, original study 52%, review 50%, case report 5%, audit 0% and service description 0%. Publication rates from other specialist meetings in Europe range from 10% to 70%. CONCLUSION: The average publication rate for an abstract submitted to a BSRM meeting is 34% for any abstract and 52% for an original study suggesting that the meeting is generating abstracts of comparable academic interest to other specialist societies.

Increased sensitivity of myoblasts to oxidative stress in amyotrophic lateral sclerosis peripheral tissues.

We compared mitochondrial respiratory chain function, mitochondrial DNA (mtDNA) integrity, and oxidative stress levels in muscle, myoblasts, fibroblasts and cybrids, from 12 amyotrophic lateral sclerosis (ALS) patients with 28 control samples. Mitochondrial respiratory chain enzyme activities were normal in muscle, myoblast and fibroblast cultures from ALS patients, as were levels of mtDNA in muscle. Rearranged muscle mtDNA species were not detected by Southern blot hybridization in any of the samples and no difference was found in the number of deleted mtDNA species detected by long-range PCR. Platelet-derived cybrid studies confirmed the absence of a systemic mtDNA abnormality. Aconitase activity measurements did not indicate increased oxidative damage in muscle tissue, or in myoblasts or fibroblasts from ALS patients cultured under basal conditions. We did, however, find an increased sensitivity to oxidative stress in myoblasts from ALS patients exposed to paraquat. This altered sensitivity appears to be due to a nuclear rather than a mtDNA abnormality. Motor neurons have a large relative size and metabolic activity, and would be expected to be exposed to a greater degree of oxidative stress than most tissues throughout life. In addition, neurons are postmitotic cells, with poor regenerative potential. We do not have a ready method to study this in neural tissue of living patients, but the oxidative stress identified in myoblasts would translate into oxidative damage more readily in motor neurons than in other tissues.

Serum IGF-I levels and IGF-I gene splicing in muscle of healthy young males receiving rhGH.

OBJECTIVE: Elevated growth hormone (GH) levels lead to increased circulating insulin-like growth factor-I (IGF-I), but the effects on localised muscle IGF-I splice variant expression is not known. The effects of rhGH administration, with or without an acute bout of high resistance exercise, were measured on serum IGF-I and on the mRNA levels of IGF-I splice variants in the vastus lateralis muscle of healthy young men. DESIGN: The study was a randomised double blind trial with a crossover design. Seven subjects were randomly assigned to a group receiving daily injections of rhGH (0.075IU kg(-1)day(-1)) or placebo for a two week period. Following a one month washout, the groups were reversed. RESULTS: Administration of rhGH increased circulating IGF-I from 31.8+/-3.2 to 109+/-5.4 nmol/L (p<0.05). There was no effect of the exercise bout. RNA was extracted from muscle biopsies obtained from exercised and non-exercised legs 2.5h after the cessation of the exercise. Transcript expression was measured using Real-time QPCR. There was no effect of either exercise or rhGH administration on IGF-I 5' (Class 1 or Class 2) or 3' (IGF-IEa, or MGF) transcripts. CONCLUSION: Although rhGH administration has an effect on liver IGF-I expression, as shown by increase in circulating IGF-I, muscle IGF-I expression is unaffected in young healthy subjects with normal GH profile. The findings contrast with those of a previous study in which GH deficient elderly men showed higher muscle IGF-I 3' splice variant levels following rhGH administration with and without resistance training. Unlike in the liver, muscle Class1 and 2 IGF-I expression do not change significantly following administration of rhGH.

The physical and psychological effects of torture in Kurds seeking asylum in the United Kingdom.

There were over 2000 applications for asylum from Turkish nationals to the UK in 2003. A large proportion of these were person of Kurdish origin, many of whom claimed to have suffered torture. We sought to evaluate the physical and psychological effects of torture in those with physical injuries. A total of 97 Kurdish asylum seekers requiring medical evaluation for evidence of torture were examined and interviewed in the presence of an interpreter. Physical injuries, pain, disability and psychopathology were documented for each. A wide variety of injuries and psychological disorders were documented. Posttraumatic stress disorder, major depression and organic brain damage were present in a substantial proportion of those surveyed. Methods of torture not previously documented were revealed. There are long term healthcare needs of this population, which are complex and require a multidisciplinary approach. Survivors of torture may be disadvantaged in the asylum process because of organic brain damage or major psychological disturbance.

Patterns of inheritance in familial ALS.

We investigated 185 families with ALS for evidence of anticipation and mitochondrial inheritance. Although initial analysis demonstrated significant anticipation of age at death between generations in patients with familial ALS, further analysis demonstrated features of regression to the mean, suggesting that the perceived differences are the result of bias. In addition, there was no evidence of an effect of preferential maternal inheritance, which would have supported transmission of mitochondrial DNA mutations.

A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia.

Mutations in the SPG7 gene, encoding the mitochondrial protein paraplegin, were the first to be identified in autosomal recessive hereditary spastic paraplegia (ARHSP). Four different SPG7 mutations have been described so far in association with both pure and complicated HSP phenotypes. Muscle biopsies from the most severely affected patients have shown histological evidence of an oxidative phosphorylation defect. We identified six ARHSP kindreds, in whom linkage to SPG7 could not be excluded, and 29 sporadic spastic paraplegia patients. The 17 exons and flanking regions of the SPG7 gene were screened for mutations using a combination of single-stranded conformation polymorphism (SSCP) analysis and sequencing. Three patients were found to carry compound heterozygous SPG7 mutations, comprising five novel and one previously described mutation. Muscle biopsies from two SPG7 mutation patients did not show any histological evidence of an oxidative phosphorylation defect. However, biochemical analysis revealed a reduction in citrate synthase-corrected complex I and complex II/III activities in muscle and complex I activity in mitochondrial-enriched fractions from cultured myoblasts, suggesting that either a primary or a secondary defect of respiratory chain function may play an important role in the pathogenesis of the disease.

No association with common Caucasian genotypes in exons 8, 13 and 14 of the human cytoplasmic dynein heavy chain gene (DNCHC1) and familial motor neuron disorders.

We have shown in a mouse model of motor neuron disease, the legs-at-odd-angles (Loa) mutant, and that mutations in the cytoplasmic dynein heavy chain gene (Dnchc1) cause motor neuron degeneration. Mice exhibiting the Loa phenotype suffer progressive loss of locomotor function and homozygous animals have neuronal inclusion bodies that are positive for SOD1, CDK5, neurofilament and ubiquitin proteins. As this phenotype models some aspects of human motor neuron degeneration disorders, we think there is a reasonable likelihood that dynein may be a causative gene or susceptibility factor in human motor neuron disease. Therefore we have screened exons of this gene in a set of human patients with familial forms of disparate motor neuron degeneration diseases, affecting both upper and lower motor neurons: amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), and hereditary spastic paraplegia. As part of this study, we have determined that DNCHC1 is a large gene of 78 exons spanning 86 kb genomic length. We have focused on the exons known to be mutated in Loa, and in a very similar mouse mutation, cramping 1 (Cra1); both mutations result in loss of anterior horn cells. The exons studied are highly conserved in a wide range of eukaryotes. We screened our patient samples by sequencing and although we detect single nucleotide polymorphisms, our results show these occur at the same frequency in our patient group as in control samples of unaffected individuals. Therefore we do not find any association between familial motor neuron disease and the genotypes presented here in the exons screened.