A randomised controlled trial of acceptance and commitment therapy for improving quality of life in people with muscle diseases.

Abstract. BACKGROUND: Chronic muscle diseases (MD) are progressive and cause wasting and weakness in muscles and are associated with reduced quality of life (QoL). The ACTMuS trial examined whether Acceptance and Commitment Therapy (ACT) as an adjunct to usual care improved QoL for such patients as compared to usual care alone. METHODS: This two-arm, randomised, multicentre, parallel design recruited 155 patients with MD (Hospital and Depression Scale ⩾ 8 for depression or ⩾ 8 for anxiety and Montreal Cognitive Assessment ⩾ 21/30). Participants were randomised, using random block sizes, to one of two groups: standard medical care (SMC) (n = 78) or to ACT in addition to SMC (n = 77), and were followed up to 9 weeks. The primary outcome was QoL, assessed by the Individualised Neuromuscular Quality of Life Questionnaire (INQoL), the average of five subscales, at 9-weeks. Trial registration was NCT02810028. RESULTS: 138 people (89.0%) were followed up at 9-weeks. At all three time points, the adjusted group difference favoured the intervention group and was significant with moderate to large effect sizes. Secondary outcomes (mood, functional impairment, aspects of psychological flexibility) also showed significant differences between groups at week 9. CONCLUSIONS: ACT in addition to usual care was effective in improving QoL and other psychological and social outcomes in patients with MD. A 6 month follow up will determine the extent to which gains are maintained.

Mobility shift of beta-dystroglycan as a marker of GMPPB gene-related muscular dystrophy.

BACKGROUND: Defects in glycosylation of alpha-dystroglycan (α-DG) cause autosomal-recessive disorders with wide clinical and genetic heterogeneity, with phenotypes ranging from congenital muscular dystrophies to milder limb girdle muscular dystrophies. Patients show variable reduction of immunoreactivity to antibodies specific for glycoepitopes of α-DG on a muscle biopsy. Recessive mutations in 18 genes, including guanosine diphosphate mannose pyrophosphorylase B (GMPPB), have been reported to date. With no specific clinical and pathological handles, diagnosis requires parallel or sequential analysis of all known genes. METHODS: We describe clinical, genetic and biochemical findings of 21 patients with GMPPB-associated dystroglycanopathy. RESULTS: We report eight novel mutations and further expand current knowledge on clinical and muscle MRI features of this condition. In addition, we report a consistent shift in the mobility of beta-dystroglycan (ß-DG) on Western blot analysis of all patients analysed by this mean. This was only observed in patients with GMPPB in our large dystroglycanopathy cohort. We further demonstrate that this mobility shift in patients with GMPPB was due to abnormal N-linked glycosylation of ß-DG. CONCLUSIONS: Our data demonstrate that a change in ß-DG electrophoretic mobility in patients with dystroglycanopathy is a distinctive marker of the molecular defect in GMPPB.

Lyme disease in the United Kingdom.

Lyme disease, while still an uncommon disease in the UK, is on the increase. Case numbers have increased by 3.6-fold since 2001, with over 950 cases reported by the Health Protection Agency (HPA) in 2011, compared with less than 500 cases annually pre-2004. HPA indications of the true incidence are suggested to be closer to 3000 cases/year, of which around 82% of cases are indigenously acquired. Three genospecies, Borrelia burgdorferi sensu stricto, Borrelia afzelli and Borrelia garinii, represent the predominant pathogenic variants in the UK. Erythema migrans is the commonest manifestation, occurring in 60%-91% of cases. In the UK, neuroborelliosis is the most common complication, while myocarditis is unusual, and death from either conduction disease or carditis is extremely rare. The role of Borrelia infection in chronic dilated cardiomyopathy in the UK remains unproven. Controversy over the existence of either 'chronic Lyme disease' and/or 'post-Lyme disease syndrome' continues unabated. National medical societies, patient advocacy groups, insurance companies, lawyers, doctors, the private health medical sector and scientific journals have all become embroiled in this bitter controversy. New developments include diagnostic tests able to detect Lyme disease at an earlier stage, shorter durations of antibiotic therapy and potential advances in vaccines against Borrelia.

Participant experiences of guided self-help Acceptance and Commitment Therapy for improving quality of life in muscle disease: a nested qualitative study within the ACTMus randomized controlled trial.

Introduction: In adults, muscle disease (MD) is typically a chronic long-term condition that can lead to a reduced quality of life (QoL). Previous research suggests that a psychological intervention, in particular Acceptance and Commitment Therapy (ACT), may help improve QoL for individuals living with chronic conditions such as MD. Methods: This nested qualitative study was incorporated within a randomized controlled trial which evaluated a guided self-help ACT intervention for people living with MD to explore their experiences of the intervention. Semi-structured interviews (n = 20) were conducted with those who had received ACT. Data were analyzed via thematic analysis. Results: There were four overarching themes. (1) Views on whether therapy sessions would help with a medical condition: participants' expectations regarding ACT varied. Some participants were skeptical about mindfulness. (2) I was able to look at things in a different way: participants described increased meaningful activity, greater awareness of thoughts and emotions and acceptance or adaptation to mobility problems. Some described improvement in the quality of relationships and a sense of feeling free. (3) Treating the body and the mind together: following the intervention participants noted that a holistic approach to healthcare is beneficial. (4) Intervention delivery: The remote delivery was generally seen as helpful for practical reasons and allowed participants to speak openly. Participants voiced a need for follow-up sessions. Discussion: Overall, the intervention was experienced as acceptable. Suggested improvements included de-emphasizing the role of mindfulness and adding follow-up sessions.

Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.

Ryanodine receptor 1 (RYR1) mutations are a common cause of congenital myopathies associated with both dominant and recessive inheritance. Histopathological findings frequently feature central cores or multi-minicores, more rarely, type 1 predominance/uniformity, fiber-type disproportion, increased internal nucleation, and fatty and connective tissue. We describe 71 families, 35 associated with dominant RYR1 mutations and 36 with recessive inheritance. Five of the dominant mutations and 35 of the 55 recessive mutations have not been previously reported. Dominant mutations, typically missense, were frequently located in recognized mutational hotspot regions, while recessive mutations were distributed throughout the entire coding sequence. Recessive mutations included nonsense and splice mutations expected to result in reduced RyR1 protein. There was wide clinical variability. As a group, dominant mutations were associated with milder phenotypes; patients with recessive inheritance had earlier onset, more weakness, and functional limitations. Extraocular and bulbar muscle involvement was almost exclusively observed in the recessive group. In conclusion, our study reports a large number of novel RYR1 mutations and indicates that recessive variants are at least as frequent as the dominant ones. Assigning pathogenicity to novel mutations is often difficult, and interpretation of genetic results in the context of clinical, histological, and muscle magnetic resonance imaging findings is essential.

Treatment for meralgia paraesthetica.

BACKGROUND: Meralgia paraesthetica is a clinical syndrome for which a number of treatments are in common use, including conservative measures, injection of corticosteroid with local anaesthetic and surgery. We aimed to examine the evidence for the relative efficacy of these interventions. This review was first published in 2008. Searches were updated in 2010 and 2012. OBJECTIVES: To assess the relative efficacy of commonly used treatments for meralgia paraesthetica. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (1 October 2012), CENTRAL (2012, issue 9 in The Cochrane Library), MEDLINE (January 1966 to October 2012), EMBASE (January 1980 to October 2012) and CINAHL Plus (January 1937 to October 2012) for randomised controlled studies. Non-randomised studies were identified by searching MEDLINE (January 1966 to October 2012) and EMBASE (January 1980 to October 2012). We also inspected the reference lists of these studies. SELECTION CRITERIA: We were unable to identify any randomised controlled trials (RCTs) or quasi-RCTs. We therefore looked for high quality observational studies meeting the following criteria: (1) At least five cases of meralgia paraesthetica. (2) Follow-up of at least three months after intervention (if any). (3) At least 80% of cases followed up. DATA COLLECTION AND ANALYSIS: Three authors independently extracted relevant data from each study meeting the selection criteria and transferred into a data extraction form. MAIN RESULTS: We found no RCTs or quasi-RCTs in the original review or updates in 20011 and 2012. Cure or improvement have been described in high quality observational studies: (1) A single study describes spontaneous improvement of meralgia paraesthetica in 20 (69%) of 29 cases. (2) Four studies evaluating the injection of corticosteroid and local anaesthetic found cure or improvement in 130 (83%) out of a combined total of 157 cases. (3) Surgical treatments have been found to be beneficial in 264 (88%) out of 300 cases treated with decompression (nine studies); and 45 (94%) out of 48 cases treated with neurectomy (three studies). (4) Ninety-nine (97%) out of 102 patients with iatrogenic meralgia paraesthetica recovered completely (three studies). AUTHORS' CONCLUSIONS: In the absence of any published RCTs or quasi-RCTs, the objective evidence base for treatment choices in meralgia paraesthetica is weak. High quality observational studies report comparable high improvement rates for meralgia paraesthetica following local injection of corticosteroid and surgical interventions (either nerve decompression or neurectomy). However, a similar outcome has been reported without any intervention in a single natural history study.

Treatment for meralgia paraesthetica.

BACKGROUND: Meralgia paraesthetica is a clinical syndrome for which a number of treatments are in common use, including conservative measures, injection of corticosteroid with local anaesthetic and surgery. We aimed to examine the evidence for the relative efficacy of these interventions. OBJECTIVES: To assess the relative efficacy of commonly used treatments. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (April 2008), MEDLINE (January 1 1966 to April 18 2008), EMBASE (January 1 1980 to May 12 2008) and CINAHL (January 1 1980 to May 12 2008) for randomised controlled studies. Non-randomised studies were identified by searching MEDLINE (January 1 1966 to April 18 2008) and EMBASE (January 1 1980 to May 12 2008). We also inspected the reference lists of these studies to identify further studies. SELECTION CRITERIA: We were unable to identify any randomised controlled or quasi-randomised controlled trials. We therefore looked for high quality observational studies meeting the following criteria:(1) At least five cases of meralgia paraesthetica.(2) Follow-up of at least three months after intervention (if any).(3) At least 80% of cases followed up. DATA COLLECTION AND ANALYSIS: Relevant data from each study meeting the selection criteria were extracted independently by all three authors and transferred into a data extraction form created for the review. MAIN RESULTS: We found no randomised controlled or quasi-controlled trials. Cure or improvement have been described in high quality observational studies:(1) A single study describes spontaneous improvement of meralgia paraesthetica in 20 (69%) out of 29 cases.(2) Four studies evaluating the injection of corticosteroid and local anaesthetic found cure or improvement in 130 (83%) out of a combined total of 157 cases.(3) Surgical treatments have been found to be beneficial in 264 (88%) out of 300 cases treated with decompression (nine studies); and 45 (94%) out of 48 cases treated with neurectomy (three studies).(4) Ninety-nine (97%) out of 102 patients with iatrogenic meralgia paraesthetica recovered completely (three studies). AUTHORS' CONCLUSIONS: In the absence of any published randomised controlled or quasi-randomised controlled trials, the objective evidence base for treatment choices in meralgia paraesthetica is weak. High quality observational studies report comparable high improvement rates for meralgia paraesthetica following local injection of corticosteroid and surgical interventions (either nerve decompression or neurectomy). However, a similar outcome has been reported without any intervention in a single natural history study.

Glial cell line-derived neurotrophic factor promotes the survival of early postnatal spinal motor neurons in the lateral and medial motor columns in slice culture.

The mechanisms by which trophic factors bring about spinal motor neuron (MN) survival and regulate their number during development are not well understood. We have developed an organotypic slice culture model for the in vitro study of the trophic requirements and cell death pathways in MNs of postnatal day 1-2 mice. Both lateral motor column (LMC) and medial motor column (MMC) neurons died within 72 hr when grown in serum-free medium without trophic factors. Brain-derived neurotrophic factor, ciliary neurotrophic factor, and 8-(4-chlorophenylthio)-cAMP promoted the survival of a proportion of the neurons, but glial cell line-derived neurotrophic factor (GDNF) was the most effective trophic factor, supporting approximately 60% of MNs for 1 week in culture. Homozygous deficiency for bax, a proapoptotic member of the Bcl-2 family, saved the same proportion of neurons as GDNF, suggesting that GDNF alone was sufficient to maintain all "rescuable" MNs for at least 1 week. Analysis of MN survival in GFRalpha-1(-/-) mice demonstrated that the trophic effect of GDNF was completely mediated by its preferred coreceptor, GDNF family receptor alpha-1 (GFRalpha-1). None of the other GDNF family ligands supported significant MN survival, suggesting that there is little ligand-coreceptor cross talk within the slice preparation. Although MN subtypes can be clearly defined by both anatomical distribution and ontogenetic specification, the pattern of trophic factor responsiveness of neurons from the MMC was indistinguishable from that seen in the LMC. Thus, in contrast to all other factors and drugs studied to date, GDNF is likely to be a critical trophic agent for all early postnatal MN populations.

Post-traumatic dizziness.

Following an episode of syncope, a 42-year-old woman was referred to exclude a cardiac cause. This primary event was determined to be a straightforward case of vasovagal syncope, resulting in mild head trauma. Following this, the patient was left with symptoms of dizziness and a subjective "muzzy" sensation. Initially assumed to be a form of "post-concussive symptom", she was referred to a neurologist who employed neurovestibular manoeuvres to both determine the cause of these symptoms and satisfactorily resolve them.

Frequent atrophic groups with mixed-type myofibers is distinctive to motor neuron syndromes.

This study was performed to determine whether there are distinctive features to the pattern of muscle denervation in motor neuron disease. We first compared muscle biopsies from patients with amyotrophic lateral sclerosis (ALS) or Kennedy's disease with other causes of denervation. Groups of atrophic muscle fibers, with individual groups containing both fiber types I and II, occurred frequently in motor neuron disease but not other causes of denervation. We then identified 11 additional muscle biopsies with frequent atrophic groups containing mixed fiber types. Chart review revealed that 10 patients had a final diagnosis of motor neuron disease or ALS and one had multifocal motor neuropathy. We conclude that muscle biopsy may have diagnostic utility early in the course of motor neuron disease. The muscle biopsy pattern of frequent atrophic groups containing mixed fiber types should suggest a diagnosis of a motor neuron syndrome or motor neuropathy.