Iain Horrocks

Recessive desmin-null muscular dystrophy with central nuclei and mitochondrial abnormalities

missense mutations. However, very few families with a recessive mode of inheritance have also been recognized [2]. Desmin immunostaining of normal skeletal muscle shows uniform sarcoplasmic and subsarcolemmal localization, while affected muscles display cytoplasmic aggregates of misfolded filaments and disruption of the myofibrillar apparatus rather than absence of protein [2], so that individuals with desmin mutations are frequently categorized within the group of disorders known as myofibrillar myopathies. We describe a family with no history of neuromuscular or cardiac disorders with two siblings affected by autosomal recessive desminopathy manifesting as a slowly progressive, predominantly proximal muscle fatigue and weakness. The proband, a 12 year old boy, was born at term and had normal gross motor milestones, but presented poor head control when crawling, lack of facial expression and congenital ptosis. From the age of 3 he showed difficulty rising from the floor, jumping, running and going upstairs. The weakness was slowly progressive over the years and he remains independently mobile. He tires easily and benefits from short breaks. On examination he presented with shoulder, grip and hip muscle weakness, symmetrical scapular winging, mild thoracic scoliosis and mild bilateral calf hypertrophy. Muscle MRI features are shown in Fig. 1a. He shows an unusual pattern of swallowing, turning his neck to ingest food, but he has a good appetite and is generally healthy. Forced vital capacity (FVC) was 45 % of the predicted value in sitting. CK levels were raised up to 1,000 IU/L, cardiac examinations were normal. His 11 year old sister displayed a slightly less pronounced weakness, contractures of long finger flexors and shoulders and hyperextensible elbows as well as similar tiredness and swallowing habit as her brother. She has a small appetite with a weight below the 3rd centile and also presents a history of asthma and rare chest infections. Her FVC was 40 % of the predicted value Desmin is a muscle-specific intermediate filament that provides maintenance of cellular integrity and force transmission [2]. DES gene mutations cause a spectrum of adult-onset disorders, ranging from myopathies with and without cardiac involvement to cardiomyopathy without skeletal muscle involvement [3]. Distal and proximal weakness involving upper and lower limbs muscles are observed in most patients [9]. Desminopathies are usually inherited in an autosomal dominant fashion, predominantly with

A case of posterior reversible encephalopathy syndrome in a child with Crohn's disease treated with Infliximab

BACKGROUND AND AIMS Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity characterised by headache, seizures, visual disturbance, altered mental status and vasogenic oedema on neuro-imaging. We report a rare case of PRES in a 8-year-old female with Crohns disease (CD) following Infliximab administration and colectomy. METHOD Clinical case reported including a review of current literature regarding PRES and Infliximab. RESULTS This is one of several cases of PRES reported recently in proximity to Infliximab administration. CONCLUSIONS Awareness of this rare condition in patients receiving immunosuppressive treatment is important to prevent poor outcomes for patients. The increasing number of these cases recognised in patients receiving Infliximab should be kept under close clinical surveillance due to the possibility of a link between the two.

Developing standardized corticosteroid treatment for Duchenne muscular dystrophy

Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each averaged over all post-baseline visits. The study protocol includes evidence- and consensus-based treatment of DMD complications and of corticosteroid side effects. This study seeks to establish a standard corticosteroid regimen for DMD. Since all new interventions for DMD are being developed as add-on therapies to corticosteroids, defining the optimum regimen is of importance for all new treatments.

The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy

Objective With the emergence of experimental therapies for Duchenne muscular dystrophy (DMD), it is fundamental to understand the natural history of this disorder to properly design clinical trials. The aims of this study were to assess the effects produced on motor function by different DMD genotypes and early initiation of glucocorticoids. Methods Through the NorthStar Network, standardised clinical data including the NorthStar Ambulatory Assessment score (NSAA) on 513 ambulant UK boys with DMD were analysed from 2004 to 2012. For the analysis of the genetic subpopulation, we also included data from 172 Italian boys with DMD. NSAA raw scores were converted into linear scores. Results On the linearised NSAA, we observed an average decline of 8 units/year (4 units on raw NSAA analysis) after age 7. The median age at loss of ambulation (LOA) was 13 years (95% CI 12.1 to 13.5); 2 years prior to LOA, the estimated mean linearised NSAA score was 42/100 (13/34 raw scale). Starting glucocorticoids between 3 and 5 years conferred an additional gain in motor function of 3 units/year (1.3 raw units) up to age 7. When analysing the effect of genotype in the UK and Italian cumulative cohorts, individuals with deletions amenable to exons 44 and 46 skipping declined at a slower rate over 2 years (9 units (4 raw units), p<0.001), while 53 and 51 skippable deletions showed a faster decline of 14 (4.5; p<0.001) and 5 linearised units (2.4 NSAA units; p=0.02), respectively. Conclusions Our study provides a novel insight on the current natural history of DMD, which will be instrumental for the design of future clinical trials.