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In this article, we report four new patients, from three kindreds, with pathogenic variants in RBCK1 and a multisystem disorder characterised by widespread polyglucosan storage. We describe the clinical presentation of progressive skeletal and cardiac myopathy, combined immunodeficiencies and auto-inflammation, illustrate in detail the histopathological findings in multiple tissue types, and report muscle MRI findings.

International audience; Objective: Evaluation of ophthalmologic safety with focus on retinal safety in patients with spinal muscular atrophy (SMA) treated with risdiplam (EVRYSDI®), a survival of motor neuron 2 splicing modifier associated with retinal toxicity in monkeys. Risdiplam was approved recently for the treatment of patients with SMA, aged ≥ 2 months in the United States, and is currently under Health Authority review in the EU.Methods: Subjects included patients with SMA aged 2 months-60 years enrolled in the FIREFISH, SUNFISH, and JEWELFISH clinical trials for risdiplam. Ophthalmologic assessments, including functional assessments (age-appropriate visual acuity and visual field) and imaging (spectral domain optical coherence tomography [SD-OCT], fundus photography, and fundus autofluorescence [FAF]), were conducted at baseline and every 2-6 months depending on study and assessment. SD-OCT, FAF, fundus photography, and threshold perimetry were evaluated by an independent, masked reading center. Adverse events (AEs) were reported throughout the study.Results: A total of 245 patients receiving risdiplam were assessed. Comprehensive, high-quality, ophthalmologic monitoring assessing retinal structure and visual function showed no retinal structural or functional changes. In the youngest patients, SD-OCT findings of normal retinal maturation were observed. AEs involving eye disorders were not suggestive of risdiplam-induced toxicity and resolved with ongoing treatment.Interpretation: Extensive ophthalmologic monitoring conducted in studies in patients with SMA confirmed that risdiplam does not induce ophthalmologic toxicity in pediatric or adult patients with SMA at the therapeutic dose. These results suggest that safety ophthalmologic monitoring is not needed in patients receiving risdiplam, as also reflected in the United States Prescribing Information for risdiplam.

Objective: To determine the efficacy and safety of risdiplam, a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier, in infants with Type 1 spinal muscular atrophy (SMA) treated for 12 months during the confirmatory Part 2 of the FIREFISH study (NCT02913482). Design/Methods: FIREFISH is an ongoing, multicenter, open-label study of risdiplam in infants aged 1–7 months at enrollment with Type 1 SMA and two copies of the SMN2 gene. Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels (plus exploratory efficacy outcomes). The primary objective of confirmatory Part 2 (n=41) is to investigate the efficacy of risdiplam at the dose selected in Part 1. The primary efficacy endpoint is the proportion of infants sitting without support for 5 seconds after 12 months on treatment, as assessed by Item 22 of the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development, 3rd edition. Secondary outcomes include the achievement of motor milestones and respiratory endpoints such as time to permanent ventilation and percentage of infants who achieve a reduction of ≥30° in phase angle from baseline at Month 12 (as measured by respiratory plethysmography). Results: The primary endpoint of FIREFISH Part 2 at 12 months was met (data-cut: 14th November 2019). We will report efficacy and safety data, including respiratory outcomes, from the confirmatory Part 2 of the FIREFISH study in participants who have received risdiplam treatment for a minimum of 12 months. Conclusions: FIREFISH Part 2 will provide important data on the efficacy and safety of risdiplam in infants with Type 1 SMA.

McArdle disease results from a lack of muscle glycogen phosphorylase in skeletal muscle tissue. Regenerating skeletal muscle fibres can express the brain glycogen phosphorylase isoenzyme. Stimulating expression of this enzyme could be a therapeutic strategy. Animal model studies indicate that sodium valproate (VPA) can increase expression of phosphorylase in skeletal muscle affected with McArdle disease. This study was designed to assess whether VPA can modify expression of brain phosphorylase isoenzyme in people with McArdle disease. This phase II, open label, feasibility pilot study to assess efficacy of six months treatment with VPA (20 mg/kg/day) included 16 people with McArdle disease. Primary outcome assessed changes in VO2peak during an incremental cycle test. Secondary outcomes included: phosphorylase enzyme expression in post-treatment muscle biopsy, total distance walked in 12 min, plasma lactate change (forearm exercise test) and quality of life (SF36). Safety parameters. 14 participants completed the trial, VPA treatment was well tolerated; weight gain was the most frequently reported drug-related adverse event. There was no clinically meaningful change in any of the primary or secondary outcome measures including: VO2peak, 12 min walk test and muscle biopsy to look for a change in the number of phosphorylase positive fibres between baseline and 6 months of treatment. Although this was a small open label feasibility study, it suggests that a larger randomised controlled study of VPA, may not be worthwhile. CAPES Foundation Ministry of Education Brazil.

An 84-year-old lady with slowly progressive limb and axial muscle weakness with onset in her teens was referred for genetic investigations. Targeted next generation sequencing (NGS) revealed a homozygous mutation GYG1 in exon5:c.487delG:p.D163fs, confirming the diagnosis of Polyglucosan Body Myopathy 2 (PGBM2). Retrospective review of muscle pathology revealed a florid vacuolar myopathy with histochemical and ultrastructural features consistent with a polyglucosan storage myopathy. No cardiac symptoms were reported. Our case is consistent with the core phenotype of GYG1-related PGBM2 apart from an early onset of weakness without cardiac symptoms. The presence of α-amylase resistant PAS-positive material in skeletal muscle biopsy of patients with slowly progressive limb girdle muscle weakness should prompt the search for GYG1 mutations. This case highlights the combined role of muscle pathology and NGS in the molecular resolution of patients with undiagnosed neuromuscular conditions.

Mutations in calpain-3 cause limb girdle muscular dystrophy 2A. Biopsy pathology is typically dystrophic, sometimes characterized by frequent lobulated fibres. More recently calpain mutations have been shown in association with eosinophilic myositis, suggesting that calpain mutations may render muscle susceptible to inflammatory change. We present the case of a 33-year old female with mild proximal muscle weakness and high CK levels (6698 IU/L at presentation). Muscle biopsy showed clusters of fibre necrosis associated with very dense macrophage infiltrates and small numbers of lymphocytes, raising the possibility of an inflammatory myopathy. No eosinophils were observed. Immunosuppressive treatment was started without clinical improvement. MRI demonstrated bilateral fatty replacement in posterior thigh and calf muscles. Western blot results prompted Sanger sequencing of the calpain-3 gene revealing compound heterozygous mutations c.643_663del and c.1746-20C>G. Our case widens the myopathological spectrum of calpainopathies to include focal macrophage rich inflammatory change.

Objective The histopathological features of malignant hyperthermia (MH) and non-anaesthetic (mostly exertional) rhabdomyolysis (RM) due to RYR1 mutations have only been reported in a few cases. Methods We performed a retrospective multi-centre cohort study focussing on the histopathological features of patients with MH or RM due to RYR1 mutations (1987–2017). All muscle biopsies were reviewed by a neuromuscular pathologist. Additional morphometric and electron microscopic analysis were performed where possible. Results Through the six participating centres we identified 50 patients from 46 families, including patients with MH (n = 31) and RM (n = 19). Overall, the biopsy of 90% of patients showed one or more myopathic features including: increased fibre size variability (n = 44), increase in the number of fibres with internal nuclei (n = 30), and type I fibre predominance (n = 13). Abnormalities on oxidative staining, generally considered to be more specifically associated with RYR1-related congenital myopathies, were observed in 52%, and included unevenness (n = 24), central cores (n = 7) and multi-minicores (n = 3). Apart from oxidative staining abnormalities more frequently observed in MH patients, the histopathological spectrum was similar between the two groups. There was no correlation between the presence of cores and the occurrence of clinically detectable weakness or presence of (likely) pathogenic variants. Conclusions Patients with RYR1-related MH and RM exhibit a similar histopathological spectrum, ranging from mild myopathic changes to cores and other features typical of RYR1-related congenital myopathies. Suggestive histopathological features may support RYR1 involvement, also in cases where the in vitro contracture test is not informative. Electronic supplementary material The online version of this article (10.1007/s00415-019-09209-z) contains supplementary material, which is available to authorized users.

McArdle disease is a metabolic myopathy mainly characterised by symptom onset during physical activities or isometric muscle contraction. Resistance (also termed strength) training is a type of physical exercise focusing on the use of resistance (e.g., lifting weights) to induce muscular contraction, which builds muscle mass and strength. Historically people with McArdle disease were advised to avoid resistance exercises and any other form of physical activity involving high mechanical loads such as prolonged isometric contraction. Paradoxically, a clinical trial exploring the benefits of strength training in this patient population was published. The theory supporting strength training relied on the use of the ATP molecule and the creatine phosphate (ATP-phosphocreatine system) as energy sources for skeletal muscles. Here, we report two patients with McArdle disease who performed weight training at local gyms. A single set of repetitions lasted for maximum 10 seconds with minimum of 30 seconds of rest period in between sets of exercises. Benefits of this type of training included improvement in quality of life and amelioration of McArdle disease symptoms. We provide further safety evidence of this type of exercise in people with McArdle disease. We emphasise the importance of using a specific protocol developed for people affected by this condition.

Hereditary transthyretin amyloidosis (ATTR) is a genetically and clinically heterogeneous disease manifesting with predominant peripheral and autonomic neuropathy; cardiomyopathy, or both. ATTR V122I is the most common variant associated with non-neuropathic familial amyloid cardiomyopathy. We present an unusual case of V122I amyloidosis with features of amyloid neuropathy and myopathy, supported by histological confirmation in both sites and diffuse tracer uptake on (99m)Tc-3,3-Diphosphono-1,2-Propanodicarboxylic acid (DPD) scintigraphy throughout skeletal and cardiac muscle. A 64 year old Jamaican man presented with cardiac failure. Cardiac MR revealed infiltrative cardiomyopathy; abdominal fat aspirate confirmed the presence of amyloid, and he was homozygous for the V122I variant of transthyretin. He also described general weakness and EMG demonstrated myopathic features. Sural nerve and vastus lateralis biopsy showed TTR amyloid. The patient is being treated with diflunisal, an oral TTR stabilising agent. Symptomatic myopathy and neuropathy with confirmation of tissue amyloid deposition has not previously been described. Extracardiac amyloidosis has implications for diagnosis and treatment.

Introduction: Patients with HypoPP suffer debilitating attacks of muscle weakness. Animal model work has suggested bumetanide as a potential new therapeutic agent. Objectives: We conducted an RCT to assess efficacy and safety of bumetanide in treating an exercise induced attack of hand weakness in HypoPP. Method: A randomised, double-blind, placebo-controlled phase II clinical trial with crossover design using abductor digiti minimi CMAP as an objective outcome measure. Results: Nine participants completed both trial visits. There was no statistically significant difference in CMAP amplitude between the treatment groups at 1 hour (p=0.27, primary outcome). Two participants recovered from the attack of weakness within 4 hours following Bumetanide intake; none recovered following placebo intake. There were no serious adverse events. Conclusions: Bumetanide was safe but not effective to rescue a focal attack in an immobilised hand in the majority of patients. However, data supports further studies of this agent. This article is protected by copyright. All rights reserved.

Brown-Vialetto-Van Laere syndrome (BVVLS) represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter (RFVT) genes, SLC52A2 and SLC52A3, have recently been linked to BVVLS. However, the genetic frequency, neuropathology and downstream consequences of RFVT mutations have previously been undefined. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between RFVT mutations and BVVLS, identifying twenty-two pathogenic mutations in SLC52A2 and SLC52A3, fourteen of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain (ETC), we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. ETC complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila RFVT homologue revealed reduced levels of riboflavin, downstream metabolites, and ETC complex I activity. RFVT knockdown in Drosophila also resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings indicate mitochondrial dysfunction as a downstream consequence of RFVT gene defects in BVVLS and validate riboflavin esters as a potential therapeutic strategy.

Objectives: To compare the measurement of the Cobb angle on printed radiographs and on scanned radiographs viewed through the software "PixViewer". Methods: Preoperative radiographs of 23 patients were evaluated on printed films and through the software "PixViewer". The same evaluator, a spine surgeon, chose the proximal and distal limiting vertebrae of the main curve on printed radiographs, without identification of patients, and measured the Cobb angle based on these parameters. The same parameters and measurements were applied to scanned radiographs. The measurements were compared, as well as the choice of limiting vertebrae. Results: The average variation of the Cobb angle between methods was 1.48 ± 1.73°. The intraclass correlation coefficient (ICC) was 0.99, demonstrating excellent reproducibility. Conclusion: The Cobb method can be used to evaluate scoliosis through the "PixViewer" tool with the same reliability as the classic method on printed radiographs. RESUMO Objetivo: Comparar a aferição do ângulo de Cobb em radiografias impressas e em radiografias digitalizadas, visualizadas por meio da ferramenta "PixViewer". Métodos: Foram avaliadas as radiografias pré-operatórias de 23 pacientes em filmes impressos e pelo software "PixViewer". O mesmo avaliador, cirurgião de coluna, elegeu as vértebras limites proximal e distal da curva principal nas radiografias impressas, sem identificação dos pacientes, e realizou a aferição do ângulo de Cobb baseado nesses parâmetros. Os mesmos parâmetros e aferições foram aplicados às radiografias digitalizadas. As aferições foram comparadas, assim como a escolha das vértebras limites. Resultados: A variação média do ângulo de Cobb entre os métodos foi de 1,48 ± 1,73°. O coeficiente de correlação intraclasse (CCI) foi de 0,99, demonstrando replicabilidade excelente.. Conclusão: O método de Cobb pode ser utilizado para avaliação da escoliose por meio da ferramenta "PixViewer" com a mesma confiabilidade que pelo método clássico em radiografias impressas. RESUMEN Objetivo: Comparar la medición del ángulo de Cobb en radiografías impresas y en radiografías digitalizadas vistas a través de la herramienta "PixViewer" . Métodos: Se evaluaron las radiografías preoperatorias de 23 pacientes en películas impresas y a través del software "PixViewer". El mismo evaluador, cirujano de columna, eligió las vértebras proximal y distal límites de la curva principal en las radiografías impresas, sin identificación de los pacientes, y realizó la medición del ángulo de Cobb en base a estos parámetros. Los mismos parámetros y mediciones se aplicaron a las radiografías digitalizadas. Las mediciones fueron comparadas, así como la elección de las vértebras límites. Resultados: La variación promedio del ángulo de Cobb entre los métodos fue de 1,48 ± 1,73°. El coeficiente de correlación intraclase (CCI) fue de 0,99, demostrando reproducibilidad excelente. Conclusión: El método de Cobb puede ser utilizado para la evaluación de la escoliosis a través de la herramienta "PixViewer" con la misma fiabilidad que el método clásico en radiografías impresas.

McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to ‘growing pains’ and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test. A doença de McArdle é o tipo mais frequente das glicogenoses. A apresentação clínica característica na infância inclui mialgia e intolerância aos esforços/exercício físico. Frequentemente, os sinais e sintomas das crianças não são considerados devidamente, sendo muitas vezes interpretados como “dores do crescimento”, retardando o diagnóstico. Erros diagnósticos não são raros uma vez que outras doenças, como distrofia muscular ou canalopatias musculares, podem apresentar sintomas semelhantes. Entretanto, um simples teste de exercício físico realizado no ambulatório/consultório médico pode ajudar a identificar estes pacientes pois evidencia o fenômeno second wind, patognomônico da doença de McArdle. Aqui é descrito um relato de caso de um paciente ilustrando o valor do simples 12 minutes walk test.

A 45-year-old Brazilian white female was admitted with a four-year history of progressive proximal muscle weakness and myalgia. A chest radiogram was normal at the beginning of the clinical presentation. A few weeks before hospital admission, she developed diffuse weakness, dysphagia and exertion dyspnea. A physical examination showed weakness of facial and proximal muscles and severe wasting of hand muscles. Her family history was negative for neuromuscular diseases. The erythrocyte sedimentation rate was 92 mm in the first hour, and the serum creatine kinase level was high (6,683 IU/L, with a normal range being up to 176 IU/L). Antinuclear antibodies (1/640, granular pattern) and circulating anti-Ro/SSA antibodies (56.7 IU) were present. No other autoantibodies were found. A dried blood spot test for Pompe disease was negative. Neurophysiology assessment showed myopathic changes. A muscle biopsy performed 4 years after disease onset showed increased variation in fibre size, increased connective tissue, internal nuclei, occasional atrophic fibres and necrotic fibres. There was a prominent endomysial and perimysial inflammatory infiltrate composed of lymphoctes and macrophages with the formation of non-necrotic granulomas including small numbers of multinucleate giant cells (Fig. 1). A second piece of tissue taken from the same muscle showed no inflammatory features. Investigations for tuberculosis, fungi and brucellosis were negative. Lung computed tomography performed after 4 years of disease onset showed typical bilateral hilar lymphadenopathy and interstitial pneumonitis

Rhabdomyolysis is often due to a combination of environmental trigger(s) and genetic predisposition; however, the underlying genetic cause remains elusive in many cases. Mutations in CAV3 lead to various neuromuscular phenotypes with partial overlap, including limb girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, distal myopathy and isolated hyperCKemia. Here we present a series of eight patients from seven families presenting with exercise intolerance and rhabdomyolysis caused by mutations in CAV3 diagnosed by next generation sequencing (NGS) (n = 6). Symptoms included myalgia (n = 7), exercise intolerance (n = 7) and episodes of rhabdomyolysis (n = 2). Percussion-induced rapid muscle contractions (PIRCs) were seen in five out of six patients examined. A previously reported heterozygous mutation in CAV3 (p.T78M) and three novel variants (p.V14I, p.F41S, p.F54V) were identified. Caveolin-3 immunolabeling in muscle was normal in 3/4 patients; however, immunoblotting showed more than 50% reduction of caveolin-3 in five patients compared with controls. This case series demonstrates that exercise intolerance, myalgia and rhabdomyolysis may be caused by CAV3 mutations and broadens the phenotypic spectrum of caveolinopathies. In our series, immunoblotting was a more sensitive method to detect reduced caveolin-3 levels than immunohistochemistry in skeletal muscle. Patients presenting with muscle pain, exercise intolerance and rhabdomyolysis should be routinely tested for PIRCs as this may be an important clinical clue for caveolinopathies, even in the absence of other "typical" features. The use of NGS may expand current knowledge concerning inherited diseases, and unexpected/atypical phenotypes may be attributed to well-known human disease genes.

A 35-year-old Afro-Caribbean woman presented with dyspnoea, urticarial rash and myalgia 1 month after treatment for a community-acquired respiratory tract infection. Investigations revealed raised antisynthetase antibodies, lung fibrosis and an inflammatory myopathy. The patient was diagnosed with antisynthetase syndrome (ASS) and started on immunosuppressive medication. Despite treatment she died 4 weeks after presentation from a fulminant cardiomyopathy. ASS is a rare condition and is not typically associated with a cardiomyopathy. This case report intends to raise awareness that cardiomyopathy is a potentially fatal complication of ASS.

Background: There is no single test that defines properly lumbar spinal stenosis (LSS) diagnosis, and diagnosis of the syndrome continues to rely on clinical judgment. LSS symptoms may be broad and may be seen in multiple disorders in elderly. Hypothesis: To identify the role of electromyography and nerve-conduction studies on LSS diagnosis. Materials and Methods: A cross-sectional study with prospective data collection was conducted. 31 symptomatic patients with LSS confirmed by MRI were evaluated with neurophysiology tests. We compared symptoms and neurophysiologic findings. Results: All patients reported pain, 83.9% of patients reported it to be moderate or severe and 90% of patients took pain medication. LSS did not affect NCS or SSR. Electromyography confirmed high frequency of radiculopathy, particularly multiradiculopathy. L5 and S1 roots were the most susceptible to injuries. We also found a higher prevalence of L4 radiculopathy. Discussion: Correlating electromyography with clinical findings, we found that the clinical presentation, the most important starting point of an evaluation, is poor in terms of identifying radiculopathy, a frequent consequence of LSS. For this reason, we suggest that electromyography may play an important role as a diagnostic tool, being useful in determining when symptoms are neurogenic in nature. In addition, it may serve to focus treatment only in the area where it is really necessary

Introduction: The influence of cold temperatures on neuropathies has been reported previously, but its impact on carpal tunnel syndrome (CTS) is not well analyzed. Methods: We analyzed the frequency of CTS among neurophysiological evaluations according to seasonal variation in 9574 consecutive patients (4260 with CTS). Results: A higher frequency of CTS was found in the winter (50.8%), and the lowest number for CTS diagnosis was found in the summer (38.9%). In both autumn and spring the prevalence remained stable at an intermediate level between summer and winter at 42.8% and 43.5%, respectively. Conclusion: CTS frequency was much higher in winter in this center. Muscle Nerve 47: 925–927, 2013

OBJECTIVE: The aim of this study is to investigate the presenting profile of patients with carpal tunnel syndrome (CTS) at various ages. METHODS: We performed a cross-sectional study of CTS, analysing the correlation between severity and age. RESULTS: We examined 3108 subjects with CTS, whose frequency increased from 20.9% for the age group 20-29 years to 61.7% for the age group 50-59 years. It remained at almost 50% in people aged over 80 years (49.2%). More than 50% of people younger than 30 years had mild CTS. Severe CTS progressively increased, reaching more than 50% of the CTS diagnoses in people over 80 years. Of the total number of cases, 80.8% of subjects had bilateral CTS. Mild NCS-EMG abnormalities were seen in 74.1% of patients with unilateral involvement, whereas moderate and severe CTS appeared in 70.3% of patients with bilateral involvement. CONCLUSION: There was a clear trend of deterioration with advancing years when comparing severity to age. SIGNIFICANCE: CTS seems to be a chronic condition whose signs and symptoms may vary and progress, becoming worse over time.

arteri osus without clinical symptoms or haemody-namic repercussion. Association between ALS and pregnancy has rarely been described. Since 1977, 19 pregnancies in 16 women have been reported, including the present case (2 6). As foetal growth can be affected by mul-tiple factors, it is diffi cult to attribute this fi nding to the drug use. This is the fi rst report of association between riluzole use and cardiac malformation, although prevalence of cardiac malformations in the general population is considerable. Riluzole use during pregnancy is thought to be harmless, but foetal effects are unknown. It is catego-rized as a Class C drug by the Food and Drug Administration (FDA) (7). The only case of riluzole use throughout pregnancy reported a low birth weight of the newborn, but IURG was not consid-ered because of an uncertain gestational age (2). There has been another case in which riluzole was used until pregnancy diagnosis, at nine weeks GA, when the drug was discontinued (3). ALS seems not to cause obstetric complications. In advanced cases, respiratory complications have been described (4). This was not seen in our patient, whose neurological evaluation deteriorated as a normal progression. Also, uterine contractions seem not to be adversely affected by ALS (5). No clear evidence exists as to the better method of delivery. Besides incipient respiratory failure, caesarean delivery indication should follow obstetrics routine (6).

Despite the majority of patients with McArdle disease reporting symptoms including fatigue, cramps and episodes of myoglobinuria from early childhood, diagnosis is often delayed by several decades. Additionally, many individuals with rhabdomyolysis remain undiagnosed. The occurrence of symptoms during exercise, particularly isometric muscle contraction such as heavy lifting, is well known in McArdle disease. However, isometric muscle contraction that occurs with emotion is not recognised as exercise and may be missed as a trigger for rhabdomyolysis, potentially leading to a delay in diagnosis. Three patients are presented here, all with symptoms from childhood including episodes of rhabdomyolysis induced by tense emotional situations without physical exertion; two patients reported recurrent episodes while watching rather than playing football. The remaining patient developed rhabdomyolysis during a heated argument. These patients' histories emphasise the risk from sustained isometric muscle contraction that occurs in emotive situations for patients with McArdle disease.

McArdle disease is a rare condition and often people have had symptoms for many years before the diagnosis is made. There is no specific treatment for the condition but early diagnosis and appropriate management may improve exercise tolerance and prevent acute rhabdomyolysis. Here we present a patient with McArdle disease where an acute episode of neck muscle contracture causing nuchal rigidity was misdiagnosed as meningitis. The patient went onto develop an acute allergic reaction to systemic penicillin with potential life-threatening complications. The patient’s neck contracture was induced by dental extraction during which she was required to hold her mouth open and neck rigid for a prolonged time. This case illustrates that contracture in McArdle disease does not necessarily follow ’exercise’ and highlights the need for careful management during procedures.

The European Union has funded the development of a new disease registry for McArdle disease and other rare glyco (geno) lytic disorders presenting with exercise intolerance. The aim of the project is to identify as many patients as possible across all European countries and to collect important natural history and epidemiological data. Clinicians working in the European Union (EU) and patients with McArdle disease or other rare glyco (geno) lytic disorders presenting with exercise intolerance from the EU are able to participate in this project. Registration is via a secure web platform accessed through the EUROMAC website http://euromacregistry.eu/ . Both patients and doctors will need to supply epidemiological and clinical information. Data will be anonymised to ensure participants’ protection. We hope to create the largest international cohort of people with such rare conditions. Data on epidemiology and natural history will be generated, supporting knowledge about these rare disorders. We hope to increase awareness of these disorders and the website will signpost patients and clinicians to diagnostic and clinical centres of excellence across Europe. We plan to develop standards of care which will be posted on the website and we hope that the registry will be the gateway to future large scale multi-centre clinial trials. The EUROMAC is an international registry for patients with McArdle disease and other rare glyco (geno) lytic disorders presenting with exercise intolerance and it is open to all EU residents. Further information is presented online in the EUROMAC website http://euromacregistry.eu/ . We seek to recruit as many European partners as possible and welcome collaborators and volunteers both from health services and patient support organisations.

4,055 JCR (2014) Q1, posicion 27 de 192 (Clinical Neurology), posicion 61 de 252 (Neurosciences)