The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers.

BACKGROUND AND PURPOSE: Rhabdomyolysis is a medical emergency characterized by acute skeletal muscle breakdown with a sudden rise and subsequent fall of serum creatine kinase (CK) levels. Rhabdomyolysis events are provoked by exposure to external triggers, possibly in combination with an increased genetic susceptibility. We aimed to describe comprehensively the external triggers and potentially pathogenic genetic variants possibly implicated in increased rhabdomyolysis susceptibility. METHODS: We performed a retrospective single-center study, including a total of 1302 patients with an acute CK level exceeding 2000 IU/l. RESULTS: Anoxia was the most frequently reported trigger (40%). A subset of 193 patients were clinically suspected of an underlying genetic disorder (recurrent episodes, a positive family history, very high or persistently increased CK levels). In 72 of these patients, an unequivocal genetic defect was identified. A total of 22 genes with pathogenic variants were identified, including 52 different variants. Of those, 11 genes have been previously associated with rhabdomyolysis (ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, RYR1). Eleven genes are probably implicated in increased susceptibility (including AGL, CAPN3, CNBP, DMPK, MAGT1, ACADM, SCN4A, SGCA, SGCG, SMPD1, TANGO2). CONCLUSION: These findings suggest that the spectrum of genetic susceptibility for rhabdomyolysis has not yet been completely clarified. With the increasing availability of next-generation sequencing in a diagnostic setting, we expect that in more cases a genetic defect will be identified.

Phenotype and genotype of muscle ryanodine receptor rhabdomyolysis-myalgia syndrome.

OBJECTIVES: Rhabdomyolysis and myalgia are common conditions, and mutation in the ryanodine receptor 1 gene (RYR1) is suggested to be a common cause. Due to the large size of RYR1, however, sequencing has not been widely accessible before the recent advent of next-generation sequencing technology and limited phenotypic descriptions are therefore available. MATERIAL & METHODS: We present the medical history, clinical and ancillary findings of patients with RYR1 mutations and rhabdomyolysis and myalgia identified in Denmark, France and The Netherlands. RESULTS: Twenty-two patients with recurrent rhabdomyolysis (CK > 10 000) or myalgia with hyperCKemia (>1.5 × ULN) and a RYR1 mutation were identified. One had mild wasting of the quadriceps muscle, but none had fixed weakness. Symptoms varied from being restricted to intense exercise to limiting ADL function. One patient developed transient kidney failure during rhabdomyolysis. Two received immunosuppressants on suspicion of myositis. None had episodes of malignant hyperthermia. Muscle biopsies were normal, but CT/MRI showed muscle hypertrophy in most. Delay from first symptom to diagnosis was 12 years on average. Fifteen different dominantly inherited mutations were identified. Ten were previously described as pathogenic and 5 were novel, but rare/absent from the background population, and predicted to be pathogenic by in silico analyses. Ten of the mutations were reported to give malignant hyperthermia susceptibility. CONCLUSION: Mutations in RYR1 should be considered as a significant cause of rhabdomyolysis and myalgia syndrome in patients with the characteristic combination of rhabdomyolysis, myalgia and cramps, creatine kinase elevation, no weakness and often muscle hypertrophy.

Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients.

The tenascin-X (TNX) deficient type Ehlers-Danlos syndrome (EDS) is similar to the classical type of EDS. Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX-deficient type EDS is probably to be under diagnosed. We therefore performed an observational, cross-sectional study. History and physical examination were performed. Results of serum TNX measurements were collected and mutation analysis was performed by a combination of next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). Included were 17 patients of 11 families with autosomal recessive inheritance and childhood onset. All patients had hyperextensible skin without atrophic scarring. Hypermobility of the joints was observed in 16 of 17 patients. Deformities of the hands and feet were observed frequently. TNX serum level was tested and absent in 11 patients (seven families). Genetic testing was performed in all families; 12 different mutations were detected, most of which are suspected to lead to non-sense mRNA mediated decay. In short, patients with the TNX-deficient type EDS typically have generalized joint hypermobility, skin hyperextensibility and easy bruising. In contrast to the classical type, the inheritance pattern is autosomal recessive and atrophic scarring is absent. Molecular analysis of TNXB in a diagnostic setting is challenging.

RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction.

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene are associated with a wide spectrum of inherited myopathies presenting throughout life. Malignant hyperthermia susceptibility (MHS)-related RYR1 mutations have emerged as a common cause of exertional rhabdomyolysis, accounting for up to 30% of rhabdomyolysis episodes in otherwise healthy individuals. Common triggers are exercise and heat and, less frequently, viral infections, alcohol and drugs. Most subjects are normally strong and have no personal or family history of malignant hyperthermia. Heat intolerance and cold-induced muscle stiffness may be a feature. Recognition of this (probably not uncommon) rhabdomyolysis cause is vital for effective counselling, to identify potentially malignant hyperthermia-susceptible individuals and to adapt training regimes. Studies in various animal models provide insights regarding possible pathophysiological mechanisms and offer therapeutic perspectives.

The wrong end of the telescope: neuromuscular mimics of movement disorders (and vice versa).

The rapid advances in modern neurology have led to increased specialisation in clinical practice. Being an expert in a neurology subspecialty offers advantages for diagnosing and managing specific disorders. However, specialisation also risks tunnel vision: interpreting symptoms and signs within one's own framework of reference, while ignoring differential diagnostic options from other subspecialties. This is particularly relevant when the patient's presentation potentially belongs to different neurological subspecialties. We illustrate this challenge by highlighting a series of clinical features that partially overlap between two common subspecialties: movement disorders and neuromuscular disorders. An overlap in clinical presentation is not rare, and includes, for example, involuntary eyelid closure (which could be active eye closure due to blepharospasm, or ptosis due to weakness). Other overlapping features include abnormal postures, involuntary movements and gait changes. We describe two of these overlapping features in more detail and emphasise the possible consequences of 'looking through the wrong end of the telescope' in such patients, as this may lead to a wrong differential diagnosis, unnecessary investigations and a delayed treatment start.

The neuromuscular differential diagnosis of joint hypermobility.

Joint hypermobility is the defining feature of various inherited connective tissue disorders such as Marfan syndrome and various types of Ehlers-Danlos syndrome and these will generally be the first conditions to be considered by geneticists and pediatricians in the differential diagnosis of a patient presenting with such findings. However, several congenital and adult-onset inherited myopathies also present with joint hypermobility in the context of often only mild-to-moderate muscle weakness and should, therefore, be included in the differential diagnosis of joint hypermobility. In fact, on the molecular level disorders within both groups represent different ends of the same spectrum of inherited extracellular matrix (ECM) disorders. In this review we will summarize the measures of joint hypermobility, illustrate molecular mechanisms these groups of disorders have in common, and subsequently discuss the clinical features of: 1) the most common connective tissue disorders with myopathic or other neuromuscular features: Ehlers-Danlos syndrome, Marfan syndrome and Loeys-Dietz syndrome; 2) myopathy and connective tissue overlap disorders (muscle extracellular matrix (ECM) disorders), including collagen VI related dystrophies and FKBP14 related kyphoscoliotic type of Ehlers-Danlos syndrome; and 3) various (congenital) myopathies with prominent joint hypermobility including RYR1- and SEPN1-related myopathy. The aim of this review is to assist clinical geneticists and other clinicians with recognition of these disorders.

Diagnostic power of the non-ischaemic forearm exercise test in detecting glycogenosis type V.

BACKGROUND AND PURPOSE: This was a retrospective study to assess the diagnostic value of the non-ischaemic forearm exercise test in detecting McArdle's disease. METHODS: The study is a retrospective diagnostic study over 15 years (1999-2013) on a referred sample of patients suffering from exercise intolerance and various muscle complaints, generally with elevated creatine kinase (CK). In all, 1226 patients underwent the non-ischaemic forearm exercise test. Blood lactate, ammonia and CK levels were analyzed. DNA analyses and/or muscle biopsies were assessed to confirm the diagnosis of McArdle's disease. The results of 60 volunteers were used to compare with the results of study subjects. RESULTS: In this cohort, 40 patients were finally diagnosed with McArdle's disease. Absolute values of lactate and ammonia rise were used to discriminate all McArdle patients from healthy patients. A sensitivity and specificity of respectively 100% and 99.7% were calculated. The 24-h CK level showed no significant difference from the CK level at the day of the test and confirms the safety of the test. CONCLUSIONS: This study has formally assessed the diagnostic value of the non-ischaemic forearm exercise test in the detection of McArdle's disease. Very high sensitivity and specificity were observed. Furthermore, the test is easy to set up and to perform, it is non-traumatic and cost effective. It may circumvent a muscle biopsy in McArdle patients presenting the most common mutations. Hence, it is a perfect and safe screening instrument to detect patients with McArdle's disease. Glycogen storage disease type III patients, however, may show similar patterns to McArdle patients.

RYR1-related myopathies: a wide spectrum of phenotypes throughout life.

BACKGROUND AND PURPOSE: Although several recent studies have implicated RYR1 mutations as a common cause of various myopathies and the malignant hyperthermia susceptibility (MHS) trait, many of these studies have been limited to certain age groups, confined geographical regions or specific conditions. The aim of the present study was to investigate the full spectrum of RYR1-related disorders throughout life and to use this knowledge to increase vigilance concerning malignant hyperthermia. METHODS: A retrospective cohort study was performed on the clinical, genetic and histopathological features of all paediatric and adult patients in whom an RYR1 mutation was detected in a national referral centre for both malignant hyperthermia and inherited myopathies (2008-2012). RESULTS: The cohort of 77 non-related patients (detection rate 28%) included both congenital myopathies with permanent weakness and 'induced' myopathies such as MHS and non-anaesthesia-related episodes of rhabdomyolysis or hyperCKemia, manifested throughout life and triggered by various stimuli. Sixty-one different mutations were detected, of which 24 were novel. Some mutations are present in both dominant (MHS) and recessive modes (congenital myopathy) of inheritance, even within families. Histopathological features included an equally wide spectrum, ranging from only subtle abnormalities to prominent cores. CONCLUSIONS: This broad range of RYR1-related disorders often presents to the general paediatric and adult neurologist. Its recognition is essential for genetic counselling and improving patients' safety during anaesthesia. Future research should focus on in vitro testing by the in vitro contracture test and functional characterization of the large number of RYR1 variants whose precise effects currently remain uncertain.

Oral ribose supplementation in dystroglycanopathy: A single case study.

Three forms of muscular dystrophy-dystroglycanopathies are linked to the ribitol pathway. These include mutations in the isoprenoid synthase domain-containing protein (ISPD), fukutin-related protein (FKRP), and fukutin (FKTN) genes. The aforementioned enzymes are required for generation of the ribitol phosphate linkage in the O-glycan of alpha-dystroglycan. Mild cases of dystroglycanopathy present with slowly progressive muscle weakness, while in severe cases the eyes and brain are also involved. Previous research showed that ribose increased the intracellular concentrations of cytidine diphosphate-ribitol (CDP-ribitol) and had a therapeutic effect. Here, we report the safety and effects of oral ribose supplementation during 6 months in a patient with limb girdle muscular dystrophy type 2I (LGMD2I) due to a homozygous FKRP mutation. Ribose was well tolerated in doses of 9 g or 18 g/day. Supplementation with 18 g of ribose resulted in a decrease of creatine kinase levels of 70%. Moreover, metabolomics showed a significant increase in CDP-ribitol levels with 18 g of ribose supplementation (p < 0.001). Although objective improvement in clinical and patient-reported outcome measures was not observed, the patient reported subjective improvement of muscle strength, fatigue, and pain. This case study indicates that ribose supplementation in patients with dystroglycanopathy is safe and highlights the importance for future studies regarding its potential effects.

Facioscapulohumeral Disease as a myodevelopmental disease: Applying Ockham's razor to its various features.

 Facioscapulohumeral muscular dystrophy (FSHD) is an exclusively human neuromuscular disease. In the last decades the cause of FSHD was identified: the loss of epigenetic repression of the D4Z4 repeat on chromosome 4q35 resulting in inappropriate transcription of DUX4. This is a consequence of a reduction of the array below 11 units (FSHD1) or of a mutation in methylating enzymes (FSHD2). Both require the presence of a 4qA allele and a specific centromeric SSLP haplotype. Muscles become involved in a rostro-caudally order with an extremely variable progression rate. Mild disease and non-penetrance in families with affected individuals is common. Furthermore, 2% of the Caucasian population carries the pathological haplotype without clinical features of FSHD.In order to explain the various features of FSHD we applied Ockham's Razor to all possible scenarios and removed unnecessary complexities. We postulate that early in embryogenesis a few cells escape epigenetic silencing of the D4Z4 repeat. Their number is assumed to be roughly inversely related to the residual D4Z4 repeat size. By asymmetric cell division, they produce a rostro-caudal and medio-lateral decreasing gradient of weakly D4Z4-repressed mesenchymal stem cells. The gradient tapers towards an end as each cell-division allows renewed epigenetic silencing. Over time, this spatial gradient translates into a temporal gradient based on a decreasing number of weakly silenced stem cells. These cells contribute to a mildly abnormal myofibrillar structure of the fetal muscles. They also form a downward tapering gradient of epigenetically weakly repressed satellite cells. When activated by mechanical trauma, these satellite cells de-differentiate and express DUX4. When fused to myofibrils they contribute to muscle cell death in various ways. Over time and dependent on how far the gradient reaches the FSHD phenotype becomes progressively manifest. We thus hypothesize FSHD to be a myodevelopmental disease with a lifelong attempt to restore DUX4 repression.

Development of Continuum of Care for McArdle disease: A practical tool for clinicians and patients.

McArdle disease (glycogen storage disease type V; GSDV) is a rare genetic disease caused by the inability to break down glycogen in skeletal muscle due to a deficiency in myophosphorylase. Glycolysis is only partially blocked in GSDV, as muscle fibres can take up circulating glucose and convert it to glucose-6-phosphate downstream of the metabolic block. Because skeletal muscle predominantly relies on anaerobic energy during the first few minutes of transition from rest to activity, and throughout more intense activities, individuals with GSDV experience muscle fatigue/pain, tachypnea, and tachycardia during these activities. If warning signs are not heeded, a muscle contracture may rapidly occur, and if significant, may lead to acute rhabdomyolysis. Without a cure or treatment, individuals with GSDV must be consistent in employing proper management techniques; however, this can be challenging due to the nuances inherent in this metabolic myopathy. The International Association for Muscle Glycogen Storage Disease collaborated with an international team of five expert clinicians to identify areas of learning to achieve an optimal state. A Continuum of Care model was developed that outlines five pivotal steps (diagnosis; understanding; acceptance; learning and exercise) to streamline assessments and more succinctly assist clinicians in determining patient-specific learning needs. This model serves as a translational tool to help optimize care for this patient population.

Establishing the role of muscle ultrasound as an imaging biomarker in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary muscle disease, that causes weakness and wasting of skeletal muscles. In this cross-sectional cohort-study on FSHD patients, we assessed muscle ultrasound findings and their relation to clinical outcome measures, evaluating the role of ultrasound as biomarker in FSHD. We included 115 genetically confirmed FSHD patients (52% males, age-range 22-80 years). They were subjected to a standardized muscle ultrasound protocol of seven truncal and upper- and lower extremity muscles bilaterally. Muscle images were scored using the Heckmatt scale. Muscle echogenicity was quantified using z-scores. Compound echogenicity and Heckmatt scores were calculated. Nearly all patients (94%) had one or multiple muscles with an increased echogenicity z-score. The trapezius muscle was most severely affected, followed by the rectus femoris muscle. Both compound ultrasound scores strongly with multiple clinical outcome measures (ρ 0.68-0.79, p < 0.001). While most muscles showed a high level of agreement between the echogenicity z-score and Heckmatt score (>95%), the tibialis anterior and gastrocnemius muscle showed lower levels of agreement (82 and 92%). In conclusion, our study confirms the use of muscle ultrasound as clinical severity biomarker and provides a solid base for future longitudinal studies to establish ultrasound as a monitoring biomarker in FSHD.

Facing facial weakness: psychosocial outcomes of facial weakness and reduced facial function in facioscapulohumeral muscular dystrophy.

PURPOSE: To assess the psychosocial outcomes of facial weakness in facioscapulohumeral muscular dystrophy (FSHD). MATERIALS AND METHODS: A cross-sectional survey study. The severity of facial weakness was assessed by patients (self-reported degree of facial weakness) and by physicians (part I FSHD clinical score). Questionnaires on facial function, psychosocial well-being, functioning, pain, and fatigue were completed. Regression analyses were performed to explain variance in psychosocial outcomes by demographic and disease variables. RESULTS: One hundred and thirty-eight patients participated. They reported mild to moderate psychological distress, no to mild fear of negative evaluation, and moderate to good social functioning. However, patients with severe self-reported facial weakness scored lower in social functioning. Patients with more facial dysfunction experienced more fear of negative evaluation and lower social functioning. Furthermore, younger age, presence of pain, fatigue, walking difficulty, and current or previous psychological support were associated with lower psychosocial outcomes. Overall, patients report moderate to good psychosocial functioning in this study. The factors contributing to lower psychosocial functioning are diverse. CONCLUSIONS: A multidisciplinary, personalized approach, focusing on coping with physical, emotional, and social consequences of FSHD is supposed to be helpful. Further research is needed to assess the psychosocial outcomes of facial weakness in younger patients.Implications for rehabilitationResearch on the psychosocial consequences of facial weakness in facioscapulohumeral muscular dystrophy (FSHD) is limited.Patients with FSHD experience mild to moderate psychosocial distress, partly due to overall disease severity, such as reduced mobility, and partly due to facial weakness and reduced facial function.Self-reported degree of facial weakness and facial dysfunction were related to lower psychosocial outcomes (social functioning, fear of negative evaluation, and psychological distress).Physician-reported degree of facial weakness was not related to psychosocial outcomes, suggesting an absence of a strong correlation between observed facial weakness and experienced disease burden in this study.This calls for a multidisciplinary, personalized approach with a focus on coping with physical, emotional, and social consequences of FSHD.

Dystrophic Myopathy of the Diaphragm with Recurrent Severe Respiratory Failure is Congenital Myasthenic Syndrome 11.

We here present the case of a patient with a congenital myasthenic syndrome (CMS) due to pathogenic variants in the RAPSN gene. During childhood he experienced recurrent episodes of respiratory failure during respiratory infections. This and other cases were reported as isolated dystrophy of the diaphragmatic musculature. In adulthood, whole exome sequencing revealed two heterozygous pathogenic variants in the RAPSN gene. This led to the revision of the diagnosis to rapsyn CMS11 (OMIM:616326, MONDO:0014588). EMG, muscle ultrasound and the revision of muscle biopsies taken in childhood support this diagnosis. After the revision of the diagnosis, treatment with pyridostigmine was started. This resulted in a reduction of fatigability and an improvement in functional abilities and quality of life.

Eye Muscle MRI in Myasthenia Gravis and Other Neuromuscular Disorders.

INTRODUCTION: MRI of extra-ocular muscles (EOM) in patients with myasthenia gravis (MG) could aid in diagnosis and provide insights in therapy-resistant ophthalmoplegia. We used quantitative MRI to study the EOM in MG, healthy and disease controls, including Graves' ophthalmopathy (GO), oculopharyngeal muscular dystrophy (OPMD) and chronic progressive external ophthalmoplegia (CPEO). METHODS: Twenty recently diagnosed MG (59±19yrs), nineteen chronic MG (51±16yrs), fourteen seronegative MG (57±9yrs) and sixteen healthy controls (54±13yrs) were included. Six CPEO (49±14yrs), OPMD (62±10yrs) and GO patients (44±12yrs) served as disease controls. We quantified muscle fat fraction (FF), T2water and volume. Eye ductions and gaze deviations were assessed by synoptophore and Hess-charting. RESULTS: Chronic, but not recent onset, MG patients showed volume increases (e.g. superior rectus and levator palpebrae [SR+LPS] 985±155 mm3 compared to 884±269 mm3 for healthy controls, p < 0.05). As expected, in CPEO volume was decreased (e.g. SR+LPS 602±193 mm3, p < 0.0001), and in GO volume was increased (e.g. SR+LPS 1419±457 mm3, p < 0.0001). FF was increased in chronic MG (e.g. medial rectus increased 0.017, p < 0.05). In CPEO and OPMD the FF was more severely increased. The severity of ophthalmoplegia did not correlate with EOM volume in MG, but did in CPEO and OPMD. No differences in T2water were found. INTERPRETATION: We observed small increases in EOM volume and FF in chronic MG compared to healthy controls. Surprisingly, we found no atrophy in MG, even in patients with long-term ophthalmoplegia. This implies that even long-term ophthalmoplegia in MG does not lead to secondary structural myopathic changes precluding functional recovery.

Exertional Heat Stroke and Rhabdomyolysis: A Medical Record Review and Patient Perspective on Management and Long-Term Symptoms.

INTRODUCTION: Exertional heat stroke (EHS) is a medical emergency, occurring when the body generates more heat than it can dissipate, and frequently associated with exertional rhabdomyolysis (ERM). In the present study we aimed to (I) identify clinical features and risk factors, (II) describe current prehospital management, (III) investigate long-term outcomes including the impact on mental health, and review the guidance received during restarting activities. We hope that our approach will improve individual and organizational heat illness preparedness, and improve follow-up care. METHODS: We performed a prospective online survey and retrospective medical record review among athletes and military personnel with an episode of EHS/ERM in the Netherlands between 2010 and 2020. We evaluated prehospital management, risk factors, clinical features and long-term outcomes at 6 and 12 months after the event, including mental health symptoms. Furthermore, we investigated what guidance participants received during follow-up, and assessed the patients' perspective on these outcomes. RESULTS: Sixty participants were included, 42 male (70%) and 18 female (30%), of which 47 presented with EHS (78%) and 13 with ERM (22%). Prehospital management was inconsistent and in the majority of participants not conducted according to available guidelines. Self-reported risk factors included not feeling well-acclimatized to environmental heat (55%) and peer pressure (28%). Self-reported long-term symptoms included muscle symptoms at rest (26%) or during exercise (28%), and neurological sequelae (11%). Validated questionnaires (CIS, HADS and SF-36) were indicative of severe fatigue (30%) or mood/anxiety disorders (11%). Moreover, 90% expressed a lack of follow-up care and that a more frequent and intensive follow-up would have been beneficial for their recovery process. CONCLUSION: Our findings indicate major inconsistencies in the management of patients with EHS/ERM, emphasizing the compelling need for implementing standardized protocols. Based on the results of long-term outcome measures, we recommend to counsel and evaluate every patient not only immediately after the event, but also in the long-term.

Myopathy in a 20-year-old female patient with D4ST-1 deficient Ehlers-Danlos syndrome due to a homozygous CHST14 mutation.

We here report on a 20-year-old female patient with EDS due to a homozygous CHST14 single nucleotide deletion resulting in D4ST-1 deficiency, accompanied by muscle hypoplasia and muscle weakness. Findings of muscle ultrasound, electromyography, and muscle biopsy pointed to a myopathy, similarly as in other EDS types. This myopathy probably contributes to the gross motor developmental delay in this type of EDS.

Perioperative Care for Patients with Neuromuscular Disorders in the Netherlands - A Questionnaire Study Among Anaesthesiologists, Neurologists and Clinical Geneticists.

BACKGROUND: Patients with neuromuscular disorders are at increased risk of suffering perioperative complications. Current knowledge concerning this topic is based on small retrospective studies and expert opinion. Therefore, an individualized multidisciplinary approach to perioperative anaesthesia planning is invaluable to anticipate difficulties and to optimize outcomes. OBJECTIVE: To evaluate current practice regarding preoperative counselling and perioperative care of neuromuscular patients, with the aim to facilitate standardization and improvement of perioperative care for neuromuscular patients. METHODS: A questionnaire-based cross-sectional, observational study was conducted between July, 1st 2020 and December, 31st, 2020 in Dutch anaesthesia, neurology and clinical genetics departments. Main outcome measures were 1.) frequency of consultation requests for neuromuscular patients prior to surgery, 2.) current practice, educational activities and departmental approach to this topic and 3.) preoperative counselling of neuromuscular patients. RESULTS: A total of 83 departments participated. Consultations for a neuromuscular patient scheduled for anaesthesia were requested from anaesthesia and neurology department only infrequently. Local guidelines concerning perioperative care of neuromuscular patients were available in 36.4% of the participating departments. Quality of specific training for residents and staff anaesthetists/neurologists covering perioperative care of neuromuscular patients was rated as 'very good' or 'good' by 42.9%. Neuromuscular patients scheduled for surgery were 'always' or 'often' discussed in multidisciplinary meetings involving anaesthesiologists and neurologists in 20.8% of the participating departments. CONCLUSION: Perioperative care for neuromuscular patients in the Netherlands is highly variable and might benefit from guidelines, education of health care professionals and multidisciplinary meetings between anaesthesiologists and neurologists on a regular basis.