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Item does not contain fulltext, 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 compellin

Item does not contain fulltext, BACKGROUND: Variants in RYR1, the gene encoding the ryanodine receptor-1, can give rise to a wide spectrum of neuromuscular conditions. Muscle imaging abnormalities have been demonstrated in isolated cases of patients with a history of RYR1-related malignant hyperthermia (MH) susceptibility. OBJECTIVE: To provide insights into the type and prevalence of muscle ultrasound abnormalities and muscle hypertrophy in patients carrying gain-of-function RYR1 variants associated with MH susceptibility and to contribute to delineating the wider phenotype, optimizing the diagnostic work-up and care for MH susceptible patients. METHODS: We performed a prospective cross-sectional observational muscle ultrasound study in patients with a history of RYR1-related MH susceptibility (n = 40). Study procedures included a standardized history of neuromuscular symptoms and a muscle ultrasound assessment. Muscle ultrasound images were analyzed using a quantitative and qualitative approach and compared to reference values and subsequently subjected to a screening protocol for neuromuscular disorders. RESULTS: A total of 15 (38%) patients had an abnormal muscle ultrasound result, 4 (10%) had a borderline muscle ultrasound screening result, and 21 (53%) had a normal muscle ultrasound screening result. The proportion of symptomatic patients with an abnormal result (11 of 24; 46%) was not significantly higher compared to the proportion of asymptomatic patients with an abnormal ultrasound result (4 of 16; 25%) (P = 0.182). The mean z-scores of the biceps brachii (z = 1.45; P < 0.001), biceps femoris (z = 0.43; P = 0.002), deltoid (z = 0.31; P = 0.009), trapezius (z = 0.38; P = 0.010) and the sum of all muscles (z = 0.40; P < 0.001) were significantly higher compared to 0, indicating hypertrophy. CONCLUSIONS: Patients with RYR1 variants resulting in MH susceptibility often have muscle ultrasound abnormalities. Frequently observed muscle ultrasound abnormalities include muscle hypertrophy and incr

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Item does not contain fulltext, BACKGROUND AND PURPOSE: Patients with neuromuscular conditions are at increased risk of suffering perioperative complications related to anaesthesia. There is currently little specific anaesthetic guidance concerning these patients. Here, we present the European Neuromuscular Centre (ENMC) consensus statement on anaesthesia in patients with neuromuscular disorders as formulated during the 259th ENMC Workshop on Anaesthesia in Neuromuscular Disorders. METHODS: International experts in the field of (paediatric) anaesthesia, neurology, and genetics were invited to participate in the ENMC workshop. A literature search was conducted in PubMed and Embase, the main findings of which were disseminated to the participants and presented during the workshop. Depending on specific expertise, participants presented the existing evidence and their expert opinion concerning anaesthetic management in six specific groups of myopathies and neuromuscular junction disorders. The consensus statement was prepared according to the AGREE II (Appraisal of Guidelines for Research & Evaluation) reporting checklist. The level of evidence has been adapted according to the SIGN (Scottish Intercollegiate Guidelines Network) grading system. The final consensus statement was subjected to a modified Delphi process. RESULTS: A set of general recommendations valid for the anaesthetic management of patients with neuromuscular disorders in general have been formulated. Specific recommendations were formulated for (i) neuromuscular junction disorders, (ii) muscle channelopathies (nondystrophic myotonia and periodic paralysis), (iii) myotonic dystrophy (types 1 and 2), (iv) muscular dystrophies, (v) congenital myopathies and congenital dystrophies, and (vi) mitochondrial and metabolic myopathies. CONCLUSIONS: This ENMC consensus statement summarizes the most important considerations for planning and performing anaesthesia in patients with neuromuscular disorders.

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Contains fulltext : 282657.pdf (Publisher’s version ) (Open Access), Malignant hyperthermia (MH) is a life-threatening reaction triggered by volatile anesthetics and succinylcholine. MH is caused by mutations in the skeletal muscle ryanodine receptor (RYR1) gene, as is rhabdomyolysis triggered by exertion and/or pyrexia. The discrepancy between the prevalence of risk genotypes and actual MH incidence remains unexplained. We investigated the role of pre-operative exercise and pyrexia as potential MH modifying factors. We included cases from 5 MH referral centers with 1) clinical features suggestive of MH, 2) confirmation of MH susceptibility on Contracture Testing (IVCT or CHCT) and/or RYR1 genetic testing, and a history of 3) strenuous exercise within 72 h and/or pyrexia >37.5 °C prior to the triggering anesthetic. Characteristics of MH-triggering agents, surgery and succinylcholine use were collected. We identified 41 cases with general anesthesias resulting in an MH event (GA+MH, n = 41) within 72 h of strenuous exercise and/or pyrexia. We also identified previous general anesthesias without MH events (GA-MH, n = 51) in the index cases and their MH susceptible relatives. Apart from pre-operative exercise and/or pyrexia, trauma and acute abdomen as surgery indications, emergency surgery and succinylcholine use were also more common with GA+MH events. These observations suggest a link between pre-operative exercise, pyrexia and MH.

Contains fulltext : 252087.pdf (Publisher’s version ) (Open Access), PURPOSE: Patients with neuromuscular disorders (NMDs) are at increased risk of perioperative complications. The objective of this scoping review was to examine emerging evidence from published studies, case reports, and review articles on anesthetic management of patients with NMDs, following the methodological frame for scoping reviews. SOURCES: We searched PubMed and EMBASE for articles published between 1 January 2000 and 14 July 2021. PRINCIPAL FINDINGS: Three prospective and 21 retrospective studies on altered pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBA) in NMD patients were included. Furthermore, 168 case reports/series reporting 212 anesthetics in 197 patients were included. These studies showed that preanesthetic neuromuscular monitoring can be used for precise NMBA dosing in myasthenia gravis patients. Sugammadex was associated with fewer postoperative myasthenic crises. Perioperative complications were not associated with specific anesthetic agents. Case reports/series showed that in 32% (67/212) of anesthetics, at least one complication was reported. Unexpected intensive care unit admission was a frequently reported complication. Patients with a complicated disease course may have had a higher use of succinylcholine (unadjusted relative risk, 0.13; 95% confidence interval [CI], 0.20 to 0.86) and volatile anesthetics (adjusted odds ratio [OR], 0.38; 95% CI, 0.20 to 0.73; P = 0.004). CONCLUSION: Evidence on the anesthetic management and perioperative complications of patients with NMDs is mainly based on small retrospective studies and case reports. Further clinical trials or large retrospective studies are required to investigate the choice of safe anesthetic agents. Main areas of interest are the potential benefits of neuromuscular monitoring and sugammadex and the risks possibly associated with volatile anesthetics and succinylcholine.

Contains fulltext : 231548.pdf (Publisher’s version ) (Open Access), 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.

Contains fulltext : 238097.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Malignant hyperthermia (MH) and exertional rhabdomyolysis (ERM) have long been considered episodic phenotypes occurring in response to external triggers in otherwise healthy individuals with variants in RYR1. However, recent studies have demonstrated a clinical and histopathological continuum between patients with RYR1-related congenital myopathies and those with ERM or MH susceptibility. Furthermore, animal studies have shown non-neuromuscular features such as a mild bleeding disorder and an immunological gain-of-function associated with MH/ERM related RYR1 variants raising important questions for further research. Awareness of the neuromuscular disease spectrum and potential multisystem involvement in RYR1-related MH and ERM is essential to optimize the diagnostic work-up, improve counselling and and future treatment strategies for patients affected by these conditions. This study will examine in detail the nature and severity of continuous disease manifestations and their effect on daily life in patients with RYR1-related MH and ERM. METHODS: The study protocol consists of four parts; an online questionnaire study, a clinical observational study, muscle imaging, and specific immunological studies. Patients with RYR1-related MH susceptibility and ERM will be included. The imaging, immunological and clinical studies will have a cross-sectional design, while the questionnaire study will be performed three times during a year to assess disease impact, daily living activities, fatigue and pain. The imaging study consists of muscle ultrasound and whole-body magnetic resonance imaging studies. For the immunological studies, peripheral mononuclear blood cells will be isolated for in vitro stimulation with toll-like receptor ligands, to examine the role of the immune system in the pathophysiology of RYR1-related MH and ERM. DISCUSSION: This study will increase knowledge of the full spectrum of neuromuscular and multisystem features of RYR1-related MH and ERM

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Contains fulltext : 220355.pdf (publisher's version ) (Open Access)

Contains fulltext : 221721.pdf (Publisher’s version ) (Closed access), BACKGROUND: Laparoscopy is the gold standard for many surgical procedures and is embraced as minimally invasive surgery in the enhanced recovery after surgery programme. Lowering intra-abdominal pressure during laparoscopy may decrease the degree of surgical injury and further enhance patient outcomes. This study aims to assess the effect of low pressure pneumoperitoneum on peritoneal perfusion during laparoscopic surgery. MATERIALS AND METHODS: We performed a prospective randomized intervention study in 30 adults undergoing colorectal robot assisted laparoscopic surgery at a secondary care medical center in the Netherlands between June and December 2018. A 3 min video recording of the parietal peritoneum was made with the Da Vinci® Firefly mode following intravenous injection of 0.2 mg/kg indocyanine green at a pneumoperitoneum pressure of 8, 12 or 16 mmHg. Observers were blinded for the level of intra-abdominal pressure that was used. Fluorescent intensity in [-] over time was extracted from each video in MATLAB. Time to reach maximal fluorescent intensity (TMFI) and maximum fluorescent intensity (MFI) were compared among groups. The study was registered at clinicaltrials.gov (NCT03928171). RESULTS: Mean TMFI was shorter at low pressure (8 mmHg) than standard pressure (12 and 16 mmHg): 44 ± 12 versus 58 ± 18 s (p = 0.032), respectively. Mean MFI was higher at 8 mmHg than 12 and 16 mmHg (222 ± 25 versus 188 ± 54, p = 0.033). Regression analysis identified intra-abdominal pressure, mean arterial pressure and female gender as significant predictors of peritoneal perfusion. CONCLUSION: Low pressure pneumoperitoneum was associated with improved perfusion of the parietal peritoneum. Current available evidence supported feasibility and enhanced postoperative recovery. Future investigations should focus on optimizing factors that facilitate lower intra-abdominal pressure and explore effects on other clinically relevant patient outcomes such as anastomotic leakage and immu

1 november 2019, Item does not contain fulltext

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Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted.

Summary: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB pro

Acquired demyelinating syndromes (ADS) can be a first presentation of multiple sclerosis (MS) in children. The incidence of these disorders in Europe is currently unknown. Children (<18 years old) living in the Netherlands who presented with ADS were included from January 1, 2007 to December 31, 2010 by the Dutch pediatric MS study group and the Dutch surveillance of rare pediatric disorders. Demographic and clinical data were collected. Eighty-six patients were identified over 4 years, resulting in an incidence of 0.66/1,00,000 per year. Most patients presented with polyfocal ADS without encephalopathy (30%), followed by polyfocal ADS with encephalopathy (24%), optic neuritis (ON, 22%), monofocal ADS (16%), transverse myelitis (3%), and neuromyelitis optica (3%). Patients with polyfocal ADS with encephalopathy were younger (median 3.9 years) than patie

Radboud Universiteit Nijmegen, 4 juli 2011, Promotor : Booij, L.H.D.J. Co-promotores : Driessen, J.J., Egmond, J. van, Snoeck, M.M.J., Contains fulltext : 89942.pdf (publisher's version ) (Open Access)

Survival from a malignant hyperthermia (MH) crisis is highly dependent on early recognition and prompt action. MH crises are very rare and an increasing use of total i.v. anaesthesia is likely to make it even rarer, leading to the potential risk of reduced awareness of MH. In addition, dantrolene, the cornerstone of successful MH treatment, is unavailable in large areas around the world thereby increasing the risk of MH fatalities in these areas. The European Malignant Hyperthermia Group collected and reviewed all guidelines available from the various MH centres in order to provide a consensus document. The guidelines consist of two textboxes: Box 1 on recognizing MH and Box 2 on the treatment of an MH crisis

Contains fulltext : 70454.pdf (publisher's version ) (Closed access)

KUN Katholieke Universiteit Nijmegen, 11 november 2004, Promotor : Sengers, R.C.A. Co-promotor : Gielen, M.J.M., Item does not contain fulltext, In this thesis the author studied the diagnostic procedures for susceptibility to malignant hyperthermia (MH), with special emphasis upon refining the biological diagnostic test and improving protocols and guidelines for investigation of MH susceptibility. MH is a pharmacogenetic disease of skeletal muscle which is mainly of concern during and following anaesthesia. Abnormalities in the calcium release channel of skeletal muscle sarcoplasmic reticulum, the ryanodine receptor, have been implicated as the central factor in the cause of the MH syndrome. The in vitro muscle contracture test (IVCT) is the standard test to establish an individual's risk of susceptibility to MH. The diagnostic sensitivity of 99.0% and the accompanying specificity of 93.6% of the standard halothane-caffeine IVCT have been determined in a joint European study. Sevoflurane, a potent inhalational anaesthetic agent that is structurally similar to halothane, has been able to trigger an abnormal contracture in human muscle in vitro. The IVCT is invasive, time consuming and it is a technically demanding test that requires expertise. Cultured skeletal muscle cells, obtained by percutaneous needle biopsies may well be applied in diagnostic tests for MH susceptibility since the dose-dependant Ca2+ response in cultured muscle cells of MH-susceptible individuals is significantly different from that of control individuals after exposure to halothane. Because MH displays a high level of locus heterogeneity, it is not feasible to diagnose MH susceptibility, and, more specifically, to exclude MH risk, on the basis of a simple genetic test alone. Clinical practitioners and geneticists of the European MH Group have agreed on guidelines for the detection of MH susceptibility using molecular genetic techniques. Evaluation of the diagnostic procedure in 4 European MH investigation units helped to gain an insight into the need for further standardisation and quality assurance for the diagnosis of MH.

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Contains fulltext : 23590___.PDF (publisher's version ) (Open Access)