Antwerps Chirurgisch Training, Anatomie en Onderzoekscentrum

Laboratorium voor Maligne Hyperthermie - ASTARC

Laboratorium voor Maligne Hyperthermie

Universiteit Antwerpen
Campus Drie Eiken - Gebouw T – lokaal 5.62
Universiteitsplein 1
2610 Wilrijk

+32 (0)3 265 91 48

Doel

Klinisch advies met betrekking tot mogelijke MH-voorbeschiktheid
Diagnosestelling van Maligne Hyperthermie (MH) op basis van in vitro contractuur testing volgens het protocol van de Europese Groep voor MH
Opsporen van mogelijk geassociëerde structurele spierziekten
Familiale counselling
Wetenschappelijk onderzoek en medewerking aan internationale studies

Medewerkers

Dr Sultan Temurziev ^a,b sultan.temurziev@uza.be tel 03 821 30 42 (secretariaat Anesthesie UZA)
Prof Dr L Heytens^b - consulent
Prof Dr Jonathan Baets ^c,d,e
Dr Willem De Ridder ^c,d,e
Prof Dr Martin Lammens ^f
Natacha C Elizondo^e
Gerda Van de Vijver^e

^aDepartment of Anaesthesia, University Hospital Antwerp, Antwerp, Belgium

^bMH Research Unit, University of Antwerp, Antwerp, Belgium

^c Department of Neurology, Antwerp University hospital, Antwerp, Belgium

^dLaboratory of Neurogenetics and Biobank, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium

^eLaboratory of Ultrastructural Neuropathology and Biobank, Institute Born-Bunge (IBB), University of Antwerp, Antwerp, Belgium

^fDepartment of Pathology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium

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Wat is Maligne Hyperthermie?

Publicaties

Heytens L. Differential diagnosis of Malignant Hyperthermia. Acta Anaesthesiologica Belgica 41, 95 - 106, 1990.

Heytens L, Heffron JJA, F. Camu. In-vitro diagnosis of Malignant Hyperthermia susceptibility. Caffeine contracture test : caffeine citrate, caffeine benzoate or caffeine pure base? Acta Anaesth Scand. 35, 541, 1991.

Van Dessel g, Heytens L, Martin JJ, Dierick W. Lipid analysis of muscles from humans susceptible to malignant hyperthermia. Archives internationales de physiologie, de biochimie et de biophysique, B99, 46, 1991.

Van Dessel G, Heytens L, Martin JJ, Dierick W. Phosphoinositides hydrolysis in human skeletal muscle. Archives internatioles de physiologie, de biochimie et de biophysique, B99, 80, 1991.

Heytens L, Even B, Martin JJ, Bossaert L : Differential diagnosis of anesthesia induced rhabdomyolysis. A case report. Acta Neurol Belg 91, 303 - 307, 1991.

Van de Kelft E, De Hert M, Heytens L, Demey HE, Gheuens J. Management of lethal catatonia with dantrolene sodium. Critical Care Medicine 19 (11), 1449 - 51, 1991.

Heytens L, Martin JJ, Van de Kelft E, Bossaert L : In vitro contracture tests in patients with various neuromuscular diseases. British Journal of Anaesthesia 68, 72 - 75, 1992.

Heytens L, Martin JJ, Bossaert L : In vitro diagnosis of Malignant Hyperthermia : influence of electrical stimulation on the contracture response to caffeine. Brit J Anaesth 69, 87 - 91, 1992.

Iles DE, Segers B, Heytens L, Sengers RCA and Wieringa B : High-resolution physical mapping of four microsatellite repeat markers near the RYR1 locus on chromosome 19q13.1 and apparent exclusion of the MHS locus from this region in two MH susceptible families. Genomics 14, 749 - 754, 1992.

Iles DE, Segers B, Sengers RCA, Monsieurs K, Heytens L, Halsall PJ, Hopkins PM, Ellis FR, Hall-Curran JL, Stewart AD and Wieringa B. Genetic mapping of the alfa-1 and delta-subunits of the human skeletal muscle L-type voltage-dependent calcium channel on chromosome 17q and exclusion as candidate genes for malignant hyperthermia susceptibility. Human Molecular Genetics 2, 863 - 868, 1993.

Monsieurs K, Van Broeckhoven C, Martin JJ, Heytens L. Moleculair genetisch onderzoek van twee Belgische families met maligne hyperthermie : op weg naar niet-invasieve diagnostiek. Tijdschrift voor Geneeskunde 50, 391 -398, 1994.

Iles D, Lehmann-Horn F, Scherer SW, Tsui LC, Olde Weghuis D, Suykerbuyk RF, Heytens L. Localisation of the gene encoding the &2/d subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. Human Molecular Genetics 3, 969-975, 1994.

Kloeck CA, Heytens L, Monsieurs K, Martin JJ, Raman ER. A non-invasive test for predisposition for malignant hyperthermia using 31PNMRS. In 'Proceedings of the Society of Magnetic Resonance'. San Francisco, Calif 1994, 3, p 1273.

Quane KA, Keating KE, Manning BM, Healy JMS, Monsieurs K, Heffron JJA, Lehane M, Heytens L, Krivosic-Horber R, Adnet P, Ellis R, Monnier N, Lunardi J, McCarthy TV. Detection of a novel common mutation in the Ryanodine Receptor Gene in Malignant Hyperthermia : implications for diagnosis and heterogeneity studies. Human Molecular Genetics, 3, 471 - 476, 1994.

Sudbrak R, Procaccio V, Klausnitzer M, Curran JL, Monsieurs K, Ellis R, Heytens L, Hartung EJ, Kozak-Ribbens G, Heilinger D, Weissenbach H, Lehmann-Horn F, Mueller CR, Deufel Th, Stewart AD, Lunardi J. Mapping of a further malignant hyperthermia susceptibility (MHS) locus to chromosome 3q13.1. American Journal of Human Genetics. 56, 684 - 691, 1995.

Quane KA, Keating KE, Healy S, Heffron JA, Lehane M, Krivosic-Horber R, Heytens L and McCarthy T. Haplotype analysis of the RYR1 gene in Malignant Hyperthermia and Central Core Disease. Biochem Soc Transact 23(2) S372, 1995.

Heytens L. Malignant hyperthermia suggestive hypermetabolic syndrome at emergence from anesthesia. Editorial. Acta Anaesthesiol Belg 46 (2), 65 - 67, 1995.

Monsieurs K, Van Broeckhoven C, Martin JJ, Dehaene I, Heytens L. Malignant hyperthermia susceptibility in a patient with concomitant motor neuron disease. J Neurol Sciences 142, 36 - 38, 1996.

De Cauwer H, Heytens L, Lübke U, Ceuterick C, Martin JJ. Discordant light microscopic, electron microscopic, and in vitro contracture study findings in a family with central core disease. Clin Neuropathol 16(5), 237 - 242, 1997.

Ording H, Brancadoro V, Cozzolino S, Ellis FR, Glauber V, Gonano EF, Halsall PJ, Hartung E, Heffron JJA, Heytens L, Kozak-Ribbens G, Kress H, Krivosic-Horber R, Lehmann-Hron F, Mortier W, Nivoche Y, Ranklev-Twetman E, Sigurdsson S, Snoeck M, Stieglitz P, Tegazzin V, Urwyler A, Wappler F. In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group : results of testing patients surviving fulminant MH and unrelated low-risk subjects. The European MH Group. Acta Anaesthes Scand 41(8), 955-966,1997.

Robinson RL, Monnier N, Wolz W, Jung M, Reis A, Nuernberg G, Curran JL, Monsieurs K, Stieglitz P, Heytens L, Fricker R, Van Broeckhoven C, Deufel T, Hopkins PM, Lunardi J, MŸller CR. A genome wide search for susceptibility loci in three European malignant hyperthermia pedigrees. Hum Mol genet 6(6), 953-61, 1997.

Monsieurs K, Heytens L, Kloeck Ch, Martin JJ, Wuyts F, Bossaert L. Slower recovery of muscle phosphocreatine in malignant hyperthermia susceptible individuals assessed by 31P-MR spectroscopy.

J of Neurology 244, 651 - 656, 1997.

Monsieurs K, Van Broeckhoven C, Martin JJ, Van Hoof VO, Heytens L. Gly341Arg mutation indicating malignant hyperthermia susceptibility : specific cause of chronically elevated serum creatine kinase activity. J Neurological Sciences 154, 62-65, 1998.

Zukowski F, De Craemer D, Van den Branden C, De Cauwer H, Heytens L, Martin JJ. An image analysis study of vastus lateralis muscle fibers in malignant hyperthermia susceptible patients. Clinical Neuropathology, Vol 17, N¡ 11, 6 - 11, 1998.

Manning BM, Quane KA, Ording H, Urwyler A, Tegazzin V, Lehane M, O'Halloran J, Hartung E, Giblin LM, Lynch PJ, Vaughan P, Censier K, Bendixen D, Comi G, Heytens L, Monsieurs K, Fagerlund T, Wolz W, Heffron JJ, Muller CR, McCarthy TV. Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia : genotype-phenotype correlation. American J Human Genetics 62, 599-609, 1998.

De Cauwer H, Heytens L, Martin JJ. Association of caudal agenesy syndrome and sporadic central core disease. European Journal of pediatric neurology 3, 57, 1999.

Hoofdstuk " Histology in Malignant Hyperthermia" by LG Heytens, HG De Cauwer. Boek “Malignant Hyperthermia” uitgegeven bij Pabst Science Publishers J. Schulte am Esch (eds). 2000 pp 304 – 312.

Monsieurs K, Heytens L. Diagnose van voorbeschiktheid voor maligne hyperthermie : huidige inzichten. Bloedvaten, Hart en Longen vol 6, 44 – 49, 2001

Urwyler A, Deufel T, McCarthy T, S West & Malignant Hyperthermia Group. Guidelines for molecular genetic detection of susceptibility to malignant hyperthermia. Brit J Anaesth 86, 283 – 287, 2001.

De Cauwer H, Heytens L, Martin JJ. Workshop report of the 89th European Neuromuscular Centre International workshop : Central Core Disease. ‘Neuromuscular Disorders’ Vol 12, N° 6, 588 – 595, 2002

Wappler F, Anetseder M, Baur CP, Censier K, Doetsch S, Felleiter P, Fiege M, Fricer r, Halsall PJ, Heffron JJA, Heytens L, Hopkins PM, Klinler w, Lehmann-Horn F, Nivoche Y, Tegazzin V, Tzanova I, Urwyler A, von Arx E, Weishorn R, Schulte am EschJ. Multicenter evaluation of in vitro contracture testing with bolus administration of 4-chloro-m-cresol for diagnosis of Malignant Hyperthermia Susceptibility. Eur J Anaesthesiol. 2003 Jul;20(7):528-36.

Robinson R, Anetseder M, Brancadoro V, van Broekhoven C, Carsana A, Censier K, Fortunato G, Girard T, Heytens L, Hopkins PM, Jurkat-Rott K, Klingler W, Kozak-Ribbens G, Krivosic R, Monnier N, Nivoche Y, Olthoff D, Rueffert H, Sorrentino V, Tegazzin V, Mueller CR. Recent advances in the diagnosis of malignant hyperthermia susceptibility : how confident can we be of genetic testing. Eur J Hum Genet. 2003 Apr;11(4):342-8.

Robinson R, Hopkins P, Carsana A, Gilly H, Halsall J, Heytens L, Islander G, Jurkat-Rott K, Muller C, Shaw MA. Several interacting genes influence the malignant hyperthermia phenotype. Hum Genet 2003, Feb 112 (2), 217-218.

Heytens L. Molecular genetic detection of susceptibility to malignant hyperthermia in Belgian families. Acta Anaesthesiol Belg 58 (2) : 113 – 118, 2007.

Dhaese HL, Martens PR, Müller NH, Casier IM, Mulier JP, Heytens L. The use of emergency medical cooling system ads in the treatment of malignant hyperthermia. Eur J Anaesthesiol 27, 83-85, 2010.

Heytens L. RYR1-related myopathies and the malignant hyperthermia susceptibility trait. Report at the 182nd ENMC International Workshop : RYR1-related myopathies. 15-17th April 2011, Naarden, The Netherlands. Neuromuscul Disorders 22, 5, 453-462, 2012.

Heytens L. Anesthetic guidelines in Multiminicore disease. www.orphananaesthesia.eu. 2012.

Heytens L, Vercauteren M. Clinical variability in the onset of life-threatening malignant hyperthermia. European J Anaesthesiology vol 30, N° 4, 189 – 190, 2013

Heytens L. Ik heb maligne hyperthermie, zeker beter onder lokale anesthesie? Hoofdstuk in boek “Probleem georiënteerd denken voor gebruikers van lokaal anesthetica”. Nederlands tijdschrift voor anesthesiologie. De Tijdstroom. Publicatie juni 2014.

Heytens L, Forget P, Jean-Louis Scholtes, F Veyckemans. The changing face of MH : less fulminant, more insidious. Anaesthesia & Intensive Care, 43(4): 506-5011, 2015.

N. Kraeva, L Heytens, H. Jungbluth, N. Voermans, E. Kamsteeg, J. Baets, C. Ceuterick-de Groote, S. Riazi. Compound RYR1 heterozygosity resulting in a complex phenotype of malignant hyperthermia susceptibility and a core myopathy. Neuromuscular disorders, 225(7):567-76, 2015.

Ori Rokach, Marijana Sekulic-Jablanovic, Nicol Voermans, Jo Wilmshurst, Komala Pillay, Luc Heytens, Haiyan Zhou, Francesco Muntoni, Mathias Gautel, Yoram Nevo, Stella Rosenbaum, Ruben Attali, Alessia Finotti, Roberto, Gambari,Heinz Jungbluth, Francesco Zorzato & SusanTreves. Epigenetic changes as a common trigger of muscle weakness in congenital Myopathies. Human Molecular Genetics 24 (16):4636-47, 2015.

Veyckemans F, Heytens L, Scholtes JL. More on mitochondrial myopathies. Anesth Analg 122 (2): 579-580, 2016.

Heytens L. L'Hyperthermie maligne de l'anesthésie n'est qu'une des expressions des myopathies liées au gène RYR1. Le Praticien en Anesthésie Réanimation. DOI:10.1016/j/pratan.2016.04.002, 2016.

Heytens K, De Bleecker J,Verbrugghe W, Baets J, Heytens L. 'Exertional rhabdomyolysis and/or heat stroke: beware of volatile anesthetic sedation. World J Crit Care Med; 6(1): 21-27 http://dx.doi.org/10.5492/wjccm.v6.i1.21, 2017

Heytens K, De Ridder W, De Bleecker J, Heytens L, Baets J. Exertional rhabdomyolysis: Relevance of clinical and laboratory findings, and clues for investigation. Anaesth Intensive Care. Mar;47(2):128-133. doi: 10.1177/0310057X19835830. Epub 2019 May 9, 2019

Knuiman GJ, Küsters B, Eshuis L, Snoeck M, Lammens M, Heytens L, De Ridder W, Baets J, Scalco RS, Quinlivan R, Holton J, Bodi I, Wraige E, Radunovic A, von Landenberg C, Reimann J, Kamsteeg EJ, Sewry C, Jungbluth H, Voermans NC. The histopathological spectrum of malignant hyperthermia and rhabdomyolysis due to RYR1 mutations. J Neurol. Apr;266(4): 876-887. doi: 10.1007/s00415-019-09209-z. Epub 2019 Feb 20, 2019

Heytens L. Anaesthesia recommendations for Multiminicore disease. www.orphanaesthesia.eu 2019

Ibarra Moreno CA, Hu S, Kraeva N, Schuster F, Johannsen S, Rueffert H, Klingler W, Heytens L, Riazi S. An Assessment of Penetrance and Clinical Expression of Malignant Hyperthermia in Individuals Carrying Diagnostic Ryanodine Receptor 1 Gene Mutations. Anesthesiology. Jun 13. doi: 10.1097/ALN.0000000000002813. [Epub ahead of print] 2019

Luc Heytens, Mary Dos Santos Silva, Joris De Puydt, Karel Heytens, Willem De Ridder, Jonathan Baets, Geert Mortier. Malignant hyperthermia related DNA analysis (RYR1 sequence variants gene) in Belgian families. Acta Anaesth. Belg., 2019, 70, 197-205

H, Bastian B, Bendixen D, Girard T, Heiderich S, Hellblom A, Hopkins PM, Johannsen S, Snoeck MM, Urwyler A, Glahn KPE; Consensus guidelies on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group. European Malignant Hyperthermia Group.Br J Anaesth. 2021 Jan;126(1):120-130. doi: 10.1016/j.bja.2020.09.029. Epub 2020 Oct 31.PMID: 33131754

van den Bersselaar LR, Gubbels M, Riazi S, Heytens L, Jungbluth H, Voermans NC, Snoeck MMJ Mapping the current evidence on the anesthetic management of adult patients with neuromuscular disorders-a scoping review. .Can J Anaesth. 2022 Mar 23. doi: 10.1007/s12630-022-02230-3. Online ahead of print.PMID: 35322378 Review. English.

van den Bersselaar LR, Hellblom A, Gashi M, Kamsteeg EJ, Voermans NC, Jungbluth H, de Puydt J, Heytens L, Riazi S, Snoeck MM. Referral indications for malignant hyperthermia susceptibility diagnostics in patients without adverse anesthetic events in the era of next-generation sequencing. Anesthesiology. 2022 Mar 14. doi: 10.1097/ALN.0000000000004199. Online ahead of print.PMID: 35285867

L Heytens, S Temurziev. Malignant Hyperthermia in Belgium: 35 years of practice-led research. Acta anaesthesiologica Belgica Volume 74, March 2023, 13-21.

He M, Riazi S, van den Bersselaar LR, Islander G, Gillies R, Hellblom A, Voermans NC, Temurziev S, Jungbluth H, Dirksen RT. Humidity impacts volatile anesthetic and heat responses of malignant hyperthermia susceptible mice. Skelet Muscle. 2026 Jan 9. doi: 10.1186/s13395-025-00411-4. Epub ahead of print. PMID: 41514332.

Temurziev, S. (2025). Agilus®, a novel formulation of intravenous dantrolene as an alternative to Dantrium® for the treatment of a malignant hyperthermia crisis. Acta Anaesthesiologica Belgica, 76(2), 83. https://doi.org/10.56126/76.2.12