Dr. Sheila Riazi

Malignant Hyperthermia Investigation Unit

Back row left to right: Dr. Sharon Peacok (elective resident), Mrs. Anne-Marie Seko, Dr. Natalia Kraeva, Dr. Sheila Riazi
Front: Mrs. Wanda Frodis

Lab Description

MH investigation unit (MHIU) at Toronto general hospital is a combined diagnostic and research laboratory. The diagnostic aspect focuses on caffeine halothane contracture test (the most sensitive test available for diagnosis of MH). Research aspect includes genetics, metabolomics, and calcium movement in skeletal muscle cells in MH patients, and MH-like syndromes. Our laboratory sees the largest number of MH patients in North America and is the only Canadian center for MH research. Furthermore, our center is the one of the two North American that compiles both genetic and physiological results, allowing us to embark on projects to discover the pathophysiological and genetic causes of MH, and explore the non-anesthetic aspect of MH more at the cellular level. 

Research Focus

Malignant hyperthermia (MH) is the only known anesthetic-induced disease. Until recently, MH was considered a pharmacogenetic susceptibility that is subclinical in the absence of anesthetic agents. However, this view has been challenged due to the high incidence of exercise/heat induced rhabdomyolysis, premature ageing and statin-induced myopathy in MH positive patients. The new assessment of MH has brought more attention to investigations of the pathophysiology of MH and its diverse phenotypes. Our group’s research in MH is multifaceted, and focused on different aspects of MH, clinical as well as fundamental, involving genetics and cellular studies. We have one the largest, complete database of patients diagnosed with MH that helps us investigate this disease. We have performed various genetic testing, including exome sequencing on MH patients. We have also focused on details of MH pathophysiology from metabolic changes to calcium movement in these patients. The phenotypic variability among MH patients is believed to cause confusion with diagnosis and treatment, hence the reason for high morbidity, and mortality in this population. Our emphasis on pathophysiological details of MH can shed light to many questions on phenotypic variability in this group of patients.

Selected Publications

  1. Timmins M, Rosenberg H, Green Larach M, Sterling C, Kraeva N, Riazi S. Malignant Hyperthermia Testing in Probands without Adverse Anesthetic Reaction. Anesthesiology. 2015 Sep; 123(3):548-556.
  2. Kraeva N, Heytens L, Jungbluth H, Treves S, Voermans N, Kamsteeg E, Ceuterick-de Groote C, Baets J, Riazi S. Compound RYR1 heterozygosity resulting in a complex phenotype of malignant hyperthermia susceptibility and a core myopathy. Neuromuscul Disord. 2015 Jul;25(7):567-76.
  3. Rios E, Figueroa L, Manno C, Kraeva N, Riazi S. The couplonopathies. A mechanistic and comparative approach to a class of diseases of skeletal and cardiac muscle. Journal of General Physiology. 2015 Jun; 145(6):459-74.
  4. Riazi S, Kraeva N, Muldoon SM, Dowling J, Ho C, Petre MA, Parness J, Dirksen RT, Rosenberg H. Malignant hyperthermia and the clinical significance of type-1 ryanodine receptor gene (RYR1) variants: proceedings of the 2013 MHAUS Scientific Conference. Can J Anaesth. 2014 Nov;61(11):1040-1049.
  5. Riazi S, Larach MG, Hu C, Wijeysundera D, Massey C and Kraeva N. Malignant hyperthermia in Canada: characteristics of index anesthetics in 129 malignant hyperthermia susceptible probands. Anesth Analg. 2014 Feb;118(2):381-387.
  6. Kraeva N, Zvaritch E, Frodis W, Sizova O, Kraev A, MacLennan DH and Riazi S. CASQ1 gene is an unlikely candidate for malignant hyperthermia susceptibility in the North American population. Anesthesiology. 2013 Feb;118(2): 344-349.
  7. Kraeva N, Zvaritch E, Rossi AE, Goonasekera SA, Zaid H, Frodis W, Kraev A, Dirksen RT, Maclennan DH and Riazi S. Novel excitation-contraction uncoupled RYR1 mutations in patients with central core disease. Neuromuscul Disord. 2013 Feb;23(2):120-132. 
  
Sheila RiaziSheila Riazi, MD

E: malignanthyperthermia@uhn.ca
P: (416) 340-3128
F: (416) 340-4960

pie.med.utoronto.ca/mh

 

Laboratory Members:

Sheila Riazi, MD: Principal Investigator
Anne-Marie Seko: Assistant
Natalia Kraeva, PhD: Lab Manager
Wanda Frodis, BSc: CHCT Technician