Biopsy to determine susceptibility to Malignant Hyperthermia
A 42 year old gentleman was referred to a surgeon for a biopsy to determine susceptibility to Malignant Hyperthermia. He had a first degree relative who had a suspicious episode for possible MH during an anesthetic a few years ago. Informed consent was obtained and the vastus lateralis biopsy was performed in an office setting under local anesthesia. The tissue was forwarded to the local hospital pathology department and then sent to an MH biopsy center to perform the necessary testing. The patient recovered from the surgery uneventfully. What information can be determined from this procedure?
A). The biopsied muscle can be tested for MH Susceptibility
B.) The biopsied muscle can be processed for histochemical staining.
C.) The biopsy tissue can be processed or light microscopic examination for some muscle diseases.
D.) The biopsy tissue can be processed for electron microscopic examination for some muscle disease states.
2. The Caffeine Halothane Contracture Test (CHCT) for determining MH Susceptibility is:
A.) A physiologic test
B.) An anatomic test
C.) An electron microscopic examination
A.) The referred patient
B.) The first degree relative who had the suspicious episode
C.) The parent of the referred patient
D.) The parent of the patient with the suspicious episode
ANSWERS
1. Answers: B, C, D.
Tissue processed in this manner cannot be tested for MH susceptibility. It may be examined for other muscle disease states, but not for contracture testing since it is no longer living tissue.
Answer A is not correct.
2. Answer: A
The CHCT is a physiologic test, not an anatomic test. The biopsy specimen is excised gently and taken to the MH Biopsy lab directly while it is still fresh. The tissue is kept alive by perfusion with oxygen enriched physiologic buffer while it is prepared for testing.
The CHCT tissue preparation takes a few hours while tissue strips are prepared. The muscle strips are then placed in physiologic buffer in temperature –controlled (37 C) vessels and stretched to develop a baseline tension. Following a stabilization period, the strips are then electrically stimulated with a stimulator to develop a stimulation-tension response. Strips are then exposed to the addition of halothane or caffeine in the physiologic buffer and continuous recording of tension (contracture) are obtained. If the tension developed achieves the criteria set forth by the North American MH second conference, then the response of the test is considered evidence of MH Susceptibility.
The CHCT is not performed on tissue which is not immediately prepared in an MH Biopsy Testing Center. If the tissue is not appropriately prepared, then it will not be able to be considered sufficiently healthy to be able to develop tension when tested. If there is an insufficient tension developed at baseline, then the test is considered invalid. Therefore the tissue which was obtained and not immediately prepared and tested cannot be evaluated for MH susceptibility. The tissue may still be adequate for other testing according to established pathology protocols.
Whenever possible, the suspected proband should be the first patient tested by CHCT in a family. When/if the patient is unavailable or unwilling, then a medical center biopsy director will determine who next should be tested. This may involve one or both parents of the suspected proband, or other first degree relatives. Unfortunately, some probands wait many years until they are willing or referred for testing and supportive medical records are no longer available.
Only four centers are currently able to perform the CHCT test in the
A video of an actual biopsy performed and tested according to protocol is available at www.mhaus.org. This video is approximately seven minutes long demonstrating the important aspects of the many hours-long CHCT testing process. The test results are evaluated and reported to the patient usually on the same day of the procedure.
Novel genetic screening for some mutations of the Ryanodine-1-receptor is available following the initial CHCT results in some families. Although genetic screening is only 35-40% sensitive, certain families may express one of the causal mutations, and then extended family members may be tested by genetic screening and thereby avoid having each family member requiring a biopsy and CHCT. MH Biopsy Center directors are available for consultation regarding any patient that may be considered or referred.
Joe Tobin, M.D
Wake Forest University School of Medicine
Winston-Salem, NC
