President's Blog

It is very common to think about the Malignant Hyperthermia (MH) syndrome as a problem related to anesthesia exclusively. Indeed most of the concerns about MH since its first descriptions in the 1960s centered on the unexpected and often disastrous changes that can occur during the administration of general anesthesia to an otherwise healthy individual. 

That MH occurs during anesthesia and even today may lead to death and permanent or temporary disability is certainly true. What we now realize is that MH should be considered not as just a problem of anesthesia but as a medical disorder like other disorders.  To make this point, consider another inherited disorder, sickle cell disease. This condition is due to a specific genetic change that leads to a deformity of the patient’s red blood cells. In the mildest form (the heterozygote, i.e. where only one abnormal gene is inherited) patients may be asymptomatic. However, under certain circumstances the patient may experience significant problems. For example, at high altitude they may develop extreme bone and joint pain. In addition, these individuals seem to be more prone to developing infections than patients who do not have the trait. The same analogy may be made to MH, but in this case anesthetic drugs are the “environmental” change that leads to problems. 
 

Moreover, in addition to issues related to certain anesthetics, some MH patients develop muscle breakdown with exercise.  A few may even experience a lethal MH event when overheated.  I must remind the reader that it is the rare MH patient that experiences such problems (we believe).  We currently do not know how to identify which MH susceptibles are at risk of developing problems without exposure to anesthesia.  

Another issue that I have known about for a while, but never really appreciated until recently, thanks to the work of Dr. Muldoon and colleagues, is that there are some patients who, following an MH crisis, have continuing muscle pains and aches for either months or years. Just read some of the messages on the MHAUS message board for example. We don’t know why this occurs or which patients are at risk, but it does occur. 

These problems should not really surprise us, because MH is a myopathy; that is, a pathologic change in muscle. There are scores of myopathies or muscle diseases, some with predictable dire consequences such as muscular dystrophy, while others are annoying and somewhat restrictive but compatible with a normal life.  All the myopathies, MH included, have as their basis a change or set of changes in DNA which leads to abnormal protein structure and function of the muscle. This is certainly true of MH. The DNA changes in MH lead to an abnormal structure of an important regulator protein (or proteins) that controls calcium movements and concentrations within the muscle cell. Calcium levels in the cell “turn on” or “turn off” muscle contraction as well as energy production. We know that there are at least two regulatory proteins that are affected, the dihydropyridine receptor (DHPR) and the ryanodine receptor (RYR). Some studies indicate that there are other calcium regulatory proteins in muscle that when absent or deformed may also lead to the pathophysiologic changes of MH. 

As with many other inherited disorders, the study of the basic abnormality that gives rise to MH has provided insight into how normal muscle functions and what all those proteins in muscle actually do.  

Also, animals with DNA changes that are known to cause MH in humans will experience MH signs. For example, the genetically engineered mouse model of MH (that is, the insertion of an MH mutation into a normal mouse’s DNA) is providing insights into the clinical manifestations of MH.  For example, these animals regularly develop MH not only on exposure to anesthetics but also on exposure to heat. 

Another area of research regarding MH is the desire to understand the epidemiology of the disorder, its prevalence and incidence. We know neither with precision. Many states, Medicare and insurance companies track medical conditions through use of a unique numerical designation for each particular disorder. This numerical designation for each particular disorder.  This numerical designation is called the ICD-9 (International Classification of Disease, 9th. edition) code. The code for MH related to anesthesia was established in 1998. This numerical code permits researchers to query large state and governmental databases to learn more about the incidence and epidemiology of MH. Abstracts are now appearing based on such database searches. Also, the North American MH Registry of MHAUS contains details regarding MH events in over 2,000 patients. The database is searched regularly to learn more about MH. 

Patients with MH susceptibility, like patients with any other disorder, need special care and advice from physicians, nurses, genetic counselors, and others who are familiar with the disorder. MH patients have questions related to anesthesia, fitness for military service, inheritance of the disorder, problems with other medications, and most problematic, participation in sports or exposure to extreme heat. Furthermore when an MH susceptible travels abroad they have questions about what preparation should be made in regard to their MH susceptibility. Many large countries, such as China do not have dantrolene readily available. We hear of deaths or near misses from MH in countries such as the Philippines and Peru to name just a few, because dantrolene is not available.

The point of this commentary is to explain that MH is not just an adverse reaction to anesthesia - - just avoid the anesthetic triggers and you will be fine. That does not tell the whole story. There is much more to learn about MH and its implications. To put this in perspective, genetic studies show that as many as one in 3,000 people have one of the known DNA changes that are causal for MH. I believe that there are many issues that are associated with this inherited disorder of skeletal muscle that we have yet to learn about.