Why So Cold?

Does poor autonomic nervous system control of
blood vessels contribute to symptoms in
Charcot-Marie-Tooth disease?

by Lowell L. Williams, M.D.

Many patients with Charcot-Marie-Tooth syndrome (CMT) complain that their symptoms are worse in winter, that the cold weather bothers them more than their friends or mates. Although this comment is common, surprisingly few studies have addressed the nervous control of CMT blood vessels in a scientific manner. We describe here some pilot studies carried out in Columbus, OH, with donations from CMT International U.S.A., in which we are finding that CMT patients have a variety of problems during cold temperature.

In all individuals, blood pressure and blood flow through blood vessels are maintained by a special portion of the nervous system called "autonomic" since usually it is not under conscious control. It would be a tremendous nuisance to have to remember to keep one's heart beating! In addition, movements, such as sudden standing or lying down, require a complex adjustment of blood vessels to compensate for the differences in gravity pull and limb position. To keep blood pressure within bounds and blood flowing successfully to all parts of the body, there are receptors (a form of meter) in key spots in major blood vessels. These receptors monitor the rate of flow and the amount of oxygen in the blood. A series of messages are sent through co-ordinating centers in the brain directly to the blood vessels for dilatation (widening) or constriction (narrowing) to keep flow consistent. Through this nerve network, messages are also sent to organs, such as the adrenal gland, that make additional substances affecting the vessel size to add or detract from the immediate response of the direct nerve reactions. Remember that relaxing or dilating blood vessels lower the blood pressure by creating a bigger space, while constricting them increases the blood pressure or "resistance" to blood flow since there is a smaller space. This is a very complex arrangement with many nervous system and serum components that are difficult to understand and study. There have to be many "back-up controls" to allow for flexibility during possible emergencies, such as a sudden blood loss, a sudden change in temperature, sudden or prolonged exercise and movement, etc. Understanding whether this system is functioning well in CMT could be important in treatment of symptoms.

The overall ability of this complex system can be measured by producing a stressful situation. Placing the hand or foot in ice water for a period of time is a useful stress test. Before beginning, a large number of normal persons matched for age and sex must be tested to measure the normal or adequate response. Then the patient group is tested and the results compared. When the patient group findings are different, a conclusion can be drawn that a portion of the autonomic nervous system is at fault. It is then necessary to do further tests to examine each of the parts of the system separately to find out exactly where the problem lies.

We describe here our initial steps to test autonomic nervous function in CMT. We examined 21 adult patients (17 different families) who were known to have CMT (average age of 47) and 53 persons without CMT (average age 42) equally distributed by sexes. The test began with a period of 10 minutes of quiet in a room of constant temperature during which a history of symptoms was taken. Then the heart rate, pulse pressure, skin temperature and pulsatile oxygen concentration were measured in each volunteer participant. Data was recorded from the middle digit of the right hand using non-invasive methods (the Nellcor Pulse Oximeter and temperature sensor). Cold stress was then performed using the Cold Pressor Test. In this test, the entire right hand is submerged in an ice bath (temperature 12C) for 60 seconds. The amount of discomfort from the ice bath is estimated by the individual. The above measurements are repeated at the end of immersion and then again in 10, 20 and 30 minutes after cold. During that time, we do not allow attempts to warm the hand or increase circulation (by shaking, etc.).

We found that CMT responses usually were different from normals in one or more of the measurements. After cold, the average oxygen saturation value of CMT patients was significantly below that of normals for a least 20 minutes (p 0.002). This suggests that the blood oxygen was not getting into the CMT finger tissues as rapidly, possibly explaining the increased bluish discoloration of CMT hands in cold. CMT finger pulse pressure also was greater than normal at 10 minutes after cold. This suggests a vasodilatation in CMT blood vessels in an attempt to counteract the effects of cold.
This amount of cold stress usually slows the heart rate in normal persons. In CMT, about one half lacked this reflex slowing of the heart, suggesting defects in the overall nervous network communication or special efforts to correct the problems with cold. In fact, we found that the CMT average heart rate was faster than age-matched normals at every time period (p 0.002). It is true that heart problems have not been directly associated with the CMT syndrome. Therefore, the fast CMT heart rate may represent more awareness of the stress of the test in CMT or possibly poor network control. More studies need to be done on this aspect of CMT autonomic function.

It is interesting that pain perception in the cold hand was less in CMT patients than others. This result might be expected from the loss of "feeling" in CMT hands. Of course, lowered CMT sensation can lead to a danger of over-chilling when the person does not recognize that his/her limb is too cold and doesn't take measures to correct it. Despite this problem, CMT hand skin temperature returned to pre-test levels almost as rapidly as the normal group. In contrast, circulation in feet may be another story. In the few CMT feet we have tested, there was a marked difference from normals both in feeling the cold temperature and in recovery afterward. This important portion of the study is just under way.

Our results agreed with previous studies showing some peripheral and central autonomic nervous system defects in CMT. In particular, we extended the observations of Charcot himself who considered that mottled bluish extremities represented a degree of altered blood vessel control in CMT. It is not yet known just how CMT circulation problems are related to the nervous control of the blood vessels in the hands and feet and how we can use this information to help and treat CMT patients. We hope to continue our studies to find these answers.