Diaphragms are the most important muscles for breathing. The function of diaphragms requires stimulation by the phrenic nerves. Phrenic nerve impairment leading to diaphragm weakness or paralysis is an uncommon but severe, and potentially fatal condition if not recognized. The key to making the right diagnosis is a high index of suspicion for the presence of this condition. Of the hereditary neuropathies, CMT disease or hereditary motor and sensory neuropathy is undoubtedly the most common. CMT disease is characterized by chronic degeneration of peripheral nerves and roots, resulting in muscle wasting, beginning in the feet and legs and subsequently involving the hands. The association of CMT disease with diaphragm weakness resulting in major breathing difficulty was first reported by us in 19851.

In 1985, my colleagues and I at Yale diagnosed a paralysed diaphragm in a 72-year-old woman who had CMT for about 60 years1-2. Looking back, this patient had major difficulties with her breathing for about 10 years. Unfortunately, physicians caring for her did not appreciate the possible link of CMT with phrenic nerve impairment and thus diaphragm weakness or paralysis because it was not previously reported. As a result of the paralysed diaphragm, this patient suffered major complications in her heart and lungs and had impaired mental function. Even when the diaphragms are not working, most patients breathe reasonably well in the upright position with the help of gravity and the other breathing (accessory) muscles in their necks and chests. However, when they lie down the benefit of gravity is lost and the work of breathing required of these accessory breathing muscles increases. This is the reason why the very first indication of diaphragm weakness is difficulty breathing lying down. Over a period of time, months to years, the overworked breathing muscles become tired. The consequence of that is inadequate breaths which leads to a long-term deprivation of oxygen.

The effects of poor breaths and lack of oxygen can be summarized in the following categories: (1) The major impairment in breathing and oxygen intake is obviously at night during sleep when patients are lying flat, and since the brain needs a good supply of oxygen, any major drop in the oxygen supply will alert the brain. The response is awakening of patients from sleep so they can sit up to breathe deeper in order to get some oxygen into the blood. When these episodes occur repeatedly during the course of 7-8 hours sleep, major deprivation of sleep and rest follows. Because of these events during the night time, patients with these sort of problems typically complain of morning headaches, daytime sleepiness and poor mental function. (2) A long-term lack of oxygen means strains on the heart and lungs and will lead to major impairment of the heart and lung functions. The results are heart failure, presenting as swelling of the ankles, poor exercise tolerance, generalized weakness, and in severe cases, death.

Our patient experienced most of the adverse outcomes mentioned. Over a period of years, her breathing muscles became so weak that she was found at home almost dead with major breathing difficulty on her own. She was then put on a breathing machine and was transferred to a chronic ventilator hospital because it was felt that she would never come off the breathing machine and thus requires institutionalization. However, after the diagnosis of a paralysed diaphragm was made, we were able to remove the breathing machine from her during the day and put her in an upright position to maximize the benefit of gravity. At night time, she is maintained on a simple breathing machine, which she learned to operate on her own in a short period of time. Currently, I am delighted to report that our patient is living on her own at home, functioning independently and can finally breathe after 10 years of agony.

Since there was nothing in the medical literature on diaphragm impairment or breathing problems in CMT, we decided in the fall of 1985 to conduct a series of lung and diaphragm tests on the brother of our patient. He also has had CMT for about 45 to 50 years. To our surprise, even though he has minor difficulty with his breathing, his diaphragm turned out to be substantially weaker than most healthy individuals in his age group. That is why we became concerned that diaphragm weakness leading to breathing difficulties may actually be a late and perhaps rare complication in people with CMT. And especially in those individuals who have other medical problems that may affect the phrenic nerves and/or the diaphragm, such as diabetes.

With the collaboration of Mrs. Carol Barker of Connecticut, we have assessed two additional people with CMT in the State of Connecticut, one of these also had significant weakness of her diaphragm although it was much less severe compared to our index patient. After presenting these observations at the American College of Chest Physicians annual scientific meeting in September of 1986, we are pleased to report that similar patients were seen by some of our Chest colleagues in the United States.
References:
1. Chan CK, Mohsenin V, Ferranti R, Virgulto J, Loke J. Diaphragmatic dysfunction in association with Charcot-Marie-Tooth disease and diabetes mellitus. Chest 1986, 89: 454S.
2. Chan CK, Mohsenin, V, Loke J, Virgulto J, Sipski ML, Ferranti R. Diaphragmatic dysfunction in siblings with hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease). Chest 1987, in press.