How does CMT affect breathing?
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Breathing and CMT
While uncommon, some particularly severe forms of CMT can affect breathing.
BY MICHAEL E. SHY, MD, CMT CLINIC, UNIVERSITY OF IOWA HOSPITAL
We receive a number of questions in our CMT clinic about how Charcot-Marie-Tooth disease affects breathing. CMT affects peripheral nerves called “somatic nerves” that carry motor and sensory information to and from the brain. These include the phrenic nerve that goes to the diaphragm and the intercostal nerves that go to the rib cage. Both the phrenic and intercostal nerves are necessary for these muscles to contract during respiration. When they don’t function, breathing is impaired.
Like many other somatic nerves that go to the arms and legs, the phrenic and intercostal nerves are myelinated, so both the myelin and the axon surrounded by the myelin can be affected by CMT. The question then becomes how severely CMT damages these nerves. The answer depends in part on the specific type of CMT a patient has and how severely CMT affects him or her. The bottom line is that most patients with CMT do not develop clinical evidence of breathing problems even if some abnormalities can be detected on detailed evaluations.
CMT1A, the most common form of CMT, is slowly progressive and has slow nerve conduction velocities. Even though clinical symptoms typically affect the lower legs and hands, all myelinated somatic nerves will have slow nerve conduction velocities. The reason that hands and feet are affected clinically has to do with interactions between abnormal myelin and their axons. These abnormal interactions cause weakness at distal body parts (feet and hands), which are at the furthest ends of the longest nerves. The phrenic or intercostal nerve conductions are also slow in patients with CMT1A; however, partly because these nerves are not as long, patients with CMT1A rarely develop significant respiratory or breathing problems. The same is true for other common types of CMT such as CMTX.
Unfortunately, some particularly severe forms of CMT can affect breathing. In these cases, a profound weakness is usually present in infancy or early childhood. As with other neuromuscular diseases such as muscular dystrophy or spinal muscular atrophy, children have in rare cases died because of respiratory failure. Some adults with very severe forms of CMT have also succumbed because of respiratory problems. In these rare cases, patients suffer from what is called “restrictive” lung disease and become unable to breathe without ventilator support. To emphasize, these cases are very rare, but they illustrate that CMT is not always a “mild” or slowly progressive disorder.
Diaphragmatic Impairment and Pulmonary Evaluation
From time to time, particularly in cases of CMT4 or CMT2, patients have developed phrenic nerve abnormalities that result in phrenic nerve impairment so that one-half of the diaphragm becomes paralyzed or doesn’t move. The phrenic nerves are constructed so that one connects to the right side of the diaphragm and the other connects to the left. I have never seen a case that progressed to the point that neither phrenic nerve functioned, although even then a patient would still have intercostal nerves to help with breathing. In situations with phrenic nerve paralysis, patients often ask us about diaphragmatic pacing through electrical stimulation of the nerve. To the best of my knowledge, this has not been shown to work. When we see patients with impaired respiratory function, we have them evaluated by a pulmonologist (lung specialist) who has experience in neuromuscular diseases including CMT. They typically perform pulmonary function tests (PFTs) and blood tests that can help measure the volume of air patients can move in and out of their lungs, the force they can use to inhale and exhale, and the amount of oxygen that makes it into their blood. Results from these tests provide guidance as to what, if any, therapy is required.
It is increasingly recognized that patients with all types of CMT may develop sleep apnea. Sleep apnea—repetitive pauses in breathing at night—may be caused by obstructions in the upper airway, which may be caused by CMT, although the exact mechanism is unknown. Sleep apnea can result in daytime drowsiness and fatigue. It is typically associated with heavy snoring at night. Sleep apnea can be treated by techniques such as continuous positive airway pressure (CPAP) masks, although these devices can be uncomfortable to wear.
Vocal Cord Paralysis
Some patients, particularly those with CMT2A or CMT4A, have been identified with paralysis of at least one side of their vocal cords. This can make it difficult for them to generate force or loudness when speaking. It can be associated with shortness of breath. We usually have these patients evaluated by ENT (ear, nose and throat) specialists, who are best equipped to evaluate vocal cord function. Artificially building up the vocal cords is a concern in these situations because of the potential for the vocal cord to close the airway. In extreme cases surgical interventions such as tracheostomies may be necessary.
What I presented above is a summary based on our experience from over 20 years of running CMT clinics. While I believe this information to be correct, many issues concerning breathing in different forms of CMT have yet to be studied in controlled trials. Details of respiratory function in patients with CMT are not yet available, though we are starting to address this in our Inherited Neuropathies Consortium (INC) with support from the CMTA. Over the years, we have performed some studies of pulmonary function tests in patients with CMT1A and these have generally been normal, although we have not looked at changes over time. Clearly, more work needs to be done with this important issue. In the meantime, we also need to encourage patients not to smoke or do any other activities that are harmful to their lungs.
Can CMT cause diaphragmatic weakness?
Peripheral nerves going to the diaphragm are affected in various types of CMT as these are large myelinated nerves. Abnormalities can be detected by nerve conduction studies, but they are not typically performed because many CMTers are not used to the technique and it is uncomfortable.
In most people, nerve abnormalities do not result in weak or paralyzed diaphragms. Typically this occurs only in more severely affected patients. A few types of CMT, typically those that are axonal forms and severe, are more likely to result in paralyzed diaphragms. Remember that clinical abnormalities in CMT are usually length-dependent, causing problems at the far ends of the longest nerves, which are usually the hands and feet. In more severe forms, shorter nerves have problems at their far ends. This includes the phrenic nerve, which goes to the diaphragm
Are coughing spasms associated with CMT?
Coughing spasms are NOT a common symptom of CMT. Please discuss with your GP or your CMT-expert neurologist.
Can CMT be associated with difficulty in swallowing?
Although not a common symptom associated with CMT, there have been reports of people with CMT having issues swallowing. It is certainly not the norm, but other muscles besides the arms and legs can be weakened by the disease. Please see an expert CMT neurologist for further evaluation. And consulting a speech pathologist also seems like a good idea.
Does CMT affect the phrenic nerve/diaphragm? If so, would it affect breathing and speech?
CMT can affect the phrenic nerve (which innervates the diaphragm) and the recurrent laryngeal nerve (which innervates the larynx). These nerves are rarely clinically affected unless the patient has a severe neuropathy. I recommend a pulmonary specialist for the breathing and an ENT physician for the speaking, as I doubt that CMT is causing these problems.
How common is it for a person with CMT to develop breathing problems?
The first thing to stress is that this is very rare. There are two possible causes for breathing difficulties. The first is that involvement of the nerves to the diaphragm (the phrenic nerves) can cause weakness of the diaphragm. Peripheral nerves going to the diaphragm are often affected in various types of CMT as these are large myelinated nerves. Abnormalities can be detected by nerve conduction studies though these are not typically performed because many EMGers are not used to the technique and it is uncomfortable.
In most people, abnormalities from the nerves don’t result in weak or paralyzed diaphragms. Typically this occurs in more severely affected patients. A few types of CMT, typically those that are axonal forms and severe, are more likely to have paralyzed diaphragms. The clinical abnormalities in CMT are usually length dependent, causing problems at the far ends of the longest nerves which are usually the hands and feet. In more severe forms, shorter nerves cause problems at their far ends. This includes the phrenic nerve that goes to the diaphragm.
Phrenic nerve involvement can present as breathlessness, particularly when lying flat, but may also present with excessive daytime sleepiness—the reason for this is accumulation of carbon dioxide due to inefficient breathing.
The second problem can be paralysis of the vocal cords. This impairs air entry and breathing can be very noisy. Vocal cord involvement is said to be commonest in CMT Type 2C, but it probably can occur in other types.
Does pulmonary rehabilitation work for patients with CMT?
Dr. Ashraf Elsayegh* answers:
Pulmonary rehabilitation has proved beneficial in patients with obstructive pulmonary disorders and restrictive pulmonary disorders. While I am aware of no studies on the benefits of exercise on neuromuscular patients, there are suggestions by multiple healthcare professionals worldwide that pulmonary rehabilitation should have some benefit for this population. I myself have started to send some of my neuromuscular patients to our pulmonary rehabilitation center to see if and how they benefit.
One of the goals of a pulmonary rehabilitation program is upper (and lower) extremity strengthening. To exercise the remaining respiratory muscles (intercostal muscles and the diaphragm), there are commercially available devices (expiratory muscle strength trainers like the EMST, The Breather) that may be beneficial. The theory is that using these devices, which require one to breathe deeply against a pressure, will strengthen those specific muscles. However, there are no studies that I am aware of that look at the CMT population and usage of these devices. There are a few very small studies in the ALS (Amyotrophic Lateral Sclerosis) population, from which we can extrapolate some data for the CMT population. The data in ALS patients was obtained mostly from small studies (15 – 25 patients) in Florida. The results of the studies thus far have revealed a mild improvement in maximal expiratory pressures and a mild improvement in cough ability. The devices were well tolerated by the patients. However, further larger studies are needed before a firm conclusion can be reached. There is a larger study currently ongoing now. It is important to note that neuromuscular patients should only use these devices once a day for a total of five breaths (three to five times per week), with the device set at 50 percent of maximal expiratory pressure.
The benefits of conscious breathing—the technique of taking deep breaths such as in yoga or meditation—have not been studied. However, it falls into the same category as pulmonary rehabilitation programs: There may be some minimal benefit, but it has not been confirmed as of yet. Again from personal experience, I have noticed that it is very beneficial to overcome anxiety-related breathing issues in this patient population.
In neuromuscular disease, phrenic nerve damage is a significant concern as it innervates the diaphragm. As far as phrenic nerve paralysis, in general unilateral nerve paralysis is secondary to trauma or surgical damage. Bilateral phrenic nerve paralysis is almost always due to neuromuscular disease. Bilateral damage is common in neuromuscular diseases such as ALS, but much less so in CMT.
Scoliosis is much more common in CMT patients. Although scoliosis rarely affects phrenic nerves, it produces its own set of breathing problems. Severe scoliosis is associated with development of restrictive lung pathology, which leads to shortness of breath and respiratory failure. Therefore, patients with significant scoliosis should be monitored carefully with pulmonary function testing for early detection of respiratory issues.
*Ashraf Elsayegh, MD, FCCP, is an expert in the field of pulmonary medicine as it relates to neuromuscular disease and a member of the CMTA Advisory Board. He currently practices at Cedars-Sinai Medical Center in Los Angeles and is an associate clinical professor at UCLA School of Medicine. His clinical and research interests revolve around respiratory function in the neuromuscular patient with special interest in diaphragm dysfunction. Dr. Elsayegh has treated neuromuscular patients, including those with ALS and CMT, over the last 15 years.
Does intubation/ventilation pose increased risk for CMT patients?
It must be noted that intubation and ventilation comes with risks for any patient whether healthy or chronically ill. These risks include:
- Risk and side effects of the medications given to sedate and relax the patient enough to be able to intubate them. These include but are not limited to: allergic reaction to the medications, hypotension (low blood pressure), or cardiac arrest.
- Post intubation, the increased intrathoracic (in the chest cavity) pressure can result in further hypotension (low blood pressure).
- Difficulty with a particular airway may result in multiple intubation attempts which can cause edema of the airway making it more difficult to intubate the patient.
- Insertion of the endotracheal tube (breathing tube) into the esophagus accidentally.
- Tearing of the trachea while trying to insert the tube.
Although most (or all of the above) are very rare, they can happen.
- Main risk includes development of pneumonia (known as ventilator associated pneumonia).
- Very small risk of a pneumothorax (collapse of a lung).
- Mucous plugging, a buildup of mucus in the airways.
- Difficulty extubating (removing the tube from the patient).
Again, these complications are not common but possible.
Having said this, there is no increased risk (other than the above) for the average CMT patient.
If CMT patients have an underlying lung problem (asthma, emphysema, etc), then they are at an increased risk of the above as any patients with these underlying lung problems would be.
For CMT patients who have significant problems with their respiratory system (particularly respiratory muscle weakness), that small group may have higher chance of problems from some of the above risks. Mainly, those patients sometimes are more difficult to wean from and remove the endotracheal tube. Also they seem to have an increased risk of ventilator associated pneumonia.
Having said the above, intubation and mechanical ventilation is a life saving measure can easily be done if needed, usually done with minimal side effects. Just having a diagnosis of CMT does not change that fact.