MEDICAL MANAGEMENT
RESTRICTIVE LUNG DISEASE
Despite being referred to as restrictive lung disease, this NMD does not affect the lung. People with restrictive lung disease develop "weak bellows." The breathing muscles (diaphragm, chest wall, abdominals) are weak. Thus, patients with NMD may have difficulty inhaling and exhaling; this also includes coughing.
This is a common problem in many NMDs but is typically the most severe in ALS, DMD, SMA, and MMD. Respiratory failure in FSHD is not typically seen. However, a study identified 10 patients with FSHD on nocturnal ventilatory support at home, representing approximately 1% of Dutch people with FSHD. Severe muscle disease, wheelchair dependency, and kyphoscoliosis appeared to be risk factors for respiratory failure in FSHD.
Numerous cases indicate respiratory failure in people with CMT, the etiology of which has remained elusive. Electrodiagnostic and pathologic studies on the phrenic nerve in patients with CMT confirm that respiratory failure is involved in the disease.
In one study, phrenic nerve latency was abnormally prolonged in 96% of the subjects with CMT, but significant abnormalities in the results of pulmonary function tests and clinical symptoms were uncommon and did not correlate with the phrenic nerve latencies.
Although phrenic nerve latencies are markedly prolonged in CMT, they are not useful in predicting respiratory dysfunction.
The results of routine pulmonary function tests, including forced vital capacity and maximal inspiratory and expiratory pressure, should be monitored closely. The maximal inspiratory pressure reflects diaphragm strength and ventilatory ability.
Maximum expiratory pressure is indicative of abdominal and chest wall muscle strength and the ability to cough and clear secretions. Peak cough flow is another simple measurement that is indicative of the amount of pressure a patient can generate during a volitional cough.
The biggest problem in NMD is hypoventilation, which leads to hypercapnia (elevated carbon dioxide levels in the blood). End tidal carbon dioxide levels or arterial blood gases should be periodically measured, depending on the clinical circumstances.
Pulse oximetry, which measures only oxygen saturation levels, may be inadequate. Performing a thorough review of systems is important. Patients who are hypoventilating become hypercapnic at night, resulting in a morning headache.
They may also experience nocturnal restlessness, nightmares, and poor overall quality sleep, resulting in daytime somnolence. Insufficient respiration with hypoxia may also occur. This usually occurs much later in the disease process, particularly in cases of lung damage involving chronic pneumonias, infections, or aspiration.
Patients should be educated early in the disease process so that informed decisions can be made further down the line. Many options are available for noninvasive intermittent positive pressure ventilation.
Bimodal positive airway pressure (BiPAP) is generally considered the preferred modality of assisted ventilation in NMDs. BiPAP is similar to the older technology of continuous positive airway pressure (CPAP), which is used to treat sleep apnea.
In CPAP, inhalation and exhalation are assisted with continuous positive airway pressure (which feels like breathing into a stiff headwind). BiPAP cycles the pressure down on exhalation, although a net positive pressure gradient remains (as if the wind died down a bit, but not completely, while exhaling).
Typical pressures would be 8-10 cm water for inhalation and 4-6 cm water for exhalation. BiPAP can easily be used in the home but may take some work with a respiratory therapist to achieve a good face or lip seal on the pilot-type mask or nasal/oral orthotic interface that is typically used. If a mask fails to fit well or is too uncomfortable, a nose plug interface may be used, although this may not work as effectively.
Patients who use assisted oral ventilation, mainly at night, may initially avoid the need for tracheostomy and maintain a reasonable QOL. However, bulbar palsy may occur in ALS and in some rare forms of SMA.
In these cases, if better airway access becomes necessary and the informed patient wishes more aggressive care, a tracheostomy may be performed. However, an alternative procedure, the laryngeal diversion (laryngotracheal separation) procedure, has several distinct advantages over the tracheostomy.
In laryngeal diversion, the trachea is surgically separated, and a cutaneous tracheostoma is formed with the distal segment. The proximal trachea is sewn either over or side-on-end into the esophagus. This completely eliminates the possibility of aspiration and requires much less deep suctioning than a tracheostomy does.
The tracheostoma does not require any hardware, such as a tracheostomy tube, and the patient may still take some food for pleasure without risking aspiration. The primary disadvantage is the complete loss of phonation, since air no longer flows through the vocal cords. This procedure, thus, is recommended only when severe dysarthria accompanies the dysphagia and the patient's speech is unintelligible.
While preserving the ability to phonate, a tracheostomy actually increases the risk of aspiration, requires significantly more care, and provides no better airway access. Although the tracheostomy and the laryngeal diversion facilitate the use of mechanical ventilation, the patient must understand that neither procedure guarantees a better QOL. Fortunately, with the advancements in noninvasive ventilation, these surgical options are now infrequently used.
In addition to assisted ventilation, a number of new technologies may be used to improve respiratory hygiene. These technologies include cough assist machines that help a patient with NMD bring up secretions; the machines produce an artificial cough via a face mask by rapidly changing airway pressure from positive to negative.
This technique has been used since the polio epidemics of over 40 years ago and is now available in the form of several commercial products, including the Cofflator (Respironics, Pittsburgh, Pa) or the In-Exsufflator (JH Emerson Co, Cambridge, Mass).
Dysphagia and dysarthria may occur in ALS and some rare forms of SMA because of the involvement of the bulbar musculature. Early signs of dysphagia include a hoarse voice and persistent cough, particularly after swallowing liquids. This may indicate microaspiration.
At the first sign of dysphagia, consult a speech language pathologist, who can perform clinical swallowing evaluations and make recommendations on dietary modification and safe swallowing strategies. Such strategies include thickening liquids; using techniques such as double swallows, chin tucks, and head turns; and eating only foods that easily form into boluses.
A modified barium swallow study, in which the patient swallows various textures of solid food and liquid laced with barium, is helpful for accurately determining the presence of aspiration, as well as defining which food textures the patient can safely swallow. However, this study does involve exposure to radiation.
Flexible endoscopic evaluation of swallowing (FEES) is a new alternative test to the modified barium swallow that uses an endoscope specifically designed to assess the swallowing mechanism. FEES directly evaluates motor and sensory components of swallowing by direct visualization of the reaction of the larynx to a stimulus delivered by the endoscopic camera, which can then photograph the reaction.
This test clearly shows sites where sensory reactions are impaired, and this can guide the clinician in determining what foods are associated with different types of the patient's swallows.
The main advantage of FEES is that it entails direct observation through a real-time endoscopic camera that visualizes food traveling down the patient's oropharynx and esophagus.
During the test, a speech language pathologist can instruct the patient to make certain physical maneuvers to find the least restrictive method of travel for the food as it passes through the throat and into the stomach, all during the course of the FEES evaluation.
The patient can also provide feedback to the clinician during the test so the therapist can alter the volume and thickness of the food to avoid choking sensations during the exam.
Despite all of these interventions, a percutaneous endoscopic gastrostomy (PEG) tube may be needed to administer nutrition. Malnutrition, and the resulting wasting or cachexia, are grave clinical situations that may quickly occur in rapidly progressive diseases such as ALS.
A similar situation may also arise in an infant or young child with SMA who cannot take in enough nutrition orally to keep up with caloric needs. In SMA, caloric needs are often greatly increased because of respiratory compromise and the increased work necessary for breathing.
A PEG can readily address these issues and provide access for supplemental nutrition. Again, educating the patient and family is critical early in the disease process so they can make informed decisions regarding these issues.
CARDIAC COMPLICATIONS
Cardiac involvement may occur in most of the primary myopathies, including DMD, BMD, MMD, and some cases of LGMD. Cardiac involvement is not seen in the peripheral neuropathies or motor neuron diseases.
A high (60-80%) occurrence of cardiac involvement is present in patients of all ages with DMD and BMD. Dystrophin has been localized to the membrane surface of cardiac Purkinje fibers; this localization probably contributes to the cardiac conduction disturbances seen in DMD and BMD.
A high prevalence of abnormalities found via electrocardiogram (ECG) and echocardiogram exists in preadolescent patients with DMD and BMD. In spite of this, only about 30% of patients with DMD have clinically significant cardiac complications.
The myocardial impairment may remain clinically silent until the late stages of the disease. This may be because of the obligate lack of physical activity. Pulmonary hypertension also has been implicated in the cardiorespiratory insufficiency associated with DMD. Some investigators blame congestive heart failure as the cause of death in as many as 40% of patients with DMD.
An important caveat to note is that severe cardiac involvement in BMD may occasionally precede the clinical presentation of skeletal myopathy. Moreover, the cardiac compromise may be disproportionately severe relative to respiratory compromise in some patients with BMD. Thus, ECG and echocardiography screening are indicated at regular intervals for all patients with BMD.
Patients with myocardial involvement need close follow-up and treatment by a cardiologist with expertise in this area. Some patients with BMD may be suitable candidates for cardiac transplantation. Successful cardiac transplantation has been reported in patients with BMD with cardiac failure who were still ambulatory.
A high prevalence of abnormalities found via ECG exists in MMD. Studies have shown that about one third of patients with MMD have first-degree atrioventricular block, while about one fifth have left axis deviation. Only 5% have left bundle branch block. Bundle of His conduction delays have also been rarely reported. Complete heart blockage, requiring pacemaker placement, is rare but can occur. Patients with MMD should receive routine cardiac evaluations.
PAIN
Pain is a significant problem for most patients with NMD, although it is not typically a direct consequence of the disease. Immobility commonly causes the pain. This may lead to adhesive capsulitis, low back pain, pressure areas on the skin, and generalized myofascial pain. Neuropathic pain is a significant problem for patients with CMT and is likely a direct consequence of the neuropathy.
Pharmacological pain management in NMD initially includes acetaminophen (1000 mg q6h). Acetaminophen may be used along with nonsteroidal anti-inflammatory drugs, which may be particularly helpful if evidence indicates any active inflammatory processes such as joint effusion or tenosynovitis.
Tricyclic antidepressants and antiepileptic drugs are often helpful, particularly for relieving neuropathic pain. Gabapentin, an
antiepileptic drug, also has the added benefit of reducing spasticity via glutamate and gamma-amino butyric acid pathways.
Opioids may be necessary for relieving refractory pain. If required, opioids are best administered on a regular dosing schedule and titrated to the point of comfort. However, close monitoring for respiratory suppression is necessary, even in opiate-tolerant patients.
Cannabinoids, the active ingredients in marijuana (cannabis), have a number of pharmacologic properties that may be applicable to the management of ALS and other NMDs. The benefits of cannabinoids
include analgesia, muscle relaxation, bronchodilation, saliva reduction, appetite stimulation, and sleep induction.
In addition, cannabinoids have strong antioxidative and neuroprotective effects, which may prolong neuronal cell survival. Cannabis does not suppress breathing and there is no risk for overdose, which, in this regard, makes it much safer than opiates. Further investigation into the usefulness of cannabinoids in this setting is warranted.