Neuromuscular Disorders

History

Initial history of patients with complaints of weakness focuses on the acuity of the process and the potential for airway compromise. A complaint of difficulty in breathing or swallowing indicates possible bulbar or respiratory muscle compromise with the potential for life-threatening deterioration. As with other neurologic diseases, the anatomic distribution of symptoms can be the key to diagnosis. Neuromuscular diseases are often progressive or intermittent in nature, so a detailed history of the chronology of symptoms is important. Specific historical features, such as diarrhea (botulism), tick exposure (tick neurotoxin–mediated paralysis), or recurrent episodes of weakness over time (hereditary hypokalemic paralysis) may be helpful. Factors elicited during the history help to guide further history taking, targeted physical examination, and testing, as the differential diagnosis forms and is narrowed by the historical information the patient provides.

Physical Examination

The clinician should first assess adequacy of airway protection and ventilation before a more generalized examination evaluates for the degree of weakness and the location of the lesion. The presence of swallowing and a strong cough suggest that the patient has sufficient protective and ventilatory reserve. The muscles used to lift the head off the bed may weaken before those of respiration and should be assessed. A patient who is not yet intubated but is complaining of shortness of breath or difficulty in breathing should have frequent measurements of forced vital capacity (FVC). Normal FVC ranges from 60 to 70 mL/kg; when the FVC reaches 15 mL/kg, ventilatory support is necessary. Maximal negative inspiratory force (NIF), also called a maximal inspiratory pressure (MIP), is an alternative to FVC. An NIF or MIP of less than 15 cm H ₂ O suggests the need for intubation. Neuromuscular disorders interfere with ventilation not oxygenation, so capnography is a better monitoring modality than pulse oximetry in these cases. Hypercarbia is a late finding and should be regarded as a sign of impending respiratory failure. A subnormal PCO ₂ may also represent developing respiratory failure. As the patient’s respiratory effort falls, tidal volume is reduced, and alveolar CO ₂ is not exhaled sufficiently (hypopneic hypoventilation).

A systematic neurologic examination assesses the patient’s mental status, cranial nerves, motor and sensory function, deep tendon reflexes, and coordination, including cerebellar function. The motor examination begins by determining whether the weakness is unilateral or bilateral and which muscle groups are involved. Key components of the examination include motor strength, muscle bulk, and presence of fasciculations. Box 94.1 provides the grading system used in motor strength assessment. Table 94.2 provides the findings used to distinguish upper motor neuron from lower motor neuron processes.

Myelopathies

Myelopathies are spinal cord disorders that are manifested with signs of upper motor neuron dysfunction, such as muscle weakness with increased spinal reflexes, including an extensor plantar reflex (Babinski sign). There may be bladder and bowel involvement. When sensory findings are present, they often define the level of the lesion. The presence of back pain suggests a compressive lesion, such as a herniated intervertebral disk, tumor, or epidural hematoma. Concomitant systemic signs, such as a fever, or a history of intravenous (IV) drug use, can suggest an epidural abscess. Increasing postprocedural pain, for example following lumbar puncture, epidural anesthesia, or spine surgery, warrants consideration of an epidural hematoma. Acute, painless spinal cord lesions include transverse myelitis and spinal cord infarction.

Motor Neuron Disease

The characteristic findings of motor neuron disease combine signs of both upper and lower motor neuron dysfunction, including hyperreflexia, muscle wasting, and fasciculations. Pain is not a component of the clinical picture. Amyotrophic lateral sclerosis (ALS; Lou Gehrig disease) is the archetypal motor neuron disease.

Poliomyelitis affects the anterior horn cells and results in lower motor neuron disease without sensory involvement. The weakness is often asymmetric. Patients initially have a clinical picture similar to that of viral meningitis with fever and neck stiffness. The cerebrospinal fluid (CSF) analysis resembles that of viral meningitis. Polio has been eradicated in many parts of the world but remains prevalent in areas of conflict where public health systems have eroded. The United States has seen an increase in acute flaccid myelitis (AFM), a paralyzing illness affecting pediatric patients that is described as “polio-like.” AFM appears to have a temporal relationship with enteroviruses D68 and A71, but it is unclear if these viruses are the cause of the syndrome.

Neuropathies

Weakness from a neuropathy is often noted first in distal muscles and then progresses centrally. Decreased grip strength and foot drop are common initial presentations. The differential diagnosis includes Guillain-Barré syndrome, toxic neuropathies, diabetic neuropathy, and tick paralysis (which is caused by inhibition of both nerve conduction and function of the neuromuscular junction). Neuropathies are discussed in Chapter 93 .

Diseases of the Neuromuscular Junction

Disorders of the neuromuscular junction cause motor fatigability. The initial depolarization at the nerve end plate stimulates a maximum number of ACh receptors on the muscle cell, producing a normal or nearly normal strength response. Repeated stimulation leads to diminishing motor strength, which is caused by one of three mechanisms: blockage of the receptors, as in myasthenia gravis, decrease in the amount of ACh released, as in botulism, or inactivation of ACh by irreversible binding, as in organophosphate poisoning.

A decrease in the release of ACh can cause a combination of nicotinic and muscarinic effects. The clinical manifestations of this are anticholinergic findings, such as dilated pupils, confusion, urinary retention, tachycardia, low-grade fever, and dry, flushed skin. In the case of Lambert-Eaton myasthenic syndrome, weakness is more pronounced at the beginning of muscle use and improves with repeated use as more ACh builds up in the synaptic cleft with each stimulation. Muscle tone is generally diminished and sensation is preserved in diseases of the neuromuscular junction.

Myopathies

Myopathies produce generalized, symmetric weakness. Reflexes are diminished, muscle tone is usually diminished, but sensation is preserved. Myopathies due to inflammatory disorders (polymyositis, dermatomyositis, polymyalgia rheumatica, and viral myositis) cause muscle pain and tenderness. Metabolic disorders affecting muscle strength (e.g., electrolyte and endocrine disorders) cause diffuse weakness without pain. Electrolyte alterations affecting muscular and cardiac function are discussed in Chapter 114 .

Myasthenia Gravis

Principles

The age at onset of myasthenia gravis is influenced by gender; women are most commonly affected between 20 and 40 years old and men between 50 and 70 years old. Although new cases of myasthenia gravis are occasionally diagnosed in the emergency department (ED), it is much more common for patients with established disease to present with exacerbations of their disorder, often caused by precipitating factors.

In most patients with myasthenia gravis, weakness and fatigue result from circulating autoantibodies against the nicotinic ACh receptor on the junctional folds of the postsynaptic membrane. The effects are the result of several pathologic processes: direct blocking of the receptor, complement mediated destruction of the folds, and internalization and degradation of the receptors ( Fig. 94.2 ). With repeated stimulation, fewer and fewer receptor sites are available for ACh binding, and fatigue develops. Fatigability and muscle weakness are the hallmarks of myasthenia gravis. Muscarinic receptors are also affected but to a much lesser extent, so muscular weakness is the dominant presentation of myasthenia gravis. Ocular muscle weakness is the first sign of myasthenia gravis in up to 40% of patients, although 85% of patients eventually have ocular involvement. When ptosis is present, it is often worse toward the end of the day. New-onset diplopia also may signal development of myasthenia gravis. Respiratory failure is rarely the initial symptom of myasthenia gravis. Bulbar muscles may be involved myasthenia gravis, producing dysarthria or dysphagia. Facial and extremity muscles may also be involved, producing some classic symptoms of myasthenia gravis (i.e., difficulty in combing hair or brushing teeth, weakness of the muscles in the posterior neck causing a “dropped-head appearance,” and a limited ability to form a full smile due to weakness of lateral facial muscles).

The prognosis for patients with myasthenia gravis has markedly improved in recent years due to the demonstrated benefit of thymectomy and the approval of the drug eculizumab for refractory cases. Nevertheless, stable disease can be pushed to crisis by commonly used drugs that are known to exacerbate myasthenia gravis ( Box 94.2 ). Even topical medications, such as tobramycin eye drops, can cause an exacerbation. Assessing drug-disease interactions is a particularly important step when prescribing to patients with myasthenia gravis, even if the disease is well controlled.

BOX 94.2

Drugs That May Exacerbate Myasthenia Gravis

• Cardiovascular

  • Beta-blockers

  • Calcium channel blockers

  • Quinidine

  • Lidocaine

  • Procainamide

• Antibiotics

  • Aminoglycosides

  • Tetracyclines

  • Clindamycin

  • Lincomycin

  • Polymyxin B

  • Tobramycin

  • Fluoroquinolones

  • Colistin

• Other

  • Phenytoin

  • Neuromuscular blockers

  • Corticosteroids

  • Thyroid replacement

Myasthenic crisis

Myasthenic crisis is defined as respiratory failure requiring mechanical ventilation. It occurs in 15% to 20% of patients with myasthenia gravis, usually within the first 2 years of disease onset. Although it is potentially life threatening, the mortality from this complication of myasthenia gravis has declined dramatically with appropriate care in the ED and intensive care unit (ICU) and the use of plasma exchange or immunomodulatory therapy with intravenous immune globulin (IVIG).

Crises are most often precipitated by underlying infection, aspiration, and medication changes, such as stopping anticholinergic medications or initiating a new medication that precipitates weakness. Other precipitants can be surgery and pregnancy (see Box 94.2 ).

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