Introduction
Muscular disorders (see Table 54-1) are characterized by abnormalities of muscle fibers. In addition, many neurologic disorders (eg, lesions of the central or peripheral nervous system, abnormalities of neuromuscular transmission) can produce symptoms that are primarily muscular--see Table 54-2 (see also page 488) Other systemic disorders (eg, rheumatic, psychiatric, cardiovascular, respiratory, endocrine) can mimic muscular disorders but do not directly affect muscular function. These systemic disorders account for more than half of muscular complaints.
Approach to the Patient with Muscular Symptoms
History and physical examination (see Table 54-3): Abnormalities in gait and in leg muscle strength that are often symmetric may be due to lesions in the central nervous system (CNS), which can mimic abnormalities of the peripheral nervous system or of muscle fibers. Papilledema, unilateral weakness or sensory loss, and a gait disturbance with the head turned or the neck flexed suggest a CNS cause.
Difficulty in walking, unsteadiness with occasional falls, and joint stiffness with leg pains, especially at night, may also be due to rheumatic diseases (eg, degenerative joint disease, rheumatoid arthritis, polymyalgia rheumatica). Significant degenerative joint disease can limit mobility by producing structural spinal changes and joint symptoms in the limbs and occasionally by damaging the spinal cord, nerve roots, and peripheral nerves.
Muscle weakness in patients with descending motor pathway dysfunction (eg, midline subdural hematoma, midline posterior fossa mass) is frequently greater on functional testing (ie, during performance of common tasks) than on direct muscle strength testing. Muscle weakness in patients with peripheral nerve and muscle damage is similar on functional and direct muscle testing.
Muscle weakness in patients without significant joint or soft tissue disease is suggested by the inability to walk on the heels and toes, rise from a squatting position, rise from a chair without using the arms, or step onto the seat of a chair. A normal person should be able to completely extend the knee against gravity. If the knee tends to remain slightly flexed, the quadriceps of the thigh may be weak, which often causes stumbles and falls. The patient should be able to raise outstretched arms above the head easily and to blanch the knuckles with a forceful grip.
Exercise performance may be limited in patients with anxiety or depression. These patients often do not have intrinsic muscle weakness, yet experience fatigue and lack motivation for activities of daily living.
Pathologic fatigue is characterized by drooping eyelids when a person fixates on a target or by rapid exhaustion during repeated movements (eg, elevating the arms above the head, rising from a chair). When due to an abnormality in neuromuscular transmission (eg, myasthenia gravis), pathologic fatigue leads to fluctuations in the ability to chew, keep the eyes open, speak, or smile.
Muscle cramps or pain in the absence of electrolyte or pH disturbance commonly indicates a peripheral nerve disorder and less commonly an abnormality in muscle fibers. Intense pain that is most prominent in proximal muscles in the morning may indicate polymyalgia rheumatica. Pain in localized muscle regions may indicate fibromyalgia. Pain largely restricted to muscle groups and periarticular tissue may indicate diffuse arthritic disease with limited muscle function.
Focal muscle wasting indicates an abnormality in muscle fibers or motor nerves. Diffuse muscle wasting can occur after as little as 4 to 6 weeks of absolute bed rest; despite the reduced muscle mass, muscle strength is usually preserved.
Abnormalities in tendon reflexes are important to note on examination. Tendon reflexes are typically increased and plantar extensor responses are present in patients with muscle weakness due to CNS disease. However, ankle or other reflexes are absent in many elderly persons without demonstrable disease. Loss of reflexes with only mild weakness is typical for disease of the peripheral nerve or nerve root, although occasionally cerebellar lesions depress tendon reflexes, suggesting muscle weakness. Loss of reflexes in patients with primary myopathy often parallels the degree of weakness. Reflexes are usually maintained in patients with abnormalities of neuromuscular transmission but are frequently lost or hypoactive in patients with Eaton-Lambert syndrome.
Blood tests: Elevation of serum creatine kinase (CK) levels (normal < 130 U/L) is a more sensitive determinant of muscle damage than is elevation of any other serum enzyme level. However, normal exercise, depending on its intensity and the person's conditioning, can elevate CK levels as much as threefold to eightfold. Levels peak several hours after exercise, and maximum levels persist for 24 to 36 hours, partly because of the long plasma half-life of CK (38 to 118 hours). Thus, CK levels should not be measured within 48 hours of vigorous normal exercise. CK levels are also elevated by muscle damage caused by prolonged pressure, which may occur in elderly persons who lie immobile on a hard surface.
CK elevations occur in many disorders affecting the motor unit (the anterior horn cell, motor axon and terminal branches, neuromuscular junctions, and muscle fibers). Mild CK elevations (< 4 times the upper limit of the normal range) occur in some healthy persons with large muscle mass, in healthy persons after minor muscle trauma (eg, after intramuscular injections or needle electromyography), in persons predisposed to malignant hyperthermia, and in persons with certain chronic anterior horn cell diseases such as amyotrophic lateral sclerosis and postpolio syndrome. Moderate to marked CK elevations occur in inflammatory myopathies (eg, polymyositis, dermatomyositis) and after conditions that produce muscle necrosis (eg, hypokalemic myopathy).
CK isoenzymes include CK-MM (found primarily in skeletal muscle), CK-MB (in heart muscle), and CK-BB (in brain tissue); the concentration of CK-MM is > 3 times that of CK-MB and CK-BB. Normal adult skeletal muscle contains about 95% CK-MM and 5% CK-MB. However, regenerating skeletal muscle fibers revert to an embryonic isoenzyme pattern, and CK-MB increases to 10 to 50%. Thus, CK isoenzyme measurements are not useful for diagnosing or monitoring neuromuscular disorders.
Measurements of serum electrolyte and bicarbonate levels (to evaluate for acidosis or alkalosis) are helpful in diagnosing the cause of muscle weakness, particularly muscle weakness accompanied by muscle cramps and pain. Possible causes include hypokalemia, hypophosphatemia, hypocalcemia, hypermagnesemia, and chronic hypofunction or hyperfunction of the thyroid, adrenal, or parathyroid glands. ESR and other blood tests (eg, antinuclear antibody, rheumatoid factor) can be used to screen for collagen vascular diseases; serum and urine immunoelectrophoresis can be used to assess immunoglobulins and Bence Jones protein in multiple myeloma.
Imaging studies: Plain x-rays of the spine can identify many rheumatic disorders (eg, chronic osteoarthritis, chronic disk herniation with early lumbosacral spinal canal narrowing) and other disorders that might produce muscular symptoms (eg, covert metastatic disease with vertebral collapse). In patients with chronic motor neuropathies, a skeletal survey may help identify the cause (eg, multiple myeloma, osteomalacia).
Ultrasonography, CT, MRI, and radionuclide imaging can quantify muscle atrophy and identify the muscle groups with the most damage before needle biopsy is performed. Ultrasonography can also help identify a muscle abscess. CT and MRI can identify lesions in the brain and spinal cord and occasionally in soft tissues and muscle that other studies cannot identify. Examples include lesions producing symmetric dysfunction in the descending motor pathways, thymoma (in myasthenia gravis), and oat cell carcinoma of the lung (in Eaton-Lambert syndrome). Technetium diphosphonate or pyrophosphate imaging can demonstrate muscle fiber damage in polymyositis.
Electrodiagnosis: Electrodiagnostic testing (see Table 54-4) is indicated to identify axonal and demyelinating neuropathies, to demonstrate abnormalities in neuromuscular transmission, and to detect damage to muscle fibers typical of primary muscle diseases. Testing helps confirm the diagnosis of diseases such as chronic inflammatory demyelinating polyneuropathy, Eaton-Lambert myasthenic syndrome, and inflammatory myopathies. Electrodiagnostic testing is especially useful for evaluating patients who cannot undergo thorough clinical testing because of pain or cognitive impairment. Serial testing is helpful in selected patients for demonstrating improvement and aiding in decisions about treatment.
Nerve conduction assessment uses skin electrodes to stimulate a peripheral nerve at various points and other electrodes to record the motor and sensory action potentials at distal sites, so that conduction velocity of the peripheral nerve can be calculated. In healthy adults, conduction velocity typically ranges from 45 to 75 m/second. (In healthy elderly persons, velocity tends to be in the lower range.) In those with chronic demyelinating polyneuropathies, the velocity may be decreased by >= 40%.
Repetitive stimulation testing measures the action potential of the peripheral motor nerve. The nerve is stimulated at a low frequency (3 Hz), usually before and after brief maximal isometric exercise. An incremental decrease in the amplitude of the action potential usually indicates an abnormality in neuromuscular transmission (eg, myasthenia gravis). In contrast, an incremental increase is usually due to Eaton-Lambert syndrome.
Electromyography records electrical activity of muscle at rest (when normally there is none) and during mild and strong contractions. The number and amplitude of motor unit potentials increase as the strength of voluntary contraction increases. In neurogenic disorders that damage the motor axon, electromyographic findings depend on the type and duration of the neuropathy. If the damage produces axonal death, fibrillations (spontaneous activity of single muscle fibers) and positive waves (biphasic action potentials initiated by movement of the recording needle, often occurring in an area of damaged, fibrillating muscle fibers) usually develop after >= 3 weeks.
Electromyography often differentiates primary myopathy from neuropathy. Typically with myopathy, the test shows a normal number of motor unit potentials, often with decreased amplitude, during maximum contraction. With chronic denervation, the test shows a reduced number of motor unit potentials with very high amplitude. Acute neuropathy may produce fibrillations and positive waves identical to those produced after inflammatory myopathies.
Fasciculations (spontaneous activity of part or all of a motor unit) typically occur with slowly progressive diseases of the anterior horn cell or nerve roots or with electrolyte disturbances; they often do not indicate axonal death. Many normal persons develop fasciculations, especially after exercise.
Muscle biopsy: This test is useful for differentiating myopathy from neuropathy. It is also useful for diagnosing certain connective tissue diseases (eg, polyarteritis nodosa, polymyositis) and disorders such as the muscular dystrophies, congenital myopathies, and specific metabolic diseases of muscle, which are rare in the elderly.
Biopsy is not useful for diagnosing acute generalized weakness, subacute or chronic neurogenic weakness (eg, acute inflammatory polyneuritis, diabetic polyneuropathy), or abnormalities in neuromuscular transmission (eg, myasthenia gravis).
Nerve biopsy: Nerve biopsy is more difficult and traumatic than muscle biopsy and thus has limited use. It can differentiate segmental demyelination from axonal degeneration and identify inflammatory neuropathies. Nerve biopsy also can be used to diagnose uncommon diseases such as amyloidosis, sarcoidosis, leprosy, and certain unusual metabolic and hereditary neuropathies. In elderly patients, the indications are very restricted; the most common indication is diagnosis of chronic inflammatory demyelinating polyneuropathy.
Muscle mass assessment: Measurements of muscle mass are helpful in assessing disease progression or improvement (eg, in patients with chronic slowly progressive neuromuscular diseases). For example, clinical examination may not determine whether weight gain in a patient with inflammatory myopathy is due to treatment with corticosteroids or to an increase in muscle mass. Because a change in muscle strength may not be apparent for several weeks or not at all after a decline in muscle mass, measurements of muscle mass may detect a response to treatment or lack of response that is not evident on clinical examination.
The usual method is a 24-hour urinary creatinine measurement, which varies by < 10%, correlates directly and reliably with total muscle mass, and can be used to determine response to therapy. Normal findings are 1800 to 1700 mg/24 hours (15.8 to 15.0 mmol/24 hours) for persons aged 30 to 50; 1700 to 1500 mg/24 hours (15.0 to 13.2 mmol/24 hours) for those aged 50 to 60; 1600 to 1400 mg/24 hours (14.1 to 12.3 mmol/24 hours) for those aged 60 to 70; and 1400 to 1200 mg/24 hours (12.3 to 10.6 mmol/24 hours) for those aged 70 to 80. Patients must not consume meat for 3 days before urine collection. Specimens collected weeks to months apart are often helpful in documenting sequential changes in muscle mass.
Dual energy x-ray absorptiometry (DEXA) can be used to measure muscle mass and bone density (the usual indication for the test). DEXA is fast (30 minutes) and, unlike urinary creatinine measurement, requires only one session. The x-ray exposure is less than that of a standard chest x-ray. Disadvantages include significantly high cost compared with urinary creatinine measurement and low availability of the equipment required.
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