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Approach to the patient with muscle weakness

Approach to the patient with muscle weakness
Author:
Jeremy M Shefner, MD, PhD
Section Editor:
Ira N Targoff, MD
Deputy Editor:
Janet L Wilterdink, MD
Literature review current through: Jul 2022. | This topic last updated: Apr 09, 2019.

INTRODUCTION — The evaluation of the patient presenting with a complaint of "weakness" involves three steps:

Distinguishing true muscle weakness from lassitude or motor impairment not due to loss of muscle power

Localizing, within the neuromuscular system, the site of the lesion that is producing weakness

Determining the cause of the lesion

This topic will review the approach to the patient with muscle weakness by addressing these three issues. The specific tests used to assess muscle weakness are discussed separately, as are the clinical manifestations and evaluation of respiratory muscle weakness. (See "Muscle examination in the evaluation of weakness" and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation".)

DISTINGUISHING TRUE MUSCLE WEAKNESS FROM LASSITUDE — Many patients who complain of weakness are not objectively weak when muscle strength is formally tested. A careful history and physical examination will permit the distinction between lassitude, motor impairment due to pain or joint dysfunction, and true weakness.

History — Patients with a variety of systemic disorders may interpret difficulties performing certain tasks as weakness. Included in this group are cardiopulmonary disease, joint disease, anemia, cachexia from malignancy or chronic infectious or inflammatory disease, and/or depression. Patients with any of these conditions may be functionally limited but not truly weak. Furthermore, careful questioning will reveal that the patient is limited by shortness of breath, chest pain, joint pain, fatigue, poor exercise tolerance, paresthesias, or spasticity rather than a true decrease in muscle power.

Patients with lassitude often complain that they are weak. In comparison, those with true muscle weakness typically complain that they are unable to perform specific tasks, such as climbing stairs or combing hair, or that they have a feeling of "heaviness" or "stiffness" in their limbs. Muscle pain is relatively uncommon in patients with many types of myopathy and true weakness, but it is often reported by patients with overexertion, cramps, or fibromyalgia (see "Clinical manifestations and diagnosis of fibromyalgia in adults"). Similarly, patients with polymyalgia rheumatica, despite the misapplied name of the disorder, are limited by pain and stiffness but have normal muscle strength. (See "Clinical manifestations and diagnosis of polymyalgia rheumatica".)

Physical examination — As with the history, the physical examination should include a careful search for one of the disorders that can cause the perception of weakness, as well as testing of muscle strength. In addition, two general observations may be helpful:

Despite advanced generalized muscle atrophy, muscle strength is relatively preserved in patients with cachexia.

Muscle tenderness is usually not associated with one of the causes of true muscle weakness. There are, however, exceptions to this general rule including infectious myopathies such as trichinellosis and viral myositis, certain drug-induced myopathies, thyroid myopathy, and the inherited metabolic myopathies.

True muscle weakness is documented by formal muscle testing. The strength of each muscle can be assessed by determining how much force is required by the examiner to overcome maximal contraction by the patient. A widely used system to measure muscle strength is the grading system from the Medical Research Council which is based upon a scale of zero to five [1].

Zero – No muscle contraction

One – Flicker or trace of muscle contraction

Two – Limb or joint movement possible only with gravity eliminated

Three – Limb or joint movement against gravity only

Four – Power decreased but limb or joint movement possible against resistance

Five – Normal power against resistance

LOCALIZING THE SITE OF THE LESION — One useful systematic approach to the myriad lesions of the neuromuscular system that can cause true muscle weakness is to place the various lesions into categories determined by the organization of the neuromuscular system. This begins with the motor cortex and proceeds through the corticospinal tracts, anterior horn cells, spinal nerve roots, peripheral nerves, neuromuscular junction, and finally muscle (table 1). Lesions of the central and peripheral nervous systems should be identifiable from a detailed neurologic examination. The distribution of weakness, the presence or absence of deep tendon reflexes, the Babinski sign, and related sensory defects are all important in localizing the lesion in the nervous system (see "The detailed neurologic examination in adults"). Confirmation of findings derived from the physical examination can usually be obtained from electromyographic (EMG) testing in a cooperative patient [2].

Distribution of weakness as a guide to localizing the lesion — Determining the pattern of muscle weakness is also diagnostically important. Generalized weakness occurs in some cases of myasthenia gravis, long-standing periodic paralysis, advanced disuse atrophy from prolonged bed rest, muscle wasting from malignancy, or longstanding motor neuron disease (algorithm 1).

If the weakness is not generalized, it can be characterized as symmetric or asymmetric. Asymmetric weakness most likely reflects disease of the central or peripheral nervous system; furthermore, lesions of the motor cortex, spinal cord, spinal nerve root, and peripheral nerve each have distinct distribution patterns. Symmetric patterns of weakness can be divided into distal, proximal, or specific distributions.

Distal weakness is characterized by decreased grip strength, weakness of wrist flexion or extension, decreased plantar flexion strength, and foot drop. These patients have difficulty walking on their heels or toes. Foot drop can be detected by opposing the patient's attempt to dorsiflex the ankle. Distal symmetric weakness is characteristic of early motor neuron disease or peripheral neuropathy. (See "Overview of polyneuropathy".)

Proximal weakness involves the axial muscle groups, deltoids, and hip flexors. Affected patients may have difficulty flexing or extending the neck against resistance. One way to detect the presence of neck flexor weakness is to observe the patient sitting up from the supine position. In this setting, the head will lag behind as the patient sits up. Sitting up may be difficult or even impossible in patients with more severe proximal muscle weakness or, at times, may be the only objective evidence of weakness. Deltoid muscle strength can be assessed by pressing down on the patient's fully abducted arms with the elbows flexed. The examiner should not be able to overcome the patient's resistance if strength is normal.

The patient with quadriceps weakness may be unable to rise from a seated position without the use of the upper extremities and is usually unable to perform a deep knee bend. These individuals may suddenly drop into the chair when trying to sit down slowly. Patients with proximal leg weakness may rise from sitting on the floor by "climbing up their legs with their hands." This is termed Gower's sign and is characteristic of, but is not specific for, Duchenne muscular dystrophy. Proximal muscle weakness is typically seen in the various myopathies (table 2), certain muscular dystrophies, and myasthenia gravis.

Specific distributions of weakness are characteristic of certain neuropathies or muscular dystrophies. Examples of localized disorders include facioscapulohumeral dystrophy, scapuloperoneal dystrophy, and scapulohumeral dystrophy.

DETERMINING THE CAUSE OF THE LESION — Once the neuromuscular site of the lesion causing weakness has been identified, the disorders at each site can be categorized as genetic, inflammatory/immunologic, infectious, neoplastic, toxic, or metabolic in origin (table 1).

Sites of lesions

Lesions of upper motor neurons — Upper motor neuron impairment can occur with the common acute stroke syndromes, space occupying lesions of the central nervous system, and lesions of the spinal cord. Spinal cord lesions can be related to trauma, infection, tumor, vascular anomalies, hypertrophic degenerative skeletal changes, demyelinating diseases, and congenital leukodystrophies. Appropriate imaging studies of the central nervous system and spine and cerebrospinal fluid examination may be necessary to identify the primary disease. Depending upon the suspected site of the lesion, magnetic resonance imaging of the brain and/or spinal cord, plain radiographs of the spine, radionuclide bone scanning, or CT scanning may be appropriate imaging modalities.

Anterior horn cell lesions — Weakness due to involvement of the anterior horns cells is seen in motor neuron disease, familial spinal atrophy, lead poisoning, and poliomyelitis, which is still a threat to unimmunized individuals. West Nile and other virus infections represent additional causes of lower motor neuron disease. The time course of the illness, the age and family history of the affected individual, the exposure history, and the cerebrospinal fluid examination help to differentiate between these disorders. (See "Diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease".)

Lesions of the peripheral nervous system — Involvement of peripheral nerves typically presents in one of two patterns:

A symmetric polyneuropathy with weakness and sensory symptoms is a frequent sequela of diabetes mellitus. Other etiologies include a variety of toxic or metabolic insults, as well as heritable disorders. (See "Overview of polyneuropathy".)

Mononeuropathy may be the result of nerve compression (eg, carpal or tarsal tunnel syndrome, ulnar neuropathy, radial neuropathy). Mononeuropathy multiplex (ie, asymmetric polyneuropathy) occurs in diabetes mellitus or one of the vasculitic syndromes such as polyarteritis nodosa. (See "Screening for diabetic polyneuropathy" and "Clinical manifestations and diagnosis of vasculitic neuropathies".)

In addition, weakness may result from involvement of the neuromuscular junction. This can be induced by anti-acetylcholine receptor antibodies in myasthenia gravis or drug-induced myasthenia, inhibition of acetylcholinesterase by organophosphate poisoning, or interference with presynaptic calcium channel function in Lambert-Eaton syndrome. (See "Pathogenesis of myasthenia gravis" and "Organophosphate and carbamate poisoning" and "Lambert-Eaton myasthenic syndrome: Clinical features and diagnosis".)

Myopathy — The major categories of muscle disease include inflammatory disorders, endocrinopathies, metabolic myopathies, drugs and toxins, infections, and the various causes of rhabdomyolysis (table 2) [3,4].

The specific diagnosis may be suspected from the age and sex of the patient in the muscular dystrophies.

A history of recurrent episodes of exertion-related pigmenturia and weakness suggests a metabolic myopathy. However, many metabolic myopathies have a slowly progressive rather than episodic course. (See "Approach to the metabolic myopathies".)

Medication, alcohol, or substance-abuse may be a clue to drug-induced myopathy. (See "Drug-induced myopathies".)

Endocrinopathy, such as thyroid dysfunction (hypo or hyperthyroidism) or Cushing's syndrome, may be the cause of true muscle weakness. (See "Hypothyroid myopathy" and "Glucocorticoid-induced myopathy".)

Inflammatory myopathy should be suspected if there is symmetric proximal muscle weakness and no evidence of an alternative explanation for the weakness or if there are other features of a systemic rheumatic disease such as rash, interstitial lung disease, polyarthritis, or Raynaud phenomenon.

Clinical investigations

Laboratory studies — Some laboratory studies may be useful in the general evaluation of patients with true weakness.

Chemistry and urinalysis – Elevations of plasma muscle enzymes (creatine kinase, aldolase, lactate dehydrogenase, and the aminotransferases) are highly suggestive of muscle diseases. They can, however, also be elevated in motor neuron disease or can be induced by strenuous exercise, intramuscular injections, or muscle trauma in the absence of generalized muscle disease [5]. A positive test for urine blood, in the absence of red blood cells in the sediment, is suggestive of myoglobinuria. (See "Muscle enzymes in the evaluation of neuromuscular diseases" and "Clinical manifestations and diagnosis of rhabdomyolysis".)

Serologic tests – Serologic tests including antinuclear antibodies, antibodies against extractable nuclear antigens (anti-Ro/SSA, anti-La/SSB, anti-Sm, and anti-RNP), and "myositis specific" antigens (eg, anti-histidyl-t-RNA synthase [anti-Jo-1]) should be obtained if an inflammatory myopathy or associated connective tissue disease is suspected. (See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

Anti-neutrophil cytoplasmic antibody (ANCA) titers, hepatitis B and C serologies, and cryoglobulins should be obtained in patients with suspected vasculitis. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies".)

Electrophysiologic studies — Nerve conduction and electromyographic (EMG) studies are used when the site of the lesion causing weakness is suspected to be in the peripheral nervous system, the neuromuscular junction, or the muscle itself. The EMG is also of value in directing the site of muscle biopsy. (See "Overview of electromyography" and "Overview of nerve conduction studies".)

Magnetic resonance imaging — Magnetic resonance imaging (MRI) may be useful in selecting a muscle for biopsy and has an advantage over EMG in cases of suspected inflammatory myopathy in that the actual muscle to be biopsied can be identified, rather than the muscle contralateral to one with EMG abnormalities. (See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

Muscle biopsy — Muscle biopsy may be necessary to determine the precise form of myopathy. Characteristic changes of dermatomyositis, polymyositis, inclusion body myositis, certain drug-induced myopathies, the muscular dystrophies, or vasculitis may be seen on routine light microscopy. Electron microscopic examination may be useful in some cases (eg, to confirm inclusion body myositis). Some pertinent issues in performing muscle biopsy and specimen handling are discussed in more detail elsewhere (see "Clinical manifestations of dermatomyositis and polymyositis in adults" and "Clinical manifestations and diagnosis of inclusion body myositis"). Special stains can demonstrate enzyme deficiencies and abnormal accumulations of glycogen or lipid in the metabolic myopathies [2].

Genetic testing — Genetic testing is becoming increasingly useful in confirmation and categorization of patient with muscular dystrophies and heritable myopathies. (See appropriate topics.)

RESPIRATORY MUSCLE WEAKNESS — Respiratory muscle weakness may occur in patients with skeletal muscle weakness from a variety of causes and can rarely lead to respiratory failure. Patients who present with muscle weakness should also be assessed for respiratory muscle weakness, particularly in the presence of signs or symptoms of ventilatory compromise (eg, tachypnea, shortness of breath, or somnolence) or oropharyngeal muscle weakness (eg, a history of impaired swallowing, dysphonia, or nasal regurgitation). (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation".)

SUMMARY — The evaluation of the patient presenting with a complaint of "weakness" involves distinguishing true muscle weakness from lassitude or motor impairment not due to loss of muscle power; localizing, within the neuromuscular system, the site of the lesion that is producing weakness; and determining the cause of the lesion.

Patients whose weakness is the result of a non-neuromuscular disorder (eg, those who are easily fatigued due to cardiac or pulmonary disease, limited by joint pain or stiffness, etc) can usually be distinguished from those with weakness that is due to reduced muscle strength based upon the history and physical examination. (See 'Distinguishing true muscle weakness from lassitude' above.)

In patients in whom formal muscle testing confirms the presence of muscle weakness, a neurologic examination is performed to localize the site of the lesion (ie, to the central nervous system, peripheral nervous system, neuromuscular junction, or muscle). The distribution of muscle weakness (ie, generalized, distal, proximal, or localized) may help to narrow the number of possible causes. (See 'Physical examination' above and 'Distribution of weakness as a guide to localizing the lesion' above.)

Laboratory tests that may be useful in the evaluation of weakness include serum electrolytes, calcium, magnesium, phosphate, creatine kinase, aldolase, lactate dehydrogenase, serum aminotransferases, and thyroid stimulating hormone. In patients with clinical features that suggest a systemic rheumatic disease, serologic studies are warranted, including antinuclear antibodies (ANA), antibodies against extractable nuclear antigens (ENA), and myositis specific antibodies. A positive urine test for blood in the absence of red cells in the sediment suggests myoglobinuria. (See 'Laboratory studies' above.)

Electrophysiologic nerve and muscle testing (ie, measurement of nerve conduction velocity, sensory action potentials, and electromyography) may be of value in localizing the site of peripheral neuromuscular disorders. (See 'Electrophysiologic studies' above.)

If the evaluation suggests that myopathy is responsible for weakness and if no drug, toxin, metabolic, or endocrine disorder can be identified as the cause, then a muscle biopsy may be necessary to arrive at a specific diagnosis.(See 'Muscle biopsy' above.)

A patient who presents with a complaint of muscle weakness should also be assessed for respiratory muscle weakness, particularly if signs of ventilatory compromise or oropharyngeal muscle weakness are present. (See 'Respiratory muscle weakness' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Marc L Miller, MD, who contributed to an earlier version of this topic review.

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