Hospital Medicine

Weakness; Systemic

I. Problem/Condition.

Systemic weakness is a common complaint found by the hospitalist on a complete review of systems. Less often, it may be the primary presenting complaint that warrants the patient's admission to the hospital. It is important for the clinician to have a firm understanding of the definition of weakness and its etiology because it can often be difficult to distinguish between muscle weakness and other causes of motor impairment that are not due to loss of muscle power.

Weakness is defined as a reduction in the power exerted by one or more muscles, as differentiated from fatigue, which is the inability to perform a task after multiple repetitions that would otherwise be normal for a person of the same gender, age, or physique; a patient with primary weakness is unable to perform a given task on first attempt.

Asthenia is a feeling of weakness or exhaustion that occurs in the absence of true muscle weakness. It is common for the patient to believe asthenia is the result of muscle weakness, which can complicate the correct diagnosis. Asthenia should be differentiated from apraxia, which is a disorder of planning and initiating a learned movement that is unrelated to motor weakness.

Other important definitions include paralysis, which is the inability to contract a muscle to any degree, while paresis refers to weakness that is less severe. Tone is present when a muscle resists to passive stretch. Spasticity is increased velocity-dependent tone, which is often present with central nervous injury in antigravity muscles. Rigidity, constant increased tone throughout a range of motion, is most commonly associated with Parkinson's "cogwheel" findings. Paratonia is increased tone that varies irregularly.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

The broad differential diagnosis of intrinsic weakness should include non-intrinsic weakness that is not the result of loss of muscle power. The differential of resultant causes of asthenia includes Addison's disease, anemia, anxiety, arthritis, chemotherapy-induced weakness, chronic fatigue syndrome, chronic pain, cardiopulmonary disease, deconditioning, depression, diabetes, fibromyalgia, chronic Infections, medications (including narcotics), malignancy and paraneoplastic syndromes, pregnancy, and renal disease.

While it is necessary to distinguish between asthenia and true muscle weakness, they may share similar etiologies. For example, deconditioning, regardless of the cause, can result in both muscle weakness and a sense of fatigue in excess of muscle weakness. Another example is when asthenia and fatigue coexist with weakness, as might be the case in a patient with a myositis and depression. It is also possible for asthenia to evolve into muscle weakness. For example, a patient with COPD may have such significant asthenia that he or she develops muscular atrophy from deconditioning.

The differential of intrinsic weakness in adults usually includes medication, infections, and neurologic disorders. Medications that have a high frequency of induced weakness are amiodorone, anthithyroid agents, methinmazole, propylthiouracil, antiretroviral medications, chemotherapeutic agents, cimetidine, cocaine, corticosteroids, fibric acid derivatives, gemfibrozil, interferon, leuporlide acetate, nonsteroidal anti-inflammatory drugs, penicillin, and sulfamides.

Almost any infectious process has the potential to cause weakness but those that are more common include Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, influenza, Lyme disease, meningitis, polio, rabies, syphilis, toxoplasmosis.

Neurologic etiologies include amyotorphic lateral sclerosis, cerebrovascular disease, demyleination disorders (Guillian-Barre syndrome, multiple sclerosis), neoplasm, neuromuscular disorders (botulism, Lambert-Eaton myasthenic syndrome, myasthenia gravis, organophosphate intoxication), radiculopathies (cervical spondylosis, degenerative disc disease), spinal cord injury, and spinal muscle atrophy.

Less often, weakness may be caused by diseases of the endocrine and rheumatologic system or result from electrolyte disorders and inflammatory processes.

Endocrine etiologies include hypothyroidism (more common), hyperthyroidism, and glucocorticoid excess (either exogenous or from Cushing's syndrome). Rheumatological causes include systemic lupus erythematosus and rheumatoid arthritis. Electrolyte imbalances associated with weakness include hypokalemia, hypophosphatemia, hypocalcemia, hypomagnesemia, hypernatremia, and hyponatremia.

Inflammatory conditions include polymyositis, dermatomyositis, inclusion body myositis, and vasculitis.

Although they are unlikely to be initially diagnosed by the hospitalist, rare genetic causes of weakness include muscular and myotonic dystrophies; metabolic disorders like glycongenoses, lipdoses, and mitochondrial defects; and sarcoid and amyloid-associated myopathies.

When examining non-focal weakness, hospitalists should distinguish between quadriparesis and generalized weakness. Quadriparesis involves upper neuron causes and is associated with changes in mental status, as well spasticity.

General weakness is a disease of the muscle and does not cause changes in mental function, but it does result in hypotonia and hypoactive muscle stretch. These disease processes include electrolyte disturbances, muscle disorders (periodic paralysis and metabolic defects of muscle), neuromuscular junction disorders (myasthenia gravis, Lambert-Eaton myasthenic syndrome) and central nervous system disorders (TIAs of the brainstem, transient global cerebral ischemia, multiple sclerosis).

B. Describe a diagnostic approach/method to the patient with this problem

The diagnostic approach to a patient with weakness should employ a systematic method. First, weakness must be determined to be true weakness, which is defined as the loss of muscle power. If true weakness is thought to be unlikely, then a concomittant systemic illness, such as malignancy, fibromyalgia, or depression may be considered.

Once the determination of objective muscle weakness is made, the next step is to ascertain whether the pattern of weakness is generalized (as in cachexia from multiple etiologies, periodic paralysis, some cases myasthenia gravis, or chronic motor neuron disease) or localized.

Localized or focal weakness is then characterized as symmetric or asymmetric. Asymmetric disease is generally a disease of the central or peripheral nervous system, with the most common causes being cerebral vascular or spinal cord disease, demyelination disorders, or compression neuropathy. Symmetric disease is divided into three categories, although the categories can overlap: proximal weakness (which involves the axial muscle groups, hip flexors, and deltoids), distal weakness (characterized by weakness of wrist flexion and extension and diminished strength of plantar flexion and wrist grip), and specific distributions (found in neuropathies like muscular dystrophy).

1. Historical information important in the diagnosis of this problem.

The clinician should attempt to determine how the patient is employing the term "weakness" in describing his or her history. Patients often confuse functional deficit with weakness, such as when a patient reports that he or she has limited strength because of dypsnea on exertion, fatigue, joint or muscle pain, or spasticity, none of which represent true weakness. Specifically, a patient may complain that he or she is unable to perform a specific chore, such as climbing stairs or cooking dinner. These complaints are more likely to represents asthenia or fatigue than true weakness.

If the history indicates true weakness, the chronicity of symptoms may prove important. Generally, acute onset is associated with a focal process, such as acute cerebral accident or infection. Subacute onset is often consistent with hypoperfusion, hypoxia, myositis, or electrolyte disorders. A chronic progressive weakness is a more classic presentation of a less common genetic myopathy, such as glycogen storage disease. Intermittent weakness is strongly suggestive of the diagnosis of myasthenia gravis, so the patient should always be asked whether repeated activity worsens their condition.

Certain movements or postures that result in increased weakness may suggest a focal weakness like entrapment neuropathy, radiculopathy, or position-dependent compromised vascular flow. If the patients reports a random pattern of weakness that improves in less than thirty minutes, the symptoms may represent transient ischemia.

As described in the differential, questions specific to the pattern of weakness are crucial in determining the etiology of weakness, and questions should seek to elicit this history. For example, proximal weakness is found in the hip muscles and shoulder girdle, so a patient should be asked whether he or she has difficulty standing or raising the hands above the head. A patient's complaint of difficulty doing fine motor tasks with the hands is consistent with distal weakness, which affects the intrinsic muscles of the hand.

A complete history includes a careful review of recent medication usage, alcohol intake, and sexual history. Family history of weakness is usually a strong indicator of a genetic myopathy. Family history should also be reviewed for rheumatological disorders and inflammatory diseases like lupus or myositis. A history of ocular rash and dysphagia may be specific to dermatomyositis.

2. Physical examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

True muscle weakness should be assessed with formal muscle testing. The Medical Research Council has produced the most commonly used grading system using a 0-5 scale.

Grade 5: The muscle contracts normally against full resistance.

Grade 4: Muscle strength is reduced but muscle contraction can still move the joint against resistance.

Grade 3: Muscle strength is further reduced such that the joint can be moved only against gravity with the examiner's resistance completely removed.

Grade 2: The muscle can move only if the resistance of gravity is removed.

Grade 1: Only a trace or flicker of movement is seen or felt in the muscle, or fasciculations are observed in the muscle.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

The laboratory and radiographic workup will vary based on the patient’s presentation and the clinician’s diagnostic concern. The initial workup of the affected patient should include basic electrolytes (sodium, potassium, calcium, glucose, and magnesium), serum aminotransferases, and a urinalysis (the classic finding of which is a UA positive for blood in the absence of red blood cells, which is suggestive of myoglobinuria).

An initial workup may also include muscle enzymes and TSH if there is suspicion of myositis or endocrine involvement. Creatine kinase is nonspecific and usually normal in endocrinopathies and electrolyte disturbances, but it is generally elevated in inflammatory myopathies. Creatine kinase will also be mildly elevated in sarcoidosis, infections, medicine-induced myositis, and alcoholism. Metabolic myopathies will demonstrate more mildly increased creatine kinase.

If endocrinopathy is considered a possibility, workup will include the specific assays for diseases like Cushing's or acromegaly.

Initial serologic screening testing for rheumatologic disease may include erythrocyte sedimentation rate (ESR) and an antinuclear antibody assay (ANA). If these are positive, further testing specific to rheumatoid arthritis (rheumatoid factor), lupus (anti-double-stranded DNA) or scleroderma (anticentromere antibodies) may be considered, based on diagnostic suspicion.

If neuromuscular disease is suspected, antibodies against acetylcholine receptors or (less common) muscle antigens is indicated.

If infectious cause is suspected, the usual workup specific to the suspected disease states should be ordered. Screening tests to be considered when weakness is part of the presenting systems include VDRL/RPR, HIV testing, and Lyme titer.

The workup for generalized weakness may necessitate muscle biopsy when myopathy is suspected and there is no clear evidence of endocrine, metabolic or drug etiology. Dermatomyositis, polymyositis, muscular dystrophies, vaculitis, and inclusion body myosities may then be seen on routine light microscopy. MRI of the muscle can be employed to ascertain the best site for the biopsy, as necrotic muscle will have a lower diagnostic yield. EMG is generally utilized as part of the workup for focal muscle weakness, but it may also have value in determining the best site for muscle biopsy.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

N/A

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

N/A

III. Management while the Diagnostic Process is Proceeding

A. Management of Systemic Weakness.

N/A

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem

N/A

What's the Evidence?

Saquil, A.. " Evaluation of the patient with muscle weakness.". Am Fam Physician. vol. 71. 2005. pp. 1327-1336.

Fauci, A, Braunwald, E, Kasper. "Harrison’s Principles of Internal Medicine". McGraw-Hill,. 2008. pp. 150.

" Aids to the examination of the peripheral nervous system,". Memoradandum no. 45. Her Majesty's Stationery Office. 1981.

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