Weakness

Many patients report weakness when their problem is fatigue. Fatigue can prevent maximal effort and muscle performance during strength testing.

Common causes of fatigue include acute severe illness of almost any cause, cancers, chronic infections (eg, HIV infection, hepatitis, endocarditis, mononucleosis), endocrine disorders, renal failure, hepatic failure, heart failure, and anemia. Multiple sclerosis can cause daily fatigue that increases with exposure to heat and humidity.

Patients with fibromyalgia, depression, or chronic fatigue syndrome may report weakness or fatigue but have no defined objective abnormalities.

History of present illness should begin with open-ended questions, asking patients to describe in detail what they are experiencing as weakness. Then, specific questions can be asked, particularly about the ability to do specific tasks, including brushing teeth or hair, speaking, swallowing, rising from a chair, climbing stairs, and walking.

Clinicians should also ask about the onset of weakness (sudden or gradual) and progression (eg, constant, worsening, intermittent) of symptoms. Close questioning is needed to differentiate sudden onset from sudden recognition; patients may suddenly recognize symptoms only after slowly progressive weakness crosses a threshold that prevents them from doing some normally routine task (eg, walking, tying shoes).

Important associated symptoms include sensory changes, double vision, memory loss, difficulty using language, seizures, and headaches. Factors that worsen weakness, such as heat (suggesting multiple sclerosis) or repetitive use of a muscle (suggesting myasthenia gravis), are noted.

Review of systems should seek symptoms suggesting possible causes, including the following:

• Daily fatigue and weakness that increases with heat and humidity: Multiple sclerosis

• Diurnal variation of fatigue and weakness: Myasthenia gravis

• Rash: Dermatomyositis, Lyme disease, or syphilis

• Fevers: Chronic infection

• Muscle pain: Myositis

• Neck pain: Cervical myelopathy

• Vomiting or diarrhea: Botulism

• Shortness of breath: Heart failure, a pulmonary disorder, or anemia

• Anorexia and weight loss: Cancer or other chronic illness

• Change in color of urine: Porphyria or a liver or kidney disorder

• Heat or cold intolerance: Thyroid dysfunction

• Depressed mood, poor concentration, anxiety, and loss of interest in usual activities: Mood disorder

Past medical history should identify known disorders that can cause weakness or fatigue, including

• Thyroid, liver, kidney, or adrenal disorders

• Cancer or risk factors for cancer (paraneoplastic syndromes—eg, Eaton-Lambert syndrome) such as heavy smoking

• Osteoarthritis (cervical myelopathy)

• Infections

Clinicians should assess risk factors for possible causes, including those for infection (eg, unprotected sexual intercourse, blood transfusions, exposure to tuberculosis) and stroke (eg, hypertension, atrial fibrillation, atherosclerosis).

Complete drug history should be reviewed.

Family history should include known hereditary disorders (eg, hereditary muscle disorders, channelopathies, metabolic myopathies, hereditary neuropathies) and presence of similar symptoms in family members (suggesting a possible unrecognized hereditary disorder). Hereditary motor neuropathies often go unrecognized in families because of variable, incomplete phenotypic expression. Hammer toes, high arches in the feet, and poor performance in sports may indicate an undiagnosed hereditary motor neuropathy.

Social history should note the following:

• Use of alcohol: Suggesting alcohol myopathy

• Occupational or other exposure to toxins (eg, organophosphate insecticides, heavy metals, industrial solvents)

• Recent travel: Suggesting Lyme disease, tick paralysis, diphtheria, or a parasitic infection

• Social stressors: Suggesting depression

A complete neurologic and muscle examination is done to identify localizing or diagnostic findings. Key findings usually involve

• Cranial nerves

• Motor function

• Coordination

• Gait

• Sensation

• Reflexes

Cranial nerve examination includes inspection of the face for gross asymmetry and ptosis; mild facial asymmetry can be normal. Extraocular movements and facial muscles, including masseters (for strength), are tested. Palatal weakness is suggested by a nasal voice quality; testing the gag reflex and looking at the palate directly are less helpful. Tongue weakness is suggested by inability to clearly articulate certain consonants (eg, saying "ta-ta-ta") and slurring of speech (lingual dysarthria). Mild asymmetry during tongue protrusion may be normal. Sternocleidomastoid and trapezius strength is tested by having the patient rotate the head and shrug the shoulders against resistance. The patient is asked to blink repeatedly to see whether blinking fatigues.

Motor examination includes inspection, assessment of tone, and strength testing. The body is inspected for kyphoscoliosis (sometimes suggesting chronic weakness of paraspinal muscles) and for surgical and traumatic scars. Dystonic posturing (eg, torticollis) may interfere with movement, mimicking weakness. Muscles are inspected for fasciculations and atrophy; both may begin focally or asymmetrically in amyotrophic lateral sclerosis (ALS). Fasciculations may be most visible in the tongue in patients with advanced ALS. Diffuse atrophy may be most evident in the hands, face, and shoulder girdle.

Muscle tone is assessed using passive motion. Tapping a muscle (eg, hypothenar) may induce fasciculations in neuropathies or a myotonic contraction in myotonic dystrophy.

Strength testing should include muscles that are proximal, distal, extensor, and flexor. Some tests of large, proximal muscles include standing from a sitting position; squatting and rising; and flexing, extending, and turning the head against resistance.

Motor strength is often rated on a 0 to 5 scale:

1. 0: No visible muscle contraction

2. 1: Visible muscle contraction with no limb movement

3. 2: Limb movement but not against gravity

4. 3: Movement against gravity but not resistance

5. 4: Weakness against resistance

6. 5: Full strength

Although these numbers seem objective, rating strength between 3 and 5 (the typical levels during early weakness, when diagnosis usually occurs) is rather subjective; if symptoms are unilateral, comparison with the unaffected side improves discrimination. Describing specifically what the patient can or cannot do is often more useful than simply assigning a number for level of weakness, particularly for assessing changes in weakness over time. A cognitive deficit may cause motor impersistence (inability to focus attention on completing a motor task), motor perseveration, apraxia, or incomplete effort. Malingering and other functional weakness is often characterized by give-way weakness, in which normal strength of effort suddenly gives way.

Coordination testing includes finger-to-nose and heel-to-shin maneuvers and toe-heel tandem gait to check for cerebellar dysfunction, which can accompany cerebellar stroke, vermian atrophy (eg, due to alcohol abuse), some hereditary spinocerebellar ataxias, multiple sclerosis, and the Miller Fisher variant of Guillain-Barré syndrome.

Gait is observed for the following:

• Ignition failure (temporary freezing in place when starting to walk, followed by festination): Parkinson disease

• Apraxia, as when feet stick to the floor: Normal-pressure hydrocephalus or other frontal lobe disorders

• Festination: Parkinson disease

• Limb asymmetry, as when patients drag a leg, have reduced arm swing, or both: Hemispheric stroke

• Ataxia: Midline cerebellar disease

• Instability during turns: Parkinsonism

Walking on the toes and heels is tested; distal muscle weakness makes these maneuvers difficult. Walking on the heels is particularly difficult when corticospinal tract lesions are the cause of weakness. Spastic gait is notable for scissoring (legs flexed slightly at the hips and knees, giving the appearance of crouching, with the knees and thighs hitting or crossing in a scissors-like movement) and walking on the toes. A steppage gait and foot drop may occur with peroneal nerve palsy.

Sensation is tested; sensory deficits can help localize some lesions causing weakness (eg, sensory level localizes the lesion to a spinal cord segment) or suggest certain specific causes of weakness (eg, distal sensory loss helps confirm clinical suspicion of Guillain-Barré syndrome).

A truncal bandlike tingling and pressure in a dermatomal distribution is a spinal cord sign that occurs with both intrinsic and extrinsic lesions.

Reflexes are tested. If deep tendon reflexes appear absent, they may be elicited by augmentation with Jendrassik maneuver (eg, trying to pull the hands apart while they are clasped together). Hyporeflexia may be normal throughout life or occur with aging, but findings should be symmetric and augmentation should elicit reflexes that are otherwise absent. The plantar reflex (extensor, flexor) is tested. The following responses suggest certain disorders or locations of lesions:

• The classic Babinski reflex (the great toe extends and the other toes fan apart) is highly specific for a corticospinal tract lesion (except in infants, where the reflex is physiologic because the corticospinal tract is immature).

• A normal jaw jerk and hyperreflexic arms and legs suggest a cervical lesion affecting the corticospinal tract, usually cervical stenosis.

• Anal tone, anal wink reflex, or both are reduced or absent in spinal cord injury but are preserved in ascending paralysis due to Guillain-Barré syndrome.

• Abdominal reflexes are absent below the level of spinal cord injury (except in ALS where they are inexplicably preserved).

• A cremasteric reflex can test the integrity of the upper lumbar cord and roots in males.

Evaluation also includes

• Testing for back tenderness to percussion (present with vertebral inflammation, some vertebral tumors, and epidural abscess)

• Straight leg raising (painful with sciatica)

• Checking for scapular winging (suggesting weakness of the shoulder girdle muscles)

If patients have no objective motor weakness, the general examination is particularly important; in such patients, nonneuromuscular disorders should be sought.

Signs of respiratory distress (eg, tachypnea, weak inspiration) are noted. The skin is examined for jaundice, pallor, rash, and striae. Other important findings during inspection include the moon facies of Cushing syndrome and the parotid enlargement, smooth hairless skin, ascites, and vascular spiders of chronic alcohol use.

The neck, axillae, and inguinal area should be palpated for adenopathy; any thyromegaly is noted.

Heart and lungs are auscultated for crackles, wheezes, prolonged expiration, murmurs, and gallops.

The abdomen is palpated for masses, including, if spinal cord dysfunction is possible, a grossly enlarged bladder.

Joint range of motion is assessed.

If tick paralysis is suspected, the skin, particularly the scalp, should be thoroughly inspected for ticks.

In patients with weakness, the following findings are of particular concern:

• Weakness that becomes severe over a few days or less

• Dyspnea

• Inability to raise the head against gravity

• Bulbar symptoms (eg, difficulty chewing, talking, and swallowing)

• Loss of ambulation

• Urinary retention or incontinence or fecal incontinence

The history helps differentiate weakness from fatigue, defines the time course of the illness, and gives clues to the anatomic pattern of weakness. Weakness and fatigue tend to cause different symptoms:

• Weakness: Patients typically complain that they cannot do specific tasks. They may also report limb heaviness or stiffness. Weakness usually has a particular pattern in time, anatomy, or both. Difficulty working overhead, combing or brushing hair, ascending stairs, or getting off a toilet seat all imply proximal muscle weakness.

• Fatigue: Fatigue reported as weakness tends to have no temporal pattern (eg, “tired all of the time”) or anatomic pattern (eg, “weak everywhere”); complaints center more on being tired than on being unable to do specific tasks.

The temporal pattern of symptoms is useful.

• Weakness that becomes severe within minutes or less is usually caused by severe trauma or stroke; in stroke, weakness is usually unilateral and can be mild or severe. Sudden weakness, numbness, and severe pain localized to a limb are more likely caused by local arterial occlusion and limb ischemia, which can be differentiated by vascular assessment (eg, pulse, color, temperature, capillary refill, differences in Doppler-measured limb blood pressures). Spinal cord compression can also cause paralysis that evolves over minutes (but usually over hours or days) and is readily distinguished by incontinence and clinical findings of a discrete cord sensory and motor level.

• Weakness that progresses steadily over hours to days may be caused by acute or subacute disorders (eg, spinal cord compression, transverse myelitis, spinal cord ischemia or hemorrhage, Guillain-Barré syndrome, sometimes muscle wasting caused by a critical illness, rhabdomyolysis, botulism, organophosphate poisoning).

• Weakness that progresses over weeks to months may be caused by subacute or chronic disorders (eg, cervical myelopathy, most inherited and acquired polyneuropathies, myasthenia gravis, motor neuron disorders, acquired myopathies, most tumors).

• Weakness that fluctuates from day to day may be caused by multiple sclerosis and sometimes metabolic myopathies.

• Weakness that fluctuates over the course of a day may be caused by myasthenia gravis, Eaton-Lambert syndrome, or periodic paralysis.

The anatomic pattern of weakness is characterized by specific motor tasks that are difficult to do. Anatomic patterns suggest certain diagnoses:

• Proximal muscle weakness impairs reaching upward (eg, combing hair, lifting objects over the head), ascending stairs, or getting up from a sitting position; this pattern is typical of inflammatory myopathies.

• Distal muscle weakness impairs tasks such as stepping over a curb, holding a cup, writing, buttoning, or using a key; this pattern is typical of polyneuropathies and myotonic dystrophy. Many disorders (eg, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, myasthenia gravis, radiculopathies, Eaton-Lambert syndrome) cause proximal and distal weakness, but one pattern may be more prominent at first.

• Bulbar weakness can cause facial weakness, dysarthria, and dysphagia, with or without impairment of ocular movements; these manifestations are typical of certain neuromuscular disorders, such as myasthenia gravis, Eaton-Lambert syndrome, or botulism, but also certain motor neuron disorders, such as ALS or progressive supranuclear bulbar palsy.

Physical examination further helps localize the lesion. First, general patterns are discerned:

• Weakness that affects extensors more than flexors in the upper extremities or flexors more than extensors in the lower extremities is a pattern of weakness that has central nervous system causes.

• Weakness primarily of proximal muscles suggests myopathy.

• Weakness accompanied by hyperreflexia and increased muscle tone suggests upper motor neuron (corticospinal or other motor tract) dysfunction, particularly if an extensor plantar (Babinski) reflex is present.

• Disproportionate impairment of fine finger dexterity (eg, fine pincer movements, playing the piano) with relatively preserved grip strength indicates selective disruption of the corticospinal (pyramidal) tract.

• Complete paralysis accompanied by absent reflexes and severely depressed muscle tone (flaccidity) occurs in sudden, severe spinal cord injury (spinal shock).

• Weakness accompanied by hyporeflexia, decreased muscle tone (with or without fasciculations), and chronic muscle atrophy suggests lower motor neuron dysfunction.

• Weakness that is most noticeable in muscles innervated by the longest nerves (ie, distal more than proximal, legs more than arms), particularly with loss of distal sensation, suggests lower motor neuron dysfunction due to peripheral polyneuropathy.

• Absence of neurologic abnormalities (ie, normal reflexes, no muscle wasting or fasciculations, normal strength or poor effort during strength testing) or poor effort in patients with tiredness or with weakness that has no temporal or anatomic pattern suggests fatigue rather than true muscular weakness. However, if weakness is intermittent and is absent at the time of examination, abnormalities may be missed.

Additional findings can help localize the lesion more precisely. For example,

• Weakness accompanied by upper motor signs plus other signs such as aphasia, mental status abnormalities, or other cortical dysfunction: A brain lesion

• Unilateral upper motor neuron signs (spasticity, hyperreflexia, extensor plantar response) and weakness involving an arm and a leg on the same side of the body: A contralateral hemispheric lesion, most often a stroke

• Upper or lower motor neuron signs (or both) plus loss of sensation below a segmental spinal cord level and loss of bowel or bladder control (or both): A spinal cord lesion

Weakness with lower motor neuron signs may result from a disorder affecting one or more peripheral nerves; such a disorder has very specific patterns of weakness (eg, wristdrop in radial nerve injury). When the brachial or lumbosacral plexus is damaged, motor, sensory, and reflex deficits are often patchy and do not follow any one peripheral nerve pattern.

Sometimes combinations of findings suggest a cause (see table Findings Related to Weakness Suggesting a Specific Disorder).

If no symptoms or signs of true weakness (eg, characteristic anatomic and temporal pattern, objective signs) are present and patients complain only of overall weakness, fatigue, or lack of energy, clinicians should consider nonneurologic disorders. However, among older patients who feel too weak to walk, determining the contribution of muscle weakness may be difficult because gait dysfunction is often multifactorial (see Geriatrics Essentials: Weakness).

Patients with many disorders may be functionally limited but lack true loss of muscle strength. For example, cardiopulmonary dysfunction or anemia can cause fatigue due to dyspnea or exercise intolerance. Joint dysfunction (eg, due to arthritis) or muscle pain (eg, due to polymyalgia rheumatica or fibromyalgia) may make doing physical tasks difficult. These and other physical disorders that cause complaints of weakness (eg, influenza, infectious mononucleosis, renal failure) typically are already diagnosed or are suggested by findings during the history, physical examination, or both.

In general, if history and physical examination do not detect abnormalities suggesting physical disorders, these disorders are unlikely; disorders that cause constant, generalized fatigue with no physiologic temporal or anatomic pattern (eg, depression; chronic fatigue syndrome; an as-yet undiscovered systemic illness such as severe anemia, hypothyroidism, or Addison disease; an adverse drug effect) should be considered.

In patients with fatigue rather than weakness, history and physical examination focus on identifying subtle manifestations of underlying illness (particularly infections, endocrine and rheumatologic disorders, anemia, and depression) that can be used to guide testing, but testing may be unnecessary.

Although many tests can be done if patients have true muscular weakness, such testing is often only adjunctive.

If no true weakness is present, other clinical findings (eg, dyspnea, pallor, jaundice, heart murmur), if present, are used to guide testing.

If patients have no abnormal clinical findings, test results are unlikely to be abnormal. In such cases, testing practices vary widely. Initial tests usually include some combination of a complete blood count (CBC), electrolytes (including calcium and magnesium), glucose, kidney and liver function tests, thyroid-stimulating hormone (TSH), erythrocyte sedimentation rate (ESR), and hepatitis C serologic testing.

If sudden or severe true general weakness or any respiratory symptoms are present, forced vital capacity and maximal inspiratory force must be tested to assess risk of acute ventilatory failure. Patients with vital capacity < 15 mL/kg or inspiratory force < 20 cm H2O are at increased risk.

If true weakness is present (and usually after risk of acute ventilatory failure is assessed), initial testing typically focuses on determining the mechanism of weakness. Unless the cause is obvious, routine laboratory tests (CBC, electrolytes [including calcium and magnesium], glucose, kidney and liver function tests, TSH, ESR, hepatitis C serologic testing) are usually done.

Tests done to determine the location and mechanism of weakness depend on clinical findings.

If brain upper motor neuron dysfunction is suspected, the key test is MRI. CT is used when MRI testing is not possible (eg, in patients with a cardiac pacemaker).

If myelopathy is suspected, MRI can detect lesions in the spinal cord. It also detects other causes of paralysis that may mimic myelopathy, including lesions of the cauda equina, spinal roots, and brachial and lumbosacral plexuses. CT myelography may be used when MRI testing is not available. Other tests are done (see table Some Causes of Muscle Weakness). Cerebrospinal fluid (CSF) analysis may be unnecessary for some disorders diagnosed during imaging (eg, epidural tumor) and is contraindicated if CSF block (eg, due to epidural spinal cord compression) is suspected. CSF analysis is useful in patients with Guillain-Barré syndrome; albuminocytologic dissociation (high protein level with a normal white cell count) is almost pathognomonic.

If polyneuropathies, myopathies, or neuromuscular junction disorders are suspected, the key tests that help differentiate these mechanisms of weakness are electrodiagnostic testing (electromyography and nerve conduction studies).

After nerve injury, changes in nerve conduction and muscle denervation can take up to a few weeks to develop, so electrodiagnostic testing may not help when the disorder is acute. However, these studies can help differentiate among certain acute disorders, such as acute demyelinating neuropathy (eg, Guillain-Barré syndrome), acute botulism, and other acute neuromuscular junction disorders.

If myopathy

Clinicians can use MRI to identify muscle inflammation, as occurs in inflammatory myopathies. Muscle biopsy may be necessary ultimately to diagnose myopathy or myositis. MRI or electromyography can help find a suitable site for muscle biopsy. However, needlestick artifact can mimic muscle pathology and must be avoided; thus, biopsy should never be done in the same muscle tested by electromyography.

Genetic testing can help confirm certain hereditary myopathies.

If motor neuron disorders (eg, ALS) are suspected, tests include electromyography and nerve conduction studies to confirm the diagnosis and exclude treatable disorders that mimic motor neuron disorders (eg, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy with conduction block). Brain MRI may show degeneration of the corticospinal tracts when ALS is advanced. Spinal cord MRI (or CT myelography) is done routinely to rule out spinal cord compression or other myelopathies (see table Some Causes of Muscle Weakness).

Testing for specific disorders may be needed:

• If findings suggest myasthenia gravis, an ice pack test and serologic testing (eg, acetylcholine receptor antibody levels, sometimes anti–muscle-specific tyrosine kinase antibodies)

• If findings suggest vasculitis, autoantibody testing

• If family history suggests a hereditary disorder, genetic testing

• If findings suggest polyneuropathy, other tests (see table Some Causes of Muscle Weakness)

• If myopathy is unexplained by drugs, metabolic, or endocrine disorders, possibly muscle biopsy