Weakness is one of the most common reasons patients present to primary care clinicians. Weakness is loss of muscle strength, although many patients also use the term when they feel generally fatigued or have functional limitations (eg, due to pain or limited joint motion) even though muscle strength is normal.
Weakness may affect a few or many muscles and develop suddenly or gradually. Other symptoms may be present depending on the cause. Weakness of specific muscle groups can cause disorders of eye movement, dysarthria, dysphagia, or respiratory weakness.
Voluntary movement is initiated in the cerebral motor cortex, at the posterior aspect of the frontal lobe. The neurons involved (upper motor or corticospinal tract neurons) synapse with neurons in the spinal cord (lower motor neurons). Lower motor neurons transmit impulses to the neuromuscular junction to initiate muscle contraction. Common mechanisms of weakness thus include dysfunction of
Upper motor neurons (corticospinal and corticobulbar tract lesions)
Lower motor neurons (eg, due to peripheral polyneuropathies or anterior horn cell lesions)
Muscle (eg, due to myopathies)
The location of certain lesions correlates with physical findings:
Upper motor neuron dysfunction disinhibits lower motor neurons, resulting in increased muscle tone (spasticity) and increased muscle stretch reflexes (hyperreflexia). An extensor plantar (Babinski) reflex is specific for corticospinal tract dysfunction. However, upper motor neuron dysfunction can decrease tone and reflexes if motor paralysis is sudden and severe (eg, in spinal cord transection, in which tone first decreases, then increases gradually over days to weeks) or if the lesion damages the motor cortex of the precentral gyrus and not nearby motor association areas.
Lower motor neuron dysfunction disrupts reflex arcs, causing hyporeflexia and decreased muscle tone (flaccidity), and may cause fasciculations; with time, muscles atrophy.
Peripheral polyneuropathies tend to be most noticeable in the longest nerves (ie, weakness is more prominent in the distal limb than the proximal and in legs more than arms) and produce signs of lower motor neuron dysfunction (eg, decreased reflexes and muscle tone).
The most common disorder of the neuromuscular junction—myasthenia gravis—typically causes fluctuating weakness that worsens with activity and lessens with rest.
Diffuse muscle dysfunction (eg, in myopathies) tends to be most noticeable in the largest muscle groups (proximal muscles).
The many causes of muscle weakness are categorized by location of the lesion (see Table 6: Approach to the Neurologic Patient: Some Causes of Muscle Weakness). Usually, lesions in a given location manifest with similar clinical findings. However, some disorders have characteristics of lesions in more than one location. For example, patients with amyotrophic lateral sclerosis (ALS) may have findings of both upper and lower motor neuron dysfunction. Disorders of the spinal cord may affect tracts from upper motor neurons, lower motor neurons (anterior horn cells), or both.
Common causes of focal weakness include
Stroke (the most common cause of unilateral weakness)
Neuropathies, including those that are caused by trauma or entrapment (eg, carpal tunnel syndrome) and that are immune-mediated (eg, Bell palsy)
Spinal root entrapment (eg, herniated intervertebral disk)
Spinal cord compression (eg, cervical spondylosis, epidural cancer metastasis, trauma)
The most common causes of generalized weakness are
Deconditioning due to inactivity (disuse atrophy) resulting from illness or frailty, especially in the elderly
Generalized muscle wasting due to prolonged immobilization in an ICU (ICU myopathy)
Critical illness polyneuropathy (ICU neuropathy)
Common myopathies (eg, alcoholic myopathy, hypokalemia, corticosteroid myopathy)
Use of paralytic drugs in a critical care patient
Fatigue: 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, hepatitis, endocarditis, mononucleosis), endocrine disorders, renal failure, hepatic failure, heart failure, and anemia. Patients with fibromyalgia, depression, or chronic fatigue syndrome may report weakness or fatigue but have no defined objective abnormalities.
Some Causes of Muscle Weakness
Brain upper motor neuron lesions
Increased muscle tone, hyperreflexia, extensor plantar (Babinski) reflex
Possibly more stiffness and loss of fine motor control (finger dexterity) than weakness (hand grip)
Brain imaging with CT or MRI
Myelopathies (involving upper or lower motor neuron dysfunction or both)
Spinal cord compression (eg, due to spondylosis, epidural tumor, hematoma, or abscess)
Cauda equina syndrome
Spinal cord ischemia or infarction
Autoimmune disorders (eg, multiple sclerosis, neuromyelitis optica, vasculitis)
Infections (eg, HTLV-1, HIV, syphilis, human herpes simplex 6, EBV, varicella-zoster)
Subacute combined degeneration
Dysfunction of upper motor neurons, lower motor neurons, or both
Commonly erectile dysfunction, incontinence of bowel and bladder, absence of sphincter reflexes (eg, anal wink, bulbocavernosus)
Progressive limb weakness and fatigability, clumsiness, spasticity (legs first, then arms with gradual spinal cord compression)
Classically dermatomal sensory level
Tests to help identify the cause: Possibly including vitamin B12 level, HIV test, ANA, RPR, NMO-IgG autoantibody (anti–aquaporin-4 antibody), HTLV-1 or VDRL, genetic testing, serum copper, and ceruloplasmin
Spinal cord MRI, CT myelography, or both
CSF analysis (eg, protein, VDRL, IgG index, oligoclonal banding, viral titers, PCR)
Somatosensory evoked potentials
Motor neuron disorders (upper, lower, or both)
Amyotrophic lateral sclerosis
Inherited motor neuron diseases (eg, spinal muscular or spinocerebellar atrophies, including Kennedy disease)
Progressive bulbar palsy
Viral polio-like disorders
Progressive weakness and fatigability, clumsiness, spasticity (upper motor neuron)
Hyporeflexia or flaccidity (lower motor neuron)
Muscle atrophy (lower motor neuron)
Fasciculations (lower motor neuron)
Gynecomastia, diabetes, and testicular atrophy (Kennedy disease)
Electromyography and brain and spinal cord MRI, CT myelography, or both
Other tests: Possibly including 24-h urine heavy metal screen to exclude lead neuropathy, anti-GM1 antibody titers (for multifocal motor neuropathy), and genetic testing (eg, for Kennedy disease)
Polyneuropathies (mostly, peripheral polyneuropathies)†
Critical illness polyneuropathy
Demyelinating neuropathies (eg, CIDP, Guillain-Barré syndrome)
Drug-induced neuropathies (eg, by vincristine
Infectious neuropathies (eg, diphtheria, hepatitis C, HIV/AIDS, Lyme disease, syphilis)
Toxic neuropathies (eg, heavy metals)
Vitamin deficiency (eg, thiamin, vitamin B6 or B12)
Hyporeflexia, sometimes fasciculations
If chronic, muscle atrophy
In peripheral polyneuropathy, disproportionate weakness of most distal muscles and often sensory deficits in the same (stocking-glove) distribution (common exceptions include CIDP, which affects proximal and distal nerves and muscles equally)
Tests to confirm the presence of neuropathy: Electrodiagnostic tests
Tests to help identify the cause: Possibly including plasma glucose, 2-h oral glucose tolerance test, hemoglobin A1c (HbA1c), RPR, HIV test, folate, vitamin B12, serum protein immunofixation electrophoresis, chest CT and serum ACE level (for sarcoidosis), 24-h urine heavy metals screen, anti-MAG antibodies (present in some demyelinating neuropathies), anti-GM1 antibody titers (for multifocal motor neuropathy), and genetic testing
Neuromuscular junction disorders
Weakness that fluctuates in intensity (eg, in myasthenia gravis or Eaton-Lambert syndrome)
Often, prominent bulbar findings (eg, in myasthenia gravis, botulism, or organophosphate poisoning)
Sometimes hyporeflexia (eg, in Eaton-Lambert syndrome, tick paralysis, or organophosphate poisoning)
Tests to confirm mechanism: Electrodiagnostic testing
Other testing as needed to help determine specific disorder (eg, acetylcholine receptor antibody, edrophonium testing for suspected myasthenia gravis)
Hereditary muscle disorders (eg, muscular dystrophies)
Polymyositis or dermatomyositis
Disproportionate weakness of proximal muscles (equally)
If chronic, muscle wasting
With some types, muscle tenderness
Tests to confirm mechanism: Electrodiagnostic testing, muscle enzymes (eg, CK, aldolase), and sometimes MRI to confirm muscle atrophy, hypertrophy, or pseudohypertrophy
Tests to help identify the cause: Possibly including muscle biopsy with special stains and genetic testing for certain hereditary disorders
Generalized muscle wasting due to illness and disuse
Prolonged bed rest
Diffuse muscle atrophy, normal sensation and reflexes, no fasciculations
Clinically apparent risk factors
*Testing may vary; additional testing may be indicated depending on which disorders are clinically suspected.
†Multiple mononeuropathy (mononeuritis multiplex), if sufficiently widespread, may cause deficits clinically similar to those of diffuse polyneuropathies.
ANA = antinuclear antibodies; anti-GM1 = anti-ganglioside monosialic acid; anti-MAG = antimyelin-associated glycoprotein; CIDP = chronic inflammatory demyelinating polyneuropathy; EBV = Epstein-Barr virus; HTLV = human T-lymphotropic virus; NMO-IgG = neuromyelitis optica antibody; RPR = rapid plasma reagin; VDRL = Venereal Disease Research Laboratory.
Evaluation should try to distinguish true muscular weakness from fatigue, then check for findings that help establish the mechanism and, when possible, the cause.
History: 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 (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 rash (dermatomyositis, Lyme disease, syphilis); fevers (chronic infection); muscle pain (myositis); neck pain (cervical myelopathy); vomiting or diarrhea (botulism); shortness of breath (heart failure, a pulmonary disorder, anemia); anorexia and weight loss (cancer, other chronic illness); change in color of urine (porphyria, liver or kidney disorder); heat or cold intolerance (thyroid dysfunction); and 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); and infections. Clinicians should assess risk factors for possible causes, including those for infection (eg, unprotected sexual intercourse, blood transfusions, exposure to TB) 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 use of alcohol (suggesting alcoholic myopathy), illicit drug use (suggesting increased risk of HIV/AIDS, bacterial infections, TB, or stroke due to cocaine use), 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), and social stressors (suggesting depression).
Physical examination: A complete neurologic and muscle examination is done to identify localizing or diagnostic findings. Key findings usually involve
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 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 (see Approach to the Neurologic Patient: Muscle strength):
0: No visible muscle contraction
1: Visible muscle contraction with no limb movement
2: Limb movement but not against gravity
3: Movement against gravity but not resistance
4: Weakness against resistance
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 ignition failure (temporary freezing in place when starting to walk, followed by festination, as occurs in Parkinson disease) and apraxia, as when feet stick to the floor (normal-pressure hydrocephalus, 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); and 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 bandlike tingling and pressure 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, particularly with aging, but findings should be symmetric and augmentation should elicit reflexes that are otherwise absent. The plantar reflex (extensor, flexor) is tested. The classic Babinski reflex (the great toe extends and the other toes fan apart) is highly specific for a corticospinal tract lesion. 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. 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), and checking for scapular winging (suggesting weakness of the shoulder girdle muscles).
General examination: 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. A rectal examination is done to check for heme-positive stool. Joint range of motion is assessed.
If tick paralysis is suspected, the skin, particularly the scalp, should be thoroughly inspected for ticks.
Red flags: The following findings are of particular concern:
Weakness that becomes severe over a few days or less
Inability to raise the head against gravity
Bulbar symptoms (eg, difficulty chewing, talking, and swallowing)
Loss of ambulation
Interpretation of findings: 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.
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 BPs). 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 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 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 suggests 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 suggest 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) suggest 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 pelvic plexus is damaged, motor, sensory, and reflex deficits are often patchy and do not follow any one peripheral nerve pattern.
Determination of a specific causative disorder: Sometimes combinations of findings suggest a cause (see Table 7: Approach to the Neurologic Patient: Findings Related to Weakness Suggesting a Specific Disorder).
Findings Related to Weakness Suggesting a Specific Disorder
Disorders to Consider
Rapidly progressive generalized weakness; prominent ophthalmoplegia, dysarthria, and dysphagia, particularly if preceded by gastroenteritis
Symptoms and signs suggesting dissemination of lesions in time and space, history of relapses and remissions, monocular visual loss due to optic neuritis, diplopia due to internuclear ophthalmoplegia
Acute or chronic weakness, dysarthria, dysphagia, hyporeflexia, excessive cholinergic symptoms and signs (eg, salivation, lacrimation, urination, pupillary constriction, abdominal cramping, diarrhea, bradycardia)
Unilateral weakness, upper motor neuron signs
Single brain lesion, such as acute stroke (ischemic or hemorrhagic), tumor, or abscess
Chronic progressive quadriparesis, upper motor neuron signs, preserved cranial nerves, normal jaw jerk
Cervical myelopathy due to spondylosis
Prominent extraocular muscle palsy (possibly only diplopia during extreme gaze)
Myasthenia gravis, botulism, Miller Fisher variant of Guillain-Barré syndrome
Fatigability detected by sequential testing (eg, eye blinking)
Asymmetric limb weakness, dysarthria, dysphagia, prominent tongue fasciculations
Amyotrophic lateral sclerosis
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 elderly patients who feel too weak to walk, determining the contribution of muscle weakness may be difficult because gait dysfunction is often multifactorial (see Approach to the Neurologic Patient: Geriatrics Essentials). 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) should be considered.
Testing: Testing may be unnecessary in patients with fatigue rather than weakness. 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. If done, initial tests usually include some combination of CBC, electrolytes, glucose, Ca, Mg, kidney and liver function tests, thyroid-stimulating hormone (TSH), ESR, and hepatitis C serologic testing.
If sudden or severe 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, glucose, Ca, Mg, kidney and liver function tests, TSH, ESR, hepatitis C serologic testing) are usually done.
If brain upper motor neuron dysfunction is suspected as the cause of weakness, 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 pelvic plexuses. CT myelography may be used when MRI testing is not available. Other tests are done (see Table 6: Approach to the Neurologic Patient: Some Causes of Muscle Weakness). 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.
If polyneuropathies, myopathies, or neuromuscular junction disorders are suspected, the key tests that help differentiate these mechanisms of weakness are electrodiagnostic studies (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 studies 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 is suspected (suggested by muscle weakness, muscle cramping, and pain), muscle enzymes (eg, CK, aldolase, LDH) may be measured. Elevated levels are consistent with myopathy but can also be high in neuropathies (reflecting muscle atrophy) and very high in ischemic rhabdomyolysis. Also, levels may not be high in all myopathies. Regular crack cocaine use can also cause chronically moderately elevated CK levels (mean value, 400 IU/L).
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 6: Approach to the Neurologic Patient: Some Causes of Muscle Weakness).
Testing for specific disorders may be needed:
If findings suggest myasthenia gravis, edrophonium 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 6: Approach to the Neurologic Patient: Some Causes of Muscle Weakness)
If myopathy is unexplained by drugs, metabolic, or endocrine disorders, possibly muscle biopsy
Causes are treated. For patients with life-threatening, acute weakness, ventilatory support may be needed. Physical and occupational therapy can help people adapt to permanent weakness and minimize loss of function.
Some decrease in deep tendon reflexes is normal with aging, but asymmetry or absence of these reflexes with augmentation is abnormal.
Because the elderly are more likely to have preexisting sarcopenia, bed rest can cause debilitating muscle wasting rapidly, sometimes after only several days.
The elderly take more drugs and are more susceptible to drug-induced myopathies, neuropathies, and fatigue; thus, drugs are a common cause of weakness in the elderly.
Feeling too weak to walk often has multiple causes. Factors may include muscle weakness (eg, caused by stroke, use of certain drugs, myelopathy due to cervical spondylosis, or muscle atrophy), but also hydrocephalus, parkinsonism, painful arthritis, and age-related loss of neural networks mediating postural stability (vestibular system, proprioceptive pathways), coordination (cerebellum, basal ganglia), vision, and praxis (frontal lobe). Evaluation should focus on reversible factors.
Physical therapy and rehabilitation are generally helpful no matter what the etiology of the weakness is.
Distinguish loss of muscle strength from a feeling of fatigue.
If fatigue has no anatomic or temporal pattern of weakness in patients with a normal physical examination, suspect chronic fatigue syndrome, an as yet undiscovered systemic illness (eg, severe anemia, hypothyroidism, Addison disease), a psychologic problem (eg, depression), or an adverse drug effect.
If patients have true muscle weakness, first focus on determining whether weakness is caused by dysfunction of the brain, spinal cord, plexuses, peripheral nerves, neuromuscular junction, or muscles.
If patients have hyperreflexia and increased muscle tone (spasticity), particularly if Babinski reflex is present, suspect an upper motor neuron (eg, corticospinal tract) lesion in the brain or spinal cord; MRI is usually required.
If patients have hyporeflexia, decreased muscle tone, muscle atrophy, and muscle fasciculations, suspect a lower motor neuron lesion. If patients have hyporeflexia and predominantly distal muscle weakness, particularly with distal sensory deficits or paresthesias, suspect polyneuropathy.
If patients have difficulty climbing stairs, combing hair, and standing up with predominantly proximal muscle weakness and intact sensation, suspect myopathy.
- Spasticity (onnurimedicine.me)
- A Failure to Communicate (ramblingmanofals.com)
- RNA Binding Ability Of FUS Essential To Development Of ALS (medicalnewstoday.com)