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.
Pathophysiology of 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 Myasthenia Gravis Myasthenia gravis is characterized by episodic muscle weakness and easy fatigability caused by autoantibody- and cell-mediated destruction of acetylcholine receptors. It is more common among... read more —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).
Etiology of Weakness
The many causes of muscle weakness are categorized by location of the lesion (see table ). 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 Amyotrophic Lateral Sclerosis (ALS) and Other Motor Neuron Diseases (MNDs) Amyotrophic lateral sclerosis and other motor neuron diseases are characterized by steady, relentless, progressive degeneration of corticospinal tracts, anterior horn cells, bulbar motor nuclei... read more (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
Neuropathies Peripheral Neuropathy Peripheral neuropathy is dysfunction of one or more peripheral nerves (the part of a nerve distal to the root and plexus). It includes numerous syndromes characterized by varying degrees of... read more , including those that are caused by trauma or entrapment (eg, carpal tunnel syndrome Carpal Tunnel Syndrome Carpal tunnel syndrome is compression of the median nerve as it passes through the carpal tunnel in the wrist. Symptoms include pain and paresthesias in the median nerve distribution. Diagnosis... read more ) and that are immune-mediated (eg, Bell palsy Facial Nerve Palsy Facial nerve (7th cranial nerve) palsy is often idiopathic (formerly called Bell palsy). Idiopathic facial nerve palsy is sudden, unilateral peripheral facial nerve palsy. Symptoms of facial... read more )
Spinal cord compression Spinal Cord Compression Various lesions can compress the spinal cord, causing segmental sensory, motor, reflex, and sphincter deficits. Diagnosis is by MRI. Treatment is directed at relieving compression. (See also... read more (eg, cervical spondylosis, epidural cancer metastasis, trauma)
Temporary focal weakness may occur as part of postictal (Todd) paralysis, which usually resolves over several hours, or result from a transient ischemic attack Transient Ischemic Attack (TIA) A transient ischemic attack (TIA) is focal brain ischemia that causes sudden, transient neurologic deficits and is not accompanied by permanent brain infarction (eg, negative results on diffusion-weighted... read more (TIA).
The most common causes of generalized weakness are
Deconditioning due to inactivity (disuse atrophy) resulting from illness or frailty, especially in older patients
Generalized muscle wasting due to prolonged immobilization in an intensive care unit (ICU)—a condition called critical illness myopathy
Critical illness polyneuropathy (ICU neuropathy)
Common myopathies (eg, alcohol myopathy, hypokalemia, corticosteroid myopathy)
Use of paralytic agents in a critical care patient
Many patients report weakness when their problem is fatigue Fatigue Fatigue is difficulty initiating and sustaining activity due to a lack of energy and accompanied by a desire to rest. Fatigue is normal after physical exertion, prolonged stress, and sleep deprivation... read more . 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 Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more , hepatitis Causes of Hepatitis Hepatitis is inflammation of the liver characterized by diffuse or patchy necrosis. Hepatitis may be acute or chronic (usually defined as lasting > 6 months). Most cases of acute viral hepatitis... read more , endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more , mononucleosis Infectious Mononucleosis Infectious mononucleosis is caused by Epstein-Barr virus (EBV, human herpesvirus type 4) and is characterized by fatigue, fever, pharyngitis, and lymphadenopathy. Fatigue may persist weeks or... read more ), endocrine disorders, renal failure Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more , hepatic failure Acute Liver Failure Acute liver failure is caused most often by drugs and hepatitis viruses. Cardinal manifestations are jaundice, coagulopathy, and encephalopathy. Diagnosis is clinical. Treatment is mainly supportive... read more , heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more , and anemia Etiology of Anemia Anemia is a decrease in the number of red blood cells (RBCs), which leads to a decrease in hematocrit and hemoglobin content. (See also Red Blood Cell Production.) The RBC mass represents the... read more . Multiple sclerosis Multiple Sclerosis (MS) Multiple sclerosis (MS) is characterized by disseminated patches of demyelination in the brain and spinal cord. Common symptoms include visual and oculomotor abnormalities, paresthesias, weakness... read more can cause daily fatigue that increases with exposure to heat and humidity.
Patients with fibromyalgia Fibromyalgia Fibromyalgia is a common, incompletely understood nonarticular, noninflammatory disorder characterized by generalized aching (sometimes severe); widespread tenderness of muscles, areas around... read more , depression Depressive Disorders Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more , or chronic fatigue syndrome Chronic Fatigue Syndrome Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS]) is a syndrome of life-altering fatigue lasting > 6 months that is unexplained and is accompanied... read more may report weakness or fatigue but have no defined objective abnormalities.
Evaluation of Weakness
Evaluation of weakness should try to distinguish true muscular weakness from fatigue, then check for findings that help establish the location or mechanism (eg, whether weakness is caused by dysfunction of the brain, spinal cord, plexuses, peripheral nerves, neuromuscular junction, or muscles) and, when possible, the cause.
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 Multiple Sclerosis (MS) Multiple sclerosis (MS) is characterized by disseminated patches of demyelination in the brain and spinal cord. Common symptoms include visual and oculomotor abnormalities, paresthesias, weakness... read more
Rash: Dermatomyositis Autoimmune Myositis Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) or in the skin and muscles (dermatomyositis)... read more , Lyme disease Lyme Disease Lyme disease is a tick-transmitted infection caused by the spirochete Borrelia species. Early symptoms include an erythema migrans rash, which may be followed weeks to months later by... read more , or syphilis Syphilis Syphilis is caused by the spirochete Treponema pallidum and is characterized by 3 sequential symptomatic stages separated by periods of asymptomatic latent infection. Common manifestations... read more
Fevers: Chronic infection
Muscle pain: Myositis
Shortness of breath: Heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more , a pulmonary disorder, or anemia Etiology of Anemia Anemia is a decrease in the number of red blood cells (RBCs), which leads to a decrease in hematocrit and hemoglobin content. (See also Red Blood Cell Production.) The RBC mass represents the... read more
Anorexia and weight loss: Cancer or other chronic illness
Heat or cold intolerance: Thyroid dysfunction
Depressed mood, poor concentration, anxiety, and loss of interest in usual activities: Mood disorder Overview of Mood Disorders Mood disorders are emotional disturbances consisting of prolonged periods of excessive sadness, excessive elevated mood, or both. Mood disorders can occur in adults, adolescents, or children... read more
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 Paraneoplastic Syndromes Paraneoplastic syndromes are symptoms that occur at sites distant from a tumor or its metastasis. Although the pathogenesis remains unclear, these symptoms may be secondary to substances secreted... read more —eg, Eaton-Lambert syndrome) such as heavy smoking
Osteoarthritis (cervical myelopathy)
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 Introduction to Inherited Muscular Disorders Muscular dystrophies are inherited, progressive muscle disorders resulting from defects in one or more genes needed for normal muscle structure and function; dystrophic changes (eg, muscle fiber... read more , channelopathies Overview of Channelopathies Channelopathies are a group of genetic, autoimmune, or inflammatory conditions that alter cardiomyocyte ion channel function in a manner that predisposes to bradyarrhythmias or tachyarrhythmias... read more , metabolic myopathies, hereditary neuropathies Hereditary Neuropathies Hereditary neuropathies include a variety of congenital degenerative peripheral neuropathies (eg, Charcot-Marie-Tooth disease). (See also Overview of Peripheral Nervous System Disorders.) Hereditary... read more ) 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
Illicit drug use: Suggesting increased risk of HIV/AIDS, bacterial infections, tuberculosis, or stroke due to cocaine use
Occupational or other exposure to toxins (eg, organophosphate insecticides, heavy metals, industrial solvents)
Recent travel: Suggesting Lyme disease Lyme Disease Lyme disease is a tick-transmitted infection caused by the spirochete Borrelia species. Early symptoms include an erythema migrans rash, which may be followed weeks to months later by... read more , tick paralysis Tick Paralysis Tick paralysis is a rare, ascending, flaccid paralysis that occurs when toxin-secreting Ixodidae ticks bite and remain attached for several days. In North America, some species of Dermacentor... read more , diphtheria Diphtheria Diphtheria is an acute pharyngeal or cutaneous infection caused mainly by toxigenic strains of the gram-positive bacillus Corynebacterium diphtheriae and rarely by other, less common... read more , 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 nerve examination How to Assess the Cranial Nerves The cranial nerves originate in the brain stem. Abnormalities in their function suggest pathology in specific parts of the brain stem or along the cranial nerve's path outside the brain stem... read more 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 How to Assess the Motor System Motor weakness can be due to dysfunction in the corticospinal tract, basal ganglia, spine, peripheral nerves, or muscle. A careful examination of the motor system enables the clinician to localize... read more 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 How to Assess Muscle Strength Patients who report weakness may mean fatigue, clumsiness, or true muscle weakness. Thus, the examiner must define the precise character of symptoms, including exact location, time of occurrence... read more 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:
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 How to Assess Gait, Stance, and Coordination Normal gait, stance, and coordination require integrity of the motor, vestibular, cerebellar, and proprioceptive pathways (see also Movement and Cerebellar Disorders). Lesions in these pathways... read more 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 Hereditary ataxias Cerebellar disorders have numerous causes, including congenital malformations, hereditary ataxias, and acquired conditions. Symptoms vary with the cause but typically include ataxia (impaired... read more , multiple sclerosis Multiple Sclerosis (MS) Multiple sclerosis (MS) is characterized by disseminated patches of demyelination in the brain and spinal cord. Common symptoms include visual and oculomotor abnormalities, paresthesias, weakness... read more , and the Miller Fisher variant of Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought... read more .
Gait is observed for the following:
Ignition failure (temporary freezing in place when starting to walk, followed by festination): Parkinson disease Parkinson Disease Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and eventually gait and/or... read more
Apraxia, as when feet stick to the floor: Normal-pressure hydrocephalus Normal–Pressure Hydrocephalus Normal-pressure hydrocephalus is characterized by gait disturbance, urinary incontinence, dementia, enlarged brain ventricles, and normal or slightly elevated cerebrospinal fluid pressure. ... read more 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
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 How to Assess Sensation Similar to the motor examination, the sensory examination is designed to localize dysfunction and help determine whether the problem is in the cerebral cortex, thalamus, sensory pathways in... read more 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 How to Assess Reflexes (See also Introduction to the Neurologic Examination.) Deep tendon (muscle stretch) reflex testing evaluates afferent nerves, synaptic connections within the spinal cord, motor nerves, and descending... read more 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 Tick Paralysis Tick paralysis is a rare, ascending, flaccid paralysis that occurs when toxin-secreting Ixodidae ticks bite and remain attached for several days. In North America, some species of Dermacentor... read more 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
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
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. 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 Spinal Cord Compression Various lesions can compress the spinal cord, causing segmental sensory, motor, reflex, and sphincter deficits. Diagnosis is by MRI. Treatment is directed at relieving compression. (See also... read more 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 Spinal Cord Compression Various lesions can compress the spinal cord, causing segmental sensory, motor, reflex, and sphincter deficits. Diagnosis is by MRI. Treatment is directed at relieving compression. (See also... read more , transverse myelitis Acute Transverse Myelitis Acute transverse myelitis is acute inflammation of gray and white matter in one or more adjacent spinal cord segments, usually thoracic. Causes include multiple sclerosis, neuromyelitis optica... read more , spinal cord ischemia or hemorrhage, Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought... read more , sometimes muscle wasting caused by a critical illness, rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more , botulism Botulism Botulism is poisoning that is due to Clostridium botulinum toxin and that affects the peripheral nerves. Botulism may occur without infection if toxin is ingested, injected, or inhaled... read more , organophosphate poisoning Organophosphate Poisoning and Carbamate Poisoning Organophosphates and carbamates are common insecticide ingredients that inhibit cholinesterase activity, causing acute muscarinic manifestations (eg, salivation, lacrimation, urination, diarrhea... read more ).
Weakness that progresses over weeks to months may be caused by subacute or chronic disorders (eg, cervical myelopathy Cervical Spondylosis and Spondylotic Cervical Myelopathy Cervical spondylosis is osteoarthritis of the cervical spine causing stenosis of the canal and sometimes cervical myelopathy due to encroachment of bony osteoarthritic growths (osteophytes)... read more , most inherited and acquired polyneuropathies Polyneuropathy A polyneuropathy is a diffuse peripheral nerve disorder that is not confined to the distribution of a single nerve or a single limb and typically is relatively symmetrical bilaterally. Electrodiagnostic... read more , myasthenia gravis Myasthenia Gravis Myasthenia gravis is characterized by episodic muscle weakness and easy fatigability caused by autoantibody- and cell-mediated destruction of acetylcholine receptors. It is more common among... read more , motor neuron disorders Amyotrophic Lateral Sclerosis (ALS) and Other Motor Neuron Diseases (MNDs) Amyotrophic lateral sclerosis and other motor neuron diseases are characterized by steady, relentless, progressive degeneration of corticospinal tracts, anterior horn cells, bulbar motor nuclei... read more , 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 Neurologic paraneoplastic syndromes , or periodic paralysis Familial Periodic Paralysis Familial periodic paralysis is a rare autosomal dominant condition with considerable variation in penetrance characterized by episodes of flaccid paralysis with loss of deep tendon reflexes... read more .
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 Autoimmune Myositis Autoimmune myositis is characterized by inflammatory and degenerative changes in the muscles (polymyositis, necrotizing immune-mediated myopathy) or in the skin and muscles (dermatomyositis)... read more .
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 Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Chronic inflammatory demyelinating polyneuropathy is an immune-mediated polyneuropathy characterized by symmetric weakness of proximal and distal muscles and by progression continuing > 2 months... read more , Guillain-Barré syndrome Guillain-Barré Syndrome (GBS) Guillain-Barré syndrome is an acute, usually rapidly progressive but self-limited inflammatory polyneuropathy characterized by muscular weakness and mild distal sensory loss. Cause is thought... read more , myasthenia gravis Myasthenia Gravis Myasthenia gravis is characterized by episodic muscle weakness and easy fatigability caused by autoantibody- and cell-mediated destruction of acetylcholine receptors. It is more common among... read more , radiculopathies Nerve Root Disorders Nerve root disorders result in segmental radicular deficits (eg, pain or paresthesias in a dermatomal distribution, weakness of muscles innervated by the root). Diagnosis may require neuroimaging... read more , Eaton-Lambert syndrome Eaton-Lambert syndrome Disorders of neuromuscular transmission affect the neuromuscular junction; they commonly cause fluctuating muscle weakness with no sensory deficits. (See also Overview of Peripheral Nervous... read more ) 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 Amyotrophic Lateral Sclerosis (ALS) and Other Motor Neuron Diseases (MNDs) Amyotrophic lateral sclerosis and other motor neuron diseases are characterized by steady, relentless, progressive degeneration of corticospinal tracts, anterior horn cells, bulbar motor nuclei... read more or progressive supranuclear bulbar palsy Progressive Supranuclear Palsy (PSP) Progressive supranuclear palsy is a rare, degenerative central nervous system disorder that progressively impairs voluntary eye movements and causes bradykinesia, muscular rigidity with progressive... read more .
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.
Determination of a specific causative disorder
Sometimes combinations of findings suggest a cause (see table ).
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 Geriatrics Essentials: Weakness 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... read more ).
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 Evaluation Fatigue is difficulty initiating and sustaining activity due to a lack of energy and accompanied by a desire to rest. Fatigue is normal after physical exertion, prolonged stress, and sleep deprivation... read more 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 ). 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 is suspected (suggested by muscle weakness, muscle cramping, and pain), muscle enzymes (eg, creatine kinase [CK], aldolase, lactic dehydrogenase [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 Amyotrophic Lateral Sclerosis (ALS) and Other Motor Neuron Diseases (MNDs) Amyotrophic lateral sclerosis and other motor neuron diseases are characterized by steady, relentless, progressive degeneration of corticospinal tracts, anterior horn cells, bulbar motor nuclei... read more (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 ).
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 )
If myopathy is unexplained by drugs, metabolic, or endocrine disorders, possibly muscle biopsy
Treatment of Weakness
Causes of muscle weakness 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, regardless of the cause.
Geriatrics Essentials: Weakness
Some decrease in deep tendon reflexes is common with aging, but asymmetry or absence of these reflexes with augmentation is abnormal.
Because older adults are more likely to have preexisting sarcopenia, bed rest can cause debilitating muscle wasting rapidly, sometimes after only several days.
Older adults take more medications and are more susceptible to drug-induced myopathies, neuropathies, and fatigue; thus, medications are a common cause of weakness in older adults.
Feeling too weak to walk often has multiple causes. Factors may include the following:
Muscle weakness (eg, caused by stroke, use of certain substances or medications, myelopathy due to cervical spondylosis, or muscle atrophy)
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 medication 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.
Physical therapy is usually helpful in improving strength for all causes of weakness.
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