Weakness and paralysis

Weakness is a common symptom that can occur in a wide variety of conditions. In medical settings, “weakness” is best used to refer to decreased strength specifically attributable to neuromuscular abnormalities, rather than to systemic abnormalities of energy and metabolism. Degree of neurological weakness ranges from paresis (mild to moderate) to paralysis (severe or complete). The approach to patients with weakness requires careful clinical evaluation, including a detailed history and physical examination focusing on neurological examination and muscle strength grading. Specific patterns (e.g., acute vs. chronic, upper motor neuron vs. lower motor neuron) can help narrow down the etiology. Aggravating and alleviating factors, associated symptoms, and exposure history can often provide clues to a specific diagnosis. Diagnostic testing is guided by clinical evaluation and includes routine laboratory studies, targeted testing for specific neuromuscular disorders, neuroimaging, and electrodiagnostic studies. Specialist evaluation, e.g., by a neurologist, is often required. The management of weakness or paralysis varies significantly depending on the underlying cause and acuity of presentation and ranges from immediate respiratory support to supportive care, rehabilitation, and long-term pharmacotherapy.

See “Malaise and fatigue” for a more general approach not limited to neuromuscular causes.

The following terms have imprecise definitions, and their usage can vary and overlap in both medical and lay contexts. ^[1]

• Weakness: a lack of strength in the body or a body part
  • In medical contexts, “weakness” is best reserved for describing neuromuscular weakness.
  • Usage varies in the literature and in lay contexts; the term “generalized weakness” may also signify: ^[1][2][3]
    • Malaise, fatigue, lethargy, or asthenia (See “Malaise and fatigue.”)
    • Disability, exercise intolerance, or functional decline
    • Related symptoms, e.g., muscle pain, incoordination, altered mental status, presyncope
• Muscle fatigue: inability to continue a physical task after multiple repetitions ^[3]
  • Can be physiological (e.g., after excessive activity)
  • Can occur pathologically in patients with neuromuscular weakness (e.g., myasthenia gravis, myopathy)
  • See “Malaise and fatigue” for other types of fatigue.
• Neuromuscular weakness ^[4]
  • Impairment in motor function (e.g., limitation in strength and/or range of motion) attributable to abnormalities in any of the following:
    • Muscle structure and function
    • Neurons
    • Neuromuscular junction
  • Can be generalized or localized, unilateral or bilateral, progressive or intermittent
  • Most often measurable (e.g., using muscle strength grading)
    • Paresis: mild to moderate degree of muscle weakness
    • Paralysis: severe or complete loss of active muscle movement ^[5]

Clarify the intended meaning of potentially imprecise reported symptoms (e.g., weakness or fatigue) to avoid misdiagnosis, miscommunication, and unnecessary investigations.

Several causes of neuromuscular weakness can have overlapping effects on muscles, neurons, and the neuromuscular junction. In extreme cases, they can cause paralysis. See “Malaise and fatigue” for non-neuromuscular causes of generalized weakness.

Muscular ^[1][6][7]

• Acquired
  • Sarcopenia and deconditioning (can coexist with frailty)
  • Rhabdomyolysis
  • Drug-induced myopathy; drugs associated with myopathy include: ^[3][6]
    • Corticosteroids: See “Steroid-induced myopathy.”
    • Statins: See “Statin myopathy.”
    • Antineoplastics or antimetabolites, e.g., vincristine, hydroxyurea, colchicine
    • Antiarrhythmics, e.g., procainamide, amiodarone
    • Antivirals, e.g., interferon alpha, lamivudine, zidovudine (see “Zidovudine-induced myopathy.”)
    • Antibiotics: e.g., fluoroquinolones, sulfonamides
    • Recreational drugs: e.g., cocaine (see “Cocaine-induced myopathy.”)
  • Critical illness myopathy
  • Cushing syndrome
  • Hypothyroid myopathy
  • Acute alcohol-induced myopathy
  • Inflammatory myopathies, e.g., dermatomyositis, polymyositis, inclusion body myositis
  • See also “Differential diagnoses of myopathies.”
• Hereditary
  • Duchenne muscular dystrophy
  • Becker muscular dystrophy
  • Limb-girdle muscular dystrophy
  • Facioscapulohumeral muscular dystrophy
  • Myotonic syndromes, e.g., myotonic dystrophy
  • Periodic paralysis (can also be acquired)

Neuromuscular junction (NMJ) ^[1][6]

• Autoimmune: myasthenia gravis
• Paraneoplastic: Lambert-Eaton myasthenic syndrome (LEMS)
• Toxic
  • Botulism
  • Cholinergic poisoning, e.g., organophosphates
  • Tick paralysis
  • Snake envenomation

Lower motor neuron (LMN) ^[1][6][7]

• Infectious
  • Poliomyelitis
  • Diphtheria
• Autoimmune: Guillain-Barré syndrome (often post-infectious)
• Inflammatory: chronic inflammatory demyelinating polyneuropathy (CIDP)
• Hereditary
  • Spinal muscular atrophy
  • Hereditary motor sensory neuropathy
• Others
  • Progressive muscular atrophy (early)
  • Critical illness polyneuropathy
  • Alcoholic polyneuropathy
  • Diabetic neuropathy
  • Motor deficits are rare in drug-induced peripheral neuropathy but can occur with: ^[8]
    • Chemotherapy-induced peripheral neuropathy
    • Amiodarone
    • Metronidazole
    • Leflunomide
    • Biological agents

Upper motor neuron (UMN) and CNS ^[3][6]

• Structural ^[6]
  • TBI
  • Spinal cord injury
  • Brain tumor
  • Spinal tumor
  • Spinal stenosis
• Vascular
  • Stroke
  • Anterior spinal artery syndrome
• Inflammatory
  • Multiple sclerosis (MS)
  • Acute disseminated encephalomyelitis
  • Transverse myelitis
• Metabolic: central pontine myelinolysis
• Congenital or hereditary
  • Cerebral palsy
  • Hereditary spastic paraplegia
  • Subacute combined degeneration of spinal cord

Mixed syndromes ^[6]

• Mixed UMN and LMN effects
  • Amyotrophic lateral sclerosis (ALS)
  • Progressive muscular atrophy (late stages)
• Mixed CNS and PNS effects
  • Systemic diseases (e.g., diabetic neuropathy, lupus) ^[9][10]
  • Neuroborreliosis
  • Vitamin B₁₂ deficiency
  • Paraneoplastic syndromes
  • Heavy metal poisoning, e.g., lead poisoning, mercury poisoning
  • Cholinergic poisoning
  • Amyloidosis
  • Puffer fish poisoning

Electrolyte disturbances ^[6]

Can affect neurons and/or myocytes.

• Hypokalemia or hyperkalemia
• Hypocalcemia or hypercalcemia
• Hyponatremia or hypernatremia
• Hypomagnesemia or hypermagnesemia
• Hypophosphatemia or hyperphosphatemia

Approach ^[1][6]

• Identify red flags in neuromuscular weakness.
• Provide acute stabilization for neuromuscular weakness.
• Exclude life-threatening mimics of neuromuscular weakness.
• Ascertain the onset of symptoms to narrow the diagnosis.
  • See “Acute causes of neuromuscular weakness.”
  • See “Chronic causes of neuromuscular weakness.”
• Localize the lesion on neurological examination, e.g.:
  • UMN signs vs. LMN signs
  • Weakness patterns and associated lesions

Red flags in neuromuscular weakness ^[1]

These suggest an acutely life-threatening cause that requires urgent intervention:

• Signs of airway compromise (especially bulbar palsy)
• Signs of respiratory muscle weakness
• Neurogenic shock
• Rapidly progressive neurological symptoms, e.g., ascending paralysis
• Clinical features of acute ischemic stroke
• Signs of elevated ICP
• Cerebral herniation syndromes

Classic respiratory distress signs (e.g., increased work of breathing) may be absent due to neuromuscular weakness. Signs may be limited to shallow breaths, low SpO₂, tachycardia, cyanosis, and/or altered mental status.

Acute stabilization for neuromuscular weakness ^[1][3]

Consider the following immediate steps in patients with red flags:

• Airway management and ventilation
  • Measure bedside PFTs.
  • Predictors for the need for mechanical ventilation include:
    • Vital capacity < 15 mL/kg
    • Maximal inspiratory pressure less negative than - 30 cm H₂O
  • Provide respiratory support as required (see “Ventilation strategy for neuromuscular weakness”).
• Immediate hemodynamic support
• Neuroprotective measures
• ICP management
• Consult neurology or neurosurgery urgently for definitive treatment of neurological emergencies (e.g., stroke or intracranial hemorrhage).
• Consult ICU for patients requiring critical care(see “Disposition”).

Avoid succinylcholine as a paralytic agent for intubation in patients with suspected denervation or neuromuscular disorders to prevent life-threatening hyperkalemia. ^[1]

Intracranial hypertension can worsen during airway management. Follow the approach to intubating patients with increased ICP to avoid complications such as cerebral herniation. ^[1][11][12]

Focused history ^[1][3][6]

Include the following:

• Onset and duration: e.g., acute, subacute, chronic
• Pattern: e.g., proximal, distal, symmetrical, asymmetrical
• Progression: e.g., steady, episodic, fluctuating, ascending
• Aggravating and alleviating factors: e.g., physical activity, rest
• Associated neurological symptoms: e.g., sensory abnormalities, pain, tremors
• Drug history: e.g., medications associated with myopathy
• Past medical history: e.g., hypothyroidism
• Exposures: e.g., toxins, tick bites, recent infections
• Vaccination history: e.g., polio vaccination status, recent vaccines
• Family history: e.g., muscular dystrophy, porphyria

Causes of transient or episodic weakness include multiple sclerosis, myasthenia gravis, and compressive peripheral neuropathies. ^[3]

Ascending bilateral weakness is seen in Guillain-Barré syndrome and tick paralysis, while descending weakness is characteristic of botulism. ^[3]

Focused examination ^[1][6]

• Thorough neurological examination
  • Grade muscle strength using the Medical Research Council scale.
  • Identify patterns, e.g., UMN signs vs. LMN signs, proximal vs. distal, symmetrical vs. asymmetrical.
  • Pay close attention to:
    • Associated sensory deficits
    • Muscle tone, atrophy, and fasciculations
    • Reflexes (e.g., Babinski reflex)
    • Coordination and gait assessment
    • Cranial nerve examination
  • Localize the lesion, if possible (see “Weakness patterns and associated lesions”).
• Non-neurological clinical signs
  • Skin rashes
  • Cardiovascular abnormalities
  • Cushingoid features
  • Signs of dysautonomia
  • Cholinergic toxidrome

In patients with isolated motor weakness, consider ALS and botulism.

Difficulty performing a physical task on the first attempt suggests true neurological weakness. Difficulty sustaining repeated physical tasks suggests muscle fatigue. ^[3]

Lesion localization based on affected body parts

See also “Stroke symptoms by affected vessel,” “Lacunar syndromes,” “Brainstem syndromes,” and “Medullary syndromes.”

Proximal symmetrical weakness is a classic finding of most myopathies. ^[3][6]

Asymmetrical weakness suggests focal lesions of the brain, spinal cord, or peripheral nerves rather than a systemic cause. ^[1][6]

Routine studies ^[6]

• Consider screening for common systemic conditions (e.g., CBC, renal function tests, LFTs, septic workup, TFTs).
• Obtain targeted studies based on clinical evaluation findings, e.g.:
  • Serum electrolytes: calcium, magnesium, phosphate
  • Creatine kinase (CK): for muscle damage or myopathy
  • CSF analysis: for infectious or inflammatory causes
  • Neuroimaging and spinal imaging: for structural causes
  • Serologies: e.g., AChR-Ab for myasthenia gravis, Lyme serology
  • Further studies, e.g., HIV testing, diagnostics for Cushing syndrome

Advanced studies ^[6]

Seek specialist guidance (e.g., neurology).

• Electrodiagnostic studies to assess nerve and muscle function ^[6]
• Muscle biopsy for objective weakness with abnormal CK levels or electrodiagnostic studies
• Genetic testing for suspected hereditary neuromuscular disorders, such as muscular dystrophies

Further evaluation

• Consult a specialist as needed, e.g., neurology, rheumatology.
• Consider the possibility of somatic symptom disorder or conversion disorder in patients with:
  • Extensive prior workup with no identifiable cause
  • Physical findings inconsistent with reported symptoms
  • See “Approach to patients with suspected somatic symptom and related disorders” for details.

Supportive care

• Pain management
• Fluid replacement
• Supportive care for decreased mobility
  • Decubitus ulcer prophylaxis
  • VTE prophylaxis
  • Urinary catheterization
• Medical rehabilitation

• Admission is usually required for: ^[1]
  • Vascular CNS causes of weakness, e.g., stroke
  • Severe or rapidly progressive LMN or muscular weakness, e.g., botulism, Guillain-Barré syndrome
  • New UMN weakness, e.g., spinal cord injury, MS exacerbation
• ICU admission is usually required for ascending paralysis, respiratory failure, airway compromise, and neurogenic shock.
• Admission to a stroke center or neurocritical care unit may be indicated. ^[1]

Complete the following steps as required.

• Follow the ABCDE approach.
• Obtain a full set of vitals.
• Identify red flags in neuromuscular weakness.
• Follow the initial management of acute stroke.
• Start ICP management.
• Follow the management of compressive spinal emergencies.
• Initiate treatment of spinal cord injuries.
• Perform a neurological examination.
• Obtain laboratory studies, e.g., CK, CMP.
• Start empiric antibiotics for bacterial meningitis.
• Obtain urgent neuroimaging for suspected structural causes.
• Provide supportive care as indicated, e.g.:
  • Decubitus ulcer prophylaxis
  • VTE prophylaxis
  • Urinary catheterization
• Consult neurology, neurosurgery, or rheumatology as needed.

The following conditions can be conflated with or mistaken for neuromuscular weakness. For causes of neuromuscular weakness, see the “Etiology” section. See “Stroke mimics” for differential diagnoses of focal or diffuse neurological deficits. ^[1]

• Potentially life-threatening mimics of neuromuscular weakness
  • Hypoglycemia
  • Shock, hypovolemia
  • Infection, sepsis
  • DKA
  • Traumatic brain injury
  • Acute heart failure
  • Acute coronary syndrome
  • Bradycardia
  • Poisoning, e.g., with cellular toxins
• Other general symptoms
  • Malaise or fatigue
  • Altered mental status and coma (e.g., due to sedative-hypnotic drug overdose)
  • Presyncope
  • Vertigo
  • Functional decline
• Other neurological symptoms
  • Pain-induced motor dysfunction
  • Incoordination or ataxia
• Disorders of circulation and oxygen delivery
  • Dehydration
  • Anemia or polycythemia

The differential diagnoses listed here are not exhaustive.