Table: Some Causes of Muscle Weakness-MSD Manual Professional Edition

Some Causes of Muscle Weakness

Cause	Suggestive Findings	Diagnostic Approach*,†
Brain upper motor neuron lesions
Brain tumors Multiple sclerosis Stroke	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 For multiple sclerosis: MRI of the brain and the cervical and thoracic spinal cord (not CT); sometimes lumbar puncture
Myelopathies (involving upper or lower motor neuron dysfunction or both)
Autoimmune disorders (eg, multiple sclerosis, neuromyelitis optica, vasculitis) Cauda equina syndrome Infections (eg, HTLV-1, HIV infection, syphilis, human herpes simplex 6, EBV infection, varicella-zoster) Spinal cord compression (eg, due to spondylosis, epidural tumor, hematoma, or abscess) Spinal cord ischemia or infarction Spinocerebellar ataxias Subacute combined degeneration Transverse myelitis	Dysfunction of upper motor neurons, lower motor neurons, or both Commonly erectile dysfunction, bowel and bladder incontinence or retention, 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	Spinal cord MRI, CT myelography, or both Somatosensory evoked potentials Other tests as needed to help identify the cause:
Motor neuron disorders (upper, lower, or both)
Amyotrophic lateral sclerosis Inherited motor neuron diseases (eg, spinal muscular or spinocerebellar atrophies, including Kennedy disease) Postpoliomyelitis syndrome 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 as needed to help identify the cause: Possibly including 24-hour 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)†,‡
Alcohol-related neuropathy Critical illness polyneuropathy Demyelinating neuropathies (eg, CIDP, Guillain-Barré syndrome) Diabetic neuropathy Hereditary neuropathies Infectious neuropathies (eg, diphtheria, hepatitis C, HIV/AIDS, Lyme disease, syphilis) Multifocal motor neuropathy Sarcoidosis Toxic neuropathies (eg, heavy metals) Vitamin deficiency (eg, thiamin, vitamin B6, vitamin 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 testing Other tests as needed to help identify the cause: Possibly including plasma glucose, 2-hour oral glucose tolerance test, hemoglobin A1C, RPR, HIV test, folate, vitamin B12, serum protein immunofixation electrophoresis, chest CT and serum ACE level (for sarcoidosis), 24-hour urine heavy metals screen, anti-MAG antibodies (present in some demyelinating neuropathies), anti-GM1 antibody titers (for multifocal motor neuropathy), and genetic testing (for hereditary neuropathies) Sometimes cerebrospinal analysis
Neuromuscular junction disorders
Botulism Eaton-Lambert syndrome Myasthenia gravis Tick paralysis	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 tests as needed to help identify the cause: Possibly including assays for toxins and acetylcholine receptor antibody and ice pack testing (for myasthenia gravis)
Organophosphate or carbamate poisoning	Tearing of the eyes, blurred vision, increased salivation, sweating, coughing, vomiting, frequent bowel movements and urination, and fasciculations	Often clinical examination alone Sometimes blood tests to identify the toxin
Myopathies
Alcohol myopathy Channelopathies Corticosteroid myopathy Cushing syndrome Hereditary muscle disorders (eg, muscular dystrophies) Hypocalcemia Hypokalemia Hypomagnesemia Hypophosphatemia Hypothyroid myopathy Metabolic myopathies Polymyositis or dermatomyositis Rhabdomyolysis Statin-induced myopathy Thyrotoxic myopathy Viral myositis	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 Other testing as needed to help identify the cause: Possibly including muscle biopsy with special stains and genetic testing for certain hereditary disorders, serum electrolytes (particularly calcium, potassium, magnesium, and phosphate), serum TSH, and herpes zoster titers
Generalized muscle wasting due to illness and disuse
Burns Cancer Prolonged bed rest Sepsis Starvation	Diffuse muscle atrophy, normal sensation and reflexes, no fasciculations Clinically apparent risk factors	History and physical examination alone
* Clinical examination is always done but is mentioned in this column only when that can be the sole means of diagnosis.
† 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.
ACE = angiotensin-converting enzyme; ANA = antinuclear antibodies; anti-GM1= anti-ganglioside monosialic acid; anti-MAG = antimyelin-associated glycoprotein; CIDP = chronic inflammatory demyelinating polyneuropathy; CK = creatine kinase; EBV = Epstein-Barr virus; HTLV = human T-lymphotropic virus; MOG = myelin oligodendrocyte glycoprotein, NMO-IgG = neuromyelitis optica antibody; RPR = rapid plasma reagin; TSH = thyroid-stimulating hormone; VDRL = Venereal Disease Research Laboratory.

Cause

Suggestive Findings

Diagnostic Approach*,†

Brain upper motor neuron lesions

Brain tumors

Multiple sclerosis

Stroke

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

For multiple sclerosis: MRI of the brain and the cervical and thoracic spinal cord (not CT); sometimes lumbar puncture

Myelopathies (involving upper or lower motor neuron dysfunction or both)

Autoimmune disorders (eg, multiple sclerosis, neuromyelitis optica, vasculitis)

Cauda equina syndrome

Infections (eg, HTLV-1, HIV infection, syphilis, human herpes simplex 6, EBV infection, varicella-zoster)

Spinal cord compression (eg, due to spondylosis, epidural tumor, hematoma, or abscess)

Spinal cord ischemia or infarction

Spinocerebellar ataxias

Subacute combined degeneration

Transverse myelitis

Dysfunction of upper motor neurons, lower motor neurons, or both

Commonly erectile dysfunction, bowel and bladder incontinence or retention, 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

Spinal cord MRI, CT myelography, or both

Somatosensory evoked potentials

Other tests as needed to help identify the cause:

Motor neuron disorders (upper, lower, or both)

Amyotrophic lateral sclerosis

Inherited motor neuron diseases (eg, spinal muscular or spinocerebellar atrophies, including Kennedy disease)

Postpoliomyelitis syndrome

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 as needed to help identify the cause: Possibly including 24-hour 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)†,‡

Alcohol-related neuropathy

Critical illness polyneuropathy

Demyelinating neuropathies (eg, CIDP, Guillain-Barré syndrome)

Diabetic neuropathy

Hereditary neuropathies

Infectious neuropathies (eg, diphtheria, hepatitis C, HIV/AIDS, Lyme disease, syphilis)

Multifocal motor neuropathy

Sarcoidosis

Toxic neuropathies (eg, heavy metals)

Vitamin deficiency (eg, thiamin, vitamin B6, vitamin 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 testing

Other tests as needed to help identify the cause: Possibly including plasma glucose, 2-hour oral glucose tolerance test, hemoglobin A1C, RPR, HIV test, folate, vitamin B12, serum protein immunofixation electrophoresis, chest CT and serum ACE level (for sarcoidosis), 24-hour urine heavy metals screen, anti-MAG antibodies (present in some demyelinating neuropathies), anti-GM1 antibody titers (for multifocal motor neuropathy), and genetic testing (for hereditary neuropathies)

Sometimes cerebrospinal analysis

Neuromuscular junction disorders

Botulism

Eaton-Lambert syndrome

Myasthenia gravis

Tick paralysis

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 tests as needed to help identify the cause: Possibly including assays for toxins and acetylcholine receptor antibody and ice pack testing (for myasthenia gravis)

Organophosphate or carbamate poisoning

Tearing of the eyes, blurred vision, increased salivation, sweating, coughing, vomiting, frequent bowel movements and urination, and fasciculations

Often clinical examination alone

Sometimes blood tests to identify the toxin

Myopathies

Alcohol myopathy

Channelopathies

Corticosteroid myopathy

Cushing syndrome

Hereditary muscle disorders (eg, muscular dystrophies)

Hypothyroid myopathy

Metabolic myopathies

Polymyositis or dermatomyositis

Rhabdomyolysis

Statin-induced myopathy

Thyrotoxic myopathy

Viral myositis

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

Other testing as needed to help identify the cause: Possibly including muscle biopsy with special stains and genetic testing for certain hereditary disorders, serum electrolytes (particularly calcium, potassium, magnesium, and phosphate), serum TSH, and herpes zoster titers

Generalized muscle wasting due to illness and disuse

Burns

Cancer

Prolonged bed rest

Sepsis

Starvation

Diffuse muscle atrophy, normal sensation and reflexes, no fasciculations

Clinically apparent risk factors

History and physical examination alone

* Clinical examination is always done but is mentioned in this column only when that can be the sole means of diagnosis.

† 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.

ACE = angiotensin-converting enzyme; ANA = antinuclear antibodies; anti-GM1= anti-ganglioside monosialic acid; anti-MAG = antimyelin-associated glycoprotein; CIDP = chronic inflammatory demyelinating polyneuropathy; CK = creatine kinase; EBV = Epstein-Barr virus; HTLV = human T-lymphotropic virus; MOG = myelin oligodendrocyte glycoprotein, NMO-IgG = neuromyelitis optica antibody; RPR = rapid plasma reagin; TSH = thyroid-stimulating hormone; VDRL = Venereal Disease Research Laboratory.