II. Pathophysiology: Injury affects one of four components

  1. Neuronal or Axonal Neuropathy
    1. Affects cell body or axon of nerve
    2. See Symmetric Peripheral Neuropathy (Polyneuropathy)
    3. See Asymmetric Peripheral Neuropathy (Mononeuropathy)
    4. See Peripheral Nerve Injury
  2. Demyelinating Neuropathy (Myelinopathy)
    1. Affects myelin swan cell sheath around axon
    2. See Symmetric Peripheral Neuropathy (Polyneuropathy)
    3. See Asymmetric Peripheral Neuropathy (Mononeuropathy)
  3. Infiltrative Neuropathy: Affects supporting tissue
    1. Appears similar to demyelinating Neuropathy
    2. Sarcoidosis
    3. Myelomatosis
    4. Amyloidosis
  4. Ischemic Neuropathy: Affects nerve vascular supply
    1. Diabetes Mellitus
    2. Collagen vascular disease

III. History

  1. What is the distribution of nerve involvement?
    1. Symmetric: Polyneuropathy
      1. Usually due to systemic or hereditary condition
      2. Idiopathic in 20% of cases
    2. Asymmetric: Mononeuropathy
      1. Usually due to nerve compression or inflammation
      2. Mononeuropathy: Isolated to a single nerve
      3. Mononeuropathy Multiplex: >1 discrete nerve
  2. Is the deficit sensory, motor or sensorimotor?
    1. Most neuropathies affect both sensory and motor
    2. Pure motor or sensory seen in distal Mononeuropathy
    3. Is motor more than sensory involvement?
      1. Amyotrophic Lateral Sclerosis
      2. Poliomyelitis or other chronic infectious cause
      3. Hereditary sensorimotor Neuropathy
      4. Toxin exposure
    4. Is sensory more than motor involvement?
      1. Toxin exposure
      2. Vitamin B12 Deficiency
      3. Hereditary sensory Neuropathy
      4. Systemic condition
        1. Diabetes Mellitus
        2. Uremia
        3. Myelomatosis
        4. Dysproteinemia
  3. When was the onset of symptoms?
    1. Acute over hours or days
      1. Motor Neuropathy most common
        1. See Acute Motor Weakness Causes
        2. Acute motor loss is risk for respiratory failure
        3. Requires urgent evaluation
      2. Sensory Neuropathy: Herpes Zoster
    2. Subacute over days to weeks
    3. Chronic over months
      1. Accounts for most cases of Neuropathy

IV. Signs: Sensory

  1. Pathognomonic neuropathic findings
    1. Allodynia (pain from non-painful stimulus - such as light touch)
    2. Hyperalgesia (excessive pain from a painful stimulus)
  2. Demyelinating or infiltrative Neuropathy
    1. Loss of vibration sense
    2. Loss of joint position sense
    3. Loss of tactile discrimination
  3. Axonal Neuropathy
    1. Sensory modes affected equivalently
    2. Neuropathy begins distally and moves proximally
    3. Injured Nerve Cell body cannot pump to axon end
    4. Results in stocking-and-glove distribution
    5. Long axons (e.g. legs) lose distal function first
      1. First: Sensory loss begins in feet
      2. Next: Deficit progresses proximally to knees
      3. Next: Hands begin to lose sensation
      4. Face is rarely affected (generally short axons)

V. Signs: Motor

  1. Demyelinating or infiltrative Neuropathy
    1. Early loss of Deep Tendon Reflexes
    2. Sensory often affected more than motor function
  2. Axonal Neuropathy
    1. Initial: Damage to anterior horn cell at spinal cord
      1. Weakness
      2. Muscle wasting
      3. Muscle fasciculations
    2. Later
      1. Deep Tendon Reflex loss in chronic Neuropathy
      2. Demyelination may occur secondary to axonal loss
        1. Differentiate from primary demyelination as above
    3. Motor loss follows same pattern as for sensory loss
      1. Distal affected before proximal involvement

VI. Causes

  1. See Symmetric Peripheral Neuropathy (Polyneuropathy)
  2. See Asymmetric Peripheral Neuropathy (Mononeuropathy)
  3. Painful Neuropathy causes
    1. Alcoholic Neuropathy
    2. Amyloidosis
    3. Chemotherapy
    4. Diabetic Neuropathy
    5. Porphyria
  4. Neuropathy with autonomic findings
    1. All painful neuropathies also cause autonomic features
    2. Paraneoplastic syndrome
    3. Heavy metal toxicity
    4. Vitamin B12 Deficiency

VII. Labs: Initial

VIII. Labs: Axonal Neuropathy Suspected

  1. First-line
    1. Hemoglobin A1C
    2. HIV Test
    3. Lyme Antibody test
    4. Rapid Plasma Reagin (RPR) or VDRL
    5. Antinuclear Antibody (ANA)
    6. P-ANCA and C-ANCA
  2. Second-line (if first-line tests negative or suggest additional specific testing)
    1. Serum Protein Electrophoresis (SPEP)
    2. Urine Protein Electrophoresis (UPEP)
    3. Urine 224 hour collection for heavy metals
    4. Paraneoplastic syndrome testing

IX. Diagnostics

  1. Indications
    1. Testing indicated if persistent symptoms or unclear etiology
    2. Distinguishes axonal and demyelinating types of Peripheral Neuropathy
  2. General
    1. EMG and NCS used in combination
    2. Differentiate axonal from myelin-infiltrative cause
    3. See Nerve Conduction Velocity for Interpretation
  3. Studies
    1. Needle Electromyography (EMG)
    2. Nerve Conduction Studies (Nerve Conduction Velocity)
    3. Nerve biopsy
  4. Additional studies
    1. MRI Brain
    2. Lumbar Puncture

X. Evaluation

  1. Obtain initial labs above
  2. Treat specific evident causes (e.g. Diabetic Neuropathy)
  3. If symptoms persist, obtain diagnostic studies above
  4. Type of Neuropathy based on EMG
    1. Axonal
      1. Consider second-line and third-line lab testing as listed above
    2. Demyelinating
      1. Uniform: Hereditary Neuropathy
      2. Nonuniform
        1. Acute: Guillain-Barre Syndrome
        2. Subacute or Chronic: Chronic Inflammatory Demyelinating Polyneuropathy

XI. Precautions: Red flags

  1. Focal weakness (risk of respiratory failure)

XII. Management: Symptomatic

  1. General Measures
    1. Neuropathic pain tends to be worse at night (when less distracted or trying to initiate sleep)
    2. Non-specific measures
      1. Warm soaks
      2. Moisturizing rubs
      3. Desensitizing massage
  2. First-line medications: Tricyclic Antidepressants (NNT 3-4)
    1. Desipramine
    2. Amitriptyline or Nortriptyline
      1. Start at 10-30 mg at bedtime
      2. Goal dose 75-100 mg nightly
  3. Second-line medications: SNRI (NNT 6-7)
    1. Duloxetine (Cymbalta)
      1. Goal dose 60 mg daily
    2. Venlafaxine
  4. Third-line medications (NNT 7-8)
    1. Gabapentin (Neurontin)
      1. Goal dose 1800-3600 daily divided three times daily
    2. Pregabalin (Lyrica)
      1. Goal dose 300-600 mg daily divided twice daily
  5. Additional measures
    1. Consider combining medications listed above
    2. Lidocaine Patch
  6. Other medications (typically started by neurology)
    1. Lamotrigine
    2. Topomax
    3. Carbamazepine

XIII. References

  1. Gallagher in Marx (2002) Rosen's Emergency Med, p. 1506
  2. Pryse-Phillips in Noble (2001) Primary Care, p. 1579
  3. Azhary (2010) Am Fam Physician 81(7): 887-92 [PubMed]
  4. Finnerup (2015) Lancet Neurol 14(2): 162–73 [PubMed]
  5. Hughes (2002) BMJ 324(7335): 466-9 [PubMed]

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Ontology: Neuropathy (C0442874)

Definition (CHV) nervous system disorder
Definition (CHV) nervous system disorder
Definition (CHV) nervous system disorder
Definition (NCI_NCI-GLOSS) A nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Neuropathy may be caused by physical injury, infection, toxic substances, disease (such as cancer, diabetes, kidney failure, or malnutrition), or drugs, including anticancer drugs.
Definition (NCI) A disorder affecting the cranial nerves or the peripheral nervous system. It is manifested with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.
Concepts Disease or Syndrome (T047)
ICD10 G62.9
SnomedCT 42658009, 277317008, 193167000, 277878001, 386033004, 264554005
English nerve disorders, nerve disorders (diagnosis), Neuropathy NOS, Neuropathy - (NOS), neuropathies, disorders neuropathy, neuropathy, neuropathy (diagnosis), Neuropathy (nerve damage), NEUROPATHY, Neuropathy (disorder), nerve; disorder, Neuropathy, NOS, Neuropathy
Spanish Neuropatía, Neuropatía NEOM, Neuropatía (NEOM), NEUROPATIA, neuropatía (trastorno), neuropatía
Italian Neuropatia NAS, Neuropatia, Neuropatia - (NAS)
French Neuropathie SAI, Neuropathie, NEUROPATHIE
Dutch neuropathie (NAO), neuropathie NAO, neuropathie, zenuw; aandoening
German Neuropathie, Neuropathie NNB, Neuropathie - (NNB), NEUROPATHIE
Portuguese Neuropatia, Neuropatia NE, NEUROPATIA
Japanese ニューロパチー, ニューロパチーNOS, ニューロパチー(NOS), ニューロパチー, ニューロパチーNOS
Czech Neuropatie, Neuropatie - (NOS), Neuropatie NOS
Hungarian Neuropathia, Neuropathia k.m.n., Neuropathia - (k.m.n.)