Peripheral Neuropathy

A. See also

Periperhal Nerve Anatomy, p. 89; Weakness, p. 129.

B. H&P

Ask about weakness, paresthesias, numbness, distal vs. proximal, symmetric vs. focal, ANS sx, limb injuries, alcoholism, DM, medications, HIV status, hepatitis, FH, reflexes.

C. DDx

CNS lesion; myopathy, NMJ dz, metabolic (e.g., paresthesias from alkalosis)….

D. Tests

EMG/NCS, KCl/Ca/Mg/Phos, CPK, B₁₂, MCV, ESR, TSH, hemoglobin A1c, Lyme titer, syphilis, SPEP/UPEP, LFTs, HIV, ANA. Consider ANCA, ALA, ACE level/chest film, heavy metals, fat pad biopsy for amyloid, HCV, HBV, cryoglobulins.

E. Types of neuropathy

Polyneuropathy (usually axonal degeneration or demyelination); mononeuropathy or mononeuropathy multiplex (usually entrapment, trauma); sensorimotor; motor; sensory.

F. Causes of neuropathy

1. A mnemonic: DANG THERAPIST: DM, Alcohol, Nutritional, GBS, Trauma, Hereditary, Endocrine/Entrapment, Renal/Radiation, AIDS/Amyloid, Paraprotein/Porphyria, Infectious (e.g., leprosy), Systemic/Sarcoid, Toxins.
2. Causes categorized: By acuity, distribution, and EMG finding:
- a. Acute, generalized:
  - 1) Axonal degeneration:
    - a) Infections: Lyme, HIV, EBV, hepatitis, CMV.
    - b) ICU neuropathy: Proximal, sensorimotor, in setting of SIRS, multiorgan failure.
    - c) Misc: Porphyria, “axonal Guillain-Barré syndrome.”
  - 2) Demyelination: Guillain-Barré syndrome, arsenic, infections, e.g., HIV and diphtheria.
- b. Chronic, generalized:
  - 1) Axonal degeneration: Dying back, stocking-glove pattern.
    - a) Nutritional: Alcohol, folate, vitamin B₁₂ or E deficiency, B₆ toxicity.
    - b) Toxic: DPH, vincristine, heavy metals (thallium, mercury, lead, arsenic), antiretrovirals, acrylamide, etc.
    - c) Endocrine: DM, hypothyroidism.
    - d) Infectious: HIV, Lyme.
    - e) Genetic: Charcot-Marie-Tooth (CMT) type II, familial amyloidosis, Friedreich’s ataxia, etc.
    - f) Lipid problems: Fabry’s dz, Tangier dz, Bassen-Kornzweig dz.
    - g) Other: Uremia, liver disease, vasculitis, sensory neuropathy (anti-Hu paraneoplastic, Sjögren’s), lipid dzs (Fabry’s, Tangier, Bassen-Kornzweig).
  - 2) Demyelination:
    - a) Uniform slowing on EMG: CMT types 1A, 1B, and X; myelin dysmetabolism, e.g., metachromatic leukodystrophy, Refsum dz, Krabbe dz.
    - b) Nonuniform slowing:
      - i. Infectious or inflammatory: HIV, CIDP, multifocal neuropathy with conduction block.
      - ii. Paraprotein: Lymphoma, myeloma, Waldenstrom’s, cryoglobulinemia, POEMS syndrome (Polyneuropathy with Organomegaly, Endocrinopathy, M-protein, and Skin changes), MGUS (Monoclonal Gammopathy of Uncertain Significance).
- c. Mononeuropathy multiplex (multifocal or asymmetric):
  - 1) Axonal:
    - a) Vascular: DM, vasculitis, connective tissue dz, subacute bacterial endocarditis.
    - b) Infectious or inflammatory: HIV, Lyme, leprosy, VZV, hepatitis A, sarcoid.
    - c) Neoplastic: Neurofibromatosis, lymphoma, leukemia, direct local invasion.
    - d) Miscellaneous: Genetic, e.g., inherited brachial plexus neuropathy; traumatic, e.g., multiple compressions.
  - 2) Demyelinating:
    - a) Inflammatory: Guillain-Barré; multifocal motor neuropathy with conduction block.
    - b) Genetic: HNPP: hereditary neuropathy with liability to pressure palsies.
    - c) Multiple compressions.