The Massachusetts General Hospital Handbook of Neurology

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > Adult Neurology > Peripheral Neuropathy

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-Barr syndrome.

    • 2) Demyelination: Guillain-Barr 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, Sj gren'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.

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        • 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-Barr ; multifocal motor neuropathy with conduction block.

      • b) Genetic: HNPP: hereditary neuropathy with liability to pressure palsies.

      • c) Multiple compressions.

G. Specific neuropathies

• 1. Inflammatory demyelinating polyneuropathies: E.g., Guillain-Barr syndrome, CIDP. see p. 36.

• 2. Charcot-Marie-Tooth dz: The most common hereditary neuropathies. CMT-1 is demyelinating, CMT-2 is axonal. Both start in the feet, usually before age 20, with weakness, numbness, pes cavus.

• 3. Cranial neuropathies: Important to distinguish central from peripheral neuropathies. See also individual nerves or sx.

  • a. Cranial polyneuropathy syndromes:

    • 1) Cavernous sinus syndromes: see p. 50.

    • 2) Basilar meningitis.

    • 3) Jugular foramen syndromes: Variable compression of the lower four cranial nerves. Look for corticospinal signs or Horner's syndrome as evidence for brainstem compression.

    • 4) Polyneuritis cranialis: A variant of Guillain-Barr syndrome; see p. 37.

    • 5) Myasthenia gravis: see p. 81.

    • 6) Botulism.

  • b. Bell's palsy: Idiopathic CN VII palsy. R/o secondary palsies.

    • 1) H&P: Pressure/pain behind ear, hyperacusis, decreased taste, subjective but not objective numbness. Unilateral face weakness including brow, eye closure (can see eye roll up, Bell's phenomenon). Examine eardrum to rule out Ramsay-Hunt syndrome (geniculate VZV reactivation affecting CN VII and VIII) unrelated to the Ramsay-Hunt syndrome of myoclonus and spinocerebellar atrophy (see Eponym rant, p. 28).

    • 2) Rx: Eye protection (drops during day, ointment and patch at night). Consider PO prednisone and valacyclovir/acyclovir if within 1 wk of symptom onset.

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    • 3) Tests: Consider Lyme Ab, CBC, ESR, ANA, ANCA, chest film (to r/o TB, sarcoid, adenopathy), ACE, HIV, UBJ/SPEP if elderly, MRI, CSF if suspect carcinomatous meningitis.

• 4. Diabetic neuropathy: By far the most common cause of neuropathy. Can affect any nerve.

  • a. Polyneuropathy: Distal, sensory > motor, axonal degeneration on EMG. R/o tarsal tunnel syndrome.

  • b. Autonomic neuropathy: Gastroparesis, orthostasis, burning pain, erectile dysfunction, sphincter involvement.

  • c. Diabetic amyotrophy: Asymmetric painful lumbosacral plexopathy. Recovers spontaneously.

  • d. Mononeuropathy: E.g., pupil-sparing third nerve palsy (see p. 46). Also CN IV, VI, VII. Usually recovers. DDx: Entrapment neuropathies.

  • e. Rx: See Neuropathic pain, p. 87, and Diabete mellitus, p. 199.

• 5. Neuropathy in kidney failure: Uremia causes a dying-back neuropathy and increases risk of compression neuropathies.

• 6. Plexopathies:

  • a. Brachial plexopathy: See Figure 11, p. 90.

    • 1) H&P: Sudden, severe shoulder pain, worse with arm movement, then weakness of shoulder, arm, hand. Often with numbness on upper arm. Ask about previous viral syndrome; smoking history. Look for Horner's syndrome.

    • 2) DDx of brachial plexopathy: Pancoast tumor, post radiation therapy, DM, Lyme, vasculitis, trauma (p. 94), idiopathic brachial neuritis (Parsonage Turner syndrome) .

    • 3) Tests: CXR, glucose, ANA, ESR; EMG (not positive <3 wk after sx start), MRI with contrast of shoulder. CSF nl.

    • 4) Rx: Steroids do not help idiopathic cases.

    • 5) Prognosis: Idiopathic cases usually start to recover in 4 wk; upper plexus may fully recover by 1 yr; lower plexus may take 2-3 yr.

  • b. Lumbosacral plexitis: Rarely idiopathic.

    • 1) H&P: Sudden leg pain, then weakness, paresthesias but little objective sensory loss. Straight leg raise may be positive, but there should be no back pain or exacerbation of pain by Valsalva maneuver. Pt. needs pelvic and rectal exams.

    • 2) DDx: Pelvic mass, DM, Lyme, vasculitis, femoral neuropathy, radiculopathy, cauda equina syndrome, post-XRT .

    • 3) Tests: Consider CEA, PSA, glucose, ANA, ESR, pelvic CT. EMG not positive <3 wk after sx start but is crucial for dx: should see at least two spinal levels involved, with sparing of the paraspinal muscles. MRI with contrast of pelvis.

    • 4) Rx: Steroids do not help.

    • 5) Prognosis: Pain gets better before strength; only slow, incomplete recovery.

• 7. Entrapment neuropathies and traumatic nerve injuries:

  • a. H&P: Ask about worsening at night; repetitive stresses, e.g., typing; comorbid dz, e.g., alcoholism, DM, hypothyroidism, acromegaly, arthritis, cancer; previous entrapments (consider hereditary neuropathy with pressure palsies). Light touch is often

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    lost before pin prick (opposite to spinal cord injuries). Pain may be referred; e.g., pain above wrist from carpal tunnel syndrome.

  • b. Tests for compression: See syndromes below. Consider EMG if surgery is an option. EMG may be normal for the first 2-4 wk after onset of sx.

  • c. Rx of entrapment: Splint, NSAIDS, gabapentin, duloxetine; consider surgery if weak.

  • d. Brachial plexus trauma: See Figure 11.

    • 1) Upper plexus lesion: Erb-Duchenne palsy. Often from trauma pulling head away from shoulder.

      • a) Motor: Bellhop's tip position: internal rotation at shoulder, with elbow extension. Weak shoulder abduction and extension, weak biceps and triceps.

      • b) Sensory: Numb over deltoid, radial forearm.

    • 2) Lower plexus lesion: D j rine-Klumpke palsy. Often from forced arm abduction or lung apex tumor (pancoast tumor; often with Horner's syndrome). See claw deformity similar to ulnar neuropathy, below.

  • e. Common entrapment syndromes: (See also Spinal level by nerve, p. 90.)

    • 1) Median nerve entrapment:

      • a) Anterior interosseous nerve syndrome: Branches just distal to elbow. Decreased flexion of D1-2 causes weak pinch. No sensory loss.

      • b) Carpal tunnel syndrome (CTS):

        • i. H&P: Tingling or numbness in D1-4 (through medial but not lateral ring finger). Pain may radiate above wrist, but not to neck. Pain awakens pt from sleep. Exam is not that sensitive. May see weak grip, thenar atrophy.

        • ii. Phalen's sign: 60 sec of wrist flexion paresthesias.

        • iii. Tinel's sign: Tapping on wrist causes paresthesias.

        • iv. DDx: Cervical radiculopathy, thoracic outlet syndrome, pronator teres syndrome, de Quervain's dz .

    • 2) Radial nerve entrapment:

      • a) Mid-upper arm compression (Saturday night or honeymoon palsy): See wrist and finger drop; no triceps weakness.

      • b) Forearm compression: Finger drop without wrist drop. Consider surgery for entrapment.

    • 3) Ulnar nerve entrapment: Ulnar claw deformity: fingers 4 and 5 have metacarpal hyperextension with finger flexion.

      • a) Wrist (Guyon's canal) vs. elbow compression: Make a fist; if poor flexion of 4 and 5, then lesion is above wrist.

      • b) Elbow compression: Cubital tunnel syndrome (under arcuate ligament) vs. ulnar groove.

    • 4) Thoracic outlet syndrome:

      • a) Compression of the brachial plexus by a cervical rib or elongated transverse process of C7. However, cervical ribs are common in normal persons. Maneuvers to look for obliteration of radial pulse have very low specificity.

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      • b) Droopy shoulder syndrome: Usually young women. Pulling down on arm worsens sx.

    • 5) Peroneal nerve palsy: From calf compression or long bed rest. See foot drop, steppage gait. Numb lateral calf and foot dorsum. Weak foot inversion suggests L5 root lesion. In trauma, anterior compartment syndrome, which requires immediate fasciotomy, can cause peroneal palsy.

    • 6) Meralgia paresthetica: Lateral femoral cutaneous nerve compression, often from weight change, causes thigh tingling.

    • 7) Tarsal tunnel syndrome: CTS of the foot. Posterior tibial nerve compression causes sole paresthesias.