Peripheral Nerve Disorders

Peripheral Nerve Disorders: Injury Patterns - Shocking Revelations

• Nerve Fiber Components: Axon, Myelin sheath (Schwann cells in PNS), Connective tissues (Endoneurium, Perineurium, Epineurium).
• Key Injury Responses:
  • Wallerian Degeneration: Occurs distal to axonal transection or severe crush.
    • Axon & myelin breakdown; phagocytosis by macrophages.
    • Central chromatolysis (cell body swelling, Nissl dispersion).
    • Proximal stump attempts regeneration (axonal sprouting).
  • Segmental Demyelination: Myelin loss with axon preservation.
    • Caused by Schwann cell dysfunction/damage (e.g., Guillain-Barré Syndrome, diphtheria toxin).
    • Results in ↓ conduction velocity; remyelination is possible.
  • Axonal Degeneration (Dying-back Neuropathy): Distal parts of axon degenerate first, progressing proximally.
    • Often due to metabolic derangements or toxic exposures.

⭐ Sunderland Classification (Grades I-V) is crucial for categorizing nerve injury severity, directly impacting prognosis and guiding management. Grade I (neurapraxia) involves temporary conduction block with full recovery.

Peripheral Nerve Disorders: Inflammatory - Immune System Mayhem

• Guillain-Barré Syndrome (GBS)
  • Acute inflammatory demyelinating polyradiculoneuropathy (AIDP).
  • Rapidly progressive, ascending symmetrical weakness/paralysis; often post-infectious (e.g., Campylobacter jejuni due to molecular mimicry).
  • CSF: ↑ Protein (albuminocytologic dissociation), normal cells after 1st week.
  • Variant: Miller Fisher Syndrome (ophthalmoplegia, ataxia, areflexia).
  • Treatment: IVIg, plasmapheresis. Steroids NOT effective.
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
  • Chronic (>8 weeks), progressive or relapsing-remitting sensorimotor neuropathy.
  • Symmetrical proximal & distal weakness, sensory loss.
  • Nerve biopsy:

Peripheral Nerve Disorders: Metabolic & Hereditary - Sweet & Inherited Woes

• Diabetic Neuropathy: Most common metabolic neuropathy.

  • Pathogenesis: Advanced glycation end-products (AGEs), sorbitol accumulation, oxidative stress, microangiopathy.
  • Patterns:
    • Distal Symmetrical Polyneuropathy (DSPN): "Stocking-glove" sensory loss (most common).
    • Autonomic Neuropathy: Gastroparesis, orthostatic hypotension.
    • Mononeuropathies: Cranial nerves (CN III, VI), focal limb.
  • Morphology: Axonal degeneration, segmental demyelination, endoneurial arteriolar hyalinization.

• Hereditary Sensory & Motor Neuropathies (HSMN) / Charcot-Marie-Tooth (CMT):

  • CMT1 (AD): Demyelinating. PMP22 gene duplication (1A) most common.
    • Features: ↓ Nerve Conduction Velocity (NCV), palpable nerves, pes cavus, "stork leg" deformity.
    • Morphology: "Onion bulb" formations (repetitive demyelination & remyelination).
  • CMT2 (AD): Axonal. Normal/mildly ↓ NCV. MFN2 mutations common.
  • CMTX (X-linked): Demyelinating. GJB1 (connexin-32) mutations.
  • Hereditary Neuropathy with liability to Pressure Palsies (HNPP): PMP22 deletion. Recurrent focal neuropathies. Tomacula ("sausage-like" myelin thickenings).

⭐ CMT1A, due to PMP22 gene duplication, is the most common inherited neuropathy, characterized by hypertrophic "onion bulb" Schwann cell changes visible on biopsy.

Peripheral Nerve Disorders: Other Key Types - Traps, Toxins & Bugs

• Entrapment Neuropathies (Traps):
  • Carpal Tunnel Syndrome (CTS): Median nerve at wrist; Phalen's, Tinel's signs.
  • Saturday Night Palsy: Radial nerve compression (spiral groove); wrist drop.
  • Meralgia Paresthetica: Lateral femoral cutaneous nerve under inguinal ligament.
  • Tarsal Tunnel Syndrome: Tibial nerve compression at ankle.
• Toxic Neuropathies:
  • Lead: Predominantly motor neuropathy; wrist drop, foot drop.
  • Arsenic: Painful sensorimotor neuropathy; Mees' lines on nails.
  • Alcohol: Chronic use; axonal degeneration, painful sensory > motor.
  • Drugs: Isoniazid (give B6), Vincristine, Amiodarone.
• Infectious Neuropathies (Bugs):
  • Leprosy (Hansen's Disease): M. leprae; affects cool areas, palpable thickened nerves, sensory loss.

    ⭐ Leprosy is a major global cause of peripheral neuropathy, with characteristic anaesthetic skin patches and thickened nerves.

  • Diphtheria: C. diphtheriae exotoxin; bulbar palsy, polyneuropathy.
  • Lyme Disease: B. burgdorferi; facial nerve palsy (often bilateral).

High‑Yield Points - ⚡ Biggest Takeaways

• Guillain-Barré syndrome: Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), ascending paralysis, albumino-cytological dissociation in CSF.
• Charcot-Marie-Tooth disease (CMT1A): PMP22 duplication, hereditary demyelinating neuropathy, pes cavus, onion bulbs.
• Diabetic neuropathy: Most common; distal symmetric polyneuropathy ("stocking-glove"), axonal degeneration and demyelination.
• Leprosy: M. leprae infects Schwann cells; Tuberculoid (localized) vs. Lepromatous (widespread anesthesia).
• Wallerian degeneration: Anterograde axonal degeneration distal to injury; forms myelin ovoids.
• Lead neuropathy: Predominantly motor neuropathy, causing wrist drop and foot drop.