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Neuropathy, Peripheral

BASICS

Description

  • Disorder of PNS with diverse etiologies (diabetes, toxins, alcohol, nutrition, immune, injury, genetics, idiopathic).
  • Motor neuropathy: Muscle atrophy, weakness, cramps, fasciculations.
  • Sensory neuropathy: Loss of sensation, balance, or pain/tingling; large fiber: touch/vibration; small fiber: pin/temperature.
  • Autonomic neuropathy: Cardiovascular, GI, or sudomotor symptoms.
  • Types: Mononeuropathies, multifocal, polyneuropathies.

EPIDEMIOLOGY

  • Most common cause: Diabetic peripheral neuropathy (DPN) – 50% of diabetics develop PN.
  • Chemotherapy-induced PN: ~30% at 6 months post-chemotherapy.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Acquired: Diabetes (distal sensory polyneuropathy in 75%), vascular, infectious (HIV, hepatitis C, Lyme, VZV), trauma, autoimmune, metabolic (renal failure, B12 deficiency), iatrogenic (chemo, meds, toxins, alcohol), neoplastic/paraneoplastic.
  • Hereditary: ~50% of undiagnosed PN.
  • Patterns: Demyelinating (GBS, CIDP), axonal (DPN), small-fiber, large-fiber.

RISK FACTORS

  • Diabetes, alcoholism
  • Other: Chemotherapy, toxins, nutritional deficiency

GENERAL PREVENTION

  • Control of underlying diseases: Glycemic control, correct nutritional deficiencies, avoid neurotoxins

DIAGNOSIS

History

  • Symptoms: Numbness, tingling, burning, pain, “wrapped” sensation, unsteady gait
  • Motor: Foot drop, weak grip (distal > proximal)
  • Autonomic: Orthostatic dizziness, sweating, constipation, ED, voiding difficulty
  • Pattern: Acute (infection, toxin, trauma, GBS), subacute (metabolic, neoplastic), chronic (CIDP, hereditary, idiopathic)
  • Progression: Stable, progressive, relapsing, monophasic

Physical Exam

  • Pattern: Distal symmetric (“stocking-glove”) common; small-fiber (allodynia, pin/thermal loss), large-fiber (vibration, proprio loss, ataxia, Romberg), muscle atrophy, foot deformity (hereditary), DTRs reduced/absent.
  • Cranial nerves: May be involved in multifocal PN (GBS, Lyme, sarcoid)
  • ALERT: Hyperreflexia/spasticity → not isolated PN (suggests UMN lesion)

Differential Diagnosis

  • Mononeuropathy: Compression, trauma
  • Mononeuropathy multiplex: Plexopathy, polyradiculopathy

Diagnostic Tests

  • Labs: CBC, creatinine, HbA1C, B12 (methylmalonic acid), LFTs, SPEP, TSH
  • NCS/EMG: Gold standard for DPN; distinguishes axonal vs demyelinating, defines pattern/severity
  • Others: Autonomic testing, QST, epidermal skin biopsy (small fiber), rarely nerve biopsy (vasculitis, amyloid)
  • Neuroimaging: Only if CNS or focal findings

Interpretation

  • Demyelinating: Slow conduction, conduction block, increased latency (NCS)
  • Axonal: Low amplitude, preserved conduction velocity (NCS)
  • Small fiber: Reduced intraepidermal nerve fiber density (skin biopsy)

TREATMENT

General Measures

  • Foot care, monitor for skin breakdown
  • Treat underlying causes

Medication

  • First Line:
  • Anticonvulsants: Gabapentin (PHN), pregabalin (DPN, PHN), oxcarbazepine (DPN), carbamazepine (trigeminal neuralgia)
  • SNRI: Duloxetine, venlafaxine (DPN)
  • TCAs: Amitriptyline, nortriptyline
  • Topicals: Lidocaine 5% patch, capsaicin 8% patch
  • Supplements: α-lipoic acid, acetyl-L-carnitine
  • Second Line: Mexiletine
  • Third Line: Tapentadol (DPN)

Additional Therapies

  • Combination therapy (e.g., gabapentin + TCA/SNRI/tramadol)
  • Botulinum toxin (subcut, intradermal, or nerve) for trigeminal neuralgia, DPN, CRPS
  • Immunotherapies: IVIG (GBS, CIDP, MMN), plasma exchange (GBS, CIDP), corticosteroids (CIDP), other immunosuppressants
  • Autonomic symptom treatment: Compression stockings, midodrine, fludrocortisone, pyridostigmine (immune dysautonomia)
  • Physical therapy: For strength, balance

Surgery/Procedures

  • Decompressive surgery for entrapment (e.g., carpal tunnel)

CAM

  • TENS, acupuncture, meditation, dietary supplements (G-agmatine, methylcobalamin, inositol)

ALERT

  • Vitamin B6: Only supplement for proven deficiency—can cause neurotoxicity

ONGOING CARE

  • Monitor: Muscle strength, function, foot care
  • Avoid: Flu vaccine in 1st year post-GBS
  • Diet: Address B12/thiamine deficiency, heavy metal exposure, high-carb diet in diabetics

PROGNOSIS

  • Late-onset idiopathic axonal PN: Indolent
  • GBS: 80% near-complete/good recovery
  • CIDP: 80% respond, but relapsing possible

COMPLICATIONS

  • Increased risk of falls

ICD-10 CODES

  • G62.9 Polyneuropathy, unspecified
  • G60.9 Hereditary and idiopathic neuropathy, unspecified
  • G60.8 Other hereditary and idiopathic neuropathies

Clinical Pearls

  • Diagnosis: history, exam, labs, NCS/EMG, skin/ANS testing
  • Early-onset, family history, or foot deformity: consider hereditary PN
  • GBS: Monophasic, up to 4 weeks; CIDP: >8 weeks, often progressive/relapsing if untreated