What are the typical symptoms and treatment options for large fibre neuropathy?

Large Fiber Neuropathy: Symptoms and Treatment Options

Large fiber neuropathy primarily presents with impaired proprioception, vibration sense, and deep tendon reflexes, and should be treated with duloxetine or pregabalin as first-line pharmacological therapy.

Clinical Presentation

Characteristic Symptoms

• Sensory symptoms:

  • Numbness in a "glove and stocking" distribution
  • Impaired proprioception (position sense)
  • Decreased vibration sensation
  • Paresthesia (tingling, pins and needles)
  • Suppression or reduction of deep tendon reflexes 1
  • Sensory ataxia and difficulty with balance

• Motor involvement:

  • Less common than sensory symptoms
  • May include distal weakness when present
  • Trembling and difficulty maintaining posture 1
  • Progressive ataxia in advanced cases

Diagnostic Assessment

• Clinical tests for large fiber function:

  • Vibration perception using 128-Hz tuning fork
  • 10-g monofilament testing (protective sensation) 1
  • Assessment of deep tendon reflexes
  • Proprioception testing

• Electrophysiological findings:

  • Low amplitude of sensory action potentials
  • Length-dependent, sensory, axonal polyneuropathy 1
  • Nerve conduction studies may show abnormalities in ≥2 nerves 2

Etiology and Risk Factors

Common causes of large fiber neuropathy include:

• Metabolic disorders:

  • Diabetes mellitus (most common)
  • Hypothyroidism
  • Vitamin B12 deficiency

• Toxic exposures:

  • Chemotherapeutic agents (platinum compounds, taxanes, vinca alkaloids) 1
  • Alcohol abuse
  • Arsenic exposure 3

• Immune-mediated conditions:

  • Systemic sclerosis 2
  • Monoclonal gammopathy
  • Paraneoplastic syndromes

• Other causes:

  • Renal insufficiency
  • HIV infection
  • Amyloidosis 4
  • Idiopathic (no identifiable cause)

Treatment Approach

First-Line Pharmacological Therapy

1. Pregabalin:

   • Starting dose: Low dose initially, titrated upward
   • Efficacy: Effective for neuropathic pain in diabetic peripheral neuropathy 5
   • Common side effects: Dizziness (21%), somnolence (12%), peripheral edema (9%) 5
   • Caution: May cause weight gain, cognitive effects

2. Duloxetine:

   • Dosing: 30 mg/day for one week, then 60 mg/day 4
   • Evidence level: Level I, Grade B for neuropathic pain 4
   • Side effects: Less sedating than pregabalin or gabapentin

3. Gabapentin:

   • Alternative to pregabalin with similar mechanism
   • Requires more frequent dosing than pregabalin

Second-Line Options

• Venlafaxine: 50 mg initially, followed by 37.5 mg twice daily 4
• Tricyclic antidepressants: Effective but higher side effect profile, particularly in elderly patients

Non-Pharmacological Approaches

• Exercise therapy: Improves muscular strength and sensorimotor functions (Level II, Grade C evidence) 4
• Protective measures: Prevention of injuries to areas with decreased sensation
• Glycemic control: Critical for diabetic neuropathy to prevent progression 1

Monitoring and Follow-Up

• Regular assessment of neuropathic symptoms using standardized scales
• Monitoring for medication side effects, particularly dizziness and somnolence with pregabalin
• Evaluation of response to therapy and adjustment as needed
• Annual 10-g monofilament testing in diabetic patients to identify feet at risk for ulceration 1

Prognosis

Large fiber neuropathy typically follows a slowly progressive course. The primary goals of treatment are to:

• Manage symptoms, particularly neuropathic pain
• Prevent complications such as falls and injuries
• Maintain functional independence
• Address underlying causes when possible

Early recognition and treatment of large fiber neuropathy is essential to improve quality of life and prevent complications associated with sensory loss and impaired proprioception.