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Case-Based Learning Module

Peripheral Neuropathy (PN)

Learning Objectives

By the end of this session, learners should be able to:

  1. Recognize that PN typically presents with symmetric symptoms, with the longest nerves affected first (“stocking–glove distribution”).
  2. Understand that hyperglycemia and diabetes mellitus are the most common causes.
  3. Appreciate that a significant proportion of PN cases remain idiopathic, despite thorough evaluation.

Case History

Patient: IP, a 67-year-old hotel manager.

Chief complaint: Progressive numbness in both feet for 10 months.

  • Symptoms:
    • Symmetric sensory loss, dorsal and plantar surfaces, below the ankles.
    • Burning pain worsened by light touch (allodynia, e.g., bed sheets).
    • Daily occurrence, no clear activity relation.
    • No bowel/bladder dysfunction, no back pain or trauma.
  • Past Medical History: Mild diabetes mellitus, alcoholism (sober x22 years).
  • Medications: Metformin (glucophage).
  • Family History: Father – diabetes, stroke; mother – essential tremor.
  • Social History: No current tobacco/alcohol; heavy past use.
  • Review of Systems: No fever, rash, joint pain, bowel/bladder dysfunction, or systemic illness.

Examination

  • Vitals: P 77, BP 130/81.
  • General: Pleasant, mildly obese, well-appearing.
  • Cranial Nerves: Intact.
  • Motor:
    • Normal strength arms.
    • Distal leg atrophy (tibialis anterior, EDB) with mild weakness.
    • Hammer toes noted.
  • Reflexes:
    • Biceps normal.
    • Patellar reduced.
    • Achilles absent.
    • Plantar response: flexor.
  • Sensation:
    • Hands: normal.
    • Feet: impaired vibration, proprioception, and pinprick below ankles to mid-calf (stocking distribution).
  • Coordination/Gait: Heel–toe walk intact. Heel–knee–shin, finger–nose normal. Romberg negative.

Summary of findings: Symmetric, distal sensorimotor neuropathy with sensory loss, areflexia, distal weakness, and foot deformities.

Localization & Neuroanatomy

  • PN affects peripheral nerves, beginning with the longest fibers (distal axonopathy).
  • Clinical hallmark: symmetric stocking–glove pattern with sensory, motor, and reflex abnormalities.
  • Distinguishing from spinal cord/radiculopathy:
    • PN is bilateral, symmetric, distal-first.
    • Myelopathy/radiculopathy often asymmetric, segmental, or associated with UMN signs.

Differential Diagnosis

Most common U.S. causes:

  • Diabetes mellitus / hyperglycemia (leading cause).
  • Alcoholism.
  • Vitamin B12 deficiency.
  • Idiopathic (no cause found after evaluation).
  • Chemotherapy/toxin-related.
  • Hereditary neuropathies.
  • Metabolic/endocrine: Uremia, thyroid disease.

Less common but important causes:

  • Infectious: HIV, Lyme disease, syphilis.
  • Paraneoplastic / monoclonal gammopathy (e.g., myeloma, lymphoma).
  • Inflammatory / autoimmune: Guillain–Barré variants, vasculitic neuropathy.
  • Toxic: Heavy metals, organic solvents.
  • Amyloid-related neuropathy:
    • Can occur with primary (AL) amyloidosis, hereditary transthyretin (ATTR) amyloidosis, or secondary systemic amyloidosis.
    • Typically causes a progressive, painful, axonal polyneuropathy, often with autonomic features (orthostasis, GI dysmotility, bladder dysfunction).
    • Should be suspected in otherwise unexplained progressive neuropathy, especially with family history of neuropathy or cardiac disease.

Diagnostic Approach

  • Bedside exam often sufficient to diagnose PN.
  • Nerve conduction studies / EMG: Helpful when diagnosis unclear, or to differentiate PN from radiculopathy/myelopathy.
  • Screening labs (first-line):
    • Fasting glucose/HbA1c
    • Vitamin B12
    • Thyroid function tests
    • Serum protein electrophoresis (SPEP ± immunofixation)
    • Renal function, CBC
  • Second-line (if unexplained): Heavy metal screen, autoimmune serologies, genetic testing (if family history).

Treatment

  • Treat underlying cause:
    • Diabetes → optimize glycemic control.
    • Vitamin B12 deficiency → supplementation.
    • Thyroid disease, uremia → treat primary disorder.
    • Toxin exposure → remove source ± chelation.
    • Paraneoplastic or amyloid-related → oncology/hematology evaluation.
  • Symptom management:
    • Neuropathic pain: gabapentin, pregabalin, duloxetine, amitriptyline.
    • Refractory cases: pain interventional approaches, spinal cord stimulation.
    • Physical/occupational therapy: gait training, hand function.
    • Preventive care: protective footwear, daily foot checks, injury avoidance.

Review Questions

  1. The history or exam of a case of peripheral neuropathy should include which of these features?
    a. Tingling, numbness, paresthesias
    b. Diminished sensation in multiple nerve territories (stocking distribution)
    c. Both A and B ✅
    d. Decreased reflexes
    e. Hyperglycemia
  2. To help diagnose the cause of PN, you should consider these screening tests:
    a. Fasting blood sugar
    b. Serum vitamin B12
    c. SPEP
    d. 24-hour urine heavy metal screen
    e. All of the above ✅
  3. Which of these best ranks the frequency of PN causes (most to least common)?
    a. Chemotherapy, alcoholism, diabetes, idiopathic, B12 deficiency
    b. Diabetes, B12 deficiency, chemotherapy, idiopathic, inflammatory
    c. B12 deficiency, diabetes, alcoholism, chemotherapy, idiopathic
    d. Diabetes, idiopathic, alcoholism, B12 deficiency, chemotherapy ✅
    e. Alcoholism, idiopathic, B12 deficiency, diabetes, chemotherapy