CBL: Peripheral Neuropathy

A 67-year-old with progressive bilateral foot numbness and burning pain.

Topic: Peripheral Neuropathy Level: Resident

Vignette

Learning Objectives

  • Recognize symmetric, length-dependent symptoms (stocking–glove distribution).
  • Understand that hyperglycemia/diabetes is the most common cause.
  • Appreciate that many cases remain idiopathic despite 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) below the ankles.
    • Burning pain with allodynia (e.g., bed sheets).
    • Daily occurrence, no activity relation.
    • No bowel/bladder dysfunction; no back pain or trauma.
  • Past Medical History: Mild diabetes mellitus; alcoholism (sober ×22 years).
  • Medications: Metformin.
  • 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 in arms; distal leg atrophy (tibialis anterior, EDB) with mild weakness; hammer toes present.
  • Reflexes: Biceps normal; patellar reduced; Achilles absent; plantar responses flexor.
  • Sensation: Hands normal; feet with impaired vibration, proprioception, and pinprick below ankles to mid‑calf (stocking distribution).
  • Coordination/Gait: Heel–toe walk intact; heel–knee–shin and finger–nose normal; Romberg negative.
  • Summary: Symmetric, distal sensorimotor neuropathy with sensory loss, areflexia, distal weakness, and foot deformities.

Localization & Neuroanatomy

  • Peripheral neuropathy affects the longest fibers first (distal axonopathy).
  • Hallmark: symmetric stocking–glove pattern with sensory, motor, and reflex abnormalities.
  • Distinguish from myelopathy/radiculopathy: PN tends to be bilateral, symmetric, and distal-first; spinal cord/radicular processes are often asymmetric/segmental or show UMN signs.

Differential Diagnosis

Common (U.S.)

  • Diabetes mellitus / hyperglycemia (leading cause)
  • Alcohol use disorder
  • Vitamin B12 deficiency
  • Idiopathic
  • Chemotherapy / toxin-related
  • Hereditary neuropathies
  • Metabolic/endocrine: uremia, thyroid disease

Less common but important

  • Infectious: HIV, Lyme disease, syphilis
  • Paraneoplastic / monoclonal gammopathy (e.g., myeloma, lymphoma)
  • Inflammatory / autoimmune: GBS variants, vasculitic neuropathy
  • Toxic: heavy metals, organic solvents
  • Amyloid-related (AL, hereditary ATTR, or secondary): progressive, painful axonal polyneuropathy; often autonomic features

Diagnostic Approach

  • Bedside exam often sufficient to diagnose PN.
  • NCS/EMG when diagnosis is unclear or to distinguish PN from radiculopathy/myelopathy.
  • First-line labs: fasting glucose/HbA1c; vitamin B12; TSH; SPEP ± immunofixation; renal function; CBC.
  • Second-line (if unexplained): heavy metal screen, autoimmune serologies, genetic testing (if family history).

Treatment

  • Treat underlying cause: optimize glycemic control; replete B12; treat thyroid/uremia; remove toxins ± chelation; evaluate paraneoplastic/amyloid etiologies.
  • Symptom management: neuropathic pain agents (gabapentin, pregabalin, duloxetine, amitriptyline); refractory cases may consider interventional pain or SCS.
  • PT/OT for gait/hand function; preventive foot care.

Question 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

Question 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

Teaching Points

  • Length-dependent, symmetric symptoms (“stocking–glove”) with distal sensory loss and reduced/absent ankle reflexes strongly suggest distal symmetric polyneuropathy (DSP).
  • First-line labs that change management: fasting glucose/HbA1c, vitamin B12 (consider MMA if borderline), TSH, SPEP ± immunofixation, basic renal panel, and CBC.
  • Electrodiagnostics (NCS/EMG) help confirm neuropathy, characterize axonal vs demyelinating patterns, and distinguish from radiculopathy or myelopathy when the exam is equivocal.
  • Diabetes and prediabetes are the most common U.S. causes; optimize glycemic control to slow progression and reduce pain.
  • Neuropathic pain options with evidence: duloxetine, gabapentin/pregabalin, and tricyclics; set expectations—analgesia is partial and titration is key.
  • Screen for red flags (asymmetry, subacute progression, prominent motor deficits, systemic features) that warrant expanded testing (e.g., vasculitis, amyloid, immune-mediated).

References

  1. England JD, Gronseth GS, Franklin G, et al. Practice Parameter: Evaluation of distal symmetric polyneuropathy: Role of laboratory and genetic testing. Neurology. 2009;72(2):185–192.
  2. Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic neuropathy: A position statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136–154.
  3. Bril V, England JD, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Neurology. 2011;76(20):1758–1765.