Peripheral Neuropathy Made Easy

Step 1: What system is involved – motor, sensory, autonomic or mixed?

a. Sensory involvement

  • Positive neuropathic sensory symptoms (PNSS) – suggest Acquired polyneuropathy
    • prickling, tingling, asleep like numbness
  • Pain – suggest Small fiber neuropathy due to toxic, metabolic, ischemic or idiopathic cause
    • electric shock, burning, freezing, tightness, throbbing, allodynia (discomfort or pain to apparently painless stimuli), hyperalgesia (exaggerated pain response)
    • often accompanied by reduced or absent sensation of pinprick or temperature
  • Negative neuropathic sensory symptoms – suggest acquired or inherited cause
    • loss of sensation, imbalance

Sensory examination:

1. Sensation: Begin distally at toes or fingertips – move proximally if abnormal

  • Vibration: 128 Hz tuning fork
  • Pinprick: Disposable safety pin
  • Light touch: Cotton swab
  • Temperature: Warming or cooling tuning fork’s prongs

2. Joint position sense: Ask patient to close eyes – then, move distal phalanx of toes or finger up or down by small increments and ask the patient to tell the direction of movement

3. Casual and tandem gait: for unsteadiness or ataxia

b. Motor involvement:

Often combined with sensory symptoms:

  • Motor symptoms > Sensory symptoms: Immune-mediated like AIDP (Gullian-Barre Syndrome), CIDP
  • Sensory symptoms > Motor symptoms: In many other polyneuropathies especially length-dependent neuropathies caused by metabolic or toxic disorders

c. Autonomic involvement:

Symptoms include – lightheadedness, syncope, diarrhea, constipation, postprandial bloating, early satiety, urinary complaints, erectile dysfunction, abnormal or absent sweating, dry mouth and eyes


  • Pre-syncopal symptoms: Bedside orthostatics or tilt-table testing
  • Early satiety or postpradnial bloating: Gastric emptying test

Commonly acquired polyneuropathies with autonomic invovlement:

  1. Diabetic neuropathy
  2. Amyloid neuropathy
  3. AIDP (Guillain-Barre syndrome)
  4. Paraneoplastic neuropathy (Small cell lung cancer)
  5. Sjogren’s syndrome associated neuropathy
  6. HIV
  7. Vincristine
  8. Porphyria
  9. Pandysautonomia

Step 2: Where – distribution of nerve involvement ?

a. Distal (length-dependent) and symmetric: Metabolic, toxic, inherited or idiopathic

b. Not length-dependent and asymmetric: immune-mediated or infectious

  • Motor neuropathies (ALS)
  • Sensory neuropathies (Paraneoplastic syndrome)
  • Demyelinating disease (AIDP, CIDP)
  • Mononeuritis complex (Vasculitis)

Step 3: When – onset and course ?

  • Acute (<1 month) and Subacute (1-2 months): Immune-mediated or Infectious process
  • Chronic (>2 month): Inherited, metabolic, toxic or idiopathic

Step 4: What setting – review of comorbidities and medications?

Common causes of acquired polyneuropathies:

  • Diabetes mellitus
  • Chronic kidney disease
  • Alcohol dependence
  • Vitamin B1 and B12 deficiency

Positive family history of: high arched foot or hammer toes – Charcot Marie Tooth (CMT) Disease i.e. Hereditary Sensory and Motor Neuropathy

Step 5: Electrodiagnostic test

  • Define – distribution and extent of neuropathy
  • Differentiate – axonal and demyelinating or mixed process
  • Limitation – normal in small fibre neuropathy (skin biopsy is helpful in these cases)

Step 6: Blood tests

a. For distal symmetric neuropathy:

  1. Fasting glucose or 2 hour oral glucose tolerance test: Diabetes and impaired glucose tolerance (pre-diabetes)
  2. Serum protein electrophoresis: Paraproteinemias
    • Demyelinating: MGUS i.e. Monoclonal Gammopathy of Undetermined Significance, Waldenstorm’s macroglobulinemia, Osteosclerotic myeloma
    • Axonal: Amyloidosis, Mixed cryoglobulinemia
  3. RFT, Electrolytes, Calcium, Phosphorous: Uremic neuropathy
  4. Hepatitis C titer: usually asymmetric and as mononeuritis complex, but sometimes as distal and symmetric
  5. Serum B12 level

b. Specific:

  1. Metabolic/toxic:
    • Elevated MCV: alcoholism, vitamin B12 deficiency
    • Thiamine deficiency: alcoholism, bariatric surgery
    • Urine heavy metals: Heavy metal intoxication
    • Thyroid function tests: Hypothyroid neuropathy (rare)
  2. Inflammatory:
    • CBC: mononeuritis complex
    • Markers or vasculitis or systemic inflammation (ESR, ANCA, RF, ANA, cryoglobulins): Vasculitis, Cryoglobulinemic neuropathy (Hepatitis C)
    • CSF: protein elevation in AIDP and CIDP
  3. Neoplastic/Paraneoplastic:
    • Paraneoplastic serology: especially subacute and severe neuropathy in smokers
    • Chest X-ray and other imaging for cancers: Small cell lung cancer and other malignancies
    • CSF cytology: carcinomatous or lymphomatous polyradiculopathy
  4. Infections:
    • CSF: pleocytosis
    • Lyme titres (serum, CSF): Lyme neuroborreliosis
    • HIV testing: HIV associated neuropathy
    • Hepatitis C (Cryoglobulin testing): Hepatitis C – mixed cryoglobulinemia


peripheral neuropathy


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