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

Tests:

• 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

Summary