Peripheral Neuropathies

MRCP PACES Peripheral Neuropathies

Approach

What systems are involved? Motor, sensory, autonomic or combinations?
- Pure motor
  - Motor neurone disease (LMN variant)
  - Multifocal motor neuropathy
  - Spinal muscular atrophy
  - Kennedy’s disease
  - Motor-predominant CIDP
  - Lead neuropathy
  - Acute porphyric neuropathy
- Sensory predominant – see (3) below
- Motor and sensory
  - AIDP
  - CIDP
  - Vasculitic neuropathy
- Autonomic predominant
  - Diabetic neuropathy
  - Amyloidosis
  - AIDP
What is the distribution of weakness? Distal, proximal, generalized, asymmetrical or symmetrical?
- Distal symmetrical weakness in axonal (length-dependent) neuropathy
  - Infections
    - Human immunodeficiency virus
    - Lyme disease
    - Leprosy
    - Herpes zoster
    - Hepatitis C
  - Diabetic neuropathy
  - Alcoholic neuropathy
  - Drug-induced neuropathy
    - Antibiotics: isoniazid, nitrofurantoin, Ethambutol, metronidazole
    - Chemotherapy: vincristine, cisplatin, etoposide, docetaxel
    - Antivirals: zidovudine, stavudine
    - Immunosuppressants: TNF-α antagonists, tacrolimus
    - Pyridoxine toxicity (doses exceeding 50mg/day)
  - Inherited neuropathies
    - Charcot-Marie-Tooth
    - Hereditary neuropathy with susceptibility to pressure palsy
  - B12 deficiency
- Proximal and distal weakness
  - CIDP
  - AIDP
  - Guillain-Barré syndrome
- Asymmetrical
  - Radiculopathy
  - Plexopathy
  - Mononeuritis multiplex
  - Tumours of nerve sheath or sarcomas causing compression
  - Compression neuropathy
  - Diabetic amyotrophy
  - Leprosy
What modality of sensation is involved? Pain and temperature or proprioceptive loss?
- Pain – caused by small fiber involvement
  - Diabetes
  - Amyloidosis
  - Fabry disease
  - Inflammatory disorders
    - Vasculitic neuropathy (usually with mononeuritis multiplex)
    - AIDP
- Proprioceptive loss
  - Asymmetrical – sensory ganglionopathy
    - Paraneoplastic, usually associated with anti-Hu antibodies
    - Sjögren’s syndrome
  - Symmetrical
    - AIDP
    - IgM paraprotein demyelinating neuropathy
    - Degeneration of dorsal column – not peripheral neuropathy
      - B12 deficiency
      - Tabes dorsalis

Is there any evidence of upper motor neurone involvement?
- Motor neurone disease
- B12 deficiency
- Friedreich’s ataxia
- Taboparesis
- Cervical myelopathy
- Two pathologies: peripheral neuropathy with UMN lesion, e.g. stroke
What is the temporal evolution? Acute, sub-acute, chronic (wasting)
Is there any evidence for a hereditary neuropathy? Family history, skeletal deformities, pressure palsies

Relevant physical signs

Inspection
- Wasting
- Fasciculations
- Diabetic dermopathy
- Vasculitic rashes (purpura, livedo reticularis)
- Hyperpigmentation (POEMS syndrome)
- Oral ulcers (Behcet’s disease, HIV, SLE)
- Hair loss over the extremities (lead poisoning, length-dependent neuropathies)
- Deformities – pes cavus (CMT), Charcot foot
Limbs
- Tone: flaccid
- Reflexes: diminished or absent
- Power: distribution of weakness
- Sensation
  - Which sensory modality is affected
  - Demonstrate length-dependency (polyneuropathy)
  - Pattern of innervation in mononeuritis
  - Dermatomes involved if radiculopathy or plexopathy
- Coordination normal unless too weak to test
Ask for:
- Vitals and postural blood pressure (dysautonomia)
- Examine the cranial nerves

Investigations

Nerve conduction studies to confirm diagnosis
Consider magnetic resonance imaging of the spine in radiculopathies or plexopathies
Fasting blood glucose, HbA1c measurement
Vitamin B12 with methalmalonic acid and homocysteine measurement
Consider evaluation for connective tissue disease if history and clinical findings correlate
- ANA
- Anti-dsDNA
- ANCA
- Cryoglobulins secondary to hepatitis C
In pure motor neuropathies, consider anti-GM1 ganglioside antibodies for MMN
Consider age-appropriate malignancy screening and anti-Hu antibodies for paraneoplastic syndrome
If autonomic neuropathy dominant: consider rectal fat pad biopsy for amyloidosis
Consider genetic testing if not previously done in the family

Management