Chronic inflammatory demyelinating polyneuropathy

Background

• Prevalence of 1 to 2 per 100,000 adults
• Autoimmune condition leading to cellular and humoral immune response to proteins on myelin sheath likely due to molecular mimicry from infectious process
  • Has been associated with melanoma
• Acute variant is Guillain-Barre syndrome
  • GBS is self limited whereas CIPD is progressive for more than two months

Clinical Features

• Symmetrical proximal and distal muscle weakness that is progressive for GREATER than two months
  • Muscle weakness more predominant feature than sensory symptoms
• Reduced or absent deep tendon reflexes in upper and lower extremities
• Elevated CSF protein without pleocytosis
• Electrodiagnostic evidence of a demyelinating neuropathy
• Segmental nerve demyelination on nerve biopsies
• Can be relapsing or chronic and progressive

Differential Diagnosis

Weakness

• Neuromuscular weakness
  • Upper motor neuron:
    • CVA
    • Hemorrhagic stroke
    • Multiple sclerosis
    • Amyotrophic Lateral Sclerosis (ALS) (upper and lower motor neuron)
  • Lower motor neuron:
    • Spinal and bulbar muscular atrophy (Kennedy's syndrome)
  • Spinal cord disease:
    • Infection (Epidural abscess)
    • Infarction/ischemia
    • Trauma (Spinal Cord Syndromes)
    • Inflammation (Transverse Myelitis)
      • Acute flaccid myelitis
    • Degenerative (Spinal muscular atrophy)
    • Tumor
  • Peripheral nerve disease:
    • Guillain-Barre syndrome
    • Toxins (Ciguatera)
    • Tick paralysis
    • Diabetic peripheral neuropathy
  • Neuromuscular junction disease:
    • Myasthenia gravis crisis
    • Botulism
    • Organophosphate toxicity
    • Lambert-Eaton myasthenic syndrome
  • Muscle disease:
    • Rhabdomyolysis
    • Dermatomyositis
    • Polymyositis
    • Alcoholic myopathy
• Non-neuromuscular weakness
  • Can't miss diagnoses:
    • ACS
    • Arrhythmia/Syncope
    • Severe infection/Sepsis
    • Hypoglycemia
    • Periodic paralysis (electrolyte disturbance, K, Mg, Ca)
      • Hypokalemic periodic paralysis
      • Thyrotoxic periodic paralysis
    • Respiratory failure
  • Emergent Diagnoses:
    • Symptomatic Anemia
    • Severe dehydration
    • Hypothyroidism
    • Polypharmacy
    • Malignancy
    • Aortic disease - occlusion, stenosis, dissection
  • Other causes of weakness and paralysis
    • Acute intermittent porphyria (ascending weakness)

Evaluation

• Clinical diagnosis with electrophysiological studies
• 3 separate criteria can be used to diagnose CIPD
  • Only the American Academy of Neurology requires a lumbar puncture and nerve-biopsy specimen
• Closest differential is Guillain-Barre syndrome
  • The onset of GBS is usually easily identified, while the precise onset of CIDP is typically less clear
  • Antecedent events are more frequent with GBS than in CIDP
  • ~70% of GBS cases are preceded by an infectious illness, vaccination, or surgery by three to four weeks prior to the onset of clinical symptoms.
  • By contrast, most studies have found an antecedent event prior to CIDP in no more than 30% of patients.
  • Prominent sensory signs (ie, sensory ataxia and impaired vibration and pinprick sensation) favor CIDP
  • The need for ventilator support favors GBS
  • Autonomic dysfunction (tachycardia, urinary retention) much more common in GBS than CIPD
  • Progression or relapse beyond eight weeks from onset suggests acute-onset CIDP rather than GBS
  • May be difficult to distinguish initially between CIPD and GBS if recognized early but relapsing-remitting course over months with identify CIPD

Workup

• Lumbar puncture can be performed inpatient
  • Will show elevated protein without pleocytosis
• Nerve biopsy will show demyelination and demyelination often with signs of inflammation
  • Often unnecessary and of low yield due to proximal nerve involvement, but still performed if diagnosis uncertain
• MRI may show gadolinium enhancement and enlargement of proximal nerves or roots
• Electrophysiological diagnostic procedures with show evidence of demyelination

'	American Academy of Neurology	Saperstein Criteria	Inflammatory Neuropathy Cause and Treatment Group
Presentation	Motor and sensory dysfunction in > 1 limb	Major: symetric proximal and distal weakness; Minor: Exclusive distal weakness or sensory loss	Progressive or relapsing motor and sensory dysfunction of > 1 limb
Time course in months	≥ 2	≥ 2	> 2
Reflexes	Reduced or absent	Reduced or absent	Reduced or absent
Electrodiagnostic Criteria	Any 3 of the following 4 criteria: partial conduction block of ≥1 motor nerve, reduced conduction velocity of ≥2 motor nerves, prolonged distal latency of ≥2 motor nerves, or prolonged F-wave latencies of ≥2 motor nerves or the absence of F waves	2 of the 4 AAN electrodiagnostic criteria	Partial conduction block of ≥2 motor nerves and abnormal conduction velocity or distal latency or F-wave latency in 1 other nerve; or, in the absence of partial conduction block, abnormal conduction velocity, distal latency, or F-wave latency in 3 motor nerves; or electrodiagnostic abnormalities indicating demyelination in 2 nerves and histologic evidence of demyelination
CSF	WBC < 10/mm^3, negative VDRL, elevated protein	Protein > 45mg/dL; WBC <10/mm^3	Recommended but not mandatory
Biopsy	Demylelination and remyelination	Demyelination	Not mandatory

Management

• Requires neurology consult
• Therapy is tailored to each patient, no difference in efficacy between the three treatment options
  • IVIG
  • Plasma exchange
  • Corticosteroids
  • May be placed on azathioprine, cyclophosphamide, or cyclosporine to prevent relapse

Disposition

• Often require admission for physical therapy, occupation therapy, treatment, and possible placement for rehab if unable to perform ADLs

References

• Köller, H., Kieseier, B. C., Jander, S., & Hartung, H.-P. (2005). Chronic inflammatory demyelinating polyneuropathy. The New England Journal of Medicine, 352(13), 1343–1356.