Introduction

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a progressive polyneuropathy with an estimated prevalence of 2.81 per 100,000. The typical clinical features involve distal and proximal weakness with sensory deficits developing over at least 8 weeks, but pure motor and pure sensory variants also exist. The underlying cause is not fully understood, but involves a deranged immune response causing peripheral nerve myelin damage and CIDP is thus classed as an autoimmune disorder. Although the majority of patients with CIDP experience a partial or total response to one or a combination of available treatments, some patients’ symptoms do not resolve.

Epidemiology

  • Incidence: 1.60 cases per 100,000 person-years
  • Peak incidence: 50-60 years
  • Sex ratio: 1:1
Condition Relative
incidence
Guillain-Barre syndrome1.25
Chronic inflammatory demyelinating polyneuropathy1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

A proposed auto-antigen that activates inflammatory T cells is thought to originate CIDP, although no direct causal factors have been identified.

  • The condition is between 1.5 and 4 times more common in med than in women.
  • The incidence of CIDP increases with increasing age.
  • The prevalence rate is 2.81 per 100,000, and no geographical variance in prevalence or incidence of CIDP has been found.

Pathophysiology

The proposal that CIDP is an autoimmune condition is supported by the clinical response to drugs that target the immune system.

  • Although not yet fully defined, it is thought that it results from cell-mediated and humoural mechanisms. Inflammatory CD4 and CD8 T cells and autoantibodies to myelin proteins are thought to be key mediators of the attack on peripheral nerve tissue.

  • A key step is the breakdown of the blood-nerve barrier allowing attack on the endoneurium.

  • The resulting inflammatory lesions affecting peripheral myelin in combination with proposed auto-antibody binding to nodes of Ranvier cause the electrophysiological deficits observed and the clinical symptoms.

Clinical features

No definitive clinical criteria have been described, and diagnosis is based on the constellation of typical clinical signs and electrophysiological test results. Furthermore, the variance in clinical pattern makes diagnosis difficult: 50% of patients present with typical CIDP (motor and sensory symptoms), whilst 5-35% have sensory-predominant CIDP, and 7-10% present with motor-dominant CIDP.

  • The European Federation of Neurological Societies describe typical CIDP as a ‘chronically progressive, step-wise, or recurrent symmetrical proximal and distal weakness and sensory dysfunction of all extremities, developing over at least 2 months (cranial nerves may be affected), and absent or reduced tendon reflexes in all extremities.’

This is accompanied by supportive electrodiagnostic criteria for typical CIDP which include:
  • More than 50% prolongation of motor distal latency above upper limit of normal (ULN) in 2 nerves
  • More than 30% reduction of motor conduction velocity below the lower limit of normal (LLN) in 2 nerves

Clinical features of atypical CIDP include:
  • Predominantly distal weakness; distal acquired demyelinating symmetrical neuropathy
  • Pure motor or sensory presentations
  • Asymmetrical presentation (Lewis-Sumner syndrome)
  • Focal presentation (e.g., involvement of the brachial or lumbosacral plexus or 1 or more upper-extremity or lower-extremity peripheral nerves).

Investigations

The European Federation of Neurological Societies recommends the following primary tests to diagnose CIDP:
  • Sensory and motor nerve conduction studies, performed bilaterally
    • Electrodiagnostic test results form a key part of diagnostic criteria
  • Lumbar puncture, including cytology and protein analysis
    • Elevated CSF protein with leukocyte count <10/mm3 supports the diagnosis of CIDP
  • MR imaging
    • Gadolinium enhancement and/or hypertrophy of the cauda equina, lumbosacral or cervical nerve roots, or the brachial or lumbosacral plexuses supports CIDP diagnosis.
  • Nerve biopsy
    • Evidence of demyelination and/or remyelination by electron microscopy of nerve biopsy supports CIDP diagnosis

Recommended adjuvant tests to rule out differential diagnoses:
  • Serum and urine paraprotein detection by immunofixation
  • Blood tests:
    • Full blood count
    • U&Es
    • Fasting blood glucose
    • Liver function tests
    • Antinuclear factor
    • HIV test
    • Thyroid function tests
    • Borrelia burgdorferi (Lyme disease) serology
    • Diphtheria toxin testing
  • Investigation of possible hereditary neuropathy cause:
    • Examination of parents and siblings
    • Appropriate gene testing (especially PMP22 duplication and connexin 32 mutations)

Differential diagnosis

There are many causes of peripheral neuropathy including complications of common conditions, as well as rare diseases.

  • Guillain-Barre Syndrome
    • Typical onset is less that 4 weeks, often with clinical history of infection prior to onset of symptoms.
    • More common cranial nerve involvement and respiratory failure than CIDP.
  • Diabetic distal symmetric polyneuropathy (DSPN)
    • Patients with diabetes can develop distal polyneuropathy similar to CIDP. Features include early pain and dysaesthesia owing to small-fibre involvement, and sensory loss greater than motor loss.
    • Although the clinical features are very similar, the electrophysiological deficits seen in DSPN are less severe than those in CIDP and this allows for reliable differentiation of the two conditions.
  • Thyroid disease
    • Hyper- and hypothyroidism may present with distal weakness and sensory loss, but should improve with normalisation thyroid status. Thyroid test and clinical examination for diagnosis.
  • Neuropathy associated with infections
    • Lyme disease, HIV, hepatitis, diphtheria may have neuropathy as part of their presenting features. Serology to rule these out.
  • Drug-induced neuropathy
    • Many drugs can cause peripheral neuropathy. A thorough clinical history and timeline of recent medications will help in discerning if any are responsible for the presenting symptoms.
    • Some implicated drugs include statins, amiodarone, chemotherapy drugs, isoniazide, metronidazole, immunomodulating drugs and nucleoside reverse transcriptase inhibitors (NRTIs)
  • Monoclonal gammopathy of undetermined significance (MGUS)
    • A pre-malignant haematological disorder which clinically mimics CIDP, but high levels of monoclonal proteins differentiate the condition.
  • POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinology, Monoclonal gammopathy and Skin changes)
    • A rare paraneoplastic disorder presenting with a range of systemic symptoms with polyneuropathy.
    • Major differentiating features from CIDP include presence of sclerotic lesions on CT and high levels of serum vascular endothelial growth factor (VEGF).

Management

Guidelines suggest that patients with confirmed CIDP whose symptoms are mild or do not interfere with activities of daily living may be observed without treatment initially.

In those requiring treatment:
  • Corticosteroids
    • 60mg OD oral prednisolone for 6 weeks recommended as first line
  • Plasma exchange
    • Effective for quick relief of symptoms, but requires combining with other treatments to demonstrate longer term benefits.
  • Intravenous immunoglobulin (IVIG)
    • A Cochrane systematic review concluded that IVIG improves symptoms for at least 2-6 weeks compared with placebo, with one trial demonstrating benefits up to 48 weeks.
  • Analgesia for neuropathic pain
    • Some patients may require analgesia e.g. gabapentin, pregabalin for neuropathic pain if this contributes a significant part of their symptoms.

Prognosis

Prognosis varies greatly, and there are no currently available biomarkers or other tests to aid in prognostication.
  • Approximately 15% of patients with CIDP fail to respond to any of the current available treatments.
  • However, most patients see partial or complete resolution of symptoms with single or combination therapy which may need to be continued for a period of months or years.
  • A 5-year follow up of 38 cases of CIDP found that 25% of patients were in remission and 61% had partial remission.