Chronic inflammatory demyelinating polyneuropathy
- Incidence: 1.60 cases per 100,000 person-years
- Peak incidence: 50-60 years
- Sex ratio: 1:1
|Chronic inflammatory demyelinating polyneuropathy||1|
- 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.
- 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.
- 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).
- 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
- 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)
- 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).
In those requiring treatment:
- 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.
- 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.