A. Characteristics

1. Chronic Inflammatory peripheral neuropathy
   1. Slow onset of weakness, areflexia, and impaired sensation
   2. Monophasic illness with onset in weeks to months
   3. Chronic demyelination syndrome, likely autoimmune etiology
2. Usually affects middle aged women
3. Evolution occurs in weeks-months
4. Association with certain HLA types

B. Etiology

1. Inflammatory destruction of peripheral nerves
2. Often this is a paraneoplastic syndrome
3. Commonly lymphoma, myeloma
   1. Rare with solid tumors of lung, breast, and stomach
   2. Associated with Waldenstrom's Macroglobulinemia, Gamma Heavy Chain Disease
4. Segmental demyelination and inflammation of peripheral nerves
5. Occasionally seen with HIV, especially with hyperglobulinemia

C. Symptoms

1. Chronic progressive or relapsing weakness
2. Sensory Loss
3. Does not involve autonomic System
4. High CSF Protein
5. Paraneoplastic CIDP includes serum paraprotein, usually monoclonal IgM
   1. May react with myelin associated glycoprotein in peripheral nerve myelin
   2. Osteosclerotic myeloma and monoclonal IgG or IgA may be found
   3. These antibodies do not react with myelin
   4. Antibodies against sugar groups have been demonstrated in some cases [3]

D. Diagnostic Criteria

1. Various criteria have been developed; Sapertein criteria used here [1]
2. Major: symmetric proximal and distal weekness
3. Minor: Exclusively distal weakness or sensory loss
4. Time course at least 2 months
5. Reflexes reduced or absent
6. Any 2 of the following 4 Electrodiagnostic Criteria:
   1. Conduction block of at least 1 motor nerve
   2. Reduced conduction velocity of at least 2 motor nerves
   3. Prolonged distal latency of at least 2 motor nerves
   4. Prolonged F-wave latencies of at least 2 motor nerves or the absence of F waves
7. Cerebrospinal Fluid (CSF): protein <45mg/dL, white cells <10/µL
8. Nerve Biopsy: predominant features of demyelination; inflammation may be seen

E. Differential Diagnosis [1,3]

1. Guillain-Barre Syndrome - acute demyelination, usually after viral infection
2. Multifocal Motor Neuropathy - weakness and muscular atrophy
3. Inherited Neuropathy - motor and sensory neuropathies
4. Metabolic neuropathy - diabetes, liver disease, acromegaly, hypothyroidism
5. Neuropathy with monoclonal gammopathy
6. Infectious Disease - HIV, leprosy
7. Collagen-vascular disease - sarcoidosis, amyloidosis, vasculitis, Behcet's, cryoglobulins
8. Toxic neuropathy - alcohol, metals, drugs
9. Nutritional deficiency
10. Porphyria associated neuropathy

F. Treatment [1]

1. Early therapy to allow remyelination and prevent axonal degeneration (permanent loss)
2. Treatment of underlying disease may result in remission or stabilization
3. Glucocorticoids, IVIg, and plasma exchange are all about equally effective
4. Glucocorticoids
   1. High dose intravenous initially - 500-1000mg/day x 3 days
   2. Followed by 0.5-1.0mg/kg oral prednisone with slow taper
   3. Often requires alkylating agents for steroid sparing and remission maintenance
5. Intravenous Immunoglobulin (IVIg) [4]
   1. Appears as effective as plasmapheresis
   2. Dose is typically 400mg/kg IV qd x 5 days monthly
   3. May administer weekly doses after initial loading dose
6. Plasma Exchange
7. Resistant Disease
   1. Cyclophosphamide
   2. Other alkylating agents
   3. Azathioprine and prednisone not more effective than prednisone alone

G. POEMS Syndrome [3]

1. Polyneuropathy (CIDP)
2. Organomegaly
3. Endocrinopathy
4. Monoclonal Gammopathy
5. Skin Changes
6. Usually associated with neoplastic B cell disease

H. Multifocal Motor Neuropathy [1,4]

1. Very slow onset of weakness and muscular atrophy
2. Areflexia and preservation of sensation occur
3. Conduction block of motor neurons
4. Usually with antibodies to GM1 gangliosides
5. Poor response to plasmapheresis or steroids
6. Excellent response to IVIg
7. Cyclophosphamide (1gm/m2) may be useful in resistant cases

References

1. Koller H, Kieseier BC, Jander S, Hartung HP. 2005. NEJM. 352(13):1343
2. Sander HW and Hedley-Whyte ET. 2003. NEJM. 348(8):735 (Case Record)
3. Ropper AH and Gorson KC. 1998. NEJM. 338(22):1601
4. Dalakas MC. 1997. Ann Intern Med. 126(9):721