Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

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Author: Joel Steinberg

 

Definition:

Slowly evolving ascending symmetric weakness of the limbs over at least eight weeks, often accompanied by paresthesias, usually in a recurring pattern, often with spontaneous improvement, that reflects inflammation-mediated damage of peripheral nerve myelin. 

• Additional features include areflexia and elevated spinal fluid protein.

 

Causes:

Generally accepted to be an autoimmune disorder, wherein the body’s immune system, macrophages as well as likely humoral factors, attacks peripheral nerve myelin.

• Triggers of attacks are unknown.

 

Scope of the Problem:

• Incidence as high as 1.5 new cases per 100,000 population identified annually. 

• CIDP often runs a protracted course, over years.

• Thus its prevalence, the number of cases present at any one time, may run about 9/100,000.

• If left untreated, permanent nerve damage and disability may evolve; early diagnosis is thus important.

 

Differential Diagnosis:

Other likely autoimmune peripheral neuropathies
Multifocal (i.e., asymmetric) acquired demyelinating sensory and motor neuropathy (Lewis-Sumner syndrome)

Compression neuropathies
Spinal stenosis

Spinal cord nerve tract pathology
Amyotrophic lateral sclerosis

Autoimmune neuromuscular junction disorders
Myasthenia gravis

Multisystem disorders via deranged plasma cells
POEMS syndrome (a.k.a., Takatsuki syndrome, osteoclerotic myeloma), consisting of polyradiculoneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes

Hereditary peripheral neuropathies
Charcot-Marie-Tooth syndrome, affecting principally the arms and legs

 

Diagnosis:

History:

• Typical patient presents with slowly progressive weakness of their legs, extending over at least 8 weeks, leading to difficulty arising from a chair, walking and climbing stairs.

• Weakness of arms leads to difficulty using utensils and gripping objects.

• Sensory involvement also common, with loss of feeling and distal paresthesias, of the feet and hands.

PE:

• Limb weakness, with, e.g., difficulty arising, climbing onto an exam table, and a waddling gait.

• Deep tendon reflexes of weak limbs are diminished or absent.

• Some abnormal peripheral nerve issues commonly seen in acute demyelinating inflammatory polyneuropathy (AIDP or Guillain-Barré syndrome) are rare in CIDP, such as cranial nerve and autonomic nervous system involvement and breathing problems.

Lab:

• Electrodiagnostic criteria, i.e., nerve conduction velocity-electromyography findings to support a diagnosis of definite or probable CIDP have been established by the European Federation of Neurological Societies and Peripheral Nerve Society. See end.

• Spinal fluid protein usually elevated without a concomitant elevation in cells.

• When the diagnosis is questionable a nerve biopsy, read by a pathologist familiar with neuropathology, may be helpful.

Imaging:

• Occasionally an MRI of the spine will demonstrate enlarged nerve root or plexus.

• CT of the head can rule out CNS involvement.

 

Treatment:

General guidelines - early diagnosis and initiation of treatment likely help preserve nerve function.

1. Medications and Blood Derived Products

   • Most patients respond to at least one of three immunologic system interventions:

     1. High dose immunoglobulins. Traditionally given intravenously (a.k.a., IVIG) or delivered by the subcutaneous (SC) route. The IVIG brand, Gamunex^® and the SC formulation, Hizentra^® have FDA approval for treatment of CIDP. Treatments are typically given as a course over 5 days and eventually repeated if weakness recurs.

     2. Plasma exchange (a.k.a., plasmapheresis), i.e., removal of the liquid portion of blood (and its replacement with a solution substitute). As with IVIG, treatments are typically given over 5 days and repeated if weakness recurs.

     3. Corticosteroids. Ease of administration and low cost make corticosteroids an attractive first line therapy choice, but untoward side effects may limit its use.

   • Should patients respond poorly to the 3 first line treatment choices, various immunosuppressive drugs can be tried. All are off-label uses, i.e., not FDA approved.

   • These include: rituximab (Rituxan^®), cyclophosphamide, cyclosporine, azathioprine (Imuran^®), mycophenolate mofetil (Cellcept^®)

2. Physical Therapy

   • Adjunctive physical and occupational therapy will often help the patient improve function such as mobility and other activities of daily living.

3. Natural History of CIDP

   • Many CIDP cases slowly dissipate or burn out, enabling a decrease in the frequency of treatment dosing.

4. Supportive Care

   • Medical and lay literature, including patient support available through the GBS/CIDP Foundation International at www.gbs-cidp.org.

 

Clinical Pearl:

If left untreated, CIDP can lead to permanent nerve damage and disability.
Hence, unexplained weakness with difficulty walking warrants prompt evaluation, usually a nerve conduction velocity study to look for slowed conduction and other indicators of peripheral nerve demyelination.

 

Addendum:

Electrodiagnostic Criteria for CIDP (abbreviated version; see original publication for details)

1. Definite: at least one of the following _a
   • (a) Motor distal latency prolongation ‡50% above ULN in two nerves, or
   • (b) Reduction of motor conduction velocity ‡30% below LLN in two nerves, or
   • (c) Prolongation of F-wave latency ‡30% above ULN in two nerves, or
   • (d) Absence of F-waves in two nerves, or
   • (e) Partial motor conduction block, or
   • (f) Abnormal temporal dispersion (>30% duration increase between the proximal and distal negative peak CMAP), or
   • (g) Distal compound muscle action potential (CMAP) duration increase in ‡1 nerve
2. Probable
   ‡30% amplitude reduction of the CMAP's proximal negative peak relative to distal peak

ULN, upper limit of normal values; LLN, lower limit of normal values. _a Any nerve meeting any of the criteria (1.1-1.7).

PYK Van den Bergh et al.; 2010; EFNS and Peripheral Nerve Society European Journal of Neurology 17, 356–363.