Chronic Inflammatory Polyradiculoneuropathy (CIDP) by bsr14041

VIEWS: 250 PAGES: 36

									Chronic Inflammatory Polyradiculoneuropathy (CIDP)

•   General
•   Clinical Manifestations
•   Diagnosis
•   Treatment and prognosis

• Acquired, immune-mediated polyradiculoneuropathy
• Heterogeneous disorder with a wide range of clinical
  expression ranging from subacute to a progressive or
  relapsing-remitting course
• Diagnosis is based on clinical symptoms and
  signs, electrodiagnostic studies, CSF
  examination, and other laboratory tests
                CIDP: Clinical Manifestations

• Demyelination
   – May be detected on nerve conduction studies or nerve
   – Multifocal demyelination is a diagnostic hallmark of CIDP,
     but distribution of demyelinative lesions varies among
• Weakness
   – Characteristically, involves both proximal and distal muscles
   – Typically symmetric, but can begin asymmetrically
• Sensory symptoms are common but motor symptoms usually
• Autonomic system dysfunction can occur
             CIDP: Clinical Manifestations

• Slow progressive course is seen in approximately 2/3
  of cases
• Children usually have a more precipitous onset of
• Relapsing course with partial or complete recovery
  between recurrences is seen in approximately 1/3 of
   – Periods of worsening and improvement usually
     last weeks or months
   – Patients with a younger age of onset are said to
     have a higher frequency of relapsing course
                       CIDP: Incidence

• In one study, prevalence was estimated to range
  from 1-7.7 per 100,000
   – These are likely underestimates, since the criteria
     to select cases were strict
• CIDP accounted for 13% of patients seen in one
  neuromuscular center
• Incidence increases with increasing age
   – Children are rarely affected
                CIDP: Pathophysiology

• In one study, CIDP occurred within a few weeks after
  an infectious event in 16% of the patients
   – Because of the insidious onset, documenting
     precipitating illnesses or events is very difficult
   – Both respiratory and gastrointestinal infections
     have been cited, but no causative organism has
     been identified
   – With Guillain-Barre syndome, the most common
     preceding infection is Campylobacter

                                          Bouchard et al. NEUROLOGY 1999;52:498–50
               CIDP: Regional Variants

• The classical phenotype that suggests CIDP is the
  presence of proximal and distal weakness, with large
  fiber sensory loss and areflexia
   – Few patients present with classic symtpoms
• Some authors have suggested subclassifications
  based on the clinical phenotype in order to aid in
  diagnosis and treatment
   – Currently these subclasses are not thought to be
     distinct diseases
                  CIDP: Regional Variants

• Lewis-Sumner syndrome        • ANTI-MAG (Myelin
• Distal acquired                Associated
  demyelinating sensory          Glycoprotein)
  neuropathy and sensory         Neuropathy
  CIDP                         • CIDP with Hypertrophic
• Multifocal demyelinating       nerves
  neuropathy with persistent
  conduction block             • Subacute demyelinating
• Distal CIDP
• Sensory CIDP                 • Chronic Inflammatory
              CIDP: Associated Conditions

• Most frequently CIDP is an idiopathic illness
• Has been known to occur with several conditions
   – In these cases, the associated condition is
     included in the main diagnosis to separate those
     cases from the idiopathic variety
      • Example: “CIDP with HIV infection”
             CIDP: Associated Conditions

• HIV infection
       • Mild lymphocytic pleocytosis and increased
         gamma globulin level in the CSF are seen
• Hodgkin lymphoma
   – Associated neuropathy is not caused by direct
     infiltration of the peripheral nerves but is a
     consequence of the autoimmune cascade that
     occurs with this disease, but the mechanism is not
     completely clear
• Paraproteinemias and/or plasma cell dyscrasias
               CIDP: Associated Conditions

• CIDP is seen with monoclonal gammopathies (eg
  MGUS), most frequently gammopathy of
  immunoglobulin M (IgM)
   – Evidence suggests that CIDP with IgM MGUS has
     specific clinical and electrophysiologic
         – Usually predominance of distal weakness
            with sensory symptoms greater than motor
   – Multiple sclerosis
       • Reports describe CNS white matter changes in
         patients with CIDP
       • Whether a true association exists between
         CIDP and multiple sclerosis remains unclear
            CIDP: Associated Conditions

• Systemic lupus erythematosus
• Chronic active hepatitis (B or C)
   – CIDP associated with hepatitis should be
     differentiated from cryoglobulinemic vasculitis
   – The latter causes either symmetric distal
     sensorimotor polyneuropathy or mononeuropathy
     multiplex but on pathologic examination shows
     wallerian degeneration and not the segmental
     demyelination seen in CIDP
             CIDP: Associated Conditions

• Inflammatory bowel disease
   – CIDP has been described in association with
      Crohn disease and other inflammatory bowel
      conditions, although no direct correlation between
      the two afflictions is known
   – The mechanism of development of CIDP is
      presumed to be an autoimmune abnormality that
      is also causing the primary problem in
      inflammatory bowel disease, although the details
      are not known
             CIDP: Associated Conditions

• Diabetes mellitus
   – Increasing evidence supports the suggestion that
     some patients with diabetes who have severe
     neuropathy or unusually progressive neuropathy
     may have CIDP superimposed on their diabetic
   – Diabetes may predispose patients to CIDP
• Pregnancy
       • Known to worsen CIDP
       • Worsening usually occurs in the third trimester
         or in the postpartum period
            CIDP: Monitoring and Prognosis

• Sometimes difficult to assess the activity of a chronic
• Nerve biopsy can be used to detect active nerve
  lesions and inflammatory infiltrates
• Axonal loss has more long-term prognostic impact
  than active demyelination or inflammatory infiltrates
  in demyelinating disorders of the peripheral and
  central nervous systems
                    CIDP: Diagnosis

• The diagnosis of CIDP is typically based on the
  clinical presentation, absence of other causes of the
  neuropathic syndrome, and results of
  electrodiagnostic studies
• Presence of increased cerebrospinal fluid (CSF)
  protein and demyelinating changes on nerve biopsy
  are supportive of the diagnosis, but these are not
  always present
                    CIDP: Diagnosis

• Because of the clinical heterogeneity and the lack of
  a diagnostic test, various diagnostic criteria have
  been proposed
   – In one series of patients all of whom had proximal
     and distal weakness and in whom 95% of patients
     had improvement with treatment, only 30% had
     the classic triad of slow nerve conduction velocity,
     elevated CSF protein and demyelination on nerve
        American Association of Neurology: Criteria

• Developed criteria for the identification of patients with CIDP for
  research studies
   – Pathologic criteria
   – Electrophysiologic criteria: Require 3 demyelinating range
     abnormalities (either slow conduction velocity, prolonged
     distal motor latencies or F wave latencies or conduction
     block) in 2 nerves
   – Criteria are not sensitive and may miss more than 50 % of
     patients with CIDP
   – Specificity approaches 100%
   – Majority of patients seen in clinical practice fail to meet all of
     the criteria
               Laboratory Studies: CSF

• Protein level is increased significantly in 80% of
   – Usually between 50 and 200 mg/dL, but can be
• 10% of patients also have mild lymphocytic
  pleocytosis (<50 cells) and increased gamma
  globulin (usually associated with HIV infection)
• CBC, sedimentation rate, antinuclear antibody,
  biochemistry profile, and serum and urine
  immunoelectrophoresis are necessary to exclude
  important associated systemic disorders
                         CIDP: EMG

• Critical test to determine whether the disorder is truly a
  peripheral neuropathy and whether the neuropathy is
• Findings of a demyelinating neuropathy
   – Multifocal conduction block or temporal dispersion of
      compound muscle action potential
   – Prolonged distal latencies
   – Variable conduction slowing to less than 70% of normal
   – Absent or prolonged F wave latencies
   – As the disease progresses, patients tend to develop
      secondary axonal degeneration
            CIDP: Peripheral nerve biopsy

• Indications
   – Patients in whom the diagnosis is not completely
   – Cases where other causes of neuropathy (eg,
     hereditary, vasculitic) cannot be excluded
   – Caes where profound axonal involvement is
     observed on EMG
   – Some experts recommend biopsy for most
     patients prior to initiating immunosuppressive
                CIDP: Histologic Findings

• Interstitial and perivascular infiltration of the
  endoneurium with inflammatory T cells and
  macrophages with local edema
• Evidence exists of segmental demyelination and
  remyelination with occasional onion bulb formation,
  particularly in relapsing cases
• Some evidence of axonal damage also is observed,
  with loss of myelinated nerve fibers
• The inflammatory infiltrate with neutrophil infiltration
  is observed in only a minority of patients
CIDP: Histology

        • Note the decreased
          density of nerve fibers
        • Demyelinated fibers (D)
        • Fibers undergoing
          demyelination (M)

                  Bouchard, et al. NEUROLOGY 1999;52:498–50
                       CIDP: Therapy

• Prednisone, IVIg and plasmapheresis have all been
  demonstrated to be effective in controlled clinical
   – In one study, response was seen to at least 1 of
      these 3 main therapies in 66% of patients
• Only 1/3 of patients have a sustained remission after
  initial treatment and most require ongoing treatment
• Early treatment is advisable to prevent axonal loss
  and motor neuron loss which leads to functional
   – May be irreversible
                         CIDP: Therapy

• A positive therapeutic response is measured by improvement or
  stabilization of previously documented progressive weakness,
  sensory loss, or ataxia
• In responsive patients, treatment is continued until maximal
  improvement or stabilization is achieved, at which point it can be
  tapered or discontinued
• If there is further deterioration or a relapse, the therapy can be
• Patients with chronic progressive disease require maintenance
  therapy, although tapering the treatment can be re-attempted
  periodically to determine continued need
                  CIDP: Therapy

• Prednisone
   – First line therapy
• Agents used for refractory patients
   – Cyclosporine (Sandimmune, Neoral)
   – Cyclophosphamide (Cytoxan)
   – Azathioprine (Imuran)
   – Mycophenolate (CellCept)
                  CIDP: Therapy

• Neuropathic pain
   – Antiepileptics
      • Carbamazepine (Tegretol)
      • Gabapentin (Neurontin)
   – Tricyclic antidepressants
      • Amitriptyline (Elavil)
                CIDP: Plasmapheresis

• Several controlled studies confirmed benefit
• Proposed mechanism
   – Removal of antibodies and complement
     components that are responsible for immune-
     mediated damage of peripheral nerves
• Has been shown to have similar efficacy as IVIg in
  treatment of CIDP
                CIDP: Plasmapheresis

• Treatment regimens
   – Not standardized due to a lack of controlled
   – Common regimen
      • 3 plasma exchanges per week for first 2 weeks
      • Additional treatment is determined by clinical
                          IV Ig

• Solution composed mostly of heterogenous human
  IgG but also small amounts of IgA and IgM
• Proposed mechanism of action
   – IVIg contains random set of antibodies that would
     neutralize immune factors, causing damage to
     peripheral nerve in CIDP
   – Activates complement cascade and provides
     multitude of antibodies capable of neutralization of
     many microorganisms, toxins, viruses, and
     presumably autoantibodies
                     IV Ig

• Used in infectious diseases to provide
  immediate passive immunity in situations in
  which time constraints do not allow
  development of active immunity via
• Also used to treat multiple immune-mediated
  conditions, such as idiopathic
  thrombocytopenic purpura, GBS, and
  myasthenia gravis
                   CIDP: IV Ig

• Several studies showed significant benefit in
   – Useful alternative to plasmapheresis
• On average, improvement seen by day 10
  and continues through day 42
• Serum half-life is approximately 21-29 days
• Patients usually require repeated treatments
  every few weeks or months to maintain
  remission or treat recurrences
                    CIDP: Prognosis

• The outcome of CIDP is difficult to predict owing to
  the variety of clinical patterns and evolution
• If left untreated, it can become disabling, with loss of
  ability to ambulate, work, or function independently

• “Acquired demyelinating neuropathy”. Brain. 119.
• Ad Hoc Subcommittee of the American Academy of
  Neurology, AIDS Task Force (1991). “Research
  criteria for diagnosis of chronic inflammatory
  demyelinating polyradiculoneuropathy (CIDP)”.
  Neurology. 41. 617–618.

• Bouchard, et al. “Clinicopathologic findings and
  prognosis of chronic inflammatory demyelinating
  polyneuropathy”. Neurology. February (1 of 1). 1999.
  52. 498-503.
• Kuwabara, S, et al. “Distribution patterns of
  demyelination correlate with clinical profiles in chronic
  inflammatory demyelinating polyneuropathy”. Journal
  of Neurology Neurosurgery and Psychiatry. 2002.
  72. 37-42.
• Latov N. “Diagnosis of CIDP”. Neurology. 59. S2–S6.

To top