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Chronic Inflammatory Polyradiculoneuropathy (CIDP)

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Chronic Inflammatory Polyradiculoneuropathy (CIDP) Outline General Clinical Manifestations Diagnosis Treatment and prognosis CIDP Acquired, immune-mediated ... – PowerPoint PPT presentation

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Title: Chronic Inflammatory Polyradiculoneuropathy (CIDP)


1
Chronic Inflammatory Polyradiculoneuropathy (CIDP)
2
Outline
  • General
  • Clinical Manifestations
  • Diagnosis
  • Treatment and prognosis

3
CIDP
  • 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

4
CIDP Clinical Manifestations
  • Demyelination
  • May be detected on nerve conduction studies or
    nerve biopsy
  • Multifocal demyelination is a diagnostic hallmark
    of CIDP, but distribution of demyelinative
    lesions varies among patients
  • Weakness
  • Characteristically, involves both proximal and
    distal muscles
  • Typically symmetric, but can begin asymmetrically
  • Sensory symptoms are common but motor symptoms
    usually predominate
  • Autonomic system dysfunction can occur

5
CIDP Clinical Manifestations
  • Slow progressive course is seen in approximately
    2/3 of cases
  • Children usually have a more precipitous onset of
    symptoms
  • Relapsing course with partial or complete
    recovery between recurrences is seen in
    approximately 1/3 of cases
  • 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

6
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

7
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 199952498503
8
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

9
CIDP Regional Variants
  • Lewis-Sumner syndrome
  • Distal acquired demyelinating sensory neuropathy
    and sensory CIDP
  • Multifocal demyelinating neuropathy with
    persistent conduction block
  • Distal CIDP
  • Sensory CIDP
  • ANTI-MAG (Myelin Associated Glycoprotein)
    Neuropathy
  • CIDP with Hypertrophic nerves
  • Subacute demyelinating polyneuropathy
  • Chronic Inflammatory demyelinating neuropathies

10
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

11
CIDP Associated Conditions
  • HIV infection
  • Mild lymphocytic pleocytosis and increased gamma
    globulin level in the CSF are seen frequently
  • 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

12
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
    characteristics
  • 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

13
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

14
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

15
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
    disorder
  • Diabetes may predispose patients to CIDP
  • Pregnancy
  • Known to worsen CIDP
  • Worsening usually occurs in the third trimester
    or in the postpartum period

16
CIDP Monitoring and Prognosis
  • Sometimes difficult to assess the activity of a
    chronic neuropathy
  • 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

17
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

18
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 biopsy

19
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

20
Laboratory Studies CSF
  • Protein level is increased significantly in 80
    of patients
  • Usually between 50 and 200 mg/dL, but can be
    higher
  • 10 of patients also have mild lymphocytic
    pleocytosis (lt50 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

21
CIDP EMG
  • Critical test to determine whether the disorder
    is truly a peripheral neuropathy and whether the
    neuropathy is demyelinating
  • 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

22
CIDP Peripheral nerve biopsy
  • Indications
  • Patients in whom the diagnosis is not completely
    clear
  • 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 therapy

23
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

24
CIDP Histology
  • Note the decreased density of nerve fibers
    (arrows)
  • Demyelinated fibers (D)
  • Fibers undergoing active macrophagemediated
    demyelination (M)

Bouchard, et al. NEUROLOGY 199952498503
25
CIDP Therapy
  • Prednisone, IVIg and plasmapheresis have all been
    demonstrated to be effective in controlled
    clinical trials
  • 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 decline
  • May be irreversible

26
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 re-instituted
  • Patients with chronic progressive disease require
    maintenance therapy, although tapering the
    treatment can be re-attempted periodically to
    determine continued need

27
CIDP Therapy
  • Prednisone
  • First line therapy
  • Agents used for refractory patients
  • Cyclosporine (Sandimmune, Neoral)
  • Cyclophosphamide (Cytoxan)
  • Azathioprine (Imuran)
  • Mycophenolate (CellCept)

28
CIDP Therapy
  • Neuropathic pain
  • Antiepileptics
  • Carbamazepine (Tegretol)
  • Gabapentin (Neurontin)
  • Tricyclic antidepressants
  • Amitriptyline (Elavil)

29
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

30
CIDP Plasmapheresis
  • Treatment regimens
  • Not standardized due to a lack of controlled
    studies
  • Common regimen
  • 3 plasma exchanges per week for first 2 weeks
  • Additional treatment is determined by clinical
    response

31
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

32
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 vaccination
  • Also used to treat multiple immune-mediated
    conditions, such as idiopathic thrombocytopenic
    purpura, GBS, and myasthenia gravis

33
CIDP IV Ig
  • Several studies showed significant benefit in
    CIDP
  • 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

34
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

35
References
  • Acquired demyelinating neuropathy. Brain. 119.
    257270.
  • 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. 617618.

36
References
  • 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.
    S2S6.
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