Ferri – Chronic Inflammatory Demyelinating Polyneuropathy

Mar 25, 2020 admin Uncategorized 0

Chronic Inflammatory Demyelinating Polyneuropathy

  • Chloe Mander Nunneley, M.D.
  • Joseph S. Kass, M.D., J.D
  • John Sladky, M.D.

 Basic Information

Definition

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic autoimmune neuropathy manifesting with symmetric proximal and distal weakness with associated sensory loss along with reduced or absent reflexes. By definition, the symptoms reach nadir no earlier than 8 weeks after onset.

Synonyms

  1. Chronic inflammatory demyelinating polyradiculoneuropathy

  2. CIDP

ICD-10CM CODES
G61.81 Chronic inflammatory demyelinating polyneuritis

Epidemiology & Demographics

Prevalence

0.5/100,000 children; 1 to 2/100,000 adults

Predominant Sex and Age

Slightly higher in males

Risk Factors

It is associated with certain systemic medical conditions (see under “Differential Diagnosis”), but the association is unclear.

Physical Findings & Clinical Presentation

  1. •

    Symmetric weakness in both proximal and distal muscles that peaks after at least 8 weeks; onset may appear acute in a minority of patients, and the disease course may be either relapsing or progressive.

  2. •

    Impaired sensation with distal paresthesias, poor balance, and/or impaired proprioception.

  3. •

    Reduced or absent deep tendon reflexes.

  4. •

    Facial, oropharyngeal, and ocular involvement in a small minority of patients.

  5. •

    Autonomic dysfunction occurs very infrequently compared with Guillain-Barré syndrome.

Etiology

Immune-mediated disorder emerging from interplay of both cell-mediated and humoral immune responses directed against incompletely characterized peripheral nerve antigens. May also be associated with antecedent illness, although no infectious etiologies have been consistently linked with disease occurrence.

Diagnosis

There is no universal consensus regarding diagnostic criteria for CIDP. The three most widely used criteria are the American Academy of Neurology (AAN), Saperstein, and Inflammatory Neuropathy Cause and Treatment (INCAT) criteria. See Table E1 for a complete review of differences. Of note are the following:

TABLEE1 Diagnostic Criteria
Feature American Academy of Neurology (AAN) Criteria Saperstein Criteria Inflammatory Neuropathy Cause and Treatment Criteria
Clinical involvement Motor dysfunction, sensory dysfunction of >1 limb or both Major: Symmetric proximal and distal weakness; minor: exclusively symmetrical distal weakness or sensory loss Progressive or relapsing motor and sensory dysfunction of >1 limb
Time course ≥2 mo ≥2 mo ≥2 mo
Reflexes Reduced or absent Reduced or absent Reduced or absent
Electro-diagnostics Any 3 of the following 4 criteria: partial conduction block of ≥1 motor nerve, reduced velocity of ≥2 motor nerves, prolonged distal latency of ≥2 motor nerves, or prolonged F-waves of ≥2 motor nerves 2 of the 4 AAN electrodiagnostic criteria Partial conduction block of ≥2 motor nerves and abnormal conduction velocity or distal latency or F-wave latency in 1 other nerve; or, in the absence of partial conduction block, abnormal conduction velocity, distal latency, or F-wave latency in 3 motor nerves; or electrodiagnostic abnormalities indicating demyelination in 2 nerves and histologic evidence of demyelination
CSF analysis WBC count <10, negative CSF VDRL, and elevated protein (supportive) Protein >45, WBC <10 (supportive) CSF recommended but not mandatory
Biopsy findings Evidence of demyelination and remyelination Predominant features of demyelination; inflammation (not required) Not mandatory (except in cases with electrodiagnostic abnormalities in only 2 motor nerves)
  1. •

    The AAN and INCAT criteria have the least stringent clinical criteria and require electrodiagnostic assessment of motor and sensory function in only one limb. The Saperstein criteria are more stringent, requiring both symmetrical proximal and distal weakness. Therefore, a patient with distal acquired demyelinating symmetric neuropathy (DADS) could fulfill AAN and INCAT criteria for CIDP.

  2. •

    All require cerebrospinal fluid analysis to assess for albuminocytologic dissociation.

  3. •

    All require some features of demyelination evident on nerve conduction studies, including prolonged distal latencies and F-waves, slowed conduction velocities, and at least one nerve demonstrating partial conduction block, a feature of acquired demyelination.

  4. •

    INCAT criteria do not require a nerve biopsy.

Differential Diagnosis

  1. •

    Other demyelinating neuropathies such as the following:

    1. 1.

      Distal acquired demyelinating symmetric neuropathy (DADS)

    2. 2.

      Multifocal motor neuropathy (MMN)

    3. 3.

      Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM; Lewis-Sumner syndrome)

  2. •

    Inherited neuropathies: Charcot-Marie-Tooth subtypes

  3. •

    Metabolic neuropathies due to diabetes, uremia

  4. •

    Paraneoplastic and neoplastic neuropathies: lymphoma and carcinoma

  5. •

    Neuropathy associated with monoclonal gammopathy:

    1. 1.

      Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome

    2. 2.

      Multiple myeloma

    3. 3.

      Monoclonal gammopathy of undetermined significance (MGUS)

    4. 4.

      Waldenström’s macroglobulinemia

  6. •

    Neuropathy associated with infectious diseases: HIV and leprosy

  7. •

    Neuropathy associated with systemic inflammatory or immune-mediated diseases:

    1. 1.

      Sarcoidosis

    2. 2.

      Amyloidosis

    3. 3.

      Vasculitis: PAN, Behçet’s, Sjögren’s, cryoglobulinemia, lupus, Castleman’s disease, granulomatosis with polyangiitis (formerly Wegener’s granulomatosis), and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss)

  8. •

    Toxic neuropathies: ETOH, acrylamide, drugs (platinum-based agents, amiodarone, tacrolimus, perhexiline)

Workup

Nerve conduction studies and EMG to assess for demyelinating polyneuropathy with features of acquired demyelination (temporal dispersion) and conduction block (Fig. E1)

FIG.E1 

Conduction block.

Laboratory Tests

  1. •

    CSF analysis to assess for albuminocytologic dissociation (i.e., elevated protein with normal cell count), along with appropriate laboratory studies to exclude associated conditions.

  2. •

    Nerve biopsy specimens (rarely done now) also reveal signs of demyelination with variable degrees of inflammation and secondary axonal loss.

Imaging Studies

MRI with/without gadolinium of the lumbar spine may show enlargement and enhancement of the proximal nerve root segments (Figs. E2 and E3).

FIG.E2 

Contrast-enhanced MRI shows enhancement of nerve roots.
FIG.E3 

T2-weighted axial MRI shows enlarged nerve roots.

Treatment

Therapies are directed at blocking the underlying immune processes to arrest demyelination and inflammation and to prevent secondary axonal degeneration. The first-line agents for immunomodulatory therapy are intravenous immunoglobulin (IVIg), plasmapheresis, and corticosteroids. There is no difference in efficacy among these three treatment modalities. Azathioprine, mycophenolate mofetil, cyclophosphamide, rituximab, and cyclosporine may be used second-line.

Nonpharmacologic Therapy

Orthotics or braces may be useful for significant distal weakness.

Acute General Rx

  1. •

    Prednisone 60 mg per day or 100 mg every other day

  2. •

    IVIg 2 g/kg divided over 2 to 5 days

  3. •

    Plasmapheresis (5 to 6 exchanges)

Chronic Rx

  1. •

    Oral prednisone: 1 mg/kg daily starting dose, typically changed to every other day after 1 month or when strength plateaus. Reduce by 10 mg per month until dose reaches 20 mg every other day; then reduce by 5 mg per month. Supplement calcium and vitamin D. Patients should receive a tuberculin skin test prior to administration as well as surveillance exams for cataracts, glaucoma, diabetes, and gastroesophageal reflux.

  2. •

    Dexamethasone: PREDICT study compared dexamethasone 40 mg daily for 4 days per month with prednisone 60 mg daily for 2 months and then tapered over 27 weeks. No difference in efficacy was found between the two groups. However, pulse steroids were associated with less weight gain, fewer cushingoid features, but more sleep and psychological disturbances.

  3. •

    Pulse methylprednisilone: no standard regimen. However, 1000 mg for 3 days can be used, followed by 1000 mg per week with the goal of reduced frequency to every 2 to 12 weeks.

  4. •

    IVIg: 0.4 to 1 g/kg administered every 2 to 3 weeks, with adjustment based on therapeutic response. Baseline IgA level, renal function, and coagulation studies should be assessed.

  5. •

    Mycophenolate mofetil: Initial dose of 500 mg every other day; increase to 2 g orally divided twice daily in 2 to 4 weeks. Complete blood counts and liver panel should be assessed monthly for the first 3 months, then every 3 months thereafter. May cause GI upset.

  6. •

    Azathioprine: Initial dose of 25 to 50 mg every other day; increase to 100 mg twice daily in 4 weeks. Complete blood counts and liver panel should be assessed for first 3 months, then every 3 months thereafter. Idiosyncratic reaction of fever and GI upset may occur.

  7. •

    Cyclophosphamide: used for severe cases. 1000 mg/m2 monthly for 6 months (moderate dose) or 50 mg/kg daily for 4 days (high dose).

  8. •

    Other treatments used (case reports/anecdotal evidence): etanercept, rituximab, tacrolimus, interferon beta-1a.

Prognosis

  1. •

    Although available data on the long-term prognosis of patients are limited, most patients improve and reach stability. Relapses may occur in 50% of patients. A small minority of patients remain severely disabled, and up to 11% die from the disease.

  2. •

    Patients with CIDP associated with IgM monoclonal gammopathy often respond poorly to treatment.

  3. •

    Younger age, female gender, and relapsing-remitting course may portend a more favorable prognosis. Four-limb weakness at onset and prominent axonal loss on EMG may signify poor prognosis.

Referral

  1. •

    Neurologist, physical therapy/occupational therapy, orthotics

Pearls & Considerations

  1. •

    Patients are compliant with azathioprine treatment if MCV >100.

  2. •

    Always place PPD prior to initiation of steroid treatment.

  3. •

    Consider trimethoprim-sulfamethoxazole 3 times weekly in patients taking steroids and other immunosuppressant agents for Pneumocystis pneumonia prophylaxis (especially in patients with coexisting lung disease).

  4. •

    Look for acquired features of demyelination on nerve conduction studies (conduction block and temporal dispersion).

  5. •

    Examine CSF for albuminocytologic dissociation (high CSF protein with normal cell count).

  6. •

    CIDP can present like Guillain-Barré syndrome. Sensory symptoms and proximal weakness are more common in CIDP, and symptoms continue to evolve over more than 8 weeks.

Patient/Family Education

CIDP is a chronic illness usually characterized by a relapsing-remitting course that typically responds well to treatment. Early referral to a neurologist is important, and education on steroid side effects and mitigating factors is paramount.

 

 

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