What is the treatment approach for conditions associated with CASPR2 (Contactin-Associated Protein 2) antibodies, specifically using CASPR-IgG (Immunoglobulin G) CBA (Cell-Based Assay) testing?

Treatment Approach for CASPR2 Antibody-Associated Conditions

First-line immunotherapy should be initiated promptly for CASPR2 antibody-associated conditions, consisting of high-dose corticosteroids, followed by intravenous immunoglobulin or plasma exchange if needed, without waiting for antibody test results once infection is ruled out. 1

Diagnostic Approach

• CASPR2 antibodies are considered highly clinically relevant surface antibodies that can be detected using cell-based assay (CBA) testing 1

• Common clinical presentations include:

  • Limbic encephalitis (42% of cases) 2
  • Morvan syndrome (29% of cases) 2
  • Seizures (present in 88.9% of cases with CSF antibodies) 3
  • Memory disorders (94.4% of cases with CSF antibodies) 3
  • Cerebellar ataxia (33.3% of cases) 3

• Diagnostic workup should include:

  • Brain MRI (shows T2-weighted temporolimbic abnormalities in 93.3% of cases) 3
  • CSF analysis (abnormal in 75% of patients) 3
  • EEG (especially if encephalopathic or having seizures) 1
  • Serum and CSF testing for CASPR2 antibodies using cell-based assay 1

Treatment Algorithm

First-Line Treatment

• Initiate immunotherapy promptly without waiting for antibody results once infection is ruled out 1
• Begin with high-dose corticosteroids (intravenous methylprednisolone) 1, 4
• If no clinical improvement after initial steroid treatment, add:
  • Intravenous immunoglobulin (IVIG) or
  • Plasma exchange (PLEX), particularly in patients with severe symptoms or high thromboembolic risk 1, 4

Second-Line Treatment

• For patients with inadequate response to first-line therapy after 2-4 weeks, consider:
  • Rituximab or
  • Cyclophosphamide, or both 1

Tumor Screening

• Comprehensive tumor screening is essential as CASPR2 antibodies can be paraneoplastic (19% of patients have tumors, most commonly thymoma) 2
• Recommended screening includes:
  • CT chest, abdomen, and pelvis
  • Additional targeted imaging based on clinical suspicion 1

Monitoring and Follow-up

• Monitor antibody levels in serum and CSF when available 1
• Careful weaning of immunotherapy to prevent relapses (which occur in 25% of patients) 1, 2
• Follow patients for at least 6 months (median follow-up period is 34 months in studies) 3

Prognosis

• Treatment response occurs in 93% of patients 2
• Early immunotherapy is crucial for better outcomes and prevention of cognitive dysfunction 4
• Presence of IgG1 isotypes (in addition to the always-present IgG4) is associated with poorer clinical outcomes at 1-year follow-up 5

Important Considerations

• CASPR2 antibody-associated conditions predominantly affect elderly men (median age 66 years, 89% male) 2
• The disease may have a protracted clinical course with median time to nadir of 4 months (>1 year in 30% of cases) 2
• CSF antibodies are associated with limbic encephalitis, while serum-only antibodies are more common in neuromyotonia and Morvan syndrome 3
• Recognition of the spectrum of symptoms is important for early diagnosis and treatment 2

Pitfalls to Avoid

• Delaying immunotherapy while waiting for antibody test results can worsen outcomes 4
• Failing to screen for underlying malignancy, especially thymoma 1, 2
• Inadequate duration of follow-up, as the disease can have a protracted course 2
• Overlooking CASPR2 antibodies in cases with atypical presentations, such as those mimicking cerebral infarction 6