What is the treatment protocol for Intravenous Immunoglobulin (IVIG) in a patient with cerebellar ataxia of suspected autoimmune etiology?

IVIG Treatment for Cerebellar Ataxia

For suspected autoimmune cerebellar ataxia, initiate IVIG at 0.4 g/kg/day for 5 days (total dose 2 g/kg) as first-line immunotherapy, either alone or in combination with high-dose corticosteroids, particularly when infection has been ruled out and autoimmune etiology is suspected. 1

Initial Diagnostic Workup

Before initiating IVIG, confirm autoimmune etiology through:

• Serum and CSF autoantibody testing for GAD antibodies, anti-gliadin antibodies, anti-thyroid antibodies (TPO, thyroglobulin), VGKC-complex antibodies, NMDAR antibodies, and paraneoplastic antibodies (Hu, Yo, Tr/DNER, mGluR1) 1
• Brain MRI with contrast to assess for cerebellar atrophy patterns and exclude structural lesions 1
• CSF analysis including cell count, protein, glucose, oligoclonal bands, and IgG index to support inflammatory etiology 1
• Cancer screening with CT chest/abdomen/pelvis in adults, particularly for paraneoplastic syndromes associated with SCLC, breast, or ovarian malignancies 1

IVIG Dosing Protocol

Standard regimen: 0.4 g/kg/day IV for 5 consecutive days (total cumulative dose of 2 g/kg) 1

This dosing is consistent across multiple guideline sources for autoimmune neurological conditions and has shown efficacy in case series of autoimmune cerebellar ataxia 2, 3, 4.

When to Use IVIG as First-Line Therapy

IVIG is preferred over corticosteroids when:

• Patient is agitated or has significant behavioral disturbance 1
• Bleeding disorders are present 1
• Corticosteroids are contraindicated 1

IVIG can be used as monotherapy or combined with corticosteroids from the outset in severe presentations 1. The 2021 autoimmune encephalitis guidelines suggest combination therapy (steroids plus IVIG or PLEX) may be more effective than sequential therapy, particularly in severe cases 1.

Antibody-Specific Considerations

Anti-GAD Antibody Cerebellar Ataxia

• IVIG has shown efficacy in multiple case reports, with improvement or stabilization of symptoms 2, 5, 6
• Early treatment before significant cerebellar atrophy develops is critical for better outcomes 6
• Consider adding rituximab if inadequate response to IVIG alone 6

Anti-Gliadin/Gluten Ataxia

• IVIG demonstrated effectiveness in anti-gliadin antibody-positive patients with cerebellar cortical atrophy 2
• Dietary gluten removal should be implemented concurrently 5

Paraneoplastic Cerebellar Degeneration (Anti-Yo, Anti-Hu, Anti-Tr/DNER)

• IVIG administered within 1 month of onset may induce good response with stabilization 1
• For anti-Yo syndrome specifically, early IVIG (within 1 month) shows better outcomes 1
• Anti-Tr/DNER antibody cases have responded to combined plasmapheresis followed by IVIG 3
• Tumor treatment is paramount and favorably affects neurological outcomes 1

VGKC-Complex Antibody Encephalitis with Ataxia

• High-dose corticosteroids are typically first-line, but IVIG can be added to accelerate improvement 1
• IVIG alone without steroids may be less effective at reducing antibody levels 1

Second-Line and Escalation Strategies

If no improvement after initial IVIG course (2-4 weeks):

1. Add plasma exchange (PLEX): 5-10 sessions every other day 1, 3

   • Consider PLEX first in patients with severe hyponatremia, high thromboembolic risk, or associated demyelination 1
   • Note: PLEX immediately after IVIG will remove immunoglobulin, so timing matters 1

2. Escalate to second-line agents if no response to combined first-line therapy:

   • Rituximab for antibody-mediated autoimmunity (e.g., GAD, NMDAR) 1, 6
   • Cyclophosphamide for cell-mediated autoimmunity (classical paraneoplastic syndromes) 1

3. Maintenance therapy: Monthly IVIG or IV methylprednisolone as bridging therapy after acute treatment 1

Monitoring Response

Clinical improvement markers:

• Gait stability and ability to walk unassisted 4
• International Cooperative Ataxia Rating Scale (ICARS) scores 4
• Resolution of dysarthria, limb ataxia, and nystagmus 6

Paraclinical markers:

• SPECT imaging showing increased cerebellar perfusion correlates with clinical response 2
• Serial antibody titers (though clinical response is more important than antibody levels) 1

Critical Pitfalls to Avoid

Do not delay treatment waiting for antibody results if clinical suspicion is high—empiric immunotherapy should begin once infection is excluded 1. The 2021 guidelines emphasize starting treatment based on clinical presentation rather than waiting for confirmatory antibody testing.

Do not assume treatment futility in chronic cases. Even patients with 16-year disease duration have shown response to IVIG, though earlier treatment yields better outcomes 4. However, the presence of significant cerebellar atrophy on MRI is a negative prognostic factor 6.

Recognize that paraneoplastic cerebellar degeneration with intracellular antibodies (Hu, Yo) typically shows limited response to immunotherapy alone—these are primarily T-cell mediated, and tumor removal is essential 1. In contrast, surface antibody syndromes (NMDAR, VGKC-complex) are more treatment-responsive 1.

Regular IVIG alone without steroids may be less effective at reducing antibody levels in VGKC-complex encephalitis, potentially leading to poorer outcomes 1. Combination therapy is generally preferred.