What is the recommended treatment for Hashimoto encephalitis?

Treatment and Diagnosis of Hashimoto Encephalitis

First-Line Treatment: High-Dose Corticosteroids

High-dose corticosteroids are the cornerstone of treatment for Hashimoto encephalopathy, with most patients showing rapid clinical improvement and should be initiated as soon as the diagnosis is suspected. 1

Steroid Dosing and Duration

• Start with 0.5-1 mg/kg/day of prednisolone or equivalent immediately upon clinical suspicion 1
• Continue high-dose therapy until clinical response is achieved 1
• Taper gradually over 12 months to prevent relapse after initial response 1
• Antibody levels typically normalize within 3-6 months of steroid therapy 1
• Do not delay treatment while awaiting antibody results if clinical suspicion is high, as early intervention significantly improves outcomes 1

Evidence Supporting Steroid Efficacy

• Status epilepticus in Hashimoto encephalopathy does not respond to anti-epileptic drugs but completely remits under steroid treatment in approximately three-quarters of patients 2
• Long-term steroid therapy combined with other immunomodulatory agents demonstrates excellent outcomes 3
• The British guidelines emphasize that delayed treatment results in poorer outcomes in antibody-mediated encephalitis 1

Diagnostic Confirmation

Essential Diagnostic Criteria

Before initiating immunosuppression, confirm the diagnosis through the following steps:

Laboratory Findings:

• Elevated anti-thyroid antibodies (anti-thyroid peroxidase and/or anti-thyroglobulin) in serum 1, 4
• Exclude other causes of encephalitis including autoimmune encephalitis with neuronal surface antibodies 1, 4
• Elevated CSF protein is common 3
• Hyponatremia is present in approximately 60% of cases 1

Clinical Presentation:

• Subacute onset with confusion, seizures, or altered mental status 1
• Presence of orofacial dyskinesia, choreoathetosis, or faciobrachial dystonic seizures 1
• Acute personality changes, hallucinations, or delusions 4
• Seizures (focal, generalized tonic-clonic, myoclonus, or status epilepticus) that respond poorly to anti-epileptic drugs 2

Neuroimaging:

• MRI shows hippocampal high signal in 60% of cases 1
• Nonspecific abnormalities may be present on EEG and imaging 3

Special Consideration - IgG4-Related Disease:

• Consider IgG4-related Hashimoto thyroiditis in younger males with very high thyroid antibody titers 4
• This variant has a 5:1 male predominance, younger age of onset, and more intense thyroid inflammation 4

Second-Line Treatments for Steroid-Refractory Cases

Escalation Algorithm

If response to steroids is incomplete after adequate trial:

Intravenous Immunoglobulin (IVIg):

• Dose: 0.4 g/kg/day for 5 days 1
• Do not use IVIg alone without steroids as first-line therapy, as this approach may be less effective at reducing antibody levels 1

Plasmapheresis:

• Can achieve complete remission when steroids alone are insufficient 1
• Particularly effective in drug-resistant status epilepticus cases 5
• Consider as alternative to corticosteroids in specific clinical scenarios 5

Rituximab (Anti-CD20 Therapy):

• Reserved for steroid-refractory cases in adolescents and children 6
• Requires careful monitoring due to risk of low immunoglobulin levels and associated side effects 6
• Long-term immunomodulatory agents may be combined with steroids for maintenance 3

Mandatory Tumor Screening

Screen all patients for underlying malignancy with the following approach:

• Perform CT chest/abdomen/pelvis 1
• Pelvic ultrasound in females 1
• Particularly important in cases with VGKC-complex or NMDA receptor antibodies 1
• Thymoma and small cell lung cancer are the most common associated tumors when present 1

Critical Pitfalls to Avoid

Treatment Timing

• Never delay steroid treatment while awaiting antibody results if clinical suspicion is high 1
• Early intervention significantly improves outcomes in antibody-mediated encephalitis 1

Medication Strategy

• Do not rely on anti-epileptic drugs alone for seizure control, as seizures in Hashimoto encephalopathy respond poorly to AEDs but respond to immunosuppression 2
• Do not use IVIg as monotherapy without steroids as first-line treatment 1

Diagnostic Confusion

• Do not confuse with HSV-1 encephalitis, where steroids are not routinely recommended and may facilitate viral replication 7, 8
• This contrasts sharply with Hashimoto encephalopathy where steroids are the primary treatment 1
• Exclude other autoimmune encephalitides with neuronal surface antibodies before confirming diagnosis 1, 4

Steroid Tapering

• Do not taper steroids too rapidly; use a 12-month gradual taper to prevent relapse 1
• Monitor for recurrence during tapering phase 3