From the Guidelines
Autoimmune encephalitis presenting as dementia should be promptly diagnosed and treated with immunotherapy to improve morbidity, mortality, and quality of life outcomes. The diagnosis of autoimmune encephalitis requires a comprehensive workup, including cerebrospinal fluid analysis, brain MRI, EEG, and testing for specific autoantibodies such as anti-NMDA receptor, anti-LGI1, and anti-CASPR2 antibodies, as recommended by the most recent guidelines 1.
Key Considerations
- A detailed workup is necessary to confirm the diagnosis and exclude competing possibilities like infective encephalitis or systemic/metabolic causes, as outlined in the diagnostic algorithm for autoimmune encephalitis 1.
- First-line treatment involves immunotherapy with high-dose corticosteroids, such as methylprednisolone 1000mg IV daily for 3-5 days, followed by oral prednisone taper over weeks to months, often combined with intravenous immunoglobulin (IVIG) at 2g/kg divided over 2-5 days or plasma exchange (5-7 exchanges) 1.
- For refractory cases, second-line therapies include rituximab (375mg/m² weekly for 4 weeks) or cyclophosphamide, as suggested by recent studies 1.
- Ongoing monitoring for tumor development is necessary as some cases are paraneoplastic, particularly with anti-NMDA receptor encephalitis associated with ovarian teratomas, highlighting the importance of a targeted screening approach based on clinical presentation and MRI results 1.
Diagnostic Approach
- EEG can confirm focal or multifocal brain abnormality and rule out subclinical seizures, while cerebrospinal fluid analysis should include testing for infections, inflammatory markers, and neuronal autoantibodies 1.
- Brain MRI with or without contrast is essential for identifying potential neoplasms and guiding further diagnostic testing, as outlined in the proposed best practice recommendations for diagnosis and acute management of autoimmune encephalitis 1.
- The differential diagnosis generated based on MRI results will guide what blood tests to send, emphasizing the need for a comprehensive and targeted diagnostic approach 1.
From the Research
Autoimmune Encephalitis Presenting as Dementia
- Autoimmune encephalitis can resemble neurodegenerative dementia syndromes, making diagnosis challenging 2
- A study found that 38% of patients with autoimmune encephalitis fulfilled criteria for dementia without prominent seizures early in the disease course 2
- Red flags for autoimmune encephalitis in patients with suspected dementia include:
- Rapidly progressive cognitive decline
- Subtle seizures
- Abnormalities in ancillary testing atypical for neurodegeneration 2
- Immunotherapy can improve outcomes in patients with autoimmune encephalitis, with most patients showing improvement after treatment 2
Diagnosis and Management
- The diagnosis of autoimmune encephalitis can be challenging due to the wide spectrum of clinical presentations and lack of diagnostic abnormalities on conventional brain MR-imaging 3
- Early recognition and treatment are paramount to improve outcomes and achieve complete recovery from these debilitating disorders 3
- Treatment options for autoimmune encephalitis include:
- First-line treatments: intravenous steroids, plasma exchange, and intravenous immunoglobulins 4
- Second-line agents: rituximab and cyclophosphamide 4, 5
- Third-line therapy: cytokine-based drugs, plasma cell-depleting agents, and treatments targeting intrathecal immune cells or their trafficking through the blood-brain barrier 4, 6
Clinical Spectrum
- Autoimmune encephalitis can present with a range of symptoms, including psychiatric features that mimic primary psychiatric illnesses 3
- The spectrum of antibody biomarkers of treatable autoimmune encephalopathies continues to broaden, including antibodies targeting glutamate receptors, γ-aminobutyric acid A and B receptors, and glycine receptors 5
- A nationwide observational cohort study found that patients with anti-leucine-rich glioma-inactivated 1 (LGI1), anti-NMDA receptor (NMDAR), anti-gamma-aminobutyric acid B receptor (GABABR), or anti-contactin-associated protein-like 2 (CASPR2) encephalitis often presented with dementia-like symptoms 2