CSF Picture in Anti-NMDAR Encephalitis
The CSF in anti-NMDAR encephalitis is frequently abnormal, particularly in the first phase of illness, showing lymphocytic pleocytosis (up to 500 cells/μL) with detectable NMDA receptor antibodies. 1
Key CSF Findings
Cell Count
- Lymphocytic pleocytosis is present in approximately 58-60% of patients, with white cell counts that can reach up to 500 cells/μL 1, 2
- The CSF pleocytosis is especially prominent during the first phase of illness when patients present with seizures, confusion, amnesia, and psychosis 1
- Cell count elevation is more frequent in anti-NMDAR encephalitis compared to other antibody-mediated encephalitides 3
Protein
- Protein elevation is relatively uncommon, occurring in only 18.6% of cases 2
- CSF protein content does not significantly differ from controls and is not a reliable diagnostic marker 3
Oligoclonal Bands (OCB)
- OCB are present in approximately 34-40% of anti-NMDAR encephalitis patients 3
- The presence of OCB is significantly more frequent in anti-NMDAR encephalitis compared to non-autoimmune controls, with 8.5-fold higher likelihood 3
- OCB have high specificity (96%) but low sensitivity (34%) for the diagnosis 3
Antibody Detection
- NMDA receptor antibodies are detectable in CSF and are more sensitive than serum testing 1, 4
- 100% of patients with positive serum antibodies have positive CSF samples, while only 62.8% of CSF-positive patients have positive serum 2
- CSF antibody testing is not essential for diagnosis as antibodies are also present in serum, but paired samples are most informative 1
Other Parameters
- CSF pressure is increased in approximately 39.5% of patients 2
- Blood-CSF barrier dysfunction (QAlb>Qlim) occurs in 29.3% of cases 2
- Intrathecal immunoglobulin synthesis is detected in only 17.1% of patients 2
Clinical Correlation
The typical patient is a 25-year-old female (male:female ratio 1:2) who often presents with headache and fever as early symptoms, mimicking a prodromal viral infection 1. The illness progresses through two distinct phases:
- First phase: Seizures, confusion, amnesia, and psychosis with more prominent CSF abnormalities 1
- Second phase: Involuntary movements (choreoathetosis, orofacial dyskinesia), fluctuating consciousness, dysautonomia, and central hypoventilation 1
Important Caveats
- CSF abnormalities do not correlate with prognosis or outcome 2
- A normal CSF does not exclude anti-NMDAR encephalitis—approximately 40-42% of patients have normal CSF cell counts 1, 2
- Anti-NMDAR antibodies can be detected in approximately 30% of patients during herpes simplex encephalitis, so positive results must be interpreted in clinical context 5
- The median hospital stay is 160 days (range 16-850 days), with many patients requiring ICU admission for assisted ventilation 1
Diagnostic Approach
Both serum and CSF should be tested for NMDA receptor antibodies when possible, as CSF testing has higher sensitivity 5, 2, 4. However, immunotherapy should be initiated as soon as infection is excluded based on basic CSF results (cell count, protein, glucose), without waiting for antibody confirmation 6.