Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis

Objective: To determine whether neuronal and neuroaxonal injury,
neuroinflammation, and synaptic dysfunction associate with clinical course
and outcomes in antibody-mediated encephalitis (AME), we measured
biomarkers of these processes in CSF from patients presenting with AME and
cognitively normal individuals. Methods: Biomarkers of neuronal
(total tau, VILIP-1) and neuroaxonal damage (neurofilament light chain
[NfL]), inflammation (YKL-40), and synaptic function (neurogranin,
SNAP-25) were measured in CSF obtained from 45 patients at the time of
diagnosis of NMDA receptor (n = 34) or LGI1/CASPR2 (n = 11) AME and 39
age- and sex-similar cognitively normal individuals. The association
between biomarkers and modified Rankin Scale (mRS) scores were evaluated
in a subset (n = 20) of longitudinally followed patients.
Results: Biomarkers of neuroaxonal injury (NfL) and
neuroinflammation (YKL-40) were elevated in AME cases at presentation,
whereas markers of neuronal injury and synaptic function were stable
(total tau) or decreased (VILIP-1, SNAP-25, neurogranin). The
log-transformed ratio of YKL-40/SNAP-25 optimally discriminated patients
from cognitively normal individuals (area under the receiver operating
characteristic curve 0.99; 95% confidence interval 0.97, >0.99).
Younger age (ρ = −0.56; p = 0.01), lower VILIP-1 (ρ = −0.60; p <
0.01) and SNAP-25 (ρ = −0.54; p = 0.01), and higher log10(YKL-40/SNAP-25)
(ρ = 0.48; p = 0.04) associated with greater disease severity (higher mRS
score) in prospectively followed patients. Higher YKL-40 (ρ = 0.60; p =
0.02) and neurogranin (ρ = 0.55; p = 0.03) at presentation were associated
with higher mRS scores 12 months following hospital discharge.
Conclusions: CSF biomarkers suggest that neuronal integrity is
acutely maintained in AME, despite neuroaxonal compromise. Low levels of
biomarkers of synaptic function may reflect antibody-mediated
internalization of cell surface receptors and may represent an acute
correlate of antibody-mediated synaptic dysfunction, with the potential to
inform disease severity and outcomes.