Immune-mediated inflammation of the brain has been recognized for more than 50 years,
although the initial descriptions were mainly thought to be secondary to an underlying
neoplasm. Some of these paraneoplastic encephalitides express serum antibodies, but
these were not thought to be pathogenic but instead have a T-cell-mediated pathophysiology.
Over the last two decades, several pathogenic antibodies against neuronal surface
antigens have been described in autoimmune encephalitis, which are amenable to immunotherapy.
Several of these antibodies are directed against glutamate receptors (GluRs). NMDAR
encephalitis (NMDARE) is the most common of these antibodies, and patients often present
with psychosis, hallucinations, and reduced consciousness. Patients often progress
on to develop confusion, seizures, movement disorders, autonomic instability, and
respiratory depression. Although initially described as exclusively occurring secondary
to ovarian teratoma (and later other tumors), non-paraneoplastic forms are increasingly
common, and other triggers like viral infections are now well recognized. AMPAR encephalitis
is relatively less common than NMDARE but is more likely to paraneoplastic. AMPAR
antibodies typically cause limbic encephalitis, with patients presenting with confusion,
disorientation, memory loss, and often seizures. The syndromes associated with the
metabotropic receptor antibodies are much rarer and often can be paraneoplastic-mGluR1
(cerebellar degeneration) and mGluR5 (Ophelia syndrome) being the ones described in
literature. With the advance in molecular biology techniques, it is now possible to
detect these antibodies using cell-based assays with high sensitivity and specificity,
especially when coupled with brain tissue immunohistochemistry and binding to live
cell-based neurons. The rapid and reliable identification of these antibodies aids
in the timely treatment (either in the form of identifying/removing the underlying
tumor or instituting immunomodulatory therapy) and has significantly improved clinical
outcome in this otherwise devastating group of conditions.
