Innovations in Pharmaceutical Sciences & Care

Autoimmune encephalitis (AE) is traditionally conceptualised as a brain-centred inflammatory disorder; however, accumulating evidence indicates that a subset of patients presents with spinal cord involvement as the initial manifestation. This narrative review synthesises current literature on spinal-onset autoimmune encephalitis, a rare and frequently underrecognised neuroimmunological phenotype. A comprehensive search of major databases from 2016 to 2025 identified cohort studies, case series, and reviews describing myelitis or longitudinally extensive transverse myelitis (LETM) preceding encephalitic features. Across studies, the clinical trajectory consistently demonstrated a spinal-first inflammatory process followed by delayed cerebral involvement, most commonly associated with GFAP astrocytopathy and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Early brain MRI findings were often non-specific or normal, whereas cerebrospinal fluid abnormalities showed greater diagnostic sensitivity during the transition phase. Diagnostic delay was frequent and strongly correlated with increased neurological disability and relapse risk. These findings support the recognition of spinal-onset autoimmune encephalitis as a distinct clinical continuum, highlighting the need for early CSF-based evaluation and timely immunotherapy to improve outcomes.