Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients

Area of Science:

• Neuroimmunology
• Neurology

Background:

• Leucine-rich glioma inactivated 1 (LGI1)-IgG and Contactin-associated protein 2 (CASPR2)-IgG are key autoantibodies in autoimmune encephalitis and neuropathies.
• Understanding their expanded phenotypic spectrum and longitudinal outcomes is crucial for diagnosis and management.

Purpose of the Study:

• To describe the expanded phenotypic spectrum and longitudinal outcomes in a cohort of 256 patients with LGI1-IgG and/or CASPR2-IgG antibodies.
• To identify predictors of central nervous system (CNS) versus peripheral nervous system (PNS) involvement.

Main Methods:

• Retrospective analysis of 3,910 patients tested for neural autoantibodies.
• Detailed clinical and serological data collection, including longitudinal follow-up for 95 patients.
• Multivariate analysis to identify predictors of CNS vs. PNS involvement.

Main Results:

• 196 LGI1-IgG positive, 51 CASPR2-IgG positive, and 9 dual positive cases identified.
• Serum testing was more sensitive than CSF for antibody detection.
• Older age (>50 years) predicted CNS involvement (OR=15).
• Paroxysmal dizziness spells (PDS) were a common LGI1-IgG manifestation (14%).
• Cancer was found in 44% of dual-positive patients.
• 97% showed favorable response to initial immunotherapy, with a mean modified Rankin Score improving from 3 to 1.74.

Conclusions:

• Older age is a strong predictor of CNS involvement in LGI1-IgG/CASPR2-IgG autoimmunity.
• LGI1-IgG is associated with pain, PNS manifestations, and PDS, which can delay diagnosis.
• Initial immunotherapy yields good outcomes, but some patients need long-term management for persistent disability.