Anti LGI1 Encephalitis, Beyond the Limbic System - Persistent Executive Dysfunction in Long-term Follow-up
Dror Shir1, Yael Paran2, Yifat Alcalay3, Avi Gadoth2
1Neurology, Tel-Aviv Medical Center, 2Tel-Aviv Medical Center, 3Tel Aviv Medical Center
Objective:
To investigate long-term cognitive trajectories in LGI1-AE, with a particular focus on executive function and its persistence over time.
Background:
Leucine-rich glioma-inactivated 1 (LGI1) antibody-associated autoimmune encephalitis (AE) often presents with faciobrachial dystonic seizures (FBDS), memory impairment, and behavioral disturbances. Although most patients improve following immunotherapy, long-term cognitive trajectories and the persistence of domain-specific deficits remain poorly defined. Executive deficits are often considered transient, but their persistence has not been systematically examined.
Design/Methods:
We conducted a retrospective cohort study of 18 patients with LGI1-AE followed at a single tertiary center between 2015 and 2025. Cognitive function was assessed longitudinally using domain-specific subscales from the Montreal Cognitive Assessment (MoCA), including a broad Executive Index Score (EIS), a narrow executive composite, and delayed recall. Statistical comparisons were performed to evaluate changes over time and differences by age.
Results:
Over a median [IQR] follow-up of 41.2 [24.8-50.5] months, global cognition, memory, and executive function improved significantly; MoCA scores increased from 20 [16–24] at baseline to 24 [19–27] at last follow-up (p=0.001), EIS rising from 9 [7–12] to 10.5 [9–13] (p=0.001) and the narrow executive composite from 2 [1–3] to 3 [2–4] (p=0.001). Delayed recall increased from 1 [0–2] to 2.5 [0–4] (p=0.024). However, executive function remained the most persistently impaired domain, particularly among older patients (>65 years). At last follow-up, despite similar treatment timing, older patients exhibited more severe and persistent deficits than younger patients in total MoCA (19 [15.8-24] vs. 26 [24-27.8], p=0.016) and EIS (9.5 [7.5-10.2] vs. 12.5 [11.2-13.0], p=0.009).
Conclusions:
Executive dysfunction is a prominent and persistent long-term cognitive deficit in LGI1-AE, challenging previous assumptions that it is predominantly transient. Patients over 65 have worse cognitive outcomes than younger patients. These findings underscore the need for domain-specific cognitive monitoring and targeted rehabilitation, particularly for older adults.
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