We investigated a series of patients with LGI1 antibody (Ab)–related cognitive deterioration to determine the clinical presentation, long-term outcome, and LGI1 Ab evolution.

We retrospectively analyzed the clinical information of 76 patients with LGI1 Ab–related cognitive deterioration. Presenting syndromes were classified as limbic encephalitis (LE), non-LE, or encephalopathy (normal MRI and no CSF pleocytosis). Frequency of relapses and clinical outcome were assessed in 48 patients with prolonged follow-up (median 39 months, range 18–200).

Sixty-three patients (83%) developed LE, 3 (4%) non-LE, and 10 (13%) encephalopathy. All patients received steroids, IV immunoglobulins (Ig), or both. At 2 years, 17 (35%; 95% CI 21%–49%) fully recovered, 17 (35%) became functionally independent but not at baseline or were unable to return to work, 11 (23%) required assistance because of moderate or severe cognitive deficits, and 3 (6%) died. Predictors of bad outcome included no response to initial immunotherapy (odds ratio 23.0, 95% CI 2.4–215.6, p = 0.006) and clinical relapses (odds ratio 10.2, 95% CI 1.0–100.1, p = 0.047) that occurred in 13 patients (27%). In all patients, the LGI1 Abs were IgG4 and usually detectable in both serum and CSF (only CSF, 8%). Abs remained positive in serum of 4 of 16 patients with long-term follow-up; 3 of these 4 patients fully recovered and none showed class switch to IgG1.

Up to 13% of patients with LGI1 Abs develop cognitive impairment without criteria of encephalitis. After immunotherapy, only 35% of patients return to their baseline cognitive function. Serum LGI1 Abs may remain detectable after full clinical recovery.