Objective: To characterize the long-term outcomes of patients with "possible only" or "probable" autoimmune encephalitis (AE).
Background: Despite comprising one-third of AE cases, antibody-negative cases lacking typical AE-defining features are understudied.
Design/methods: We conducted a retrospective analysis of adult patients evaluated at a tertiary center neuroimmunology practice from 2006 to 2020, meeting diagnostic criteria for "possible only" or "probable but antibody-negative" AE, with at least one year of follow-up. All patients underwent neural antibody testing.
Results: Forty-five patients (median age, 61 years [range, 20-88]; female, 21 [47%]) were included, with a median follow-up of 36 months (range, 12-174). A change in diagnosis was noted in six additional patients, who were excluded from further analysis, with only two receiving a non-autoimmune diagnosis during follow-up. The majority (41/45 [91%]) presented with significant disability (modified Rankin Scale [mRS] ≥3) at baseline. CSF was inflammatory in 20/44 (45%) and MRI was abnormal in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two cases (4%) had a paraneoplastic cause. The median time from onset to immunotherapy initiation was two months (range, 0-21), resulting in at least partial improvement in all 44 (98%) treated cases. Clinical relapses occurred in 14/45 (31%). At last follow-up, the most common symptoms were memory dysfunction (31/45 [69%]), attention deficits (17/45 [38%]), gait instability (13/45 [29%]), and visuospatial dysfunction (10/45 [22%]). Most patients achieved independence (median mRS, 2 [range, 0-6]); however, 11 patients had poor neurological outcome (mRS ≥3). Higher mRS score and gait assistance requirement at three months were predictive of poor outcome (P ≤0.01).
Conclusions: Despite significant disability at initial stages, patients with antibody-negative but clinically presumed AE show potential for improvement with immunotherapy, highlighting the importance of early intervention. Early functional status and gait assistance requirements may assist in predicting long-term prognosis.