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    Patients with antibody-negative autoimmune encephalitis (AE) can improve with immunotherapy, despite initial severe disability. Early treatment and monitoring functional status are key for better long-term outcomes in these understudied AE cases.

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    Area of Science:

    • Neuroimmunology
    • Neurology

    Background:

    • Antibody-negative autoimmune encephalitis (AE) constitutes a significant portion of AE cases but remains understudied.
    • Cases lacking typical AE-defining features are particularly underrepresented in research.

    Purpose of the Study:

    • To characterize the long-term outcomes of patients diagnosed with "possible only" or "probable" autoimmune encephalitis (AE).
    • To evaluate the efficacy of immunotherapy and identify predictors of long-term prognosis in antibody-negative AE.

    Main Methods:

    • Retrospective analysis of adult patients with "possible only" or "probable but antibody-negative" AE from 2006-2020.
    • Inclusion criteria required at least one year of follow-up; all patients underwent neural antibody testing.
    • Data collected included baseline disability (modified Rankin Scale [mRS]), CSF and MRI findings, time to immunotherapy, and clinical outcomes.

    Main Results:

    • Forty-five patients were included, with a median follow-up of 36 months. Most presented with significant disability (mRS ≥3) at baseline.
    • Immunotherapy led to at least partial improvement in 98% of treated patients, though 31% experienced relapses.
    • Common long-term symptoms included memory dysfunction (69%) and attention deficits (38%). Most achieved independence (median mRS 2), but 11 had poor outcomes (mRS ≥3).

    Conclusions:

    • Patients with clinically presumed antibody-negative AE can achieve significant improvement with immunotherapy, underscoring the importance of early intervention.
    • Early functional status (mRS) and the need for gait assistance at three months post-onset are predictive of long-term neurological outcomes.