Long-term outcomes in antibody-negative autoimmune encephalitis: a retrospective study

J Neurol. 2024 Dec;271(12):7502-7515. doi: 10.1007/s00415-024-12680-y. Epub 2024 Sep 15.

Abstract

Background and objective: Despite constituting one-third of suspected autoimmune encephalitis (AE) patients, antibody-negative cases without typical AE features are understudied. We aim to characterize the clinical phenotypes and long-term outcomes of "possible only" and "probable" AE cases.

Methods: We conducted a retrospective analysis of adult patients evaluated at Mayo Clinic's Autoimmune Neurology Clinic (01/01/2006-12/31/2020), meeting diagnostic criteria for "possible only" or "probable but antibody-negative" AE, with ≥ 1 year of follow-up. All patients underwent neural antibody testing.

Results: Among fifty-one patients, six had a change in diagnosis (non-autoimmune, 2) and were excluded from further analysis. Forty-five patients were analyzed [median age, 61 years (range 20-88); female, 21 (47%); median follow-up, 36 months (range 12-174)]. A nadir modified Rankin Scale (mRS) ≥ 3 was recorded in 41/45 (91%). CSF was inflammatory in 20/44 (45%) and MRI had encephalitic changes in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two patients (4%) had paraneoplastic causation. Relapses (> 3 months from onset) were noted in 14 (31%). Memory dysfunction (69%), attention deficits (38%), and gait instability (29%) were the most frequent at the last follow-up. Most patients (76%) were independent at the last follow-up and only two required an assistive device to ambulate; 11 patients (24%) had poor neurological outcome (mRS ≥ 3). Higher mRS score and gait assistance requirement at 3 months were predictive of poor outcome (P ≤ 0.01).

Discussion: Despite significant disability at initial disease stages, most antibody-negative AE patients regain independent functioning. Early functional status and gait assistance requirements may predict long-term prognosis.

Keywords: Autoimmune diseases of the nervous system; Encephalomyelitis; Limbic encephalitis; Meningoencephalitis; Neural autoantibodies; Seronegative autoimmune encephalitis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood
  • Autoantibodies / cerebrospinal fluid
  • Autoimmune Diseases of the Nervous System / diagnosis
  • Autoimmune Diseases of the Nervous System / immunology
  • Autoimmune Diseases of the Nervous System / physiopathology
  • Encephalitis* / cerebrospinal fluid
  • Encephalitis* / diagnosis
  • Encephalitis* / immunology
  • Female
  • Follow-Up Studies
  • Hashimoto Disease / diagnosis
  • Hashimoto Disease / immunology
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Young Adult

Substances

  • Autoantibodies

Supplementary concepts

  • Hashimoto's encephalitis