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Vol. 20 No. 3 (2026)

June 2026

Prognostic Outcomes in Seropositive and Seronegative Autoimmune Encephalitis

  • Mohammad Vafaee Shahi
  • Azita Tavassoli
  • maryam kachuei
  • varham Noruzpour
  • aina riahi
  • Leila Tahernia

Iranian Journal of Child Neurology, Vol. 20 No. 3 (2026), 1 June 2026 , Page 25-34
https://doi.org/10.22037/ijcn.v20i3.51494 Published: 2026-06-01

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Abstract

Objectives:

Autoimmune Encephalitis (AE) is an immune-mediated inflammatory disorder of the central nervous system with heterogeneous clinical manifestations and variable outcomes. The prognostic significance of antibody status (seropositive vs. seronegative) remains incompletely understood, particularly in Iranian populations. This study aimed to compare clinical characteristics, therapeutic interventions, and prognostic outcomes between seropositive and seronegative patients with AE (≤ 18 years) admitted to two tertiary referral hospitals in Tehran, Iran.

Material & Methods:

In this study, medical records of 58 patients diagnosed with AE between 2019 and 2024 at Ali Asghar and Hazrat Rasool Hospitals were reviewed. Patients were classified as seropositive or seronegative based on antibody testing.

Results:

Of the 58 patients, 31 (53.4%) were seropositive and 27 (46.6%) were seronegative. The mean age was 41.94 ± 24.87 months, and 72.4% were male. Seizures were the most common clinical manifestation. No significant differences were observed between seropositive and seronegative groups in initial disease severity, functional outcomes, neurological complications, treatment allocation (all p > 0.05). In multivariable analysis, initial disease severity (OR = 13.3, p = 0.032) and the presence of underlying diseases (OR = 31.4, p = 0.007) were independently associated with poor prognosis, whereas serologic status was not.

Conclusion:

Serologic status does not significantly influence disease severity, treatment response, or prognosis in patients with AE. Initial clinical severity and comorbidities are the primary determinants of poor outcome. Management strategies should prioritize early recognition, assessment of disease severity, and timely immunotherapy regardless of antibody status.

Keywords:
  • Autoimmune Encephalitis, Seropositive, Seronegative, Outcome
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How to Cite

Vafaee Shahi, M., Tavassoli, A., kachuei, maryam, Noruzpour, varham, riahi, aina, & Leila Tahernia. (2026). Prognostic Outcomes in Seropositive and Seronegative Autoimmune Encephalitis. Iranian Journal of Child Neurology, 20(3), 25–34. https://doi.org/10.22037/ijcn.v20i3.51494
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References

1. Dubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166–77.

2. Seery N, Butzkueven H, O’Brien TJ, Monif M. Rare antibody-mediated and seronegative autoimmune encephalitis: an update. Autoimmun Rev. 2022;21(7):103118.

3. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391–404.

4. Dalmau J, Graus F. Antibody-mediated encephalitis. N Engl J Med. 2018;378(9):840–51.

5. Abu Melha AA, Aldress AS, Alamri F, Aljomah LS, Hommady R, Al-Rumayyan A, et al. Prognostic factors and treatment outcomes in pediatric autoimmune encephalitis: a multicenter study. Front Neurol. 2024;15:1441033.

6. Flanagan EP, Geschwind MD, Lopez-Chiriboga AS, Blackburn KM, Turaga S, Binks S, et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023;80(1):30–9.

7. Simabukuro MM, da Silva GD, Castro LHM, Lucato LT. A critical review and update on autoimmune encephalitis: understanding the alphabet soup. Arq Neuropsiquiatr. 2022;80(S5):143–58.

8. Hardy D. Autoimmune encephalitis in children. Pediatr Neurol. 2022;132:56–66.

9. Pruetarat N, Netbaramee W, Pattharathitikul S, Veeravigrom M. Clinical manifestations, treatment outcomes, and prognostic factors of pediatric anti-NMDAR encephalitis in tertiary care hospitals: a multicenter retrospective/prospective cohort study. Brain Dev. 2019;41(5):436–42.

10. Madani J, Yea C, Mahjoub A, Brna P, Jones K, Longoni G, et al. Clinical features and outcomes in children with seronegative autoimmune encephalitis. Dev Med Child Neurol. 2024.

11. Qiao S, Wu H-K, Liu L-L, Zhang R-R, Wang M-L, Han T, et al. Characteristics and prognosis of autoimmune encephalitis in the east of China: a multi-center study. Front Neurol. 2021;12:642078.

12. Shim Y, Kim SY, Kim H, Hwang H, Chae J-H, Choi J, et al. Clinical outcomes of pediatric anti-NMDA receptor encephalitis. Eur J Paediatr Neurol. 2020;29:87–91.

13. Etemadifar M, Aghababaei A, Nouri H, Kargaran PK, Mohammadi S, Salari M. Autoimmune encephalitis: the first observational study from Iran. Neurol Sci. 2022;43(2):1239–48.

14. Karimzadeh P, Momeni SM, Nasehi MM, Shirvani A. Evaluation of clinical and paraclinical findings in children with autoimmune encephalitis. 2023.

15. Gao W, She J, Su L, Jin S, Yang Q, Chen X, Zhu R. Clinical features and immunotherapy outcomes in antibody-negative autoimmune encephalitis: a retrospective case-control study. Front Neurol. 2024;15:1464165.

16. Lee S, Kim HD, Lee JS, Kang HC, Kim SH. Clinical features and treatment outcomes of seronegative pediatric autoimmune encephalitis. J Clin Neurol. 2021;17(2):300–6.

17. Berger B, Hauck S, Runge K, Tebartz van Elst L, Rauer S, Endres D. Therapy response in seronegative versus seropositive autoimmune encephalitis. Front Immunol. 2023;14:1196110.

1. Dubey D, Pittock SJ, Kelly CR, McKeon A, Lopez-Chiriboga AS, Lennon VA, et al. Autoimmune encephalitis epidemiology and a comparison to infectious encephalitis. Ann Neurol. 2018;83(1):166–77.

2. Seery N, Butzkueven H, O’Brien TJ, Monif M. Rare antibody-mediated and seronegative autoimmune encephalitis: an update. Autoimmun Rev. 2022;21(7):103118.

3. Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391–404.

4. Dalmau J, Graus F. Antibody-mediated encephalitis. N Engl J Med. 2018;378(9):840–51.

5. Abu Melha AA, Aldress AS, Alamri F, Aljomah LS, Hommady R, Al-Rumayyan A, et al. Prognostic factors and treatment outcomes in pediatric autoimmune encephalitis: a multicenter study. Front Neurol. 2024;15:1441033.

6. Flanagan EP, Geschwind MD, Lopez-Chiriboga AS, Blackburn KM, Turaga S, Binks S, et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023;80(1):30–9.

7. Simabukuro MM, da Silva GD, Castro LHM, Lucato LT. A critical review and update on autoimmune encephalitis: understanding the alphabet soup. Arq Neuropsiquiatr. 2022;80(S5):143–58.

8. Hardy D. Autoimmune encephalitis in children. Pediatr Neurol. 2022;132:56–66.

9. Pruetarat N, Netbaramee W, Pattharathitikul S, Veeravigrom M. Clinical manifestations, treatment outcomes, and prognostic factors of pediatric anti-NMDAR encephalitis in tertiary care hospitals: a multicenter retrospective/prospective cohort study. Brain Dev. 2019;41(5):436–42.

10. Madani J, Yea C, Mahjoub A, Brna P, Jones K, Longoni G, et al. Clinical features and outcomes in children with seronegative autoimmune encephalitis. Dev Med Child Neurol. 2024.

11. Qiao S, Wu H-K, Liu L-L, Zhang R-R, Wang M-L, Han T, et al. Characteristics and prognosis of autoimmune encephalitis in the east of China: a multi-center study. Front Neurol. 2021;12:642078.

12. Shim Y, Kim SY, Kim H, Hwang H, Chae J-H, Choi J, et al. Clinical outcomes of pediatric anti-NMDA receptor encephalitis. Eur J Paediatr Neurol. 2020;29:87–91.

13. Etemadifar M, Aghababaei A, Nouri H, Kargaran PK, Mohammadi S, Salari M. Autoimmune encephalitis: the first observational study from Iran. Neurol Sci. 2022;43(2):1239–48.

14. Karimzadeh P, Momeni SM, Nasehi MM, Shirvani A. Evaluation of clinical and paraclinical findings in children with autoimmune encephalitis. 2023.

15. Gao W, She J, Su L, Jin S, Yang Q, Chen X, Zhu R. Clinical features and immunotherapy outcomes in antibody-negative autoimmune encephalitis: a retrospective case-control study. Front Neurol. 2024;15:1464165.

16. Lee S, Kim HD, Lee JS, Kang HC, Kim SH. Clinical features and treatment outcomes of seronegative pediatric autoimmune encephalitis. J Clin Neurol. 2021;17(2):300–6.

17. Berger B, Hauck S, Runge K, Tebartz van Elst L, Rauer S, Endres D. Therapy response in seronegative versus seropositive autoimmune encephalitis. Front Immunol. 2023;14:1196110.

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