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Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD): a scoping review

Pediatric Research (2025)Cite this article

Abstract

Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion (AESD) is a rare neurological disorder associated with infection, primarily diagnosed in Japanese children, characterized by biphasic seizures, restricted diffusion on magnetic resonance imaging (MRI), and neurological decline. We report an Italian case and provide a scoping review of cases published outside Japan in comparison with Japanese literature, using distinct sets of inclusion criteria as the reported incidence and quality of studies are different. Clinical and epidemiological characteristics are analyzed. Potential factors contributing to this unusual epidemiology are investigated. Our case (3-year-old girl) conforms to typical AESD features. AESD is very rarely reported outside Japan, where only 29 cases have been published (17 female, 2.6 ± 2.7 years). Their features closely resemble the Japanese patients. The only relevant difference is the infectious trigger distribution, with Human herpesvirus-6 (HHV6) predominantly reported in Japan (38.2%), but not in other areas. The morbidity of AESD extends beyond Japan, but it is probably underestimated with rare cases reported globally. Multicenter international studies are needed to clarify the AESD incidence around the world and their related genetic and environmental factors and to promote internationally shared diagnostic criteria and guidelines for acute encephalopathies including AESD.

Impact

  • AESD features are biphasic seizures, MRI restricted diffusion, and neuroregression.

  • AESD is more common in Japan and very rare outside Japan.

  • Clinical and instrumental features of AESD case diagnosed in Italy are reported.

  • Review of Japanese and non-Japanese literature was performed.

  • Genetics, underdiagnosis, underreporting, and environment may influence incidence.

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Fig. 1
Fig. 2: Interictal and ictal EEG at the time of biphasic seizures (day 6).
Fig. 3: Brain MRI on day 6 (acute phase).
Fig. 4: EEG background evolution (2 weeks, 1 month, 18 months).
Fig. 5: Brain MRI 6 months after onset (chronic phase).

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This study was supported by the Italian Ministry of Health (Ricerca Corrente).

Author information

Author notes

  1. These authors contributed equally: Paul B. Lemieux, Francesca Calciano.

Authors and Affiliations

  1. Pediatrics Residency, University of Milan, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Paul B. Lemieux & Francesca Calciano

  2. Child and Adolescent Neuropsychiatry Service (UONPIA), Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Antonella Giacobbe & Claudia Rigamonti

  3. Pneumology and Infectious Diseases Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Raffaella M. Pinzani

  4. Scientific Direction, Omic Science Lab, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Maria T. Molisso & Francesco Gentile

  5. Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

    Vidal Yahya

  6. Neurology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Vidal Yahya & Edoardo Monfrini

  7. Neuroradiology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Fabio Triulzi

  8. Department of Neuroscience and Mental Health, Neurophysiopathology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Robertino Dilena

Authors
  1. Paul B. Lemieux
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Contributions

Paul Bernard Lemieux: methodology, investigation and data curation, writing - original draft preparation, writing - reviewing and editing. Francesca Calciano: methodology, investigation and data curation, writing - original draft preparation, writing - reviewing and editing. Antonella Giacobbe: writing - reviewing and editing. Claudia Rigamonti, writing - reviewing and editing. Raffaella Maria Pinzani: writing - reviewing and editing. Maria Takeko Molisso, writing - reviewing and editing. Francesco Gentile: whole-exome sequencing and reviewing. Vidal Yahya: writing - reviewing and editing. Edoardo Monfrini: writing - reviewing and editing. Fabio Triulzi: writing - reviewing and editing. Robertino Dilena: conceptualization, methodology, writing - reviewing and editing.

Corresponding author

Correspondence to Maria T. Molisso.

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Signed consent was obtained by the parents of the described patient for the publication of this article. No ethical approval was required for the systematic review as it involved the analysis and synthesis of previously published data.

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Lemieux, P.B., Calciano, F., Giacobbe, A. et al. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD): a scoping review. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04550-8

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