Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb;67(2):195-207.
doi: 10.1111/dmcn.16067. Epub 2024 Aug 14.

International consensus definitions for infection-triggered encephalopathy syndromes

Hiroshi Sakuma  1 , Terrence Thomas  2 , Carly Debinski  3 , Michael Eyre  4   5 , Velda X Han  6   7 , Hannah F Jones  8 , Go Kawano  9 , Vanessa W Lee  10   11 , Stephen Malone  12 , Toyojiro Matsuishi  9   13   14 , Shekeeb S Mohammad  15 , Takayuki Mori  1   16 , Hiroya Nishida  1   17 , Margherita Nosadini  18   19 , Jun-Ichi Takanashi  20 , Masashi Mizuguchi  21 , Ming Lim  10   22 , Russell C Dale  17
Affiliations

International consensus definitions for infection-triggered encephalopathy syndromes

Hiroshi Sakuma et al. Dev Med Child Neurol. 2025 Feb.

Abstract

Aim: To develop standardized diagnostic criteria for 'infection-triggered encephalopathy syndrome (ITES)' and five specific clinical syndromes of ITES.

Method: The draft definitions were based on existing criteria, standardized, and discussed by a panel of international experts using nominal group technique over 18 months to achieve consensus. All criteria use the same format: (1) presence of infection/fever; (2) clinical features including encephalopathy; (3) neuroradiological features on magnetic resonance imaging; (4) exclusion of other causes.

Results: We first highlighted differences between ITES and infectious and autoimmune encephalitis, which is the most important differential diagnosis. Consensus was achieved to define five specific ITESs: acute encephalopathy with biphasic seizures and late reduced diffusion; acute necrotizing encephalopathy; mild encephalopathy with a reversible splenial lesion; acute fulminant cerebral oedema; and acute shock with encephalopathy and multiorgan failure. Two further conditions that are currently classified as epilepsy syndromes but have similar features to ITES, namely febrile infection-related epilepsy syndrome and hemiconvulsion-hemiplegia-epilepsy syndrome, are also discussed.

Interpretation: The consensus definition is expected to improve awareness of this disease concept, provide diagnostic framework, and facilitate future international research and clinical trials.

PubMed Disclaimer

Conflict of interest statement

ME is supported by Action Medical Research and the British Paediatric Neurology Association. ML has received consultation fees from CSL Behring, Novartis, Octapharma, and Roche; grants from Boston Children's Hospital Research Funds, Great Ormond Street Hospital, and Great Ormond Street Hospital/Guy's and St Thomas' Trust/St Mary's Hospital Charity; has received travel grants from Merck Serono; and was awarded educational grants to organize meetings by Novartis, Biogen Idec, Merck Serono, and Bayer.

Figures

FIGURE 1
FIGURE 1
Typical magnetic resonance imaging (MRI) findings in infection‐triggered encephalopathy syndromes. (a–c) MRI on day 4 in acute encephalopathy with biphasic seizures and late reduced diffusion (from Figure 2 in Takanashi and Uetani 26 ). T2‐weighted image shows (a) cortical swelling and T2 prolongation. Diffusion‐weighted image shows symmetrical high‐signal lesions in the bilateral frontoparietal subcortical white matter with (b) sparing around the central sulci with (c) reduced apparent diffusion coefficient. (d–f) MRI on day 4 in acute necrotizing encephalopathy (from Figure 7.6 in Yamanouchi et al., with permission). Bilateral symmetrical thalamic lesion shows (d) low intensity on T1‐weighted image, (e) high intensity on T2‐weighted image, with (f) restricted diffusion. (g,h) MRI in mild encephalopathy with reversible splenial lesion (from Figure 3 in Takanashi and Uetani 26 ). Diffusion‐weighted image shows restricted diffusion in the (g,h) splenium and (h) genu of the corpus callosum.
See this image and copyright information in PMC

References

    1. Mizuguchi M, Ichiyama T, Imataka G, Okumura A, Goto T, Sakuma H, Takanashi JI, Murayama K, Yamagata T, Yamanouchi H, Fukuda T, Maegaki Y. Guidelines for the diagnosis and treatment of acute encephalopathy in childhood. Brain Dev 2021; 43: 2–31. - PubMed
    1. Yamanouchi H, Yamanouchi H, Moshé SL, Okumura A, ScienceDirect . Acute encephalopathy and encephalitis in infancy and its related disorders. St. Louis: Elsevier; 2018.
    1. Mizuguchi M, Yamanouchi H, Ichiyama T, Shiomi M. Acute encephalopathy associated with influenza and other viral infections. Acta Neurol Scand 2007; 115: 45–56. - PubMed
    1. Takanashi J, Oba H, Barkovich AJ, Tada H, Tanabe Y, Yamanouchi H, Fujimoto S, Kato M, Kawatani M, Sudo A, Ozawa H, Okanishi T, Ishitobi M, Maegaki Y, Koyasu Y. Diffusion MRI abnormalities after prolonged febrile seizures with encephalopathy. Neurology 2006; 66: 1304–9; discussion 291. - PubMed
    1. Mizuguchi M, Abe J, Mikkaichi K, Noma S, Yoshida K, Yamanaka T, Kamoshita S. Acute necrotising encephalopathy of childhood: a new syndrome presenting with multifocal, symmetric brain lesions. J Neurol Neurosurg Psychiatry 1995; 58: 555–61. - PMC - PubMed