難治頻回部分発作重積型急性脳炎

BACKGROUND: Infection-triggered encephalopathy syndromes (ITES) are acute, para-infectious disorders that can cause disability or death. Recognition is increasingly important in viral pandemics, but clinical features and outcomes remain poorly understood. METHODS: PubMed search (inception to 6 March 2024) identified studies with published individual patient data (raw data were not collected from authors). The search was updated on 14 May 2026 using the same terms to identify reports and cases published after the data extraction cutoff. Data were extracted by paediatric neurologists using a standardised proforma. Major syndromes included acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), acute necrotising encephalopathy (ANE), acute shock with encephalopathy and multiorgan failure (ASEM), hemiconvulsion-hemiplegia-epilepsy syndrome (HHE), febrile infection-related epilepsy syndrome (FIRES) and mild encephalopathy with reversible splenial lesion (MERS). We performed a pooled analysis of individual-level published data investigating patient characteristics, infections, and clinical outcomes measured by six-month modified Rankin Scale (mRS). Infection-syndrome associations were analysed with chi-square normalised residuals. FINDINGS: 1946 patients from 656 studies (by ascending age of onset) included 164 ASEM (median age 0.78 years), 217 AESD (1.3 years), 95 HHE (2 years), 414 ANE (3.4 years), 562 FIRES (9 years), and 422 MERS (9.25 years). An updated search identified 658 cases from 171 studies that could be eligible for inclusion. AESD was linked to human herpesvirus 6 (z = 12.87); ANE with influenza A (z = 11.1), SARS-CoV-2 (z = 9.1) and influenza B (z = 4.3); MERS with rotavirus infection (z = 7.48); and FIRES with absence of microbiological identification (z = 18.2) (all p < 0.001).Neuroimaging was often delayed. Magnetic resonance imaging (MRI) brain restricted diffusion was the commonest finding, typically bilateral (except HHE). Characteristic patterns included thalamic involvement with or without haemorrhagic changes in ANE, corpus callosum involvement in MERS, and subcortical white matter involvement in AESD and HHE. Cerebrospinal fluid pleocytosis occurred mostly in FIRES and MERS, and elevated protein in ANE.Immunotherapy (commonly steroids, immunoglobulin) including biologics (anakinra, tocilizumab) was used most in ANE and FIRES. Acute mortality was 12% (227/1946), highest in ASEM (50%) and ANE (35%). There was good six-month outcome (mRS 0-2) in 52% (95% CI 50-55; 615/1174): MERS 99% (95% CI 97-100; 323/326), AESD 54% (95% CI 44-64; 50/93), FIRES 38% (95% CI 33-44; 120/314), ANE 33% (95% CI 27-38; 88/269), HHE 16% (95% CI 7-32; 5/32), and ASEM 15% (95% CI 9-24; 14/91). INTERPRETATION: ITES showed distinct demographic, clinico-radiological features and outcomes. This largest ITES cohort to date highlights the importance of timely imaging, intervention, and future global collaboration to advance diagnosis, treatment, and pandemic preparedness. FUNDING: No funding was received for this work.

BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) is a rare and severe epileptic encephalopathy characterized by refractory seizures following a febrile infection. FIRES is a subtype of new-onset refractory status epilepticus with an unknown etiology. Tocilizumab is an interleukin-6 receptor antagonist which has been recommended as an anti-inflammatory treatment for the acute phase of FIRES. However, the efficacy of tocilizumab for the chronic phase of FIRES remains unclear. This study aimed to analyze the efficacy and safety of tocilizumab in the treatment of pediatric patients with FIRES during the chronic phase. METHODS: We conducted a retrospective cohort study in pediatric patients with FIRES during the chronic phase who received tocilizumab treatment. The primary outcome was the response rate at 16 weeks after tocilizumab initiation, defined as the proportion of pediatric patients who achieved a 50% or greater reduction in seizure frequency. Secondary outcomes included the response rate at 28 weeks, treatment-related adverse events, and changes in the modified Rankin Scale (mRS) scores. The response rate to tocilizumab treatment, incidence of adverse reactions and factors related with the efficacy of tocilizumab were analyzed. RESULTS: Twenty-seven pediatric patients with chronic-phase FIRES were included. The median duration of seizures at tocilizumab initiation was 16 months [interquartile range (IQR): 6-34 months]. All patients received a median of four (IQR: 3-6) doses of tocilizumab. Most patients (81.5%, 22/27) did not require additional anti-seizure medications during the entire treatment period. After 16 weeks of treatment, 63.0% (17/27) of patients achieved a 50% or greater reduction in seizure frequency, and 7.4% (2/27) were seizure free; 70.4% (19/27) of the patients showed improvements in mRS scores. After 28 weeks, the response rate was 48.1% (13/27). The most common adverse events were neutropenia (33.3%, 9/27) and infections (14.8%, 4/27). CONCLUSIONS: Tocilizumab is effective in the treatment of epilepsy in the chronic phase of FIRES. Tocilizumab can reduce the seizure frequency in pediatric patients with FIRES and is relatively safe.

BACKGROUND: Febrile infection‑related epilepsy syndrome (FIRES) is a severe acute inflammation‑associated encephalopathy in children, characterized by high mortality and poor long‑term outcomes. FIRES with claustrum lesions (FIRES‑C) represents a distinct subtype. However, the relationship between its neuroimaging heterogeneity and electrophysiological phenotype remains unclear, and the association between sleep spindles and acute‑phase severity has not been systematically investigated. This study aimed to characterize the electroclinical features of FIRES‑C to facilitate improvements in diagnosis, treatment, and prognostic evaluation. METHODS: This retrospective study enrolled pediatric patients from our previously reported large cohort. We evaluated dynamic electroencephalographic changes across the acute and chronic phases, examined the correlation between sleep spindles and disease severity, and compared differences between isolated claustrum lesions and those with concurrent thalamic/temporal lobe involvement. All statistical analyses were performed using SPSS 26.0. RESULTS: Twenty-one patients with FIRES-C were included, with a median age of onset of 8.33 years. All presented with focal motor seizures and impaired consciousness. Claustrum lesions appeared >10 days after onset in 90.5% of patients, and 76.2% had additional brain involvement. Among the 19 patients who were followed up, 63.2% achieved favorable long-term outcomes. Acute-phase electroencephalography (EEG) revealed absent occipital rhythm, diffuse delta slowing, disrupted sleep architecture, and migratory focal discharges; EEG abnormalities improved markedly during the chronic phase. Patients without sleep spindles exhibited more severe acute clinical manifestations; however, this finding did not correlate significantly with long-term neurological outcomes. Univariate analyses showed that children with isolated bilateral claustrum lesions had milder acute symptoms and better long-term functional prognosis. In contrast, patients with concomitant thalamic and temporal lobe involvement tended to have impaired consciousness, significantly lower detection rates of sleep spindles on EEG, and poorer long-term functional outcomes. CONCLUSION: FIRES-C exhibits characteristic dynamic EEG evolution. The absence of sleep spindles merely indicates a trend toward more severe acute clinical manifestations and cannot serve as a predictor of long‑term functional prognosis. Univariate intergroup comparisons demonstrated that the extent of imaging lesions was correlated with acute disease severity, EEG findings, and long‑term prognosis.

OBJECTIVE(S): Infection Triggered Encephalopathy Syndrome (ITES) is a rare but potentially severe complication of infections in children. ITES is a syndrome of acute encephalopathy that occurs in the context of a febrile illness and hypothesised to result from a cytokine mediated infection-triggered cytotoxicity in the central nervous system (CNS) without parenchymal inflammatory cell infiltration. ITES is considered distinct from infectious and immune-mediated encephalitis. We aimed to describe the demographics, associated pathogens, clinical spectrum and outcomes of ITES in Australian children from May 2013 until June 2024. STUDY DESIGN: We extracted and analysed data from the prospective, multicentre Australian Childhood Encephalitis (ACE) study. Cases of ITES aged ≤14 years were reviewed and categorised by a multidisciplinary expert panel. We estimated the incidence for specific sub-types of ITES. RESULTS: Of 1160 cases of Australian children with suspected encephalitis, 220 met criteria for ITES. In 83% (n=183) an associated pathogen was detected of which influenza (50%; n=109), enterovirus (8%; n=18), SARS-CoV-2 (COVID-19) (7%; n=15), and adenovirus (6%; n=13) were most common. The median age of affected children was 4.3 years (IQR 2-8.1). Of sub-types of ITES, the most frequent was Acute Necrotising Encephalopathy (ANE) (n=28, 13%), followed by Acute Encephalopathy with biphasic Seizures and late reduced Diffusion (AESD) (n=20, 9%), then Mild Encephalopathy with Reversible Splenial lesion (MERS) (n=21, 10%), although most children did not have a specific sub-type (n=135, 61%). For ITES sub-types, incidence was highest for ANE (0.82 per 1,000,000), and lowest for Febrile Infection Related Epilepsy Syndrome (FIRES, 0.23 per 1,000,000). Most children with ITES (60%; n=132) recovered fully. Poorer outcomes were seen in children diagnosed with ITES sub-types including ANE, AESD, and Acute Fulminant Cerebral Edema (AFCE). CONCLUSION(S): ITES is an uncommon complication of common infections in Australian children. Influenza was the most frequently associated pathogen, with ANE the most frequent specific ITES sub-type. Outcomes are variable, but concerningly poor for some ITES sub-types including ANE.