Status epilepticus (SE) is a life-threatening persistent epileptic seizure that can arise from various brain structures, leaving its brain circuit unknown. In this study, we utilize brain imaging changes during SE to reveal the brain architecture and circuit of persistent seizures. Multimodal lesion mapping identified that brain imaging changes during SE localize to a specific predisposed brain architecture characterized by increased metabolic rate, high synaptic and mitochondrial density, glutamate (mGLUR5 and NMDA) and GABA receptors. Gene expression patterns within lesion locations revealed a transcriptomic profile enriched for epilepsy pathologies (including SE), neuronal and synaptic processes, and glutamate signaling. Lesion network mapping demonstrated these same lesions map to a common brain circuit, unifying a traditionally heterogeneous patient population. Findings were validated in an independent cohort and the identified SE circuit distinguished brain imaging changes during SE from other lesion etiologies with excellent accuracy (91%), significantly outperforming all other tested maps. With this SE circuit, we identify therapeutic targets for precision therapy that could modulate this circuit. This study demonstrates brain imaging changes in SE converge on a unified brain circuit that could help diagnostic workup of patients in critical care and guide clinical trials of precision therapy for persistent seizures.

Abstract Status epilepticus (SE) is a neurological emergency with a mortality of up to 39% in population-based studies. Animal studies suggest that, beyond a critical timepoint (t2), SE induces neuronal injury exceeding what can be expected from the underlying aetiology, but in vivo evidence in humans is scarce. Thirty-six prospectively recruited individuals with SE with a mean age of 59 years underwent serial high-resolution T1-weighted brain MRI over a mean follow-up period of 5 months and were compared with 34 individuals with drug-resistant focal epilepsy and 36 propensity-score matched healthy controls. Cortical thickness and deep grey matter volumes were estimated and harmonised to account for scanner-related effects. Longitudinal change was assessed using linear mixed-effects models adjusting for age at baseline, interscan interval and sex between groups. We further investigated the independent effects of SE duration, semiology and level of consciousness after mutual adjustment for each variable as well as aetiology, as well as longitudinal structural signatures associated with key locations of peri-ictal MRI abnormalities (PMA). SE was associated with pronounced bilateral hippocampal atrophy in comparison to normal aging and drug-resistant epilepsy, alongside volume increase in several deep grey matter nuclei as well as a trend for cortical thinning of medial brain structures. SE duration was the strongest independent driver of brain change, producing widespread cortical thinning and bilateral hippocampal atrophy. A convulsive semiology was independently associated with accelerated medial temporal cortical thinning and bilateral hippocampal volume loss when compared with non-convulsive (NCSE) and other prominent-motor SE, while reduced consciousness predicted faster thinning of medial frontoparietal cortex. PMA was associated with distinct longitudinal trajectories of subcortical volume, with pulvinar and hippocampus involvement predicting thalamic and hippocampal atrophy patterns. According to our findings, a single episode of SE was therefore associated with a measurable structural imprint in the brain that evolved over months beyond what would be expected for aetiology alone. Atrophy trajectories highlighted the vulnerability of the hippocampus and other limbic structures during the peri-ictal state. A long SE duration, together with convulsive semiology and impaired consciousness, independently amplified this damage. These findings corroborate the timepoint-based (t2) concept of SE and reinforce the clinical imperative of rapid seizure termination to contain long-term structural brain injury.

Objective To delineate the phenotype of juvenile myoclonic epilepsy (JME) with a focus on obsessive–compulsive personality disorder (OCPD) using multimodal psychiatric, neuropsychological, quantitative EEG (qEEG), and structural MRI markers within a predictive-processing/free-energy framework. Methods We prospectively studied 65 patients with JME and 68 matched healthy controls (HC). Participants completed DSM-IV SCID I/II interviews and a neuropsychological battery assessing working memory, psychomotor speed, mental flexibility, divided attention, inhibition, and phasic/tonic alertness; standard EEG and high-resolution structural MRI were acquired. Groups comprised HC and JME subgroups without psychiatric comorbidity, with non-OCPD Axis I/II diagnoses, and with OCPD. Welch’s t-tests (FDR-corrected) and Hedges’ g quantified neuropsychological and alpha-band coherence differences. Surface-based analyses assessed cortical thickness/surface area. Exploratory regressions tested associations of OCPD, seizure freedom, and antiseizure medication (ASM) load with cognition; Kendall’s tau tested coherence–cognition associations. Results Compared with HC, JME showed broad executive–attentional impairment, most pronounced in patients with psychiatric comorbidity. The OCPD subgroup exhibited particularly large slowing in psychomotor speed, inhibition (reaction time), and tonic alertness versus HC, while OCPD versus non-OCPD JME differences did not survive multiple-comparison correction. qEEG showed increased interhemispheric frontal and decreased temporal alpha coherence in JME, with temporal hypo-coherence strongest in those with psychiatric comorbidity; within JME, OCPD was linked to increased left fronto-temporal alpha coherence. In the MRI subsample, JME-OCPD demonstrated increased cortical thickness in left medial orbitofrontal and anterior cingulate regions (vs HC and vs JME without OCPD) and additional posterior occipito-temporal clusters versus HC. Regression and coherence–cognition associations were weak and non-significant after FDR correction. Significance JME features syndrome-level executive–attentional dysfunction and altered fronto–temporal network organization. Comorbid OCPD marks a subgroup with accentuated cognitive slowing and distinct medial prefrontal/cingulate structural and left fronto-temporal connectivity signatures, aligning with predictive-processing accounts of rigid, over-precise high-level priors. Key points JME is linked to broad executive–attentional impairment versus healthy controls. Psychiatric comorbidity amplifies cognitive deficits in JME. JME with OCPD shows particularly large slowing/inhibitory-control deficits versus controls, while OCPD vs non-OCPD differences within JME are modest. Alpha-band EEG coherence indicates altered network organization in JME and an OCPD-related increase in left fronto–temporal coherence within JME Surface-based MRI suggests an OCPD-related structural phenotype in JME, involving medial orbitofrontal/anterior cingulate cortical thickening ### Competing Interest Statement Eugen Trinka reports personal fees from EVER Pharma, Marinus, Argenx, Arvelle/Angelini, Medtronic, Bial Portela & C, S.A., NewBridge, GL Pharma, GlaxoSmithKline, Hikma, Boehringer Ingelheim, LivaNova, Eisai, UCB, Biogen, Genzyme Sanofi, GW Pharmaceuticals/Jazz, and Actavis outside the submitted work; his institution received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union, FWF Oesterreichischer Fond zur Wissenschaftsforderung, Bundesministerium fuer Wissenschaft und Forschung, and Jubilaeumsfond der Oesterreichischen Nationalbank outside the submitted work. Georg Zimmermann gratefully acknowledges the support of the WISS 2025 project 'IDA-Lab Salzburg' (20204-WISS/225/197-2019 and 20102-F1901166-KZP) The remaining authors have no conflicts of interest. ### Funding Statement This work was supported by the Austrian Science Fund (FWF), Project Number: KLI 543 B-27 and was generated within the European Reference Network for Rare and Complex Diseases EpiCARE. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All participants gave written informed consent; the study was approved by the Ethikkommission des Bundeslandes Salzburg (ethics committee of the state of Salzburg, Austria) (No. E1638) and conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data supporting the findings of this study are available from the corresponding author upon reasonable request. Study datasets are not made publicly available due to ethical and data protection restrictions.

BACKGROUND AND OBJECTIVES:Reliable prediction of short-term mortality in status epilepticus (SE) can contribute to guide clinical decisions. Current prognostic systems achieve only acceptable predictive power and show lack of generalizability or poor calibration. We aimed to identify clinical predictors of short-term mortality in patients with nonhypoxic SE and develop a predictive score. METHODS:This was a multicenter, multinational cohort study based on registry data. Participants were consecutive episodes of SE in participants aged 14 years or older from Modena (Italy) (derivation cohort) and in participants aged 18 years or older from Salzburg (Austria) (validation cohort). The predefined outcome was 30-day mortality after the onset of SE. Age, sex, level of consciousness before treatment, semiology of SE, level of disability at baseline before SE, etiology, and treatment refractoriness were assessed. Adjusted regression coefficients of each independent predictor were transformed to produce a points-based risk scoring system. RESULTS:The Italian cohort included 689 episodes, and the Austrian cohort comprised 569 episodes of SE. In the derivation cohort, the 30-day mortality rate was 27.3%. The independent risk factors were aged 75 years or older (odds ratio [OR] 5.52, 95% CI 3.45-8.83; p < 0.001), consciousness impairment (stuporous or comatose) before SE treatment (OR 1.76, 95% CI 1.09-2.82; p = 0.020), acute etiology due to primary CNS pathology (OR 2.60, 95% CI 1.60-4.23; p < 0.001), refractoriness to treatment (OR 6.40, 95% CI 3.91-10.46; p < 0.001), and disability before SE onset (OR 3.53, 95% CI 2.22-5.61; p < 0.001); remote etiology was independently associated with a lower likelihood of 30-day mortality (OR 0.28, 95% 0.13-0.61; p = 0.001). An integer-based scoring system termed Age, Consciousness, Aetiology, Refractoriness, Disability (ACARD) was developed by combining these independent predictors. In the validation cohort, the 30-day mortality rate was 11.6%. The area under the curve of the ACARD score was 0.864 (95% CI 0.836-0.891) in the derivation cohort and 0.845 (95% CI 0.801-0.888) in the validation cohort. Calibration plot indicated good fit of predicted and observed data in both cohorts. DISCUSSION:The ACARD score is a user-friendly tool developed to predict 30-day mortality after nonhypoxic SE. It has the potential to identify participants at high risk of short-term mortality and outperform the performance of other available scoring systems.

OBJECTIVE:Status epilepticus (SE) is the most severe expression of seizures, encompassing both SE with prominent motor symptoms and nonconvulsive SE (NCSE). Ictal-interictal continuum (IIC), an electroencephalographic phenomenon, is characterized by periodic discharges (PD), spike-and-waves or sharp-and-waves (SW), or lateralized rhythmic delta activity (LRDA). Peri-ictal magnetic resonance imaging (MRI) abnormalities (PMA) may offer a potential surrogate marker for ictal activity, yet their association with IIC remains unclear. We aimed to investigate the occurrence of PMA in patients with SE and IIC, and to determine the relationship between IIC patterns and PMA through a latent cluster analysis (LCA). METHODS:In a prospective cohort study, 223 adult patients diagnosed with SE or IIC underwent electroencephalography (EEG) and MRI within 48 h of diagnosis. Patients were stratified into two groups: the IIC group and SE group. PMA were assessed using the following MRI sequences: diffusion-weighted imaging, fluid-attenuated inversion recovery, and arterial spin labeling. LCA was performed to identify classes based on etiology, EEG patterns, and their localization. RESULTS:PMA were as frequent in patients of the IIC group (23/49, 47%) as in patients of the SE group (64/149, 43%, p = .37). In the IIC group, peri-ictal hyperperfusion was more frequently associated with lower frequency PD/SW (.5-1 Hz; 12/19, 63%), followed by LRDA (4/13, 31%) and higher frequency PD/SW (>1-2.5 Hz; 4/17, 24%). LCA revealed two classes; Class 1, characterized by nonunilateral high-frequency PD/SW and triggering factors in epilepsy, had fewer PMA (18%) as compared to Class 2, characterized by predominantly unilateral low-frequency PD/SW and diverse etiologies (50%; odds ratio = 5.79, p = .02). SIGNIFICANCE:PMA occurrence in IIC aligned closely with that in SE, suggesting an overlap between IIC and SE and raising the critical question of whether patients with IIC may have NCSE. We propose an etiology-driven approach for EEG interpretation in IIC, which may enhance diagnostic accuracy and treatment strategies.

Background and Objectives Status epilepticus (SE) is a neurologic emergency with possible long-term sequelae, including the development of epilepsy. We aimed to determine whether peri-ictal MRI abnormalities (PMA) are associated with unprovoked seizures after de novo SE.Methods Adults without epilepsy and a first nonhypoxic SE were included from a prospective database of the Christian Doppler University Hospital, Salzburg, Austria. MRI scans performed within 48 hours of SE diagnosis were evaluated for PMA on diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated inversion recovery (FLAIR), and arterial spin labeling (ASL). The outcome was unprovoked seizures, assessed by retrospective review of hospital records and telephone interviews. Cumulative risk of seizures stratified by PMA occurrence (PMA on DWI/FLAIR, hyperperfusion on ASL, no PMA) was evaluated through survival analysis. Multivariable analysis using logistic regression was conducted to assess the influence of PMA, etiology, semiology, and ictal EEG patterns on seizure occurrence.Results Among 135 patients included (median age 70 [interquartile range (IQR) 58-80] years and 55% female), 43 (32%) experienced seizures during a median follow-up of 23 (IQR 9-39) months. The cumulative seizure probability at 1 and 4 years was 34% (95% CI 17-47) and 61% (95% CI 37-75) in patients with PMA on DWI/FLAIR; 0% and 13% (95% CI 0-29) in patients with hyperperfusion on ASL; and 25% (95% CI 14-34) and 36% (95% CI 19-49) in those without PMA. Other SE features associated with higher seizure risk were treatment refractoriness (odds ratio [OR] 2.93, 95% CI 1.23-6.98, p = 0.02), longer SE duration (OR 1.003, 95% CI 1.001-1.004, p = 0.02), and lateralized periodic discharges on ictal EEG (OR 3.59, 95% CI 1.37-9.83, p = 0.005). In multivariable analysis, PMA on DWI/FLAIR (log-odds 1.23, 95% CI 0.13-2.33, p = 0.03) and remote etiology (log-odds 1.85, 95% CI 0.45-3.25, p = 0.009) were independently associated with increased seizure probability.Discussion PMA on DWI or FLAIR were independently linked to a cumulative seizure risk exceeding 60% after de novo SE, consistent with a diagnosis of epilepsy. The findings of our study may help guide long-term treatment decisions in patients with de novo SE.

OBJECTIVE:Polymicrogyria (PMG) is one of the most common human malformations of cortical development and is often classified by its radiographic pattern of distribution. Unilateral polymicrogyria (uPMG) is a subtype of PMG affecting a portion or all of one cerebral hemisphere. As most PMGs occur bilaterally, there has been no specific investigation as to whether the genetic underpinnings of uPMG comprise a subset of or a distinct entity from bilateral PMG. In this study, our goal was to assess both the genetic etiology of uPMG and the value of diagnostic genetic testing in this setting. METHODS:We conducted a retrospective analysis of clinical data from individuals with uPMG seen in the Brain Development and Genetics Clinic and/or research participants of the Walsh Laboratory at Boston Children's Hospital. The final study cohort included 35 individuals from 30 families who were diagnosed with uPMG on brain magnetic resonance imaging (MRI) and also underwent genetic testing. RESULTS:A likely genetic cause was identified in 26.7% (8/30) of unrelated individuals with uPMG in this cohort and segregated within one family (10/35 total subjects). Recessive genetic causes included ASPM, WDR62, and TMEM216. Dominant causes included 22q deletion syndrome, DYNC1H1, SCN3A, and hereditary hemorrhagic telangiectasia (HHT) genes, ACVRL1 and ENG. This is the first report of variants in DYNC1H1, TMEM216, and ACVRL1 in association with uPMG. INTERPRETATION:The genetic causes of bilateral PMG and uPMG can overlap, but some are unique to certain distributions of the malformation. Genetic explanations for uPMG are found at comparable rates to bilateral PMG, suggesting that germline testing for this unique presentation is warranted. ANN NEUROL 2026;99:1277-1286.

OBJECTIVE:Crossed cerebellar diaschisis is a neuroimaging phenomenon observed in various neurological conditions, including status epilepticus. This systematic review aims to summarize the clinical and radiological characteristics of patients developing crossed cerebellar diaschisis following status epilepticus and to discuss potential pathophysiological mechanisms. METHODS:A systematic literature search was conducted using MEDLINE/PubMed, Embase, Web of Science, and CENTRAL from inception to October 2025. Studies reporting crossed cerebellar diaschisis in patients with status epilepticus, confirmed by neuroimaging (MRI, PET, or SPECT), were included. Data on demographics, semiology, etiology, imaging findings, EEG, and outcomes were extracted and synthesized. A spatial analysis of supratentorial MRI abnormalities associated with crossed cerebellar diaschisis was performed in 18 cases with suitable imaging. RESULTS:Sixty patients from 50 studies were included. Mean age was 46.1 years; 50% were female. Convulsive status epilepticus was present in 62% of cases. Etiology was acute in 40%, unknown in 45%. Crossed cerebellar diaschisis was most frequently detected via DWI hyperintensity (55%) and FLAIR/T2 changes (52%). Arterial spin labelling and SPECT often showed hyperperfusion in the acute phase. Spatial mapping of supratentorial MRI abnormalities revealed a predominant involvement of cortical temporo-occipital regions, with minimal subcortical involvement, aligning with known cerebro-cerebellar connectivity patterns. Cerebellar symptoms were rare (5%), but cerebellar atrophy was reported in 7% of cases. Mortality was 10%; 30% recovered completely, while 33% had neurological deficits at discharge. SIGNIFICANCE:Crossed cerebellar diaschisis is a dynamic phenomenon, presenting with both hyper- and hypoperfusion or metabolism, based on the timing and severity of status epilepticus. It may result from increased inhibitory cerebellar activity during seizures, followed by metabolic exhaustion and Purkinje cell loss. Although often clinically silent, it might lead to long-term cerebellar atrophy and neurological sequelae.

OBJECTIVE:Patterns within the ictal-interictal continuum (IIC) are frequently encountered in critically ill patients undergoing continuous electroencephalographic studies and may reflect ongoing ictal activity or secondary brain injury. Peri-ictal neuroimaging abnormalities (PNA) have been described in association with status epilepticus (SE), but their occurrence in patients with IIC across different neuroimaging modalities remains incompletely characterized. We aimed to assess the occurrence of PNA in adults with IIC across structural and functional neuroimaging techniques. METHODS:We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Embase, and Scopus were searched up to January 2026 for studies reporting PNA in adults with IIC. Eligible modalities included magnetic resonance imaging (MRI), CT perfusion (CTP), and positron emission tomography (PET). Pooled detection rates were estimated using random-effects generalized linear mixed models. RESULTS:Of 8400 records identified, seven studies met the inclusion criteria. Of these, four contributed MRI data (98 patients), two-CTP data (38 patients), and two-PET data (30 patients); no SPECT study was identified. One study contributed data to two modalities. Pooled proportion of PNA was 0.41 (95% CI: 0.30-0.52; I2 = 30.4%) for MRI, 0.34 (95% CI: 0.21-0.50; I2 = 0%) for CTP, and 0.90 (95% CI: 0.73-0.97; I2 = 0%) for PET. SIGNIFICANCE:There are currently a limited number of studies evaluating PNA in IIC. PET showed the highest pooled proportion of PNA, although these findings should be interpreted cautiously. Further studies are required to better define the neuroimaging spectrum within the IIC and to clarify its clinical and diagnostic implications.

OBJECTIVE:To assess and compare the detection rates of peri-ictal abnormalities using magnetic resonance imaging (MRI) and computed tomography perfusion (CTP) in patients with non-convulsive status epilepticus (NCSE). METHODS:We conducted a systematic literature search in five databases up to February 2025. Studies reporting peri-ictal MRI abnormalities (PMAs) or cerebral perfusion abnormalities (CPAs) in patients with NCSE were included. Meta-analyses of proportions were performed using a random-effects model. Subgroup analyses and meta-regression were used to compare detection rates across imaging modalities. RESULTS:Nineteen studies were included (15 MRI, 4 CTP), comprising 562 patients for MRI and 72 for CTP. The pooled detection rate of peri-ictal abnormalities was 50.0% (95% confidence interval [CI]: 34.0%-65.0%) for MRI and 79.3% (95% CI: 54.3%-92.5%) for CTP. Among the MRI modalities, arterial spin labeling (ASL) demonstrated the highest detection rate at 88.8% (95% CI: 32.9%-99.2%). CTP showed a significantly higher detection rate than MRI (χ2 = 3.97, p = 0.046); meta-regression indicated increased odds of detection with CTP (odds ratio [OR] = 4.06, 95% CI: 0.97-16.99, p = 0.055). No statistically significant difference was found between ASL and CTP (χ2 = 0.22, p = 0.636). CONCLUSIONS:CTP demonstrates a higher detection rate than conventional MRI for peri-ictal abnormalities in patients with NCSE, supporting its utility in rapid diagnosis and differential workup. Among MRI sequences, ASL showed the highest detection rates, highlighting its potential role in the diagnostic assessment of NCSE. Although MRI remains essential for clarifying etiology, its effectiveness in detecting PMA is highly dependent on the sequences used.

Background/Objectives: Brain magnetic resonance imaging (MRI) often reveals acute peri-ictal abnormalities (PMAs) during or shortly after status epilepticus (SE) but also following single seizures (SiS) or clusters of seizures (CS). However, the incidence, characteristics, and progression remain not clearly known. This study aimed to investigate incidence, clinical correlations, and evolution of PMAs in SE, CS, and SiS patients. Methods: This prospective observational study enrolled patients with SE, CS, and SiS who underwent MRI within 120 h of the ictal event. Demographic, clinical, EEG, and MRI data were collected. Patients with PMAs (PMAs+) underwent serial follow-up MRI. Incidence, association with clinical characteristics, and progression of PMAs were analyzed across the three groups. Results: Among 76 patients (30 SE, 22 CS, 24 SiS), PMAs were observed in 31 (41%), with a significant difference between groups (p = 0.011), as PMAs were less frequent in SiS (17%) compared to SE (57%) and CS (45%) patients. Acute symptomatic SE/seizures were significantly more common in PMAs+ compared to PMAs− in the overall cohort (52% vs. 29%; p = 0.045) and in the SiS group (100% vs. 25%; p = 0.031). History of epilepsy was less frequent in PMAs+ in the whole cohort (13% vs. 40%; p = 0.011) and in SE in particular (12% vs. 46%, p = 0.049). No association between PMAs and seizure type, SE duration, etiology, time to MRI, and EEG findings (p > 0.005) was found. The temporal cortex and hippocampus were most frequently affected by PMAs. Follow-up MRI performed in 16 patients showed resolution of PMAs in 75% (5/7 SE, 3/6 CS, 3/3 SiS) within a median time of 24 days (IQR: 8–39). Conclusions: PMAs were more common in SE and CS than in SiS. Acute underlying pathology was frequently associated with PMAs. While duration of ictal activity is an important factor, it was not the sole determinant. Most PMAs resolved, particularly in SiS. Further studies are needed to clarify the pathophysiological mechanism and clinical implications of PMAs.

Epilepsy is widely known as a network disease. Ictal and interictal activities are generated and spread within the existing networks involving different regions of the brain. Network alterations affect both grey and white matter, deep brain nuclei, including those of the ascending reticular formation. These structures may be involved in a disorganized connectome associated with epilepsy. A growing body of neuroimaging and neuropsychological findings suggests that global and focal network aberrations are closely linked to cognitive deficits in epilepsy patients. This evidence relates equally to focal epilepsies, such as temporal lobe epilepsy or extra-temporal lobe epilepsy, as well as generalized epilepsies, such as juvenile myoclonic epilepsy. Network abnormalities have been associated with a broad range of cognitive impairments, including language, memory, and executive functions, as well as sensory and motor functions. Whole-brain structural connectome models help in the understanding of seizure generation and spread. Identifying key nodes of seizure propagation may help in planning surgical procedures in individual patients by simulating epilepsy surgery on virtual models. Functional connectomic profiles may predict seizure outcomes in patients who undergo deep brain stimulation due to intractable seizures. Therefore, individualized interventional strategies could be developed based on connectome characteristics.

OBJECTIVE:We aimed to investigate timing of occurrence of peri-ictal MRI abnormalities - a potential risk biomarker of status epilepticus-related cerebral injury (t2). METHODS:This prospective study enrolled adult patients with status epilepticus and acute magnetic resonance imaging (MRI); patients with peri-ictal MRI abnormalities underwent follow-up MRI 4 weeks later. Predictive model, using logistic regression, integrated clinical factors (duration, semiology, and etiology of status epilepticus and the patients' level of consciousness) to prognosticate occurrence of peri-ictal MRI abnormalities. Cerebral injury due to status epilepticus was assessed by comparative volumetric analysis of acute and follow-up MRIs. RESULTS:Among 256 patients, 137 (53%) had peri-ictal MRI abnormalities. The likelihood of their occurrence increased over time under the influence of semiology and etiology of status epilepticus as well as the patients' level of consciousness: it was highest in non-convulsive status epilepticus caused by acute primary or secondary etiologies at 10 minutes after onset in patients with stupor/coma (81-85%); it increased at 24 hours to 92%; and at 48 hours to 95%. Conversely, in alert/somnolent patients with prominent motor symptoms and acute triggering factors associated with epilepsy, the possibility of developing peri-ictal MRI abnormalities at 24 hours was 4 to 5% and at 48 hours it was 6 to 11%. In 28 of 45 (62%) of follow-up MRIs, structural long-term consequences of status epilepticus were observed in the form of either cortical and hippocampal atrophy or global cerebral volume loss. INTERPRETATION:In this novel multimodal approach based on MRI data, the patients' level of consciousness, etiology, and duration of status epilepticus offers insights into the risk of possible brain injury in status epilepticus. ANN NEUROL 2026;99:523-534.

BACKGROUND:Accurate identification of the mode of transmission (MoT) of HIV is critical for effective prevention. However, stigma associated with behaviors such as injecting drug use (IDU) and sex between men (MSM) can lead to misclassification of MoT data. This study replicates the methodology used in Ukraine to assess MoT misclassification and trends in Kyrgyzstan, with the aim of informing evidence-based epidemic control strategies. METHODS:A cross-sectional survey was conducted among patients diagnosed with HIV in the six largest administrative units of Kyrgyzstan during the first three quarters of 2021-2023. The survey assessed pre-seroconversion HIV risk factors using self-administered, interviewer-assisted questionnaires, and HCV testing. The McNemar test compared registered and survey-based MoT, while logistic regression analyzed MoT trends over time. RESULTS:A total of 1,962 new HIV diagnoses were registered in the study period, of them 480 individuals completed the survey. The proportion of cases attributable to IDU and MSM was higher in the survey than in the registration system (8.1% vs. 4.2%, p = 0.001 for IDU; 14.2% vs. 11.7% p = 0.12, for MSM), whereas heterosexual MoT was lower (76.0% vs. 80.2%, p = 0.038). Selling sex was reported by 2.9%, and in combination with IDU and MSM, 23.5% of participants could be categorized into one of the three key populations. An additional 18.1% belonged to bridge populations. There was a 23% increase in the absolute number of registered patients in the corresponding periods over three years, but the MoT distribution did not change. CONCLUSION:We found significant misclassification in IDU and heterosexual MoT, but not in MSM, possibly due to suboptimal survey sensitivity amid the increased stigmatization of the LGBTQI+ community. At least 41% of newly registered cases in Kyrgyzstan occurred in key and bridge populations, highlighting the need for intensified prevention efforts in these groups. Understanding the mode of transmission (MoT) of HIV among newly diagnosed people living with HIV (PLHIV) is critical for monitoring the epidemic and targeting prevention efforts [1]. Assessment of MoT often relies on self-reporting of HIV risk behaviors by patients, which can be inaccurate, especially when associated with stigma or criminalization [2-4]. This is particularly true for injecting drug use (IDU), which is criminalized and stigmatized in many countries [5,6]. Stigma and discrimination against men who have sex with men (MSM) exist in many parts of the world [7,8], leading to underreporting of this behavior even in settings with increasing acceptance [9]. Misclassification of MoT in HIV surveillance systems may be exacerbated by the lack of standardized tools to collect sensitive information or by clinicians' reluctance to inquire about behaviors that have no impact on patient management.

Status epilepticus (SE) has long been linked to neuronal damage in experimental and animal studies, yet direct human evidence remains scarce. The risk of seizure-induced brain injury is central to the definition, urgency, treatment, and prognosis of SE. We studied 2,055 longitudinal MRI scans from 559 individuals, including 33 patients with new-onset refractory SE (NORSE) across multiple centres, to quantify grey matter volume changes during and after SE. We demonstrate a rapid, widespread, and irreversible decline in grey matter volume during NORSE, exceeding normal aging by 80-fold and Alzheimer's disease by 20-fold. Fluid biomarkers confirmed marked neurodegeneration during NORSE, correlated with grey matter volume reduction, and returned to low levels after SE. Accelerated atrophy was linked to longer SE duration, poorer long-term outcome, and cryptogenic aetiology. These findings underscore the urgency of treating SE to limit brain damage and provide a framework for evaluating potentially neuroprotective interventions in humans. ### Competing Interest Statement Cyril Simmen received research grants from the Betty & David Koetser Foundation for Brain Research. Marian Galovic reports compensation from Angelini Pharma, Bial, Eisai, Neuraxpharm, and UCB for consultant services. Johan Zelano reports speaker honoraria from UCB, Eisai, Angelini Pharma, and Orion Pharma and as an employee of Sahlgrenska University Hospital being investigator in clinical trials sponsored by Bial, SK Life Science, UCB, and GW Pharma. Nils Briel received research grants from Fondation suisse de recherche sur les maladies musculaires and ETH Zurich MedLab Fellowship programme, none of which are related to this work. Anton Schmick received travel grants from Novo Nordisk and Merck Pharma, none of which is related to this work. Marina Herwerth was supported by the Swiss National Science Foundation (PZ00'3\_216616/1), by the Olga-Mayenfisch-Foundation (2024) and by Betty and David Koetser Foundation. Patrick Roth has received honoraria for lectures or advisory board participation from Alexion, Bristol-Myers Squibb, Boehringer Ingelheim, CDR-Life, Debiopharm, Galapagos, Laminar, Midatech Pharma, Novartis, Novocure, OM Pharma, QED, Roche, Sanofi and Servier and research support from Merck Sharp and Dohme and TME Pharma. Raoul Sutter received research grants from the Swiss National Foundation (No 320030\_169379), the Research Fund of the University Basel, the Scientific Society Basel, and the Gottfried Julia Bangerter-Rhyner Foundation. He received personal grants from UCB-pharma and holds stocks from Alcon, Novartis, Roche, and Johnson & Johnson. Stefan Rueegg has received funding from the Swiss National Science Foundation (grant number 320030_169379/1). He has received honoraria from serving on the scientific advisory boards of Arvelle/Angelini, Bial, Eisai, GW, and UCB-pharma, and from serving as a consultant for Arvelle/Angelini, Eisai, Pfizer, Novartis, Sandoz, and UCB-pharma. He has received speaker's honoraria from Bial, Eisai and Novartis. He does not hold any stocks of any pharmaceutical industries or manufacturers of medical devices. He disclosed that he is Editor-in-chief of Zeitschrift fuer Epileptologie/ Clinical Epileptology (01/01/2022; no payments). Margitta Seeck has shares in Clouds of Care and dEEGtal, and received speaker honoraria from Bial and EISAI. She was funded by the Swiss National Science Foundation (No 180365). Matthew Walker has consulted for Angelini, EpilepsyGtX and Seer and has received honoraria from Angelini, Bioquest, Eisai and UCB pharma. Matthias Koepp or his department has received grants from Angelini, Biohavn, UCB and Xenon, has received consulting fees from Angelini, Bial, Biocodex, Eisai, Jazz Pharma, LivaNova, Sanofi and UCB Pharma, and is co-founder of PrevEp, Inc., and has received research funding from the MRC, Wellcome Trust, Epilepsy Research UK, Epilepsy Society UK, UCLH Foundation Trust, and Henry Smith Foundation. Eugen Trinka reports personal fees from Marinus, Angelini, Argenx, Alexion, Medtronic, BIAL Portela & C, S.A, NewBridge, LivaNova, Eisai, UCB, Biogen, Sanofi, Jazz Pharmaceuticals, STOKE Therapeutics, Rapport, and Actavis. He is co-director of the European Consortium on Epilepsy Trials (ECET). His institution received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union, FWF Oesterreichischer Fond zur Wissenschaftsforderung, Bundesministerium fuer Wissenschaft und Forschung, and Jubilaeumsfond der Oesterreichischen Nationalbank. None related to the presented work. Moritz L Schmidbauer received grants from the Deutsche Forschungsgemeinschaft (DFG, TRR 274). Urs Fisch received research grants from the Bangerter-Rhyner Foundation and the Bouriez Foundation, none of which are related to this work. John Duncan reports research grants from National Institute for Health Research and Epilepsy Research Institute. MH served on scientific advisory boards of Biogen, Merck Serono, Alexion, Roche and Horizon Therapeutics (Amgen), received speaker's honoraria from Biogen and received travel funding from Roche. Her institution received an unrestricted research grant from Roche. Rebecca Liu received personal fees from Angelini, Eisai and UCB Pharma and has received research funding from the Wellcome Trust. FLWVJS was supported by grants from the American Epilepsy Society (846534) and National Institutes of Health (R01NS127892). All other authors do not report conflicts of interest. ### Funding Statement The current study was funded by the Swiss National Science Foundation (Grant number 215619) and the Betty & David Koetser Foundation for Brain Research and supported by the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees of the Canton of Zurich, Canton of Geneva and Canton of Basel gave ethical approval for the Swiss cohort for this work. Ethics committee for the Region of Salzburg gave ethical approval for the Austrian cohort for this work. Ethics committee for LMU Munich gave ethical approval for the German cohort for this work. For the UK cohort, the work was performed as part of a service evaluation, registered and independently approved by the Clinical Audit and Quality Improvement Subcommittee at UCLH University College London Hospitals Trust. This waives the need for approval by an ethics committee, I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available upon reasonable request with formal applications submitted to the respective cohort to protect patient sensitive data. Data from specific cohorts can be requested from the following cohort leaders: University Hospital Zurich, MG (marian.galovic{at}usz.ch); University Hospital of Basel, UF (urs.fisch{at}usb.ch); Hopitaux Universitaires de Geneve, PdS (pia.destefano{at}hug.ch); University College London, SR (s.rajakulendran{at}ucl.ac.uk); LMU University Hospital , MLS (moritz.schmidbauer{at}med.uni-muenchen.de); Christian Doppler University Hospital Salzburg, GK (g.kuchukhidze{at}salk.at); Kantonsspital St. Gallen, DZ (dominik.zieglgaensberger{at}h-och.ch); Prospective Regional Epilepsy Database and Biobank for Individualized Clinical Treatment, JZ (johan.zelano{at}neuro.gu.se). The ADNI data can be requested at the ADNI database (https://adni.loni.usc.edu/). Healthy control data from the Neuromorphometry by Computer Algorithm Chicago and Parkinson Progression Marker Initiative can be requested at https://schizconnect.org and https://www.ppmi-info.org respectively.