European Journal of Cardiovascular Medicine

Non-traumatic acute encephalopathy (AE) in children presents with altered mental status, seizures, or behavior change and arises from diverse etiologies including infectious/immune-mediated encephalitis, autoimmune encephalitis (AEI), metabolic derangements, cerebrovascular injury, and post-anoxic injury. A rapid, structured diagnostic approach is crucial to enable time-sensitive therapies such as antivirals, immunotherapy, and seizure control.1,2 MRI—particularly DWI and FLAIR—detects cortical and subcortical cytotoxic/vasogenic edema and limbic or thalamic patterns typical of encephalitides with higher sensitivity than CT and without ionizing radiation.1–4,9 Early MRI can also stratify severity and predict short-term outcomes in pediatric encephalitis, where the burden and distribution of lesions correlate with ventilatory need and recovery.5

Practice statements and consensus documents in pediatrics emphasize minimizing unnecessary CT, optimizing MRI workflows, and leveraging fast/ultrafast MRI protocols to reduce sedation requirements and expedite acquisition in the emergency department (ED).3,4,6 Technical advances (e.g., ultrafast T2/DWI packages, motion-tolerant sequences) now permit abbreviated protocols with acceptable diagnostic performance, improving access within the first 24 hours of presentation.6,7 In autoimmune phenotypes such as anti-NMDAR encephalitis, MRI may be normal initially but can still aid differential diagnosis, while certain diffusion-restriction patterns may prompt alternative etiologies.8,9 Perfusion (e.g., arterial spin labeling) can further support early inflammatory hyperperfusion in viral encephalitis.10

Despite these developments, the optimal timing of imaging remains a practical dilemma dictated by resource availability, sedation, and clinical stability. Adult and neonatal data suggest complementary value of very early imaging (injury timing) and subacute scans (lesion evolution),11,12 but pediatric evidence directly comparing “early” versus “delayed” imaging yield in non-traumatic AE is limited and heterogeneous across centers.1,2,5,7 Consequently, many services default to CT in the ED with MRI deferred, even though CT has substantially lower sensitivity for encephalitic and autoimmune patterns and exposes children to radiation.1–3,13

This manuscript provides a rigorous, ready-to-analyze structure for comparing early versus delayed neuroimaging in pediatric AE. We (i) define clinically meaningful timing windows; (ii) specify primary and secondary outcomes centered on “actionable yield” (findings that explain AE or change management); and (iii) illustrate expected effect sizes using a simulated dataset aligned with contemporary literature favoring MRI and fast protocols. Our goal is to offer a pragmatic template that departments can populate with local data to benchmark workflows and to guide policy toward earlier MRI when feasible, in line with modern pediatric imaging guidance and encephalitis care pathways.1–7.

This is a Comparative cohort framework suitable for retrospective or prospective implementation in a tertiary pediatric ED and inpatient service. Consecutive children (1 month–18 years) presenting with non-traumatic AE are eligible.

Inclusion: (1) Age 1 month–18 years; (2) non-traumatic AE at presentation; (3) underwent neuroimaging within 7 days; (4) available clinical follow-up ≥30 days or until discharge.

Exclusion: (1) Traumatic brain injury; (2) isolated metabolic encephalopathy fully reversed within hours with no imaging; (3) known progressive neurodegenerative disease with baseline encephalopathy; (4) prior neuroimaging for the same episode at an outside facility without image access; (5) contraindication to MRI with no alternative.

Imaging protocols:
MRI brain (preferred first-line when feasible) with abbreviated ED protocol: axial DWI/ADC, T2, FLAIR, susceptibility-weighted imaging; add post-contrast and MRA/ASL as indicated.1,3,6,10 Ultrafast packages may be used in unstable patients to minimize sedation.6 CT head non-contrast reserved for rapid triage when MRI unavailable/contraindicated or to exclude hemorrhage/herniation.1–4

Definitions:

• Acute encephalopathy (AE): Altered mental status ≥1 hour or new persistent neurological dysfunction (e.g., confusion, GCS reduction, agitation, psychosis, focal deficits, status epilepticus) unexplained by head trauma.2,14
• Imaging timing windows:
  • Early: first neuroimaging (CT and/or MRI) ≤24 h from ED arrival
  • Delayed: >24–72 h
  • Late: >72 h
• Actionable diagnostic yield (primary outcome): Imaging result that (a) explains AE etiology or (b) directly changes management (initiation/cessation/intensification of antivirals, antibiotics, immunotherapy, antiepileptic escalation, PICU transfer, surgery, or anticoagulation).2,5,7
• Secondary outcomes: (i) Modality-specific yield (MRI vs CT); (ii) management change proportion; (iii) adverse events (sedation-related, contrast reactions); (iv) length of stay and PICU utilization.

Data collection: Demographics, presentation features, seizures/status epilepticus, fever/infection markers, LP/virology/autoantibody panels, hemodynamics, labs, treatment timelines, imaging modality/timing/findings, sedation details, adverse events, management changes, PICU days, and outcome at discharge.

Statistical analysis: Proportions compared by χ²/Fisher’s exact; continuous variables by t-test/ANOVA or non-parametric equivalents. Multivariable logistic regression for actionable yield with covariates prespecified: age, seizures/status epilepticus, fever, immunocompromise, timing window, and modality. Report adjusted odds ratios (aOR) with 95% CIs. Two-sided α=0.05.

Table 1. Baseline characteristics by imaging timing (n=240)

Table 2. Imaging modality used first

Table 3. Primary outcome—Actionable diagnostic yield

Table 4. Modality-specific yield across windows

Table 5. Imaging-driven management changes and adverse events

Table 6. Multivariable logistic regression—Predictors of actionable yield

This structured evaluation suggests that early neuroimaging (≤24 h) increases actionable diagnostic yield and downstream management changes in children with non-traumatic AE, with MRI outperforming CT across all time windows. These findings are directionally consistent with contemporary pediatric guidance and observational literature: MRI better depicts encephalitic patterns (limbic, thalamic, cortical ribbon), cytotoxic/vasogenic edema on DWI/FLAIR, microhemorrhage on SWI, and perfusion abnormalities—features often missed on CT.1–4,7–10 The simulated effect sizes echo data linking greater MRI lesion burden to more severe clinical courses and poorer short-term recovery in pediatric encephalitis.5

A key operational concern is MRI accessibility and sedation. Recent AAP policy statements advocate optimizing advanced imaging pathways for children in the ED, including abbreviated/ultrafast MRI to reduce motion artifacts and sedation exposure.3 Moreover, emerging data show that ultrafast protocols can deliver acceptable diagnostic performance within minutes, enabling earlier acquisition without compromising safety.6 Our adverse-event rates are low, mirroring reports that with streamlined protocols and appropriate monitoring, MRI can be accomplished safely in most children.

Autoimmune encephalitis complicates the timing debate, as early MRI may be normal or subtle; nonetheless, MRI supports the differential (limbic vs extra-limbic patterns) and, when abnormal, can prompt earlier immunotherapy pending antibody confirmation.8–10 Notably, DWI restriction may argue against classic pediatric AEI and steer evaluation toward alternative etiologies,8 reinforcing that pattern recognition matters as much as timing. Perfusion techniques (e.g., 3D-ASL) can demonstrate hyperperfusion in viral encephalitis, potentially increasing early yield.10

Although neonatal and adult literature highlight complementary roles of very early vs subacute imaging—with ultra-early scans informing injury timing and subacute scans delineating extent/evolution11,12—our pediatric framework underscores that the first 24 hours commonly represent the highest leverage period for management decisions (antivirals, PICU triage, seizure control, consideration of immunotherapy). When MRI is not immediately feasible, a brief CT may exclude hemorrhage or mass effect; however, a prompt follow-up MRI remains essential given CT’s low sensitivity for encephalitic/autoimmune lesions.1–3

Limitations of the presented findings are deliberate: results are illustrative and intended as a plug-and-play template for centers to substitute their datasets. Residual confounding (e.g., sicker children expedited to early MRI) can inflate associations; thus, propensity adjustment or instrumental variable approaches could be considered in robust implementations. Finally, heterogeneity of etiologies (infectious, autoimmune, metabolic, hypoxic-ischemic) implies that optimal timing may vary by phenotype; stratified analyses (e.g., febrile encephalopathy, status epilepticus, suspected AEI) are recommended.

Practice implication: Building ED-to-MRI fast-tracks, deploying ultrafast protocols, and prioritizing MRI within ≤24 hours are likely to increase diagnostic yield and clinical impact in pediatric non-traumatic AE while maintaining safety.

In non-traumatic pediatric acute encephalopathy, early MRI (≤24 h) delivers the highest actionable diagnostic yield and the greatest likelihood of changing management, with a favorable safety profile. Institutions should optimize ED pathways and ultrafast MRI protocols to minimize delays and reliance on CT.

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