Pediatric Neurogenic Stunned Myocardium: A Systematic Review and Individual Patient Data Analysis

Pediatric Neurogenic Stunned Myocardium: A Systematic Review and Individual Patient Data Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pediatric Neurogenic Stunned Myocardium: A Systematic Review and Individual Patient Data Analysis Cédérick Montplaisir, Sudarsan Packirisamy, Nick Lee, Farbod Niazi, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8948567/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Neurogenic stunned myocardium (NSM) is a reversible cardiac dysfunction after acute neurological injury that is well described in adults but poorly characterized in children. Objective To characterize pediatric NSM and identify factors associated with neurological outcome using individual patient data (IPD). Methods A systematic review and IPD meta-analysis were conducted according to MOOSE guidelines. PubMed, Web of Science, and CINAHL were searched from inception to November 2025 for studies reporting patients ≤ 18 years with NSM and available outcome data. Demographic, neurological, and cardiac variables were extracted. Functional outcome was assessed using the modified Rankin Scale (mRS). Results Twenty-nine studies comprising 38 patients were included (mean age 7.7 years). The mean time to NSM onset was 60.8 hours after neurological injury. Ventricular dysfunction occurred in 94.7%, commonly basal hypokinesis. Favorable outcome (mRS 0–2) occurred in 71.1%, while cardiac arrest occurred in 26.3% and mortality in 23.7%. Subarachnoid hemorrhage was associated with worse outcome, whereas absence of pupil abnormalities and preserved reflexes were associated with favorable outcome. Conclusions Pediatric NSM is usually reversible with favorable neurological outcome but remains associated with significant morbidity and mortality. Early recognition and multidisciplinary management may improve outcomes. Larger prospective studies are needed to refine prognostic stratification. pediatrics myocardial stunning brain injuries heart diseases systematic review Figures Figure 1 Figure 2 Figure 3 Introduction Neurogenic stunned myocardium (NSM) is a reversible cardiac dysfunction caused by an acute neurological event, including but not limited to subarachnoid hemorrhage (SAH), brain tumors, hydrocephalus, traumatic brain injury (TBI), acute myelitis, and iatrogenic neurosurgical complications 1 . Following an acute neurological event, the incidence of NSM is between 20% and 40%, depending on the type of injury 2 – 4 . In NSM, an acute neurological event causes an autonomic nervous system dysregulation leading to a catecholaminergic overstimulation of cardiomyocytes 5 . This stimulation results in coronary vasospasm, ischemia from increased myocardial oxygen demand, and direct catecholamine toxicity on the myocardium, all of which contribute to cardiac dysfunction 6 . Additionally, systemic inflammation and neurohormonal changes, such as pituitary gland dysfunction, may promote its pathogenesis through direct myocardial injury 7 , 8 . Clinically, NSM typically manifests similarly to myocardial infarction 9 . A classic triad of transient left ventricular dysfunction, serum cardiac enzyme elevation, and electrocardiographic changes often leads to congestive heart failure and rarely fatal cardiogenic shock 5 . Although the diagnosis of NSM is clinical, it can be difficult to distinguish from acute coronary syndrome (ACS) or Takotsubo syndrome (TTS) solely based on the clinical presentation, making it a difficult pathology to diagnose and treat appropriately 10 . TTS is a cardiac disease often caused by a sudden emotional or physical pain which triggers an abrupt increase in catecholamine levels that often cause a left ventricular dysfunction and apical akinesia in the absence of obstructive coronary disease 9 , 11 , 12 . TTS can also present as midventricular ballooning, basal, or focal wall motion abnormalities 13 . Compared to TTS, NSM presents more frequently with basal akinesia with sparing of the apical regions 7 , 9 , 14 . There are many similarities between NSM and TTS, but whether they are interchangeable as forms of stress cardiomyopathies remains controversial 1 , 15 . There are no standardized diagnostic criteria for NSM, although it can be guided by abnormal electrocardiograms, cardiac imaging, such as an echocardiogram, and cardiac biomarkers 7 , 14 . Although potentially fatal, NSM is generally linked to good prognosis if detected early and treated appropriately by managing the patient’s hemodynamic and cardiopulmonary parameters 9 . In fact, the rates of recovery range from 66% to 78%, with an average recovery timeline of 2 weeks 9 . Factors linked to poor prognosis include advanced patient age and underlying noncardiac comorbidities 7 , 14 , 16 , 17 . NSM is rarely observed in children, and the phenomenon has not yet been thoroughly investigated in this population 18 – 20 . Only a handful of reports present NSM in a pediatric setting, and there are no systematic reviews or individual patient data (IPD) meta-analyses studying the description of the patient population and predictors of outcome in pediatric NSM that are currently published in the literature. This study provides a first look upon characteristics of pediatric patients presenting with clinical NSM supported by echocardiogram abnormalities and determinants of neurological outcome following this occurrence. Materials and Methods This study was reported according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology) guidelines 21,22 . This study was not registered a priori. No funding was received. Search Strategy In order to conduct this systematic review and IPD meta-analysis, we performed an electronic search for relevant literature on 3 databases: Web of Science, PubMed, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The advanced search on these databases included articles from inception to April 2021, and our search terms were made up of 3 main categories: terms associated with “pediatric”, terms associated with “neurogenic stunned myocardium”, and terms associated with “acute neurological event”. The combinations of search terms used were therefore some variant of: (‎(‎(‎(‎(‎(‎pediatric) OR (‎infants)) OR (‎children)) OR (‎adolescents)) AND (‎(‎(‎(‎(‎(‎(‎(‎(‎neurogenic) (‎stunned) (‎myocardium)) OR (‎(‎hypothalamic-mediated) (‎sympathetic) (‎surge))) OR (‎(‎neurocardiac) (‎axis))) OR (‎(‎neurogenic) (‎stress) (‎cardiomyopathy))) OR (‎(‎cardiogenic) (‎shock))) OR (‎takotsubo)) OR (‎(‎cardiac) (‎dysfunction))) OR (‎(‎stress-induced) (‎cardiomyopathy)))) AND (‎(‎(‎(‎(‎(‎(‎(‎(‎(‎acute) (‎neurological) (‎event)) OR (‎aneurysm)) OR (‎(‎neurological) (‎surgery))) OR (‎neuroanaesthesia)) OR (‎(‎traumatic) (‎brain) (‎injury))) OR (‎(‎cerebral) (‎tumor))) OR (‎(‎cerebellar) (‎tumor))) OR (‎hydrocephalus)) OR (‎(‎subarachnoid) (‎hemorrhage)))). Only articles written in English were retained. Once all the literature was gathered from the databases, duplicates were identified and discarded using EndNote (version 20, Clarivate, London), a reference management software. The search was repeated in January 2023 on the three databases to include any new articles published since 2021. Duplicates were once again discarded using EndNote 20 (FIGURE 1 and 2). Due to a delay in the finalization of the study, a third search was conducted in November 2025 using the same three databases to include any new articles published since 2023 (FIGURE 3). Study Selection Study selection was performed by five authors (A.H., C.M., N.L., N.P., S.P.) with content expertise, while two authors were required to confirm the study selection. Reviewers first independently screened titles and abstracts for potentially relevant articles and then independently performed full-text review according to predefined eligibility criteria. References of included articles were cross-searched to identify any articles missed during the initial search. Disagreements were resolved by consulting the senior authors (A.H., A.G.W.). Eligibility Criteria All case reports, case series, case-control, cohort and randomized-control studies on pediatric NSM were included if they included (1) pediatric patients (≤18 years old), (2) reported a diagnosis of NSM or a presumed diagnosis based on author consensus, and (3) provided outcome data. The exclusion criteria for the study were as follows: reviews on pediatric NSM, adult cases of NSM, studies not reporting IPD, cases without a diagnosis of pediatric NSM or with a presentation presumed not to represent NSM based on author consensus (including but not limited to coronary ischemia, acute myocardial infarction, TTS, or other causes of cardiac failure), and studies where the full text was not available despite requests sent to authors by email. An abstract review and a full-text review was conducted independently by four reviewers (C.M., N.L., N.P., S.P.) on all compiled articles to filter relevant articles, and inclusion was confirmed by at least two independent reviewers (C.M., N.L., N.P., S.P.). Any disagreement was resolved with the help of a third reviewer (T.B.C.) and senior authors (A.H., A.G.W.) Outcome The primary outcome was the modified Rankin Scale (mRS) at the last follow-up, a scale primarily used in adult stroke patients and subsequently adapted for the pediatric population as described by Bigi et al 23 . The data extraction from the selected articles was performed by four reviewers (C.M., F.N., N.L., S.P.). All available preoperative, perioperative, and postoperative factors linked with description of the patient population and predictors of outcome in pediatric NSM were recorded. Data Extraction Three reviewers (C.M., N.L., S.P.) performed data extraction, which any of three other reviewers (A.H., C.M., S.P.) verified independently for data extraction not initially completed by themselves. Corresponding authors were not contacted when IPD were unavailable. We extracted the following when available: patient description (age, sex, past medical history and comorbidities), presentation (symptoms on presentation, Glasgow Coma Scale score, vital signs, including blood pressure, heart rate, oxygen saturation, and temperature on presentation, delay from neurological event to cardiac dysfunction, delay from presentation to clinical signs of cardiac dysfunction, delay from presentation to use of vasopressors, delay from presentation to echocardiogram, troponin levels, creatine kinase-myocardial band (CK-MB) levels, N-terminal-pro-B-type natriuretic peptide levels (BNP), electrocardiogram findings, echocardiogram findings, evidence of organ failure other than neurological or cardiorespiratory), evidence of neurological dysfunction (signs and symptoms of neurological dysfunction, evidence of brainstem dysfunction, etiology of NSM, neurological diagnosis), evidence of cardiac dysfunction (signs and symptoms of cardiac dysfunction, CPR performed), interventions (vasopressors used, anesthetics used, neurosurgical intervention performed, external ventricular drain findings), and outcome (follow-up timing, mRS outcome at last follow-up, cardiac death). The variables were categorized as descriptive or non-descriptive. Assessment of Risk Bias The Joanna Briggs Checklists for Case Reports and Case Series were used to critically appraise the case reports and case series included in the article. Each question was answered using “Yes”, “No”, or “Unclear” and case reports and case series were attributed a score out of 8 and 10, respectively (SUPPLEMENTARY TABLES S1 and S2). Upon completion of the checklists, each study was given an overall appraisal: “Exclude”, “Include”, or “Seek further info” 24 . Assessment of the quality of included studies was performed independently by four authors (C.M., F.N., N.L., S.P.) using the Quality in Prognosis Studies (QUIPS) tool 25 . Each study was given a low, moderate, or high risk of bias (low =1, moderate = 2, high = 3) in each of the six following domains: study participation, study attrition, prognostic factor measurement, outcome measurement, study confounding, and statistical analysis (TABLE 1). Synthesis Methods Using IPD, the patients were stratified into subgroups based on the etiology of NSM (surgical vs non-surgical), occurrence of cardiac arrest and their overall outcome based on mRS. Between-group comparisons for categorical variables were performed using Fisher’s exact test. Continuous variables were summarized as mean ± standard deviation and compared between subgroups using Welch’s t-test for two-group comparisons and Welch’s ANOVA for comparisons involving more than two groups; when these models could not be reliably fitted, non-parametric Wilcoxon rank-sum or Kruskal–Wallis tests were used as alternatives. Univariate associations between each continuous variable and the binary outcomes (surgical complications, cardiac arrest, favorable outcome defined as mRS 0–2) were examined using logistic regression to estimate odds ratios (ORs) with 95% confidence intervals. All tests were two-sided, and a p value < 0.05 was considered statistically significant. Results Study Selection and Characteristics In our first search (inception to 2021), we identified 2951 articles across PubMed, Web of Science, and CINAHL after duplicates were removed. Of these, 211 full texts were assessed for eligibility following a title and abstract screening, and 18 articles were included in the final review (FIGURE 1). In our second search (2021 to 2023), we identified 342 additional articles across the 3 databases with duplicates removed from which 51 full texts were assessed for eligibility and 6 studies were included in the final review. In our third search, (2023 to 2025), we identified 121 studies across PubMed, Web of Science, and CINAHL with duplicates removed. 6 full texts were assessed for eligibility and 5 were included in the final review. In total, the final review included 29 articles for a total of 38 participants eligible for inclusion in the review (FIGURE 2). All 29 studies were either case reports or case series of IPD 1,5,11,12,18,20,26-48 . Risk of Study Bias Out of 23 case reports, 18 (78.2%) received a score of 8/8 and 5 (22.7%) received a score of 7/8. Five case series received a score of 6/10, and one received a score of 8/10. Upon evaluation of these scores, all studies were deemed eligible for inclusion in the systematic review and IPD meta-analysis. All studies were deemed to be at low risk for attrition bias and were deemed to be at high risk for participation and confounding biases. Most studies (n=27, 93.1%) were deemed to be at low risk for prognostic factor measurement bias, while 2 studies were deemed to be at moderate risk. Most studies (n=25, 86.2%) were also deemed to be at low risk for outcome measurement bias, while 4 studies were deemed to be at moderate risk. Patient characteristics Demographics Out of the 38 included patients, 62.2% (n=23) were male, and the mean age was 7.74 (SD: 5.29, range 0-18 years old). Neurological and cardiorespiratory past medical history (PMHx) were present in 29.0% (n=11) and 10.5% (n=4) of patients, respectively. Etiology The onset of NSM was on average 60.8 hours after neurological event (0-312 hours). In this study, 23.7% (n=9) of the NSM cases were due to a complication of a neurosurgical intervention. The most common non-surgical causes of NSM (n=29, 76.3%) were, in decreasing order, SAH (n=7, 12.1%), cerebral edema (n=7, 12.1%), acute hydrocephalus (n=5, 8.62%), intraparenchymal hemorrhage (n=5, 8.62%), brain tumor (n=4, 6.90%), arteriovenous malformation (n=4, 6.90%), subdural hematoma (SDH) (n=4, 6.90%), infectious (n=4, 6.90%), supratentorial brain contusions localised to the frontotemporal, frontoparietal, temporoparietal, or occipital lobes (n=3, 5.17%) (TABLE 2). An altered mental status and an altered response to stimuli were significantly more common in the non-surgical group compared to the surgical group (p = 0.021 and 0.038 respectively). (TABLE 3). Clinical evidence of cardiac dysfunction The most frequent clinical manifestations of cardiac dysfunction were as follows: hypertension/hypotension (n=26, 68.4%), tachycardia/bradycardia (n=24, 63.2%), and hypoxia/acidosis (n=14, 36.8%). Cardiac arrest occurred in 26.3% (n=10) of patients. Important ECG findings were as follows: sinus tachycardia (n=14, 42.4%), abnormal ST-segment (n=8, 24.2%), T-wave inversion (n=7, 21.2%), and abnormal QTc (n=5, 15.2%). Important echocardiogram findings were as follows: ventricular dysfunction (n=36, 94.7%), systolic dysfunction (n=26, 68.4%), basal hypokinesis/akinesis (n=25, 65.8%), and apical hypokinesis/akinesis (n=23, 60.5%). Finally, enlarged atriums were more associated with the surgical group than the non-surgical group (p = 0.035) Outcome The outcome was evaluated using the Modified Rankin Scale (mRS), which ranges from 0 = no symptoms to 6 = death 23 . Overall, 71.1% (n = 27) of patients achieved a favorable outcome (mRS 0–2), whereas 26.3% (n = 10) experienced cardiac arrest. Death occurred in 23.7% (n = 9) of the studied population. The delay from the cardiac dysfunction to the neurosurgical intervention in hours was significantly higher in the population experiencing a cardiac arrest (p = 0.033, n = 6) (TABLE 4). Having a lower systolic blood pressure was associated with a favorable outcome (p = 0.050), while having either hypertension or hypotension was also associated with a favorable outcome (p = 0.002). Absence of pupil abnormality and presence of normal reflexes were associated with a favorable outcome (p = 0.047 and p = 0.011, respectively). Moreover, SAH was the only etiology associated with a worse outcome (p = 0.014) (TABLE 5). Discussion Demographics The general demographic profile of patients presenting with pediatric NSM in our study are male (62.2%) with a mean age of 8 years and without a notable neurological or cardiorespiratory prior medical history. In the adult population, the incidence of NSM is associated with the severity of the acute neurological injury rather than the presence of underlying neurological or cardiorespiratory comorbidities 7 . Other risk factors in the adult population include advanced age, which is difficult to compare within a pediatric population, and possibly the female gender 7 . None of those factors have been significant in our analysis to predict the outcome of the pediatric population. Etiology NSM in adults mostly occurs following aneurysmal SAH (≈ 30% of NSM cases), TBI (≈ 22% of NSM cases), and is also associated, to a lesser extent, with acute ischemic stroke 7 . Other less common causes include encephalitis, myelitis, Guillain-Barre syndrome, neurosurgical procedures, status epilepticus, and other acute CNS injuries 49 . Additionally, risk factors seem to play an important role in the development of NSM, including polymorphisms of genes encoding adrenergic receptors, tobacco use, and posterior aneurysmal location in SAH 7 , 49 . In the pediatric population we studied, the most common non-surgical etiologies were SAH (secondary to arteriovenous malformations or trauma) and severe cerebral edema. Other notable causes include different conditions associated with raised intracranial pressure (ICP), including acute hydrocephalus, intraparenchymal hemorrhage, SDH, and brain contusion (frontotemporal, frontoparietal, temporoparietal, or occipital). Altered mental status and impaired response to stimuli were more frequent in the non-surgical group, consistent with NSM arising in the context of acute, severe neurological insults. In our pediatric cohort, NSM was more rarely caused by post-surgical complications than non-surgical injuries. Neurosurgical procedures included ventriculoperitoneal shunting, posterior fossa exploration, suboccipital craniotomy, external ventricular draining, and hematoma excision) with the following complications: herniation of the brain, secondary hemorrhage or hematoma formation, and injury to adjacent structures during surgical manipulation. Taken together, these observations indicate that pediatric NSM shares a broadly similar etiological profile with adults, but surgical and non-surgical cases may represent partially distinct clinical phenotypes with different baseline risks. Clinical Evidence of Cardiac Dysfunction The diagnosis of NSM relies mostly on clinical manifestations, evidence of cardiac dysfunction, changes on ECG and echocardiogram, and the absence of an alternate diagnosis or cause of cardiac failure 7 . These cardiac changes are not specific to NSM, often making it difficult to distinguish from other possible diagnoses such as coronary ischemia, acute myocardial infarction, TTS, or other causes of cardiac failure (e.g. barbiturate-induced hemodynamic instability/cardiac failure) 7 , 14 . Common clinical signs of cardiac dysfunction in pediatric NSM include pulmonary edema, abnormal heart rate or blood pressure, and evidence of hypoxia/acidosis. Common ECG findings include abnormal QTc, abnormal ST segment, T-wave inversion, and sinus tachycardia. Echocardiogram findings included ventricular dysfunction, apical and basal hypo/akinesis, and systolic dysfunction. Global hypokinesis and wall motion abnormalities on echocardiogram are hallmarks in the diagnosis of adult NSM 7 , 9 , 14 . Although either can be present, basal hypokinesis is more specific to NSM than apical ballooning, more present in typical stress cardiomyopathy in adults, which is also consistent with our findings 7 , 9 , 14 . Furthermore, non-specific ECG findings are most frequently found in adult patients presenting with NSM 7 , 9 , 14 . Overall, the overlap in ECG and echocardiographic patterns between pediatric and adult cases suggests a shared underlying pathophysiology despite age-specific differences in trigger and presentation. Outcome The overall functional outcome in this study was measured using the mRS, as previously described 23 . Other measurements of outcome such as the Pediatric Cerebral Performance Category (PCPC) or the Pediatric Overall Performance Category (POPC) could not be used due to the lack of data in the included studies 50 . However, as outcomes were largely polarized between no symptoms to slight disability (mRS 0–2) and death (mRS 6), the absence of PCPC or POPC data is less likely to have influenced the interpretation; nevertheless, this polarization does not entirely preclude the possibility that intermediate outcomes were underrepresented. Most patients affected by NSM were left with no sequelae or very slight disability, which is consistent with the generally positive outcome of reversible cardiomyopathies in the adult population 7 , 9 , 14 . In adults with NSM following aneurysmal SAH or severe brain injury, the presence of cardiac complications such as arrhythmias or pulmonary edema is associated with higher mortality and worse functional recovery (based on mRS), particularly among older patients 14 . Additionally, in adults who specifically develop NSM after SAH, wall motion abnormalities, troponin, CK-MB, BNP, Q waves, ST depression, and T-wave abnormalities are associated with worse outcomes 51 . In our study, the delay between the onset of cardiac dysfunction and neurosurgical intervention was significantly longer in patients who experienced a cardiac arrest, and this subgroup also had a markedly higher mortality. While this finding is intuitive, it is based on only six patients, which limits the robustness of this conclusion. Taken together, these findings support the notion that hemodynamic instability severe enough to precipitate cardiac arrest is a marker of global illness severity and may also delay definitive neurosurgical management, thereby compounding the risk of poor outcome. The association between lower systolic blood pressure and favorable outcome, as well as the unexpected finding that documented hypertension or hypotension was also linked to favorable outcome, should be interpreted with caution given the small sample size and the risk of residual confounding. One possible explanation is that patients with more pronounced hemodynamic fluctuations may have been more closely monitored and aggressively treated in intensive care, mitigating the long-term impact of the initial cardiovascular insult. In contrast, the absence of pupil abnormalities and the presence of normal reflexes were strongly associated with favorable outcomes, which aligns with the idea that preserved brainstem function and less severe neurological injury are key determinants of recovery. Finally, SAH emerged as the only etiology significantly associated with worse outcome, which is consistent with the recognized severity of SAH related brain injury and its systemic repercussions, and suggests that pediatric patients with NSM in the context of SAH may constitute a particularly high-risk subgroup that warrants early recognition and tailored multidisciplinary management as reported in the adult population 14 . Strengths and Limitations The primary strength of this review is the size of the pediatric NSM cohort, which is notable given the rarity and heterogeneity of this presentation. In the context of a limited and heterogeneous existing literature, this review provides a robust synthesis of available evidence and examines predictors of outcome for NSM in pediatric patients, addressing an important gap in current knowledge. Furthermore, the strengths of this review include the following: we performed a comprehensive search across multiple databases, we did not exclude papers based on the date of publication, we employed a rigorous and systematic review process for article screening and data extraction, and we obtained IPD to conduct our review. Finally, we updated the literature search throughout the study period to ensure the inclusion of the most recent studies. There were several limitations to the study: 1) as a majority of the included studies were case reports, there is an important risk of publication bias derived from the reporting of stand-alone cases; 2) only case reports or case series were included from the literature, preventing us from performing mixed-effects analyses; 3) the validity of appropriate data abstraction and assessment of risk of bias is affected by heterogeneous reporting; 4) meta-analyses assumes that treatments and management of patients were comparable across centers simplifying the various bias present in each center; 5) lack of a standardized scale for overall outcome and disability in pediatric patients led to the use of the Modified Rankin Scale, primarily developed and used in adult stroke patients; and 6) despite the large sample size, the absolute number of patients sample size and relative low estimate of poor outcome renders this study underpowered to identify independent predictors of outcome. Conclusion This study represents the first systematic review and IPD meta-analysis to characterize NSM in the pediatric population. We found that the demographic profile, underlying causes, and cardiac manifestations of pediatric NSM largely mirror those reported in adults. Most children presented with reversible cardiac dysfunction and more than 70% achieved favorable neurological outcomes, though a minority experienced severe complications or death. Taken together, our results show that specific clinical and etiological factors do predict outcome in pediatric NSM. Cardiac arrest was associated with both a longer delay to neurosurgical intervention and higher mortality, whereas lower systolic blood pressure and the presence of either hypertension or hypotension, as well as the absence of pupil abnormalities and the presence of normal reflexes, were all independently associated with favorable functional outcomes. In contrast, SAH was the only etiology linked to worse prognosis. These findings underscore the importance of early recognition of NSM, meticulous hemodynamic and neurological monitoring, and timely neurosurgical and intensive care management to optimize outcomes in the pediatric population of NSM. We should consider NSM in any pediatric patient with acute neurological injury, most notably SAH, severe cerebral edema, or acute hydrocephalus, who develops sudden hemodynamic instability. Although cardiac dysfunction can occur rapidly, the mean time to onset in children is approximately 60 hours after neurological injury. Vigilant cardiorespiratory monitoring should therefore extend well beyond the initial 24-hour stabilization period. Given the rarity of pediatric NSM and the heterogeneity of published cases, larger multicenter prospective studies with standardized reporting and long-term follow-up are warranted to better delineate prognostic factors and guide evidence-based management strategies. Declarations The manuscript complies with all instructions to authors. Authorship requirements have been met, and the final manuscript was approved by all authors. CM, SP, NL, FN, AH, CK, NPG, and TBC contributed to the study design, performed the systematic literature search and data extraction, drafted the initial manuscript, and conducted critical revisions of the intellectual content. KSL, XC, and APS contributed to the critical review and editing of the manuscript. DV, GDT, and MWB were responsible for the clinical review and validation of the data and manuscript. AH and AGW contributed to the study conception and design, provided senior supervision for the project, and performed the final review and approval of the manuscript. The manuscript has not been published elsewhere and is not under consideration by another journal. Adherence to ethical guidelines was maintained. Institutional ethics approval was deemed unnecessary as all the data included had been previously published in the literature. AGW is a paid consultant for Monteris Medical Inc. and an advisory board member of Synergia SA and Reveal inc. All other authors declare that they have no competing interests and no financial disclosures relevant to the content of this manuscript. No funding was received for this work. A reporting checklist was used. AGW acknowledges funding from the Fonds de Recherche du Quebec en Santé (FRQS). The funding sources had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. References Drayer M, Geracht J, Madikians A, Harrison R. Neurogenic stunned myocardium: an unusual postoperative complication. Pediatr Crit Care Med. 2006;7(4):374–6. 10.1097/01.Pcc.0000225370.67241.Ae . (In eng). Dujardin KS, McCully RB, Wijdicks EF, et al. 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Immediate postoperative death due to hypothalamic injury following surgery for craniopharyngioma. J Clin Neurosci. 2009;16(6):850–1. 10.1016/j.jocn.2008.09.007 . Cho S, Yamashita S, Ito Y, Ogawa O. Pediatric neurogenic stunned myocardium due to blunt head trauma requiring ECMO. J Pediatr Surg Case Rep. 2022;84:102363. https://doi.org/10.1016/j.epsc.2022.102363 . Deleu D, Kettern M-A, Hanssens Y, Kumar S, Salim K, Miyares F. Neurogenic stunned myocardium following hemorrhagic cerebral contusion. Neurosciences J. 2007;12(1):65–7. https://nsj.org.sa/content/nsj/12/1/65.full.pdf . Divekar A, Shah S, Joshi C. Neurogenic stunned myocardium and transient severe tricuspid regurgitation in a child following nonaccidental head trauma. Pediatr Cardiol. 2006;27(3):376–7. 10.1007/s00246-005-1263-2 . (In eng). Haug KS, Baylen BG, Mink RB. Death from cardiac failure in a child with ruptured cerebral arteriovenous malformation. Pediatr Emerg Care. 2009;25(5):342–4. 10.1097/PEC.0b013e3181a348ea . (In eng). Heuer GG, Fenning RS, Brown M, et al. Pulmonary edema and cardiac dysfunction after resection of a fourth ventricle tumor in a toddler: case report. Childs Nerv Syst. 2011;27(11):2005–9. 10.1007/s00381-011-1573-z . (In eng). Johnson J, Ragheb J, Garg R, Patten W, Sandberg DI, Bhatia S. Neurogenic stunned myocardium after acute hydrocephalus. J Neurosurg Pediatr. 2010;5(5):428–33. 10.3171/2009.11.Peds09341 . (In eng). Kato R, Taneichi H, Takarada S, et al. Reversible left ventricular noncompaction caused by hypertensive hydrocephalus: a pediatric case report. BMC Pediatr. 2021;21(1):205. 10.1186/s12887-021-02680-6 . Koyama J, Akutsu N, Kawamura A. Pediatric takotsubo syndrome caused by hydrocephalus after posterior fossa tumor surgery. Childs Nerv Syst. 2021;37(12):3957–61. 10.1007/s00381-021-05090-2 . (In eng). Krouma M, Aboudou Soilihi A, Pech-Gourg G, et al. Takotsubo syndrome linked to paroxysmal sympathetic hyperactivity as a postoperative complication after brain tumor removal: a case report and literature review. Childs Nerv Syst. 2024;40(8):2573–9. 10.1007/s00381-024-06316-9 . (In eng). Moriya S, Inamasu J, Oheda M, Hirose Y. Neurogenic stunned myocardium associated with pediatric brain tumor may not be catecholamine-induced. Ann Pediatr Cardiol. 2015;8(3):240–2. 10.4103/0974-2069.164689 . (In eng). Mrozek S, Srairi M, Marhar F, et al. Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure. Heart Lung. 2016;45(5):406–8. 10.1016/j.hrtlng.2016.06.007 . (In eng). Pearson TE, Frizzola MA, Priest MA, Rochman MF, Froehlich CD. Pediatric Extracorporeal Cardiopulmonary Resuscitation Patient With Traumatic Subarachnoid Hemorrhage and Takotsubo Syndrome. Air Med J. 2018;37(1):64–6. 10.1016/j.amj.2017.09.002 . (In eng). Reddy A, Thappa P, Jangra K, Dhandapani S, Sihag BK. Neurogenic myocardial dysfunction post craniopharyngioma resection: A diagnostic dilemma. Pediatr Anesth. 2024;34(2):178–81. https://doi.org/10.1111/pan.14788 . Ruggieri F, Calvi MR, Beretta L. A dangerous Cushing response in a child: neurogenic heart damage. Am J Emerg Med. 2014;32(4):393.e1-3. (In eng). 10.1016/j.ajem.2013.10.028 Siroya HL, Uppar AM, Madhugiri VS, Devi BI. Heartbroken Child: A Rare Case Report of Neurogenic Pulmonary Edema and Takotsubo Cardiomyopathy following Recurrent Medulloblastoma Excision with Possible Aetio-Patho-Bio-Physiological Mechanisms. Pediatr Neurosurg. 2022;57(4):279–86. 10.1159/000524896 . (In eng). Sundaram M, Mishra RK, Uppar AM. Neurogenic stunned myocardium resulting from surgical brainstem handling during resection of paediatric recurrent medulloblastoma-a possible brain heart interaction. Childs Nerv Syst. 2022;38(10):2025–8. 10.1007/s00381-022-05523-6 . (In eng). Thomas C, Johler SM, Hermann M, et al. Takotsubo cardiomyopathy in a 12-year-old boy caused by acute brainstem bleeding-a case report. Transl Pediatr. 2021;10(11):3110–7. 10.21037/tp-21-181 . (In eng). Tsitsipanis C, Miliaraki M, Michailou M et al. Severe and Atypical Presentation of Takotsubo Cardiomyopathy in a Pediatric Patient after a Serious Crash Injury—Case Report and Literature Review. Pediatric Reports. Johnson AK, Ruban D, Ganesan R, Munoz LF. Neurogenic pulmonary edema in an infant with ventriculoperitoneal shunt malfunction. J Pediatr Intensive Care. 2013;2(2):89–93. 10.3233/pic-13056 . (In eng). Brevis Nuñez F, Tschiedel E, Felderhoff-Mueser U, Neudorf U, Chapot R, Dohna-Schwake C. Neurogenic stunned myocardium after embolization in two children with vein of Galen aneurysmal malformation. Neuroradiology. 2013;55(2):213–6. 10.1007/s00234-012-1088-7 . (In eng). Wittekind SG, Yanay O, Johnson EM, Gibbons EF. Two pediatric cases of variant neurogenic stress cardiomyopathy after intracranial hemorrhage. Pediatrics. 2014;134(4):e1211–7. 10.1542/peds.2013-1881 . (In eng). Boggs K, Kirschen M, Glau C, et al. Cardiac Point-of-Care Ultrasound in Pediatric Neurocritical Care: A Case Series. Pediatr Neurol. 2023;144:56–9. 10.1016/j.pediatrneurol.2023.03.017 . (In eng). Mierzewska-Schmidt M, Gawecka A. Neurogenic stunned myocardium - do we consider this diagnosis in patients with acute central nervous system injury and acute heart failure? Anaesthesiol Intensive Ther. 2015;47(2):175–80. 10.5603/AIT.2015.0017 . Fiser DH, Long N, Roberson PK, Hefley G, Zolten K, Brodie-Fowler M. Relationship of pediatric overall performance category and pediatric cerebral performance category scores at pediatric intensive care unit discharge with outcome measures collected at hospital discharge and 1- and 6-month follow-up assessments. Crit Care Med. 2000;28(7):2616–20. 10.1097/00003246-200007000-00072 . (In eng). van der Bilt IA, Hasan D, Vandertop WP, et al. Impact of cardiac complications on outcome after aneurysmal subarachnoid hemorrhage: a meta-analysis. Neurology. 2009;72(7):635–42. 10.1212/01.wnl.0000342471.07290.07 . (In eng). Pearson TE, Frizzola MA, Priest MA, Rochman MF, Froehlich CD. Pediatric Extracorporeal Cardiopulmonary Resuscitation Patient With Traumatic Subarachnoid Hemorrhage and Takotsubo Syndrome [published correction appears in Air Med J. Air Med J. 2018;2018;37(1):64–66. 10.1016/j.amj.2017.09.002 Tables Tables are available in the Supplementary Files section. 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17:00:31","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":352377,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Flow Diagram for Search Strategy and Study Selection for 1\u003csup\u003est\u003c/sup\u003e Search\u003c/p\u003e\n\u003cp\u003eLegend: NSM = Neurogenic Stunned myocardium; IPD = Individual Patient Data; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses\u003c/p\u003e","description":"","filename":"Figure1NSM1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948567/v1/e69d7984576615ebbbeac4e5.jpg"},{"id":104808308,"identity":"bef87a96-6f1c-4981-8068-a6a7d03310e7","added_by":"auto","created_at":"2026-03-17 12:35:46","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":394929,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Flow Diagram for Updated Systematic Reviews for 2nd Search\u003c/p\u003e\n\u003cp\u003eLegend: NSM = Neurogenic Stunned myocardium; IPD = Individual Patient Data; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses\u003c/p\u003e","description":"","filename":"Figure1NSM2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948567/v1/8adb3aa0546af23cbc57820c.jpg"},{"id":104179015,"identity":"1090d0f3-146c-41b0-b357-86f19ed2d014","added_by":"auto","created_at":"2026-03-08 17:00:31","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":381505,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA Flow Diagram for Updated Systematic Reviews for 3rd Search\u003c/p\u003e\n\u003cp\u003eLegend: NSM = Neurogenic Stunned myocardium; IPD = Individual Patient Data; PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses\u003c/p\u003e","description":"","filename":"Figure1NSM3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8948567/v1/fbda9a17ddbabb5d54ef8bbb.jpg"},{"id":105033486,"identity":"534e9560-2826-4219-94ee-aee715658346","added_by":"auto","created_at":"2026-03-20 07:18:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1835647,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8948567/v1/497bc33c-040d-4094-bf8f-07cdad39ba39.pdf"},{"id":104404582,"identity":"fb05b375-47f9-48f4-a9ba-3e9eaf17f91b","added_by":"auto","created_at":"2026-03-11 12:20:34","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":103570,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8948567/v1/6be3c9f99b18c10e46cbf196.docx"}],"financialInterests":"","formattedTitle":"Pediatric Neurogenic Stunned Myocardium: A Systematic Review and Individual Patient Data Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNeurogenic stunned myocardium (NSM) is a reversible cardiac dysfunction caused by an acute neurological event, including but not limited to subarachnoid hemorrhage (SAH), brain tumors, hydrocephalus, traumatic brain injury (TBI), acute myelitis, and iatrogenic neurosurgical complications\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Following an acute neurological event, the incidence of NSM is between 20% and 40%, depending on the type of injury\u003csup\u003e\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn NSM, an acute neurological event causes an autonomic nervous system dysregulation leading to a catecholaminergic overstimulation of cardiomyocytes\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. This stimulation results in coronary vasospasm, ischemia from increased myocardial oxygen demand, and direct catecholamine toxicity on the myocardium, all of which contribute to cardiac dysfunction\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Additionally, systemic inflammation and neurohormonal changes, such as pituitary gland dysfunction, may promote its pathogenesis through direct myocardial injury\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eClinically, NSM typically manifests similarly to myocardial infarction\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. A classic triad of transient left ventricular dysfunction, serum cardiac enzyme elevation, and electrocardiographic changes often leads to congestive heart failure and rarely fatal cardiogenic shock\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Although the diagnosis of NSM is clinical, it can be difficult to distinguish from acute coronary syndrome (ACS) or Takotsubo syndrome (TTS) solely based on the clinical presentation, making it a difficult pathology to diagnose and treat appropriately\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. TTS is a cardiac disease often caused by a sudden emotional or physical pain which triggers an abrupt increase in catecholamine levels that often cause a left ventricular dysfunction and apical akinesia in the absence of obstructive coronary disease\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. TTS can also present as midventricular ballooning, basal, or focal wall motion abnormalities\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Compared to TTS, NSM presents more frequently with basal akinesia with sparing of the apical regions\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. There are many similarities between NSM and TTS, but whether they are interchangeable as forms of stress cardiomyopathies remains controversial\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThere are no standardized diagnostic criteria for NSM, although it can be guided by abnormal electrocardiograms, cardiac imaging, such as an echocardiogram, and cardiac biomarkers\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Although potentially fatal, NSM is generally linked to good prognosis if detected early and treated appropriately by managing the patient\u0026rsquo;s hemodynamic and cardiopulmonary parameters\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In fact, the rates of recovery range from 66% to 78%, with an average recovery timeline of 2 weeks\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Factors linked to poor prognosis include advanced patient age and underlying noncardiac comorbidities\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. NSM is rarely observed in children, and the phenomenon has not yet been thoroughly investigated in this population\u003csup\u003e\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Only a handful of reports present NSM in a pediatric setting, and there are no systematic reviews or individual patient data (IPD) meta-analyses studying the description of the patient population and predictors of outcome in pediatric NSM that are currently published in the literature.\u003c/p\u003e \u003cp\u003eThis study provides a first look upon characteristics of pediatric patients presenting with clinical NSM supported by echocardiogram abnormalities and determinants of neurological outcome following this occurrence.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis study was reported according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology) guidelines\u003csup\u003e21,22\u003c/sup\u003e. This study was not registered a priori. No funding was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSearch Strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn order to conduct this systematic review and IPD meta-analysis, we performed an electronic search for relevant literature on 3 databases: Web of Science, PubMed, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The advanced search on these databases included articles from inception to April 2021, and our search terms were made up of 3 main categories: terms associated with “pediatric”, terms associated with “neurogenic stunned myocardium”, and terms associated with “acute neurological event”. The combinations of search terms used were therefore some variant of: (‎(‎(‎(‎(‎(‎pediatric) OR (‎infants)) OR (‎children)) OR (‎adolescents)) AND (‎(‎(‎(‎(‎(‎(‎(‎(‎neurogenic) (‎stunned) (‎myocardium)) OR (‎(‎hypothalamic-mediated) (‎sympathetic) (‎surge))) OR (‎(‎neurocardiac) (‎axis))) OR (‎(‎neurogenic) (‎stress) (‎cardiomyopathy))) OR (‎(‎cardiogenic) (‎shock))) OR (‎takotsubo)) OR (‎(‎cardiac) (‎dysfunction))) OR (‎(‎stress-induced) (‎cardiomyopathy)))) AND (‎(‎(‎(‎(‎(‎(‎(‎(‎(‎acute) (‎neurological) (‎event)) OR (‎aneurysm)) OR (‎(‎neurological) (‎surgery))) OR (‎neuroanaesthesia)) OR (‎(‎traumatic) (‎brain) (‎injury))) OR (‎(‎cerebral) (‎tumor))) OR (‎(‎cerebellar) (‎tumor))) OR (‎hydrocephalus)) OR (‎(‎subarachnoid) (‎hemorrhage)))). Only articles written in English were retained. Once all the literature was gathered from the databases, duplicates were identified and discarded using EndNote (version 20, Clarivate, London), a reference management software. The search was repeated in January 2023 on the three databases to include any new articles published since 2021. Duplicates were once again discarded using EndNote 20 (FIGURE 1 and 2). Due to a delay in the finalization of the study, a third search was conducted in November 2025 using the same three databases to include any new articles published since 2023 (FIGURE 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy selection was performed by five authors (A.H., C.M., N.L., N.P., S.P.) with content expertise, while two authors were required to confirm the study selection. Reviewers first independently screened titles and abstracts for potentially relevant articles and then independently performed full-text review according to predefined eligibility criteria. References of included articles were cross-searched to identify any articles missed during the initial search. Disagreements were resolved by consulting the senior authors (A.H., A.G.W.).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEligibility Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll case reports, case series, case-control, cohort and randomized-control studies on pediatric NSM were included if they included (1) pediatric patients (≤18 years old), (2) reported a diagnosis of NSM or a presumed diagnosis based on author consensus, and (3) provided outcome data. The exclusion criteria for the study were as follows: reviews on pediatric NSM, adult cases of NSM, studies not reporting IPD, cases without a diagnosis of pediatric NSM or with a presentation presumed not to represent NSM based on author consensus (including but not limited to coronary ischemia, acute myocardial infarction, TTS, or other causes of cardiac failure), and studies where the full text was not available despite requests sent to authors by email. An abstract review and a full-text review was conducted independently by four reviewers (C.M., N.L., N.P., S.P.) on all compiled articles to filter relevant articles, and inclusion was confirmed by at least two independent reviewers (C.M., N.L., N.P., S.P.). Any disagreement was resolved with the help of a third reviewer (T.B.C.) and senior authors (A.H., A.G.W.)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was the modified Rankin Scale (mRS) at the last follow-up, a scale primarily used in adult stroke patients and subsequently adapted for the pediatric population as described by Bigi et al\u003csup\u003e23\u003c/sup\u003e. The data extraction from the selected articles was performed by four reviewers (C.M., F.N., N.L., S.P.). All available preoperative, perioperative, and postoperative factors linked with description of the patient population and predictors of outcome in pediatric NSM were recorded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree reviewers (C.M., N.L., S.P.) performed data extraction, which any of three other reviewers (A.H., C.M., S.P.) verified independently for data extraction not initially completed by themselves. Corresponding authors were not contacted when IPD were unavailable. We extracted the following when available: patient description (age, sex, past medical history and comorbidities), presentation (symptoms on presentation, Glasgow Coma Scale score, vital signs, including blood pressure, heart rate, oxygen saturation, and temperature on presentation, delay from neurological event to cardiac dysfunction, delay from presentation to clinical signs of cardiac dysfunction, delay from presentation to use of vasopressors, delay from presentation to echocardiogram, troponin levels, creatine kinase-myocardial band (CK-MB) levels, N-terminal-pro-B-type natriuretic peptide levels (BNP), electrocardiogram findings, echocardiogram findings, evidence of organ failure other than neurological or cardiorespiratory), evidence of neurological dysfunction (signs and symptoms of neurological dysfunction, evidence of brainstem dysfunction, etiology of NSM, neurological diagnosis), evidence of cardiac dysfunction (signs and symptoms of cardiac dysfunction, CPR performed), interventions (vasopressors used, anesthetics used, neurosurgical intervention performed, external ventricular drain findings), and outcome (follow-up timing, mRS outcome at last follow-up, cardiac death). The variables were categorized as descriptive or non-descriptive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of Risk Bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Joanna Briggs Checklists for Case Reports and Case Series were used to critically appraise the case reports and case series included in the article. Each question was answered using “Yes”, “No”, or “Unclear” and case reports and case series were attributed a score out of 8 and 10, respectively (SUPPLEMENTARY TABLES S1 and S2). Upon completion of the checklists, each study was given an overall appraisal: “Exclude”, “Include”, or “Seek further info”\u003csup\u003e24\u003c/sup\u003e. Assessment of the quality of included studies was performed independently by four authors (C.M., F.N., N.L., S.P.) using the Quality in Prognosis Studies (QUIPS) tool\u003csup\u003e25\u003c/sup\u003e. Each study was given a low, moderate, or high risk of bias (low =1, moderate = 2, high = 3) in each of the six following domains: study participation, study attrition, prognostic factor measurement, outcome measurement, study confounding, and statistical analysis (TABLE 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSynthesis Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing IPD, the patients were stratified into subgroups based on the etiology of NSM (surgical vs non-surgical), occurrence of cardiac arrest and their overall outcome based on mRS. Between-group comparisons for categorical variables were performed using Fisher’s exact test. Continuous variables were summarized as mean ± standard deviation and compared between subgroups using Welch’s t-test for two-group comparisons and Welch’s ANOVA for comparisons involving more than two groups; when these models could not be reliably fitted, non-parametric Wilcoxon rank-sum or Kruskal–Wallis tests were used as alternatives. Univariate associations between each continuous variable and the binary outcomes (surgical complications, cardiac arrest, favorable outcome defined as mRS 0–2) were examined using logistic regression to estimate odds ratios (ORs) with 95% confidence intervals. All tests were two-sided, and a p value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy Selection and Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn our first search (inception to 2021), we identified 2951 articles across PubMed, Web of Science, and CINAHL after duplicates were removed. Of these, 211 full texts were assessed for eligibility following a title and abstract screening, and 18 articles were included in the final review (FIGURE 1). In our second search (2021 to 2023), we identified 342 additional articles across the 3 databases with duplicates removed from which 51 full texts were assessed for eligibility and 6 studies were included in the final review. In our third search, (2023 to 2025), we identified 121 studies across PubMed, Web of Science, and CINAHL with duplicates removed. 6 full texts were assessed for eligibility and 5 were included in the final review. In total, the final review included 29 articles for a total of 38 participants eligible for inclusion in the review (FIGURE 2). All 29 studies were either case reports or case series of IPD\u003csup\u003e1,5,11,12,18,20,26-48\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of Study Bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of 23 case reports, 18 (78.2%) received a score of 8/8 and 5 (22.7%) received a score of 7/8. Five case series received a score of 6/10, and one received a score of 8/10. Upon evaluation of these scores, all studies were deemed eligible for inclusion in the systematic review and IPD meta-analysis. All studies were deemed to be at low risk for attrition bias and were deemed to be at high risk for participation and confounding biases. Most studies (n=27, 93.1%) were deemed to be at low risk for prognostic factor measurement bias, while 2 studies were deemed to be at moderate risk. Most studies (n=25, 86.2%) were also deemed to be at low risk for outcome measurement bias, while 4 studies were deemed to be at moderate risk.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDemographics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of the 38 included patients, 62.2% (n=23) were male, and the mean age was 7.74 (SD: 5.29, range 0-18 years old). Neurological and cardiorespiratory past medical history (PMHx) were present in 29.0% (n=11) and 10.5% (n=4) of patients, respectively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEtiology\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe onset of NSM was on average 60.8 hours after neurological event (0-312 hours). In this study, 23.7% (n=9) of the NSM cases were due to a complication of a neurosurgical intervention. The most common non-surgical causes of NSM (n=29, 76.3%) were, in decreasing order, SAH (n=7, 12.1%), cerebral edema (n=7, 12.1%), acute hydrocephalus (n=5, 8.62%), intraparenchymal hemorrhage (n=5, 8.62%), brain tumor (n=4, 6.90%), arteriovenous malformation (n=4, 6.90%), subdural hematoma (SDH) (n=4, 6.90%), infectious (n=4, 6.90%), supratentorial brain contusions localised to the frontotemporal, frontoparietal, temporoparietal, or occipital lobes (n=3, 5.17%) (TABLE 2). An altered mental status and an altered response to stimuli were significantly more common in the non-surgical group compared to the surgical group (p = 0.021 and 0.038 respectively). (TABLE 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical evidence of cardiac dysfunction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe most frequent clinical manifestations of cardiac dysfunction were as follows: hypertension/hypotension (n=26, 68.4%), tachycardia/bradycardia (n=24, 63.2%), and hypoxia/acidosis (n=14, 36.8%). Cardiac arrest occurred in 26.3% (n=10) of patients. Important ECG findings were as follows: sinus tachycardia (n=14, 42.4%), abnormal ST-segment (n=8, 24.2%), T-wave inversion (n=7, 21.2%), and abnormal QTc (n=5, 15.2%). Important echocardiogram findings were as follows: ventricular dysfunction (n=36, 94.7%), systolic dysfunction (n=26, 68.4%), basal hypokinesis/akinesis (n=25, 65.8%), and apical hypokinesis/akinesis (n=23, 60.5%). Finally, enlarged atriums were more associated with the surgical group than the non-surgical group (p = 0.035)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe outcome was evaluated using the Modified Rankin Scale (mRS), which ranges from 0 = no symptoms to 6 = death\u003csup\u003e23\u003c/sup\u003e. Overall, 71.1% (n = 27) of patients achieved a favorable outcome (mRS 0–2), whereas 26.3% (n = 10) experienced cardiac arrest. Death occurred in 23.7% (n = 9) of the studied population.\u003c/p\u003e\n\u003cp\u003eThe delay from the cardiac dysfunction to the neurosurgical intervention in hours was significantly higher in the population experiencing a cardiac arrest (p = 0.033, n = 6) (TABLE 4).\u003c/p\u003e\n\u003cp\u003eHaving a lower systolic blood pressure was associated with a favorable outcome (p = 0.050), while having either hypertension or hypotension was also associated with a favorable outcome (p = 0.002). Absence of pupil abnormality and presence of normal reflexes were associated with a favorable outcome (p = 0.047 and p = 0.011, respectively). Moreover, SAH was the only etiology associated with a worse outcome (p = 0.014) (TABLE 5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eDemographics\u003c/h2\u003e \u003cp\u003eThe general demographic profile of patients presenting with pediatric NSM in our study are male (62.2%) with a mean age of 8 years and without a notable neurological or cardiorespiratory prior medical history. In the adult population, the incidence of NSM is associated with the severity of the acute neurological injury rather than the presence of underlying neurological or cardiorespiratory comorbidities\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Other risk factors in the adult population include advanced age, which is difficult to compare within a pediatric population, and possibly the female gender\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. None of those factors have been significant in our analysis to predict the outcome of the pediatric population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eEtiology\u003c/h2\u003e \u003cp\u003eNSM in adults mostly occurs following aneurysmal SAH (\u0026asymp;\u0026thinsp;30% of NSM cases), TBI (\u0026asymp;\u0026thinsp;22% of NSM cases), and is also associated, to a lesser extent, with acute ischemic stroke\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Other less common causes include encephalitis, myelitis, Guillain-Barre syndrome, neurosurgical procedures, status epilepticus, and other acute CNS injuries\u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. Additionally, risk factors seem to play an important role in the development of NSM, including polymorphisms of genes encoding adrenergic receptors, tobacco use, and posterior aneurysmal location in SAH\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e. In the pediatric population we studied, the most common non-surgical etiologies were SAH (secondary to arteriovenous malformations or trauma) and severe cerebral edema. Other notable causes include different conditions associated with raised intracranial pressure (ICP), including acute hydrocephalus, intraparenchymal hemorrhage, SDH, and brain contusion (frontotemporal, frontoparietal, temporoparietal, or occipital). Altered mental status and impaired response to stimuli were more frequent in the non-surgical group, consistent with NSM arising in the context of acute, severe neurological insults.\u003c/p\u003e \u003cp\u003eIn our pediatric cohort, NSM was more rarely caused by post-surgical complications than non-surgical injuries. Neurosurgical procedures included ventriculoperitoneal shunting, posterior fossa exploration, suboccipital craniotomy, external ventricular draining, and hematoma excision) with the following complications: herniation of the brain, secondary hemorrhage or hematoma formation, and injury to adjacent structures during surgical manipulation.\u003c/p\u003e \u003cp\u003eTaken together, these observations indicate that pediatric NSM shares a broadly similar etiological profile with adults, but surgical and non-surgical cases may represent partially distinct clinical phenotypes with different baseline risks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eClinical Evidence of Cardiac Dysfunction\u003c/h2\u003e \u003cp\u003eThe diagnosis of NSM relies mostly on clinical manifestations, evidence of cardiac dysfunction, changes on ECG and echocardiogram, and the absence of an alternate diagnosis or cause of cardiac failure\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. These cardiac changes are not specific to NSM, often making it difficult to distinguish from other possible diagnoses such as coronary ischemia, acute myocardial infarction, TTS, or other causes of cardiac failure (e.g. barbiturate-induced hemodynamic instability/cardiac failure)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Common clinical signs of cardiac dysfunction in pediatric NSM include pulmonary edema, abnormal heart rate or blood pressure, and evidence of hypoxia/acidosis. Common ECG findings include abnormal QTc, abnormal ST segment, T-wave inversion, and sinus tachycardia. Echocardiogram findings included ventricular dysfunction, apical and basal hypo/akinesis, and systolic dysfunction. Global hypokinesis and wall motion abnormalities on echocardiogram are hallmarks in the diagnosis of adult NSM\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Although either can be present, basal hypokinesis is more specific to NSM than apical ballooning, more present in typical stress cardiomyopathy in adults, which is also consistent with our findings\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Furthermore, non-specific ECG findings are most frequently found in adult patients presenting with NSM\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Overall, the overlap in ECG and echocardiographic patterns between pediatric and adult cases suggests a shared underlying pathophysiology despite age-specific differences in trigger and presentation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eOutcome\u003c/h2\u003e \u003cp\u003eThe overall functional outcome in this study was measured using the mRS, as previously described\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Other measurements of outcome such as the Pediatric Cerebral Performance Category (PCPC) or the Pediatric Overall Performance Category (POPC) could not be used due to the lack of data in the included studies\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. However, as outcomes were largely polarized between no symptoms to slight disability (mRS 0\u0026ndash;2) and death (mRS 6), the absence of PCPC or POPC data is less likely to have influenced the interpretation; nevertheless, this polarization does not entirely preclude the possibility that intermediate outcomes were underrepresented. Most patients affected by NSM were left with no sequelae or very slight disability, which is consistent with the generally positive outcome of reversible cardiomyopathies in the adult population\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. In adults with NSM following aneurysmal SAH or severe brain injury, the presence of cardiac complications such as arrhythmias or pulmonary edema is associated with higher mortality and worse functional recovery (based on mRS), particularly among older patients\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Additionally, in adults who specifically develop NSM after SAH, wall motion abnormalities, troponin, CK-MB, BNP, Q waves, ST depression, and T-wave abnormalities are associated with worse outcomes\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our study, the delay between the onset of cardiac dysfunction and neurosurgical intervention was significantly longer in patients who experienced a cardiac arrest, and this subgroup also had a markedly higher mortality. While this finding is intuitive, it is based on only six patients, which limits the robustness of this conclusion.\u003c/p\u003e \u003cp\u003eTaken together, these findings support the notion that hemodynamic instability severe enough to precipitate cardiac arrest is a marker of global illness severity and may also delay definitive neurosurgical management, thereby compounding the risk of poor outcome.\u003c/p\u003e \u003cp\u003eThe association between lower systolic blood pressure and favorable outcome, as well as the unexpected finding that documented hypertension or hypotension was also linked to favorable outcome, should be interpreted with caution given the small sample size and the risk of residual confounding. One possible explanation is that patients with more pronounced hemodynamic fluctuations may have been more closely monitored and aggressively treated in intensive care, mitigating the long-term impact of the initial cardiovascular insult.\u003c/p\u003e \u003cp\u003eIn contrast, the absence of pupil abnormalities and the presence of normal reflexes were strongly associated with favorable outcomes, which aligns with the idea that preserved brainstem function and less severe neurological injury are key determinants of recovery.\u003c/p\u003e \u003cp\u003eFinally, SAH emerged as the only etiology significantly associated with worse outcome, which is consistent with the recognized severity of SAH related brain injury and its systemic repercussions, and suggests that pediatric patients with NSM in the context of SAH may constitute a particularly high-risk subgroup that warrants early recognition and tailored multidisciplinary management as reported in the adult population\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eThe primary strength of this review is the size of the pediatric NSM cohort, which is notable given the rarity and heterogeneity of this presentation. In the context of a limited and heterogeneous existing literature, this review provides a robust synthesis of available evidence and examines predictors of outcome for NSM in pediatric patients, addressing an important gap in current knowledge. Furthermore, the strengths of this review include the following: we performed a comprehensive search across multiple databases, we did not exclude papers based on the date of publication, we employed a rigorous and systematic review process for article screening and data extraction, and we obtained IPD to conduct our review. Finally, we updated the literature search throughout the study period to ensure the inclusion of the most recent studies.\u003c/p\u003e \u003cp\u003e There were several limitations to the study: 1) as a majority of the included studies were case reports, there is an important risk of publication bias derived from the reporting of stand-alone cases; 2) only case reports or case series were included from the literature, preventing us from performing mixed-effects analyses; 3) the validity of appropriate data abstraction and assessment of risk of bias is affected by heterogeneous reporting; 4) meta-analyses assumes that treatments and management of patients were comparable across centers simplifying the various bias present in each center; 5) lack of a standardized scale for overall outcome and disability in pediatric patients led to the use of the Modified Rankin Scale, primarily developed and used in adult stroke patients; and 6) despite the large sample size, the absolute number of patients sample size and relative low estimate of poor outcome renders this study underpowered to identify independent predictors of outcome.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003e This study represents the first systematic review and IPD meta-analysis to characterize NSM in the pediatric population. We found that the demographic profile, underlying causes, and cardiac manifestations of pediatric NSM largely mirror those reported in adults. Most children presented with reversible cardiac dysfunction and more than 70% achieved favorable neurological outcomes, though a minority experienced severe complications or death.\u003c/p\u003e \u003cp\u003eTaken together, our results show that specific clinical and etiological factors do predict outcome in pediatric NSM. Cardiac arrest was associated with both a longer delay to neurosurgical intervention and higher mortality, whereas lower systolic blood pressure and the presence of either hypertension or hypotension, as well as the absence of pupil abnormalities and the presence of normal reflexes, were all independently associated with favorable functional outcomes. In contrast, SAH was the only etiology linked to worse prognosis. These findings underscore the importance of early recognition of NSM, meticulous hemodynamic and neurological monitoring, and timely neurosurgical and intensive care management to optimize outcomes in the pediatric population of NSM.\u003c/p\u003e \u003cp\u003eWe should consider NSM in any pediatric patient with acute neurological injury, most notably SAH, severe cerebral edema, or acute hydrocephalus, who develops sudden hemodynamic instability. Although cardiac dysfunction can occur rapidly, the mean time to onset in children is approximately 60 hours after neurological injury. Vigilant cardiorespiratory monitoring should therefore extend well beyond the initial 24-hour stabilization period.\u003c/p\u003e \u003cp\u003eGiven the rarity of pediatric NSM and the heterogeneity of published cases, larger multicenter prospective studies with standardized reporting and long-term follow-up are warranted to better delineate prognostic factors and guide evidence-based management strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe manuscript complies with all instructions to authors.\u003c/p\u003e\n\u003cp\u003eAuthorship requirements have been met, and the final manuscript was approved by all authors.\u003c/p\u003e\n\u003cp\u003eCM, SP, NL, FN, AH, CK, NPG, and TBC contributed to the study design, performed the systematic literature search and data extraction, drafted the initial manuscript, and conducted critical revisions of the intellectual content.\u003c/p\u003e\n\u003cp\u003eKSL, XC, and APS contributed to the critical review and editing of the manuscript.\u003c/p\u003e\n\u003cp\u003eDV, GDT, and MWB were responsible for the clinical review and validation of the data and manuscript.\u003c/p\u003e\n\u003cp\u003eAH and AGW contributed to the study conception and design, provided senior supervision for the project, and performed the final review and approval of the manuscript.\u003c/p\u003e\n\u003cp\u003eThe manuscript has not been published elsewhere and is not under consideration by another journal.\u003c/p\u003e\n\u003cp\u003eAdherence to ethical guidelines was maintained. Institutional ethics approval was deemed unnecessary as all the data included had been previously published in the literature.\u003c/p\u003e\n\u003cp\u003eAGW is a paid consultant for Monteris Medical Inc. and an advisory board member of Synergia SA and Reveal inc. All other authors declare that they have no competing interests and no financial disclosures relevant to the content of this manuscript.\u003c/p\u003e\n\u003cp\u003eNo funding was received for this work.\u003c/p\u003e\n\u003cp\u003eA reporting checklist was used.\u003c/p\u003e\n\u003cp\u003eAGW acknowledges funding from the Fonds de Recherche du Quebec en Santé (FRQS). The funding sources had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDrayer M, Geracht J, Madikians A, Harrison R. 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Neurology. 2009;72(7):635\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/01.wnl.0000342471.07290.07\u003c/span\u003e\u003cspan address=\"10.1212/01.wnl.0000342471.07290.07\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. (In eng).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePearson TE, Frizzola MA, Priest MA, Rochman MF, Froehlich CD. Pediatric Extracorporeal Cardiopulmonary Resuscitation Patient With Traumatic Subarachnoid Hemorrhage and Takotsubo Syndrome [published correction appears in Air Med J. Air Med J. 2018;2018;37(1):64\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.amj.2017.09.002\u003c/span\u003e\u003cspan address=\"10.1016/j.amj.2017.09.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurocritical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neca","sideBox":"Learn more about [Neurocritical Care](http://link.springer.com/journal/12028)","snPcode":"12028","submissionUrl":"https://www.editorialmanager.com/neca/default2.aspx","title":"Neurocritical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"pediatrics, myocardial stunning, brain injuries, heart diseases, systematic review","lastPublishedDoi":"10.21203/rs.3.rs-8948567/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8948567/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eNeurogenic stunned myocardium (NSM) is a reversible cardiac dysfunction after acute neurological injury that is well described in adults but poorly characterized in children.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo characterize pediatric NSM and identify factors associated with neurological outcome using individual patient data (IPD).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e A systematic review and IPD meta-analysis were conducted according to MOOSE guidelines. PubMed, Web of Science, and CINAHL were searched from inception to November 2025 for studies reporting patients\u0026thinsp;\u0026le;\u0026thinsp;18 years with NSM and available outcome data. Demographic, neurological, and cardiac variables were extracted. Functional outcome was assessed using the modified Rankin Scale (mRS).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTwenty-nine studies comprising 38 patients were included (mean age 7.7 years). The mean time to NSM onset was 60.8 hours after neurological injury. Ventricular dysfunction occurred in 94.7%, commonly basal hypokinesis. Favorable outcome (mRS 0\u0026ndash;2) occurred in 71.1%, while cardiac arrest occurred in 26.3% and mortality in 23.7%. Subarachnoid hemorrhage was associated with worse outcome, whereas absence of pupil abnormalities and preserved reflexes were associated with favorable outcome.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePediatric NSM is usually reversible with favorable neurological outcome but remains associated with significant morbidity and mortality. Early recognition and multidisciplinary management may improve outcomes. Larger prospective studies are needed to refine prognostic stratification.\u003c/p\u003e","manuscriptTitle":"Pediatric Neurogenic Stunned Myocardium: A Systematic Review and Individual Patient Data Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 17:00:24","doi":"10.21203/rs.3.rs-8948567/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-03-06T15:49:45+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-02T16:45:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Neurocritical Care","date":"2026-03-02T13:59:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-01T12:54:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurocritical Care","date":"2026-02-26T12:35:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurocritical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"neca","sideBox":"Learn more about [Neurocritical Care](http://link.springer.com/journal/12028)","snPcode":"12028","submissionUrl":"https://www.editorialmanager.com/neca/default2.aspx","title":"Neurocritical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"68fa0a89-b6a2-4819-bb45-dcde34aed209","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-08T17:00:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 17:00:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8948567","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8948567","identity":"rs-8948567","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}