Long-term Neurological Outcome Research Articles

QOL-24. NEUROLOGIC AND NEUROCOGNITIVE OUTCOMES AMONG SURVIVORS OF INFANT-TYPE HEMISPHERIC GLIOMA (IHG)

Abstract IHGs are large, hemorrhagic cerebral tumors associated with hydrocephalus, increased intracranial pressure, and herniation. Commonly diagnosed during early infancy, children with IHGs have an approximately 90% chance of overall survival when treated with surgery, chemotherapy, and, more recently, molecularly targeted therapies. However, there is limited understanding of long-term quality-of-life following treatment. Our study investigated long-term neurological and neurocognitive outcomes among IHG survivors. The medical database was reviewed for neurological sequelae and neurocognitive outcomes (intelligence [IQ], adaptive function, academic readiness) for 21 survivors. Median age of diagnosis and last follow-up were 0.8 (0.0-4.4) and 10.3 (4.8-17.6) years, respectively. Sixteen patients (76%) experienced atleast one neurological sequelae: 38% (8/21) had paresis/plegia; 24% (5/21) had spasticity, 26% (5/19) had abnormal speech, and 57% (12/21) had a long-term seizure disorder. Nine patients diagnosed with IHG at < 0.5 years had significantly higher rates of dysarthria (p = 0.019) and seizure disorders (p = 0.035) in follow-up in comparison to patients diagnosed at 0.5-1 year (n=4) and >1 year (n=8). Neurocognitive outcomes were available for 19 patients at a median of 6 years after diagnosis. Median IQ for the entire cohort was 68.0 (47.0-114.0), compared to normative expectations of 100 (SD = 15), with younger age at diagnosis associated with lower IQ (r = 0.36). Ten survivors experiencing seizures particularly had worse IQ scores (median 69.4 [47-101]). Survivors also had inferior outcomes in school readiness (median 46.0 [40.0-98.0]), compared to normative expectations of 100 (SD = 15), and adaptive function (median 48.0 [34.0-67.0]), compared to normative expectations of 50 (SD= 10), with younger age at diagnosis associated with lower performance for adaptive function (r = 0.45). CONCLUSION Children diagnosed with IHG have a high survival rate but experience substantial tumor-associated and treatment-related long-term morbidity. Future clinical trials should aim for better long-term quality of life for survivors through scientifically driven treatment modification.

Long-Term Neurologic Outcomes in Pediatric Arterial Ischemic Stroke: The Impact of Age and Lesion Location.

The impact of age-at-stroke on outcome following pediatric arterial ischemic stroke remains controversial. We studied the interaction of age-at-stroke and infarct location and extent with long-term neurological outcomes. We conducted a longitudinal prospective outcome study of children with acute pediatric arterial ischemic stroke diagnosed from 1996 to 2016 at the Hospital for Sick Children, Toronto, Canada. Pediatric Stroke Outcome Measure scores were dichotomized as normal or abnormal (ie, mild, moderate, or severe). Outcomes were analyzed by age-at-stroke (newborn: birth to 28 days; early childhood: 29 days to 5 years; middle/late childhood: >5-18 years), and infarct location, based on each of the following: model 1: circulation (anterior/posterior); model 2: cortical versus subcortical involvement; and model 3: specific arterial territory, including infarct extent (small [<50% arterial territory] or large [≥50%]). Univariable and multivariable logistic regression models were fitted. Among 285 children, the outcome at median 6.1 years was 43.5% abnormal. Controlling for infarct location, increasing age-at-stroke was associated with increasing abnormal outcome. Model 1 demonstrated that, compared with neonates, abnormal outcomes were increased in early childhood (adjusted odds ratio [aOR], 2.91 [95% CI, 1.24-7.05]) and more so in middle/late childhood (aOR, 4.46 [95% CI, 1.71-12.13]). Outcomes were worse for combined locations, including anterior+posterior (model 1: aOR, 15.4 [95% CI, 4.49-64.63]) and cortical+subcortical (model 2: aOR, 10.7 [95% CI, 3.88-32.74]). Abnormal outcomes were also increased for anterior circulation (model 1: aOR, 14.91 [95% CI, 5.29-54.21]) and subcortical locations (model 2: aOR, 4.36 [95% CI, 1.37-14.95]). Among individual arterial territories, outcomes were best for superior division middle cerebral artery (100% normal) and worst for lateral lenticulostriate artery infarcts (47.4% abnormal; model 3: aOR, 14.2 [95% CI, 3.5-67.6]). Among survivors of pediatric stroke, abnormal long-term neurological outcome is increased with increasing age-at-stroke, supporting enhanced plasticity after focal injury to the newborn brain compared with older pediatric ages.

Long-term neurological outcome in patients presenting with encephalitis.

Advances in encephalitis research have improved the definition and management of encephalitis during the acute phase. Still, little is known about long-term outcomes in different subtypes of encephalitis. To analyze the prevalence and predictors of long-term clinical outcomes in different subtypes of encephalitis. All patients discharged from a tertiary hub for acute neurology with a confirmed diagnosis of encephalitis were included. Encephalitis were classified into autoimmune (AE), infectious (IE) and of unknown origin (UE) according to guidelines. Long-term neurological sequelae were evaluated using a 16-item questionnaire assessing severity and frequency of neurological symptoms, disability was scored using the expanded Disability status scale (EDSS). Long-term symptoms distribution and predictors were evaluated using univariate and multivariate regression models. Seventy out 105 survived patients were included (AE n = 30, IE n = 12, UE n = 28). Disability at discharge was worse in AE compared to UE (p = 0.018). Additionally, AE had a higher risk of relapse (n = 8 AE, n = 1 UE, p = 0.001). 36 patients (51,4%) showed significant disability according to EDSS; whereas 72,9% reported a significant neurological long-term sequela, including cognitive deficits (50,0%), depression (41,4%) and numbness (21,0%). Older age and abnormal MRI at onset were the strongest predictors of long-term severe sequelae. independently from the subtype of encephalitis. Long-term sequelae are common in encephalitis, and are associated with MRI abnormalities, premorbid disability, and older age at onset. Further longitudinal studies are needed to focus on biological and clinical predictors, to identify patients who might benefit from cognitive and behavioral training after discharge.

A Systematic Review of EEG and MRI Features for Predicting Long-Term Neurological Outcomes in Cooled Neonates With Hypoxic-Ischemic Encephalopathy (HIE).

Neonatal hypoxic-ischemic encephalopathy (HIE) represents a significant global disease burden, but more importantly, it leaves a lasting impact of disability on individual children and their families.HIE outcome prognostication is important for guiding clinical interventions and counseling families. The objective of this study was to systematically review early electroencephalogram (EEG) and magnetic resonance imaging (MRI) features associated with long-term neurological outcomes in infants after perinatal HIE. Articles were extracted from PubMed, CINAHL, and Scopus. Twenty studies were included that assessed EEG and/or MRI patterns in neonates who underwent therapeutic hypothermia and were followed to determine long-term outcomes. Articles that did not meet the inclusion criteria were excluded. Covidence review manager (Melbourne, Australia: Covidence) was used to extract, evaluate, and synthesize review results. Of the articles included, eight focused on EEG features, eight on MRI features, and four on assessments using both EEG and MRI. Abnormal EEG background and burst suppression severity were associated with poor outcomes. Higher MRI injury scores in the basal ganglia and thalamus were also correlated with poor outcomes. Finally, studies also revealed restricted diffusion and greater lesion size in the subcortical gray matter correlated with poor outcomes. We also identified limitations in the included studies which primarily involved sample size, potential for MRI pseudonormalization, and the potential tradeoff between retention of infants able to receive long-term follow-up and attrition of those lost to follow-up. We conclude that EEG background patterns, MRI scoring, subcortical lesion burden, and MRI diffusivity are sensitive metrics for predicting outcomes. Both early EEG and MRI features may serve as high-fidelity biomarkers for secondary energy failure and for counseling families of neonates at high risk for devastating neurologic outcomes. Additionally, there is a paucity of information on the impact of HIE on brain areas outside of the standard clinical basal-ganglia and watershed patterns, especially in locations like the corpus callosum. Finally, MRI pseudonormalization may underestimate the extent of injury in these studies.

Using heart rate variability to predict neurological outcomes in preterm infants: a scoping review.

Infants born preterm are at higher risk of neurological complications, including intraventricular haemorrhage and white matter injury. After discharge, these infants may experience adverse neurodevelopmental outcomes and exhibit lower educational attainment. Early detection of brain injury and accurate prediction of neurodevelopmental impairment would allow early intervention and support. Heart rate variability (HRV) describes the variation of time intervals between each subsequent heartbeat. HRV is controlled by the autonomic nervous system, which may be affected by hypoxia and compromised blood flow. While HRV has primarily been investigated in neonatal sepsis, the association between HRV, brain injury and neurodevelopmental outcomes in preterm infants is less established. The present scoping review examines the utility of HRV monitoring for predicting short-term and long-term neurological outcomes in preterm infants. Following systematic search of Medline, Embase, Web of Science and the Cochrane Library, 15 studies were included. Nine studies examined the relationship between HRV and brain injury, with all but two showed an association. Eight studies examined the relationship between HRV and long-term outcomes and all eight found an association. This scoping review suggests that decreased HRV in the neonatal period is associated with short- and long-term neurodevelopmental outcomes in preterm infants. IMPACT: Changes in heart rate variability correlate with the occurrence of intraventricular haemorrhage in preterm infants. A decrease in heart rate variability may precede the development of intraventricular haemorrhage. Alterations in heart rate variability correlate with long-term neurodevelopmental outcomes. Significant variability exists in metrics used in assessing heart rate variability.

Letter to the Editor Regarding “Predictive Factors of Long-Term Neurologic Outcome and Progression-Free Survival in Intramedullary Spinal Cord Tumors: A 10-Year Single-Center Cohort Study and Review of the Literature”

Letter to the Editor Regarding “Predictive Factors of Long-Term Neurologic Outcome and Progression-Free Survival in Intramedullary Spinal Cord Tumors: A 10-Year Single-Center Cohort Study and Review of the Literature”

Comment on, "Longterm outcome and quality of life after CNS cavernoma resection: eloquent vs. noneloquent areas".

The study titled "Long-term outcome and quality of life after CNS cavernoma resection: eloquent vs. non-eloquent areas," by Shoubash et al. (2022) provides crucial insights into the long-term neurological outcomes and quality of life (QoL) in patients following CNS cavernoma resection. Differentiating between eloquent and non-eloquent areas, the study shows that patients generally experience non-inferior QoL, with some differences in physical role functioning. Utilizing the Short Form-12 (SF12) questionnaire at a mean follow-up of 6.5 years, the study's findings are significant for clinical decision-making and patient counseling. However, the study's small sample size and retrospective design limit its generalizability and introduce potential biases. The lack of preoperative QoL assessments further constrains its conclusions. Future research should focus on larger, prospective studies with comprehensive QoL metrics and longitudinal follow-up to better understand the impact of surgery on patient outcomes and improve clinical strategies.

Cerebral Sinus Venous Thrombosis in Pediatric Acute Lymphoblastic Leukemia: Incidence, Clinical Characteristics, and Long-term Neurologic Outcomes.

To describe the incidence, clinical characteristics, and long-term outcomes of cerebral sinus venous thrombosis in children with acute lymphoblastic leukemia. This was a retrospective cohort study comprising pediatric patients with newly diagnosed or first-relapse acute lymphoblastic leukemia who developed cerebral sinus venous thrombosis at Texas Children's Hospital from 2002 to 2019. Nineteen cases (1.7%) with cerebral sinus venous thrombosis were identified in all pediatric patients with acute lymphoblastic leukemia (n = 1129). Increased risk of cerebral sinus venous thrombosis was observed with age >10 years (P = .006). Twelve cases (63%) occurred during the induction, 4 (21%) during maintenance, and 3 (16%) during the consolidation phases of leukemia therapy. Seizures (10/19) and headaches (9/19) were the most common presenting symptoms. After treatment with anticoagulation therapy, we observed full resolution of thrombosis in 10 (53%) and partial resolution in 8 patients (42%). Long-term neurologic outcomes at follow-up in the 14 patients who survived included normal neurologic examinations (n = 10), epilepsy (n = 3), and focal neurologic deficits (n = 2). The death occurred in 5 individuals. Cerebral sinus venous thrombosis is a notable complication of pediatric acute lymphoblastic leukemia therapy. Older age (>10 years) was a risk factor for developing cerebral sinus venous thrombosis. Despite variable patient presentations and treatment durations, favorable clinical outcomes were observed in most patients after the treatment with anticoagulation for a minimum of 3 months.

Quieting the neonatal intensive care unit: A quality improvement initiative.

The neonatal intensive care unit (NICU) is vital for preterm infants but is often plagued by harmful noise levels. Excessive noise, ranging from medical equipment to conversations, poses significant health risks, including hearing impairment and neurodevelopmental issues. The American Academy of Pediatrics recommends strict sound limits to safeguard neonatal well-being. Strategies such as education, environmental modifications, and quiet hours have shown to reduce noise levels. However, up to 60% of the noises remain avoidable. High noise exposure exacerbates physiological disturbances, impacting vital functions and long-term neurological outcomes. Effective noise reduction in the NICU is crucial for promoting optimal neonatal development. To measure the sound levels in a NICU and reduce ambient sound levels by at least 10% from baseline. A quasi-experimental quality improvement project was conducted over 4 mo in a 20-bed level 3 NICU in a tertiary care medical college. Baseline noise levels were recorded continuously using a sound level meter. The interventions included targeted education, environmental modifications, and organizational changes, and were implemented through three rapid Plan-Do-Study-Act (PDSA) cycles. Weekly feedback and monitoring were conducted, and statistical process control charts were used for analysis. The mean noise values were compared using the paired t-test. The baseline mean ambient noise level in the NICU was 67.8 dB, which decreased to 50.5 dB after the first cycle, and further decreased to 47.4 dB and 51.2 dB after subsequent cycles. The reduction in noise levels was 21% during the day and 28% at night, with an overall decrease of 25% from baseline. The most significant reduction occurred after the first PDSA cycle (mean difference of -17.3 dB, P < 0.01). Peak noise levels decreased from 110 dB to 88.24 dB after the intervention. A multifaceted intervention strategy reduced noise in the NICU by 25% over 4 months. The success of this initiative emphasizes the significance of comprehensive interventions for noise reduction.

Extracorporeal cardiopulmonary resuscitation for pediatric out-of-hospital cardiac arrest: A review of the Extracorporeal Life Support Organization Registry

AimsCurrent data are insufficient for the leading resuscitation societies to advise on the use of extracorporeal cardiopulmonary resuscitation (ECPR) for pediatric out-of-hospital cardiac arrest (OHCA). The aim of this study was to explore the current utilization of ECPR for pediatric OHCA and characterize the patient demographics, arrest features, and metabolic parameters associated with survival. MethodsRetrospective review of the Extracorporeal Life Support Organization Registry database from January 2020 to May 2023, including children 28 days to 18 years old who received ECPR for OHCA. The primary outcome was survival to hospital discharge. ResultsEighty patients met inclusion criteria. Median age was 8.8 years [2.0–15.8] and 53.8% of patients were male. OHCA was witnessed for 65.0% of patients and 46.3% received bystander cardiopulmonary resuscitation (CPR). Initial rhythm was shockable in 26.3% of patients and total CPR duration was 78 min [52–106]. Signs of life were noted for 31.3% of patients and a cardiac etiology precipitating event was present in 45.0%. Survival to discharge was 29.9%. Initial shockable rhythm was associated with increased odds of survival (unadjusted OR 4.7 [1.5–14.5]; p = 0.006), as were signs of life prior to ECMO (unadjusted OR 7.8 [2.6–23.4]; p < 0.001). Lactate levels early on-ECMO (unadjusted OR 0.89 [0.79–0.99]; p = 0.02) and at 24 h on-ECMO (unadjusted OR 0.62 [0.42–0.91]; p < 0.001) were associated with decreased odds of survival. ConclusionsThese preliminary data suggest that while overall survival is poor, a carefully selected pediatric OHCA patient may benefit from ECPR. Further studies are needed to understand long-term neurologic outcomes.

Long-Term Socioeconomic and Neurologic Outcome for Individuals with Childhood-Onset Multiple Sclerosis.

Most studies on the progression of childhood-onset multiple sclerosis (MS) involve relatively short follow-up periods, focusing primarily on neurological outcomes and disability progression. The influence of these and other factors on the health-related quality of life is not known. To gain a comprehensive understanding of early-onset MS, it is crucial to evaluate the effects of treatment and the disease on quality of life. This pilot project aimed to evaluate the feasibility of using an online survey tool for long-term follow-up data collection from patients with childhood-onset MS. An anonymized, monocentric, prospective survey was conducted on a convenience cohort of patients treated at a certified centre for neuromuscular diseases in childhood between 2007 and 2019. A total of 27 patients completed the survey. There were no mandatory items, therefore some patients chose not to answer all the questions in the questionnaire. Patients exhibited promising educational achievements, low neurological disease burden, and high resilience. However, anxiety, depression, and pain significantly impacted their perceived health status. This single-centre study has yielded new insights into childhood-onset MS. To enable more accurate comparisons across different centres and countries, it is essential to establish a minimum data set and questionnaire subset for patients with paediatric-onset MS transitioning into adulthood.

Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes.

Although lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH. ICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE (≥33% and/or ≥6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed. Among 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [1.03-1.21]). Similar relationships were seen with poor 6 and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, final lesion volumes, and greater mortality, as compared to non-anemic mice. These results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.

Unfavorable neurological long-term outcome despite eTICI 3 – What are the predictors?

PurposeInterventional stroke therapy has become standard treatment for patients with acute ischemic strokes. Complete reperfusion (eTICI 3) portrays the best possible technical outcome. The purpose of this study was to determine possible predictors for an unfavorable neurological long-term outcome (mRS 3–6) despite achieving the best possible treatment success. MethodsWe evaluated 122 patients with stroke in the anterior circulation and complete reperfusion after mechanical thrombectomy (MT) between May 2010 and March 2020. We performed a binary logistic regression analysis with patient baseline data, stroke severity, comorbidities, premedication and treatment information as independent variables. Results50 of the 122 patients included in our study showed a poor clinical outcome after 90 days (41 %). Multivariable logistic regression analysis showed that older age (p = 0.033), higher admission NIHSS (p=0.009), lower admission ASPECTS (p=0.005), a pre-existing cardiovascular disease (p=0.017), and multiple passes for complete reperfusion (p=0.030) had an independent impact on unfavorable outcome. ConclusionsOlder age, higher NIHSS upon admission, lower ASPECTS upon admission, cardiovascular comorbidities and multiple passes for complete reperfusion are predictors for poor neurological long-term outcome despite complete reperfusion.

Hypertonic saline for ischemic stroke: a review

Background and Objective: Elevated intracranial pressure (ICP) is a critical complication of ischemic stroke. This review article summarizes existing literature pertaining to the role of hypertonic saline (HTS) in lowering ICP in ischemic stroke patients. Methods: Studies were selected using a comprehensive search of several research databases. Studies conducted in adult (aged 18 and older) human patients receiving HTS osmotherapy for elevated ICP were included, encompassing a wide range of neurological conditions and various administration methods, durations, and concentrations of HTS. Results: We found HTS to reduce ICP in ischemic stroke patients, on par effectively, and in some studies, superior to more conventional ICP-lowering methods such as mannitol. Patients with comorbid conditions such as cerebrovascular and renal diseases also tolerated HTS well. The risk of developing hypernatremia was significantly higher in patients receiving HTS osmotherapy. Neurological complications, such as central pontine myelinosis, were not observed in any of the participants; however, no clear benefit regarding the long-term neurologic outcome of these patients has been reported thus far. Conclusion: While encouraging, existing literature on the use of HTS as a treatment for elevated ICP still needs to be more conclusive and necessitates further research. Questions regarding duration, optimal concentration of intervention, and method of administration need to be addressed by future randomized controlled trials.

Neurological Outcomes Following Craniotomy for Extracorporeal Membrane Oxygenation-Associated Intracranial Hemorrhage: Case Series and Literature Review

BackgroundIntracranial hemorrhage (ICH) is a potential complication associated with extracorporeal membrane oxygenation (ECMO), which has been increasingly utilized in recent years. A paucity of data exists describing patient outcomes following invasive neurosurgical interventions in patients receiving ECMO therapy. The purpose of this study was to assess the clinical and functional outcomes in patients who underwent cranial neurosurgery for the management of an ECMO-associated intracranial complication. MethodsThis was a single-institution retrospective review of adult patients who underwent craniotomy or craniectomy after sustaining an intracranial hemorrhagic complication of ECMO therapy from 2008-2023. Anticoagulation status, operative indication, surgical details, post-operative course, and functional outcome were recorded. A systematic review of the prior literature was performed to contextualize our institutional results within previous reports. ResultsFour adult patients were identified at our institution who underwent craniotomy or craniectomy for the neurosurgical management of an ECMO-associated ICH. One patient (25%) ultimately made a satisfactory recovery (mRS 3 at one year). The surviving patient had a notably higher GCS (7T vs 3T), had not received anticoagulation at the time of surgery, and did not experience post-operative re-accumulation or expansion of their hemorrhage, distinguishing factors from the other three included. Review of the existing literature identified 15 adult patients who underwent craniotomy while receiving ECMO therapy, of which four (26.7%) had a long-term favorable neurologic outcome. ConclusionsThe overall prognosis following neurosurgical intervention for the management of ECMO-associated intracranial complications was poor in our case series, which was corroborated by our literature review.

Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome.

Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. https://www.clinicaltrials.gov Unique identifier: NCT01662895.

Spontaneous resolution of traumatic cervical epidural hematoma: illustrative case.

Cervical epidural hematomas are rare and can arise for many reasons. Patients typically present with pain and/or symptoms of spinal cord compression. Prompt surgical decompression is typically pursued when deficits are present in an effort to improve long-term neurological outcomes. However, the authors report the case of a patient with a traumatic dorsal cervical epidural hematoma with spontaneous resolution within 16 hours. A 49-year-old male with a history of C5-6 anterior cervical fusion 3 years prior presented with neck pain after blunt force trauma. The exam revealed only tenderness in the cervical spine. Initial computed tomography revealed fractures of C1 and C4. Urgent magnetic resonance imaging (MRI) demonstrated a dorsal cervical epidural hematoma causing compression of the spinal cord from the occiput to C5. An operation was scheduled for the following morning; however, after he reported new symptoms, repeat MRI was performed, which confirmed no evidence of a cervical epidural hematoma. This case demonstrates that a traumatic cervical epidural hematoma can resolve spontaneously within a short time frame. Close monitoring of these patients is vital, and it is important to reimage patients if new signs and/or symptoms arise to potentially change the timing and/or nature of the proposed surgery. https://thejns.org/doi/10.3171/CASE24167.

Selective Activation of G Protein-Coupled Estrogen Receptor 1 (GPER1) Reduces ER Stress and Pyroptosis via AMPK Signaling Pathway in Experimental Subarachnoid Hemorrhage.

Neuroinflammation is a critical pathogenic event following hemorrhagic stroke. Endoplasmic reticulum (ER) stress-induced apoptosis and nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3(NLRP3)-associated pyroptosis can contribute to the escalation of neuroinflammatory responses, leading to increased brain damage. G protein-coupled estrogen receptor 1(GPER1), as the most extensively characterized brain-derived estrogen, was reported to trigger neuroprotective effects. However, the anti-apoptotic and anti-pyroptotic effect of GPER1 activation and the underlying mechanism has not been fully elucidated. We established the experimental SAH model by intravascular perforation. The GPER1 selective agonist G1 was intravenously administered 1h following SAH. For mechanistic exploration, the selective inhibitor of adenosine monophosphate-activated protein kinase (AMPK), dorsomorphin, was administered via intracerebroventricular injection 30min prior to SAH induction. Post-SAH assessments included SAH grade, the short-term and long-term neurological outcomes, brain edema, cerebral blood flow, transmission electron microscopy (TEM), western blot (WB), ELISA, TUNEL staining, Fluoro-Jade C staining (FJC), and immunofluorescence staining. The expression of GPER1 was observed to elevate at 6h and peaked at 24h subsequent to SAH, predominantly co-localized with neurons. Post-treatment with G1 markedly ameliorated both the short-term and long-term neurological deficits of SAH mouse, as well as inhibiting the expression of neuronal ER stress-associated apoptotic proteins (i.e., CHOP, GRP78, Caspase-12, Cleaved Caspase-3, Bax, Bcl2) and pyroptosis-associated proteins (i.e., NLRP3, ASC, Cleaved Caspase-1). Additionally, our research revealed that inhibition of AMPK with dorsomorphin attenuated the neuroprotective effects of G1. This was accompanied by modifications in the molecular pathways associated with ER stress-induced apoptosis and pyroptosis. These data herein elucidated that GPER1 exerted neuroprotective effects by mitigating neuroinflammation in an AMPK-dependent manner, which modulates neuronal ER stress-associated apoptosis and pyroptosis. Boosting the anti-apoptotic and anti-pyroptotic effect by activating GPER1 may be an efficient treatment strategy for SAH patients.

Radiologic and Blood Markers Predicting Long-Term Neurologic Outcome Following Decompressive Craniectomy for Malignant Ischemic Stroke: A Preliminary Single-Center Study.

Malignant ischemic stroke (MIS) is defined by progressive cerebral edema leading to increased intracranial pressure (ICP), compression of neural structures, and, eventually, death. Decompressive craniectomy (DC) has been advocated as a lifesaving procedure in the management of patients with MIS. This study aims to identify pre- and postoperative predictive variables of neurologic outcomes in patients undergoing DC for MIS. We conducted a retrospective study of patients undergoing DC in a single center from April 2016 to April 2020. Preoperative workup included baseline clinical status, laboratory data, and brain computed tomography (CT). The primary outcome was the 6-month modified Rankin score (mRS). The secondary outcome was the 30-day mortality. During data capture, a total of 58 patients fulfilled the criteria for MIS, of which 22 underwent DC for medically refractory increased ICP and were included in the present analysis. The overall median age was 58.5 years. An immediate (24 hour) postoperative extended Glasgow Outcome Scale (GOSE) score ≥5 was associated with a good 6-month mRS (1-3; p = 0.004). Similarly, low postoperative neutrophils (p = 0.002), low lymphocytes (p = 0.004), decreased neutrophil-to-lymphocyte ratio (NLR; p = 0.02), and decreased platelet-to-lymphocytes ratio (PLR; p = 0.03) were associated with good neurologic outcomes. Preoperative variables independently associated with worsened 6-month mRS were the following: increased age (odds ratio [OR]: 1.10; 95% confidence interval [CI]: 1.01-1.20; p = 0.02), increased National Institutes of Health Stroke Scale (NIHSS) score (OR: 7.8; 95% CI: 2.5-12.5; p = 0.035), Glasgow Coma Scale (GCS) score less than 8 at the time of neurosurgical referral (OR: 21.63; 95% CI: 1.42-328; p = 0.02), and increased partial thromboplastin time (PTT) before surgery (OR: 2.11; 95% CI: 1.11-4; p = 0.02). Decreased postoperative lymphocytes confirmed a protective role against worsened functional outcomes (OR: 0.01; 95% CI: 0.01-0.4; p = 0.02). Decreased postoperative lymphocyte count was associated with a protective role against increased mRS (OR: 0.01; 95% CI: 0.01-0.4; p = 0.02). The occurrence of hydrocephalus at the postoperative CT scan was associated with 30-day mortality (p = 0.005), while the persistence of postoperative compression of the ambient and crural cistern showed a trend towards higher mortality (p = 0.07). This study reports that patients undergoing DC for MIS showing decreased postoperative blood inflammatory markers achieved better 6-month neurologic outcomes than patients with increased inflammatory markers. Similarly, poor NIHSS score, poor GCS score, increased age, and larger PTT values at the time of surgery were independent predictors of poor outcomes. Moreover, the persistence of postoperative compression of basal cisterns and the occurrence of hydrocephalus are associated with 30-day mortality.

Haemoglobin values, transfusion practices, and long-term outcomes in critically ill patients with traumatic brain injury: a secondary analysis of CENTER-TBI

Haemoglobin (Hb) thresholds and red blood cells (RBC) transfusion strategies in traumatic brain injury (TBI) are controversial. Our objective was to assess the association of Hb values with long-term outcomes in critically ill TBI patients. We conducted a secondary analysis of CENTER-TBI, a large multicentre, prospective, observational study of European TBI patients. All patients admitted to the Intensive Care Unit (ICU) with available haemoglobin data on admission and during the first week were included. During the first seven days, daily lowest haemoglobin values were considered either a continous variable or categorised as < 7.5 g/dL, between 7.5–9.5 and > 9.5 g/dL. Anaemia was defined as haemoglobin value < 9.5 g/dL. Transfusion practices were described as “restrictive” or “liberal” based on haemoglobin values before transfusion (e.g. < 7.5 g/dL or 7.5–9.5 g/dL). Our primary outcome was the Glasgow outcome scale extended (GOSE) at six months, defined as being unfavourable when < 5. Of 1590 included, 1231 had haemoglobin values available on admission. A mean Injury Severity Score (ISS) of 33 (SD 16), isolated TBI in 502 (40.7%) and a mean Hb value at ICU admission of 12.6 (SD 2.2) g/dL was observed. 121 (9.8%) patients had Hb < 9.5 g/dL, of whom 15 (1.2%) had Hb < 7.5 g/dL. 292 (18.4%) received at least one RBC transfusion with a median haemoglobin value before transfusion of 8.4 (IQR 7.7–8.5) g/dL. Considerable heterogeneity regarding threshold transfusion was observed among centres. In the multivariable logistic regression analysis, the increase of haemoglobin value was independently associated with the decrease in the occurrence of unfavourable neurological outcomes (OR 0.78; 95% CI 0.70–0.87). Congruous results were observed in patients with the lowest haemoglobin values within the first 7 days < 7.5 g/dL (OR 2.09; 95% CI 1.15–3.81) and those between 7.5 and 9.5 g/dL (OR 1.61; 95% CI 1.07–2.42) compared to haemoglobin values > 9.5 g/dL. Results were consistent when considering mortality at 6 months as an outcome. The increase of hemoglobin value was associated with the decrease of mortality (OR 0.88; 95% CI 0.76–1.00); haemoglobin values less than 7.5 g/dL was associated with an increase of mortality (OR 3.21; 95% CI 1.59–6.49). Anaemia was independently associated with long-term unfavourable neurological outcomes and mortality in critically ill TBI patients.Trial registration: CENTER-TBI is registered at ClinicalTrials.gov, NCT02210221, last update 2022–11–07.