Retinal hemorrhage variation in inertial versus contact head injuries.

BACKGROUND: Abusive head trauma (AHT) is frequently accompanied by dense/extensive retinal hemorrhages to the periphery with or without retinoschisis (complex retinal hemorrhages, cRH). cRH are uncommon without AHT or major trauma. OBJECTIVE: The study objectives were to determine whether cRH are associated with inertial vs. contact mechanisms and are primary vs. secondary injuries. PARTICIPANTS AND SETTING: This retrospective study utilized a de-identified PediBIRN database of 701 children <3-years-old presenting to intensive care for head trauma. Children with motor vehicle related trauma and preexisting brain abnormalities were excluded. All had imaging showing head injury and a dedicated ophthalmology examination. METHODS: Contact injuries included craniofacial soft tissue injuries, skull fractures and epidural hematoma. Inertial injuries included acute impairment or loss of consciousness and/or bilateral and/or interhemispheric subdural hemorrhage. Abuse was defined in two ways, by 1) predetermined criteria and 2) caretaking physicians/multidisciplinary team's diagnostic consensus. RESULTS: PediBIRN subjects with cRH frequently experienced inertial injury (99.4 % (308/310, OR = 53.74 (16.91-170.77)) but infrequently isolated contact trauma (0.6 % (2/310), OR = 0.02 (0.0004-0.06)). Inertial injuries predominated over contact trauma among children with cRH sorted AHT by predetermined criteria (99.1 % (237/239), OR = 20.20 (6.09-67.01) vs 0.5 % (2/339), OR = 0.04 (0.01-0.17)). Fifty-nine percent of patients with cRH, <24 h altered consciousness, and inertial injuries lacked imaging evidence of brain hypoxia, ischemia, or swelling. CONCLUSIONS: cRH are significantly associated with inertial angular acceleration forces. They can occur without brain hypoxia, ischemia or swelling suggesting they are not secondary injuries.

Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19.

OBJECTIVE: Systemic hypoxia occurs in COVID-19 infection; however, it is unknown if cerebral hypoxia occurs in convalescent individuals. We have evidence from other conditions associated with central nervous system inflammation that hypoxia may occur in the brain. If so, hypoxia could reduce the quality of life and brain function. This study was undertaken to assess if brain hypoxia occurs in individuals after recovery from acute COVID-19 infection and if this hypoxia is associated with neurocognitive impairment and reduced quality of life. METHODS: Using frequency-domain near-infrared spectroscopy (fdNIRS), we measured cerebral tissue oxygen saturation (StO2) (a measure of hypoxia) in participants who had contracted COVID-19 at least 8 weeks prior to the study visit and healthy controls. We also conducted neuropsychological assessments and health-related quality of life assessments, fatigue, and depression. RESULTS: Fifty-six percent of the post-COVID-19 participants self-reported having persistent symptoms (from a list of 18), with the most reported symptom being fatigue and brain fog. There was a gradation in the decrease of oxyhemoglobin between controls, and normoxic and hypoxic post-COVID-19 groups (31.7 ± 8.3 µM, 27.8 ± 7.0 µM and 21.1 ± 7.2 µM, respectively, p = 0.028, p = 0.005, and p = 0.081). We detected that 24% of convalescent individuals' post-COVID-19 infection had reduced StO2 in the brain and that this relates to reduced neurological function and quality of life. INTERPRETATION: We believe that the hypoxia reported here will have health consequences for these individuals, and this is reflected in the correlation of hypoxia with greater symptomology. With the fdNIRS technology, combined with neuropsychological assessment, we may be able to identify individuals at risk of hypoxia-related symptomology and target individuals that are likely to respond to treatments aimed at improving cerebral oxygenation.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period

Abstract Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2= 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10−0.02, r2= 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Transient central hypoxemia due to intermittent high-degree atrioventricular block in a heart-transplanted patient diagnosed during routine electroencephalography: a case report.

BACKGROUND: Bradycardia frequently occurs in heart-transplanted patients, mainly as a temporally restricted manifestation early after transplantation and often without symptoms. A high-degree atrioventricular block is mostly symptomatic through cerebral hypoxia induced through cerebral hypoperfusion. Only a few published cases show this specific electroencephalography result in this context. The purpose of this case is to bring attention to atypical manifestations of typical cardiac complications after heart transplantation and the importance of perseverance in the diagnostic. CASE PRESENTATION: A Central European man in his 50s with history of heart transplantation 31 years previously was admitted to the internal medicine ward for short-lived recurrent episodes of generalized weakness with multiple falls but without loss of consciousness. During routine electroencephalography, the patient perceived this recurrent sensation. This episode coincided with a transient third-degree atrioventricular block followed 8-10 seconds later by a generalized slowing of the electroencephalography, reflecting cerebral hypoxia due to cerebral hypoperfusion. Holter monitoring confirmed the diagnosis. A pacemaker was implanted, consequently resolving the episodes. CONCLUSION: This case report illustrates the pathophysiological central hypoxemic origin of episodes of generalized weakness caused by a high-degree atrioventricular block in a patient surviving 29 years after heart transplant. It highlights the benefit of electroencephalography as a diagnostic tool in well-selected patients.

Neurophysiological and Clinical Correlates of Acute Posthypoxic Myoclonus.

SUMMARY: Prognostication following cardiorespiratory arrest relies on the neurological examination, which is supported by neuroimaging and neurophysiological testing. Acute posthypoxic myoclonus (PHM) is a clinical entity that has prognostic significance and historically has been considered an indicator of poor outcome, but this is not invariably the case. "Malignant" and more "benign" forms of acute PHM have been described and differentiating them is key in understanding their meaning in prognosis. Neurophysiological tests, electroencephalogram in particular, and clinical phenotyping are crucial in defining subtypes of acute PHM. This review describes the neurophysiological and phenotypic markers of malignant and benign forms of acute PHM, a clinical approach to evaluating acute PHM following cardiorespiratory arrest in determining prognosis, and gaps in our understanding of acute PHM that require further study.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period.

Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2 = 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10-0.02, r2 = 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Temporal Patterns in Brain Tissue and Systemic Oxygenation Associated with Mortality After Severe Traumatic Brain Injury in Children.

BACKGROUND: Brain tissue hypoxia is an independent risk factor for unfavorable outcomes in traumatic brain injury (TBI); however, systemic hyperoxemia encountered in the prevention and/or response to brain tissue hypoxia may also impact risk of mortality. We aimed to identify temporal patterns of partial pressure of oxygen in brain tissue (PbtO2), partial pressure of arterial oxygen (PaO2), and PbtO2/PaO2 ratio associated with mortality in children with severe TBI. METHODS: Data were extracted from the electronic medical record of a quaternary care children's hospital with a level I trauma center for patients ≤ 18 years old with severe TBI and the presence of PbtO2 and/or intracranial pressure monitors. Temporal analyses were performed for the first 5 days of hospitalization by using locally estimated scatterplot smoothing for less than 1,000 observations and generalized additive models with integrated smoothness estimation for more than 1,000 observations. RESULTS: A total of 138 intracranial pressure-monitored patients with TBI (median 5.0 [1.9-12.8] years; 65% boys; admission Glasgow Coma Scale score 4 [3-7]; mortality 18%), 71 with PbtO2 monitors and 67 without PbtO2 monitors were included. Distinct patterns in PbtO2, PaO2, and PbtO2/PaO2 were evident between survivors and nonsurvivors over the first 5 days of hospitalization. Time-series analyses showed lower PbtO2 values on day 1 and days 3-5 and lower PbtO2/PaO2 ratios on days 1, 2, and 5 among patients who died. Analysis of receiver operating characteristics curves using Youden's index identified a PbtO2 of 30 mm Hg and a PbtO2/PaO2 ratio of 0.12 as the cut points for discriminating between survivors and nonsurvivors. Univariate logistic regression identified PbtO2 < 30 mm Hg, hyperoxemia (PaO2 ≥ 300 mm Hg), and PbtO2/PaO2 ratio < 0.12 to be independently associated with mortality. CONCLUSIONS: Lower PbtO2, higher PaO2, and lower PbtO2/PaO2 ratio, consistent with impaired oxygen diffusion into brain tissue, were associated with mortality in this cohort of children with severe TBI. These results corroborate our prior work that suggests targeting a higher PbtO2 threshold than recommended in current guidelines and highlight the potential use of the PbtO2/PaO2 ratio in the management of severe pediatric TBI.

Development of a strategy for assessing blood-brain barrier disruption using serum S100 calcium-binding protein B and neuron-specific enolase in early stage of neuroemergencies: A preliminary study.

BACKGROUND: Rapid disease progression in neuroemergencies is associated with blood-brain barrier (BBB) disruption. We investigated a less invasive strategy for assessing BBB status by evaluating S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) at early stages of the hypoxic-ischemic brain injury (HIBI) cascade. METHODS: This retrospective study used prospectively collected data from patients with out-of-hospital cardiac arrest (August 2019-July 2021). Albumin specimens obtained from serum and cerebrospinal fluid via arterial catheter and lumbar puncture were used to measure the albumin quotient (Qa), which is widely accepted as the gold standard method for detecting BBB disruption. Serum S100B and NSE levels were measured simultaneously following the return of spontaneous circulation. We conducted linear regression to evaluate the relationship between S100B and Qa and the predictive performance of S100B for abnormal Qa. The primary study outcome was abnormal Qa (>0.007). RESULTS: Forty-one patients were enrolled; 30 showed an abnormal Qa suggestive of BBB disruption. S100B levels were significantly higher than in those with a normal Qa (0.244 µg/L [interquartile range [IQR], 0.146-0.823 vs 0.754 µg/L [IQR, 0.317-2.228], P = .03). We report a positive correlation between serum S100B and Qa (R2 = 0.110; P = .04). The area under the receiver operating characteristics curve (AUROC) evaluating the predictive performance of S100B with respect to abnormal Qa was 0.718 (95% confidence interval, 0.556-0.847). The cutoff value for S100B (with respect to BBB disruption) in the total cohort was 0.283 µg/L (sensitivity, 80.0%; specificity, 72.7%). Subgroup analyses in patients with serum neuron-specific enolase (NSE) levels of <40.8 ng/mL (excluding those with established neuronal cell injury) showed an improved correlation coefficient (R2 = 0.382; P < .01) and predictive performance (AUROC, 0.836 [95% confidence interval, 0.629-0.954]) compared with the total cohort. CONCLUSIONS: Serum S100B obtained at an early stage of the HIBI cascade is associated with abnormal Qa, suggesting BBB disruption. The predictive performance of S100B and the correlation between serum S100B and Qa can be improved using a complementary strategy (i.e., evaluations of S100B and NSE levels) that combines considerations of cell damage in astrocytes and neurons.

Return to work after acute myocardial infarction with cardiogenic shock: a Danish nationwide cohort study.

BACKGROUND: Physical and mental well-being after critical illness may be objectified by the ability to work. We examined return to work among patients with myocardial infarction (MI) by cardiogenic shock (CS) status. METHODS: Danish nationwide registries were used to identify patients with first-time MI by CS status between 2005 and 2015, aged 18-63 years, working before hospitalization and discharged alive. Multiple logistic regression models were used to compare groups. RESULTS: We identified 19 799 patients with MI of whom 653 had CS (3%). The median age was similar for patients with and without CS (53 years, interquartile range 47-58). One-year outcomes in patients with and without CS were as follows: 52% vs. 83% returned to work, 41% vs. 16% did not and 6% vs. 1% died. The adjusted odds ratio (OR) of returning to work was 0.53 [95% confidence limit (CI): 0.42-0.66]. In patients with CS, males and patients surviving OHCA were more likely to return to work (OR: 1.83, 95% CI: 1.15-2.92 and 1.55, 95% CI: 1.00-2.40, respectively), whereas prolonged hospitalization (OR: 0.38, 95% CI: 0.22-0.65) and anoxic brain damage (OR: 0.36, 95% CI: 0.18-0.72) were associated with lower likelihood of returning to work. CONCLUSION: In patients with MI discharged alive, approximately 80% of those without CS returned to work at 1-year follow-up in contrast to 50% of those with CS. Among patients with CS, male sex and OHCA survivors were markers positively related to return to work, whereas prolonged hospitalization and anoxic brain damage were negatively related markers.

Early cerebral hypoxia in extremely preterm infants and neurodevelopmental impairment at 2 year of age: A post hoc analysis of the SafeBoosC II trial.

BACKGROUND: The SafeBoosC II, randomised clinical trial, showed that the burden of cerebral hypoxia was reduced with the combination of near infrared spectroscopy and a treatment guideline in extremely preterm infants during the first 72 hours after birth. We have previously reported that a high burden of cerebral hypoxia was associated with cerebral haemorrhage and EEG suppression towards the end of the 72-hour intervention period, regardless of allocation. In this study we describe the associations between the burden of cerebral hypoxia and the 2-year outcome. METHODS: Cerebral oxygenation was continuously monitored from 3 to 72 hours after birth in 166 extremely preterm infants. At 2 years of age 114 of 133 surviving children participated in the follow-up program: medical examination, Bayley II or III test and the parental Ages and Stages Questionnaire. The infants were classified according to the burden of hypoxia: within the first three quartiles (n = 86, low burden) or within in the 4th quartile (n = 28, high burden). All analyses were conducted post hoc. RESULTS: There were no statistically significant differences between the quantitative assessments of neurodevelopment in the groups of infants with the low burden of cerebral hypoxia versus the group of infants with the high burden of cerebral hypoxia. The infants in the high hypoxia burden group had a higher-though again not statistically significant-rate of cerebral palsy (OR 2.14 (0.33-13.78)) and severe developmental impairment (OR 4.74 (0.74-30.49). CONCLUSIONS: The burden of cerebral hypoxia was not significantly associated with impaired 2-year neurodevelopmental outcome in this post-hoc analysis of a feasibility trial.

Pulmonary injury as a predictor of cerebral hypoxia in traumatic brain injury: from physiology to physiopathology.

Traumatic brain injury is caused by mechanical forces impacting the skull and its internal structures and constitutes one of the main causes of morbidity and mortality in the world. Clinically, severe traumatic brain injury is associated with the development of acute lung injury and so far, few studies have evaluated the cellular, molecular and immunological mechanisms involved in this pathophysiological process. Knowing and investigating these mechanisms allows us to correlate pulmonary injury as a predictor of cerebral hypoxia in traumatic brain injury and to use this finding in decision making during clinical practice. This review aims to provide evidence on the importance of the pathophysiology of traumatic brain injury-acute lung injury, and thus confirm its role as a predictor of cerebral hypoxia, helping to establish an appropriate therapeutic strategy to improve functional outcomes and reduce mortality.

Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema.

Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.

Tubular calcium, magnesium, and phosphate excretion during therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy: A prospective study.

OBJECTIVES: Hypocalcemia, hypomagnesemia, and hyperphosphatemia are common electrolyte disturbances in perinatal asphyxia (PA). Different reasons have been proposed for these electrolyte disturbances. This study investigated the effect of the urinary excretion of calcium (Ca), magnesium (Mg), and phosphorus (P) on the serum levels of these substances in babies who were treated using therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) caused by PA. This study sheds light on the pathophysiology that may cause changes in the serum values of these electrolytes. METHODS: This study included 21 healthy newborns (control group) and 38 patients (HIE group) who had undergone therapeutic hypothermia due to HIE. Only infants with a gestational age of 36 weeks and above and a birth weight of 2000 g and above were evaluated. The urine and serum Ca, Mg, P, and creatinine levels of all infants were evaluated at 24, 48, and 72 h. RESULTS: The lower serum Ca value and the higher serum P value of the HIE group were found to be statistically significant compared to the control group (p<0.05). There was no significant difference in serum Mg values between the groups. However, hypomagnesemia was detected in five patients from the HIE group. The urine excretion of FeCa and FeMg at 24 h, and FeP excretion at 48 and 72 h were found to be significantly higher in the HIE group compared to the control group. CONCLUSIONS: This study determined that the urinary excretion of Ca, Mg, and P has an effect on the serum Ca, Mg, and P levels of infants with HIE.

[Response to perampanel in a patient with chronic post-hypoxic myoclonus]. / Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.

INTRODUCTION: Chronic post-hypoxic myoclonus is a condition in which the predominant clinical picture is myoclonus following hypoxic brain damage, usually due to cardiorespiratory arrest. It is a condition that is usually treated with antiepileptic drugs, in most cases with a modest clinical response. CASE REPORT: We report the case of a patient who started with jerking movements, compatible with myoclonus in the four limbs and the face the day after recovering from a cardiorespiratory arrest. An electroencephalogram was performed during which the myoclonias were recorded with no electrical correlates. During admission, and in successive visits after discharge, different antiepileptic treatments were tried for the myoclonias, which were refractory and affected the patient's quality of life. Two years after onset, treatment with perampanel up to a dose of 4 mg was initiated and the patient reported a significant clinical improvement, as evidenced in the visits. CONCLUSIONS: Perampanel may be an effective alternative for the treatment of myoclonias in patients with chronic post-hypoxic myoclonus.

TITLE: Respuesta a perampanel en un paciente con mioclono posthipóxico crónico.Introducción. El mioclono posthipóxico crónico es un cuadro cuya clínica predominante son las mioclonías que acontecen tras un daño cerebral hipóxico, generalmente por parada cardiorrespiratoria. Es una entidad que se trata generalmente con fármacos antiepilépticos, con una modesta respuesta clínica en la mayoría de los casos. Caso clínico. Paciente que comienza con movimientos de sacudidas, compatibles con mioclonías de las cuatro extremidades y faciales al día siguiente de una parada cardiorrespiratoria recuperada. Se realizó un electroencefalograma durante el cual se registraron las mioclonías sin presentar correlato eléctrico. Durante el ingreso, y en sucesivas visitas tras el alta, se probaron diferentes tratamientos antiepilépticos para las mioclonías, que fueron refractarias y comportaron una afectación de la calidad de vida del paciente. Tras dos años de evolución, se inició tratamiento con perampanel hasta una dosis de 4 mg y el paciente refirió una mejoría clínica importante, evidenciada en consultas. Conclusiones. El perampanel puede suponer una alternativa eficaz para el tratamiento de las mioclonías en pacientes con mioclono posthipóxico crónico.

Prehospital, post-ROSC blood pressure and associated neurologic outcome.

OBJECTIVE: To investigate the relationship between hypotension and neurologic outcome in adults with return of spontaneous circulation after out-of-hospital cardiac arrest. METHODS: Blood pressure and medication data were extracted from adult patients who had ROSC after OHCA in Alameda County and matched with neurologic outcome using the CARES database from January 1, 2018 through July 1, 2019. We used univariate logistic regression with p ≤ 0.2 followed by multivariate logistic regression and reported an odds ratio with 95% confidence intervals. RESULTS: Among the 781 adult patients who had ROSC after OHCA, 107 (13.7%) were noted to be hypotensive and 61 (57% of the hypotensive group) received vasopressors. Patients with a final prehospital blood pressure recording of <90 mmHg were more likely to have a poor neurologic outcome (adjusted odds ratio 2.13, adj p = 0.048). About twice as many patients who were not hypotensive had a good neurologic outcome compared to hypotensive patients who had a good neurologic outcome (23% to 10.3%). Additionally, patients who were hypotensive and did not receive vasopressors had a similar neurologic outcome compared to patients who did receive vasopressors. CONCLUSION: Prehospital post-ROSC hypotension was associated with worse neurologic outcome and giving hypotensive patients vasopressors may not improve neurologic outcome in the prehospital setting.

Altered hippocampal dendritic spine maturation after hypoxia-induced seizures in neonatal rats.

Cognitive comorbidities often follow early-life seizures (ELS), especially in the setting of autism and other neurodevelopmental syndromes. However, there is an incomplete understanding of whether neuronal and synaptic development are concomitantly dysregulated. We have previously shown that hypoxia-induced seizures (HS) in postnatal day (P)10 rats increase acute and later-life hippocampal glutamatergic neurotransmission and spontaneous recurrent seizures, and impair cognition and behavior. As dendritic spines critically regulate synaptic function, we hypothesized that ELS can induce developmentally specific changes in dendritic spine maturation. At intervals during one month following HS in P10 rats, we assessed dendritic spine development on pyramidal neurons in the stratum radiatum of hippocampal area CA1. Compared to control rats in which spine density significantly decreased from P10 to early adulthood (P38), post-seizure rats failed to show a developmental decrease in spine density, and spines from P38 post-seizure rats appeared more immature-shaped (long, thin). In addition, compared to P38 control rats, post-seizure P38 rats expressed significantly more synaptic PSD-95, a marker of mature synapses. These changes were preceded by a transient increase in hippocampal expression of cofilin phosphorylated at Ser3, representing a decrease in cofilin activity. These results suggest that early-life seizures may impair normal dendritic spine maturation and pruning in CA1 during development, resulting in an excess of less efficient synapses, via activity-dependent modification of actin-regulating proteins such as cofilin. Given that multiple neurodevelopmental disorders show similar failures in developmental spine pruning, the current findings may represent a deficit in structural plasticity that could be a component of a mechanism leading to later-life cognitive consequences associated with early-life seizures.