Outcomes of Repeat Surgery in Pediatric Severe Traumatic Brain Injury: An Analysis from Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial.

BACKGROUND: Early operative intervention, craniotomy, and/or craniectomy are occasionally warranted in severe traumatic brain injury (TBI). Persistent increased intracranial pressure or accumulation of intracranial hematoma postsurgery can result in higher mortality and morbidity. There is a gap in information regarding the outcome of repeat surgery (RS) in pediatric patients with severe TBI. METHODS: An observational cohort study titled Approaches and Decisions in Acute Pediatric TBI Trial data was obtained from the Federal Interagency Traumatic Brain Injury Research Informatics System. All pediatric patients who underwent craniotomy or decompressive craniectomy, survived more than 44 hours and were found to have persistent elevated intracranial pressure >20 mmHg for 2 consecutive hours were included in the study. The purpose of the study was to find the outcomes of RS in pediatric severe TBI. Propensity based matching was used to find the outcomes. The primary outcome was 60-day mortality. RESULTS: Out of 1000 total patients enrolled in the Approaches and Decisions in Acute Pediatric Trial, 160 patients qualified for this study. Propensity score matching created 13 pairs of patients. There were no significant differences found between the groups who had RS versus those who did not have repeat surgery on baseline characteristics. There were no significant differences found between the groups regarding 60-day mortality, median hospital days, median intensive care unit days, and 6-month favorable outcome on Glasgow Outcome Scale Extended score. CONCLUSIONS: There was no difference in mortality between patients who underwent a second surgery and patients who did not have to undergo a second surgery.

Long-term survival after primary decompressive craniectomy for severe traumatic brain injury: an observational study from 1 to 17 years.

Primary decompressive craniectomy (DC) is carried out to prevent intracranial hypertension after removal of mass lesions resulting from traumatic brain injury (TBI). While primary DC can be a life-saving intervention, significant mortality risks persist during the follow-up period. This study was undertaken to investigate the long-term survival rate and ascertain the risk factors of mortality in TBI patients who underwent primary DC. We enrolled 162 head-injured patients undergoing primary DC in this retrospective study. The primary focus was on long-term mortality, which was monitored over a range of 12 to 209 months post-TBI. We compared the clinical parameters of survivors and non-survivors, and used a multivariate logistic regression model to adjust for independent risk factors of long-term mortality. For the TBI patients who survived the initial hospitalization period following surgery, the average duration of follow-up was 106.58 ± 65.45 months. The recorded long-term survival rate of all patients was 56.2% (91/162). Multivariate logistic regression analysis revealed that age (odds ratio, 95% confidence interval = 1.12, 1.07-1.18; p < 0.01) and the status of basal cisterns (absent versus normal; odds ratio, 95% confidence interval = 9.32, 2.05-42.40; p < 0.01) were the two independent risk factors linked to long-term mortality. In conclusion, this study indicated a survival rate of 56.2% for patients subjected to primary DC for TBI, with at least a one-year follow-up. Key risk factors associated with long-term mortality were advanced age and absent basal cisterns, critical considerations for developing effective TBI management strategies.

Early Postoperative Seizures Following Awake Craniotomy and Functional Brain Mapping for Lesionectomy.

OBJECTIVE: Awake craniotomy with electrocorticography (ECoG) and direct electrical stimulation (DES) facilitates lesionectomy while avoiding adverse effects. Early postoperative seizures (EPS), occurring within 7 days following surgery, can lead to morbidity. However, risk factors for EPS after awake craniotomy including clinical and ECoG data are not well defined. METHODS: We retrospectively studied the incidence and risk factors of EPS following awake craniotomy for lesionectomy, and report short-term outcomes between January 1, 2020, and December 31, 2022. RESULTS: We included 138 patients (56 female) who underwent 142 awake craniotomies, average age was 50.78 ± 15.97 years. Eighty-eight (63.7%) patients had a preoperative history of tumor-related epilepsy treated with antiseizure medication (ASM), 12 (13.6%) with drug-resistance. All others (36.3%) received ASM prophylaxis with levetiracetam perioperatively and continued for 14 days. An equal number of cases (71) each utilized a novel circle grid or strip electrodes for ECoG. There were 31 (21.8%) cases of intraoperative seizures, 16 with EPS (11.3%). Acute abnormality on early postoperative neuroimaging (P = 0.01), subarachnoid hemorrhage (P = 0.01), young age (P = 0.01), and persistent postoperative neurologic deficits (P = 0.013) were associated with EPS. Acute abnormality on neuroimaging remained significant in multivariate analysis. Outcomes during hospitalization and early outpatient follow up were worse with EPS. CONCLUSIONS: We report novel findings using ECoG and clinical features to predict EPS, including acute perioperative brain injury, persistent postoperative deficits and young age. Given worse outcomes with EPS, clinical indicators for EPS should alert clinicians of potential need for early postoperative EEG monitoring and perioperative ASM adjustment.

Surgical treatment for drug-resistant epilepsy due to early brain injury in children.

BACKGROUND: The study aimed to summarize the indications and clinical features of pediatric drug-resistant epilepsy associated with early brain injury, surgical outcomes, and prognostic factors. METHODS: We retrospectively analyzed children diagnosed with drug-resistant epilepsy due to early brain injury, who had undergone surgery at the Pediatric Epilepsy Center of Peking University First Hospital from May 2014 to May 2021. Clinical data of vasculogenic and non-vasculogenic injuries from early brain damage were compared and analyzed. The surgical outcomes were assessed using the Engel grading system. RESULTS: The median ages at acquiring injury, seizure onset, and surgery among 65 children were 19.0 (0-120) days, 8.6 (0-136.5) months, and 62.9 (13.5-234) months, respectively. Of the 14 children with non-vasculogenic injuries, 12 had posterior ulegyria. Unilateral or bilateral synchronous interictal epileptiform discharges were located mainly in the posterior quadrant in 10 children (71 %), and unilateral posterior quadrant or non-lateralized ictal region in eight children (57 %). The surgical approach was mainly temporo-parieto-occipital or parieto-occipital disconnection in nine children. Of 49 children with vasculogenic injuries, magnetic resonance imaging revealed hemispheric abnormalities in 38. Unilaterally hemispheric or bilateral interictal epileptiform discharges were observed in 36 children (73 %), whereas 42 (86 %) had unilateral hemispheric or non-lateralized ictal onset. The surgical procedure involved hemispherotomy in 38 children (78 %) and lobectomy or disconnection, multilobectomy or disconnection and hemispherotomy in 5, 20, and 40 children, respectively. Fifty-five patients (84.6 %) achieved remission from seizure during follow-up at 5.4 years. Age at surgery (odds ratio = 1.022, 95 % confidence interval = 1.003-1.042, P = 0.023) and etiology (odds ratio = 17.25, 95 % confidence interval = 2.778-107.108, P = 0.002) affected the seizure outcomes. CONCLUSION: Children with drug-resistant epilepsy due to early brain injury can successfully be treated with surgery after rigorous preoperative screening. Good surgical outcomes are associated with an early age at surgery and an etiology of vasculogenic injury.

Short report: Plasma based biomarkers detect radiation induced brain injury in cancer patients treated for brain metastasis: A pilot study.

BACKGROUND: Radiotherapy has an important role in the treatment of brain metastases but carries risk of short and/or long-term toxicity, termed radiation-induced brain injury (RBI). As the diagnosis of RBI is crucial for correct patient management, there is an unmet need for reliable biomarkers for RBI. The aim of this proof-of concept study is to determine the utility of brain-derived circulating free DNA (BncfDNA), identified by specific methylation patterns for neurons, astrocytes, and oligodendrocytes, as biomarkers brain injury induced by radiotherapy. METHODS: Twenty-four patients with brain metastases were monitored clinically and radiologically before, during and after brain radiotherapy, and blood for BncfDNA analysis (98 samples) was concurrently collected. Sixteen patients were treated with whole brain radiotherapy and eight patients with stereotactic radiosurgery. RESULTS: During follow-up nine RBI events were detected, and all correlated with significant increase in BncfDNA levels compared to baseline. Additionally, resolution of RBI correlated with a decrease in BncfDNA. Changes in BncfDNA were independent of tumor response. CONCLUSIONS: Elevated BncfDNA levels reflects brain cell injury incurred by radiotherapy. further research is needed to establish BncfDNA as a novel plasma-based biomarker for brain injury induced by radiotherapy.

Direct to Operating Room for Decompressive Craniotomy/Craniectomy in Patients With Traumatic Brain Injury.

BACKGROUND: Emergent decompressive craniotomy/craniectomy can be a lifesaving surgical intervention for select patients with traumatic brain injury. Prompt management is critical as early decompression can impact traumatic brain injury outcomes. OBJECTIVE: This study aims to describe the feasibility and clinical impact of a new pathway for transporting patients with severe traumatic brain injury directly to the operating room from the trauma bay for decompressive craniotomy/craniectomy. METHODS: This is a retrospective cohort preintervention and postintervention study of severe traumatic brain injury patients undergoing decompressive craniectomy/craniotomy at a Midwestern U.S. Level I trauma center between 2016 and 2022. In the new pathway, the in-house trauma surgeon takes the patient directly to the operating room with the neurosurgery advanced practice provider to drape and prepare the patient for surgery while the neurosurgeon is en route to the hospital. RESULTS: A total of 44 patients were studied, five (5/44, 11.4%) of which were in the preintervention group and 39 (39/44, 88.6%) in the postintervention group. The median arrival-to-operating room time was shorter in the postintervention cohort (1.4 hr) than in the preintervention cohort (1.5 hr). In examining night shifts only, the preintervention cohort had shorter arrival-to-operating room times (1.2 hr) than the postintervention cohort (1.5 hr). CONCLUSION: The study demonstrated that the new pathway is feasible and expedites patient transport to the operating room while awaiting the arrival of the on-call neurosurgeon.

Ventriculostomy Associated with Reduced Mortality in Severe Traumatic Brain Injury Compared to Parenchymal ICP Monitoring: A Propensity Score-Adjusted Analysis.

BACKGROUND: There is a lack of data on whether intracranial pressure (ICP)-guided therapy with an intraparenchymal fiberoptic monitor (IPM) or an external ventricular drain (EVD) leads to superior outcomes. Our goal is to determine the relationship between ICP-guided therapy with an EVD or IPM and mortality. METHODS: Retrospective analysis of severe traumatic brain injury cases that required IPM or EVD placement for ICP-guided therapy from January 1, 2010 to December 31, 2020. The data were obtained from the Pennsylvania Trauma Systems Foundation registry. RESULTS: A total of 2305 patients met the inclusion criteria, with 1048 (45.5%) IPM and 1257 (54.5%) EVD placed. Inpatient mortality occurred in 337 (32.2%) and 334 (26.6%) patients in the IPM and EVD cohorts, respectively (P = 0.003). Even among those treated medically only, inpatient mortality occurred in 171 (30.8%) of those with an IPM and in 100 (23.4%) of those with an EVD (P = 0.010). Multivariable logistic regression analysis showed that older age (odds ratio [OR] 1.03, P < 0.001), lower Glasgow Coma Scale (GCS) score (OR 1.16, P < 0.001), requiring surgery (OR 1.22, P = 0.049), and an IPM (OR 1.40, P = 0.001) were significant predictors of mortality. Propensity score-adjusted analysis using inverse probability of treatment weighted method revealed a 28% decrease in mortality and a 14% decrease in length of hospital stay with EVD use when adjusting for age, sex, GCS, Injury Severity Score, surgery, and Hispanic ethnicity. CONCLUSIONS: A significant mortality benefit was associated with the use of EVD compared to IPM. This mortality benefit was observed regardless of whether patients required surgery or not.

Brain injury and long-term outcome after neonatal surgery for non-cardiac congenital anomalies.

BACKGROUND: There is growing evidence that neonatal surgery for non-cardiac congenital anomalies (NCCAs) in the neonatal period adversely affects long-term neurodevelopmental outcome. However, less is known about acquired brain injury after surgery for NCCA and abnormal brain maturation leading to these impairments. METHODS: A systematic search was performed in PubMed, Embase, and The Cochrane Library on May 6, 2022 on brain injury and maturation abnormalities seen on magnetic resonance imaging (MRI) and its associations with neurodevelopment in neonates undergoing NCCA surgery the first month postpartum. Rayyan was used for article screening and ROBINS-I for risk of bias assessment. Data on the studies, infants, surgery, MRI, and outcome were extracted. RESULTS: Three eligible studies were included, reporting 197 infants. Brain injury was found in n = 120 (50%) patients after NCCA surgery. Sixty (30%) were diagnosed with white matter injury. Cortical folding was delayed in the majority of cases. Brain injury and delayed brain maturation was associated with a decrease in neurodevelopmental outcome at 2 years of age. CONCLUSIONS: Surgery for NCCA was associated with high risk of brain injury and delay in maturation leading to delay in neurocognitive and motor development. However, more research is recommended for strong conclusions in this group of patients. IMPACT: Brain injury was found in 50% of neonates who underwent NCCA surgery. NCCA surgery is associated with a delay in cortical folding. There is an important research gap regarding perioperative brain injury and NCCA surgery.

Circulating Brain-Injury Markers After Surgery for Craniosynostosis.

OBJECTIVE: Historically, there have been few quantitative methods for effectively evaluating outcomes after surgery for craniosynostosis. In this prospective study, we assessed a novel approach for detecting possible postsurgery brain injury in patients with craniosynostosis. METHODS: We included consecutive patients operated on for sagittal (pi-plasty or craniotomy combined with springs) or metopic (frontal remodeling) synostosis at the Craniofacial Unit at Sahlgrenska University Hospital, Gothenburg, Sweden, from January 2019 to September 2020. Plasma concentrations of the brain-injury biomarkers neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau were measured immediately before induction of anesthesia, immediately before and after surgery, and on the first and the third postoperative days using single-molecule array assays. RESULTS: Of the 74 patients included, 44 underwent craniotomy combined with springs for sagittal synostosis, 10 underwent pi-plasty for sagittal synostosis, and 20 underwent frontal remodeling for metopic synostosis. Compared with baseline, GFAP level showed a maximal significant increase at day 1 after frontal remodeling for metopic synostosis and pi-plasty (P = 0.0004 and P = 0.003, respectively). By contrast, craniotomy combined with springs for sagittal synostosis showed no increase in GFAP. For neurofilament light, we found a maximal significant increase at day 3 after surgery for all procedures, with significantly higher levels observed after frontal remodeling and pi-plasty compared with craniotomy combined with springs (P < 0.001). CONCLUSIONS: These represent the first results showing significantly increased plasma levels of brain-injury biomarkers after surgery for craniosynostosis. Furthermore, we found that more extensive cranial vault procedures resulted in higher levels of these biomarkers relative to less extensive procedures.

Comparison of Equiosmolar Doses of 7.5% Hypertonic Saline and 20% Mannitol on Cerebral Oxygenation Status and Release of Brain Injury Markers During Supratentorial Craniotomy: A Randomized Controlled Trial.

BACKGROUND: Hyperosmolar therapy is the mainstay of treatment to reduce brain bulk and optimize surgical exposure during craniotomy. This study investigated the effect of equiosmolar doses of 7.5% hypertonic saline (HTS) and 20% mannitol on intraoperative cerebral oxygenation and metabolic status, systemic hemodynamics, brain relaxation, markers of cerebral injury, and perioperative craniotomy outcomes. METHODS: A total of 51 patients undergoing elective supratentorial craniotomy were randomly assigned to receive 7.5% HTS (2 mL/kg) or 20% mannitol (4.6 mL/kg) at scalp incision. Intraoperative arterial and jugular bulb blood samples were collected at predefined time intervals for assessment of various indices of cerebral oxygenation; multiple hemodynamic variables were concomitantly recorded. S100B protein and neuron-specific enolase levels were determined at baseline, and at 6 and 12 hours after surgery for assessment of neuronal injury. Brain relaxation and perioperative outcomes were also assessed. RESULTS: Demographic and intraoperative data, brain relaxation score, and perioperative outcomes were comparable between groups. Jugular bulb oxygen saturation and partial pressure of oxygen, arterial-jugular oxygen and carbon dioxide differences, and brain oxygen extraction ratio were favorably affected by 7.5% HTS up to 240 minutes postinfusion ( P <0.05), whereas mannitol was associated with only a short-lived (up to 15 min) improvement of these indices ( P <0.05). The changes in cerebral oxygenation corresponded to transient expansion of intravascular volume and improvements of cardiovascular performance. Increases in S100B and neuron-specific enolase levels at 6 and 12 hours after surgery ( P <0.0001) were comparable between groups. CONCLUSIONS: The conclusion is that 7.5% HTS has a more beneficial effect on cerebral oxygenation than an equiosmolar dose of 20% mannitol during supratentorial craniotomy, yet no clear-cut clinical superiority of either solution could be demonstrated.

Long-term Benefits for Younger Patients with Aggressive Immediate Intervention following Severe Traumatic Brain Injury: A Longitudinal Cohort Analysis of 175 Patients from a Prospective Registry.

BACKGROUND: The prevalence of traumatic brain injury (TBI) continues to rise, in part as a reflection of a growing elderly population. Concomitantly, nihilism may exist following substantial neurotrauma from a myriad of commonplace mechanisms, such as traffic incidents, assaults, or falls. OBJECTIVE: This study assesses long-term outcomes following aggressive surgical intervention with invasive neuromonitoring to guard against nihilism, especially for patients with advantageous characteristics such as younger age. METHODS: A consecutive series of patients with severe TBI treated between 2008 and 2018 and enrolled into the Brain Trauma Research Center (BTRC) database, an Institutional Review Board (IRB 19030228) approved prospective, longitudinal cohort study, were extracted. Demographic and clinical data were analyzed. Long-term functional outcome was recorded with the eight-point Glasgow Outcome Scale-Extended (GOS-E) score at 3-, 6-, 12-, and 24-months by trained, qualified neuropsychology technicians. Chi-squared and analysis of variance tests were used to evaluate the relationship of age groups between different variables. RESULTS: For this analysis, 175 patients with severe TBI who were enrolled in the BTRC database and required decompressive hemicraniectomy during the study period were included. Over one-third of the patients with a severe TBI, who were aged 35 years and younger, had a favorable outcome. CONCLUSIONS: Despite enduring a severe TBI, a substantial percentage of younger patients achieved favorable outcomes following aggressive treatment. As such, establishing a prognosis should be deferred to allow for recovery via individualized rehabilitation, multidisciplinary support, and community reintegration programs to cope with various long-term psychological, cognitive, and functional disabilities.

The impact of early surgical treatment of tracheal stenosis on neurorehabilitation outcome in patients with severe acquired brain injury.

INTRODUCTION: Acquired tracheal stenosis (TS) is a potentially life-threatening condition following prolonged intubation and/or tracheostomy in adult patients with severe Acquired Brain Injury (sABI), requiring a tracheal resection and reconstruction. METHODS: We included 38 sABI adult patients with TS, admitted at a post-acute Neurorehabilitation Hospital. Disability Rating Scale (DRS) and other functional assessment measures were recorded at admission (t1), before TS surgical treatment (t2), and at discharge (t3). Patients were defined as 'improved' when they changed from a more severe to a less severe disability, between time t2 and time t3, and as "not improved" when they did not show any further improvement between t2 and t3, or they already exhibited a disability improvement since time interval t1-t2. RESULTS: Time interval between the injury onset and TS surgical treatment (t2-t0) was associated with the patient's disability improvement, suggesting the t2-t0 time interval ≤ 115 days as a cutoff value for a possible functional recovery. A t2-t0 time interval ≤ 170 days is also associated to absence of persistent dysphagia. CONCLUSIONS: Early TS surgical treatment within 115 days from the injury onset contributes to the improvement of the disability level in patients with sABI, optimizing their functional outcomes and recovery potential.

[Surgical Site Infections in Patients with Traumatic Brain Injury].

Patients with traumatic brain injury(TBI)have various pathological conditions, such as direct cell destruction by external force, compression by hematoma, vascular injury, ischemia, complicated hypoxia, and hypotension. These pathological conditions occur simultaneously at the time of injury. In some cases, contaminated wounds may be treated, and infection patterns different from the scheduled neurosurgical cases should be managed. In cases of severe TBI, immunocompromised patients are considered to be at high risk of infection. Infection control during the initial stage of treatment affects patient prognosis. In addition, large craniotomy, including decompressive craniectomy, is required to manage intracranial pressure(ICP), which causes skin infection due to delayed wound healing. Furthermore, placement of drainage tubes and transducers for a long period of time might be necessary to manage ICP, and the patient is likely to develop surgical site infection(SSI). In this paper, we describe the characteristic surgical procedure and discuss ways to control SSI in TBI cases.

Mapping spreading depolarisations after traumatic brain injury: a pilot clinical study protocol.

INTRODUCTION: Cortical spreading depolarisation (CSD) is characterised by a near-complete loss of the ionic membrane potential of cortical neurons and glia propagating across the cerebral cortex, which generates a transient suppression of spontaneous neuronal activity. CSDs have become a recognised phenomenon that imparts ongoing secondary insults after brain injury. Studies delineating CSD generation and propagation in humans after traumatic brain injury (TBI) are lacking. Therefore, this study aims to determine the feasibility of using a multistrip electrode array to identify CSDs and characterise their propagation in space and time after TBI. METHODS AND ANALYSIS: This pilot, prospective observational study will enrol patients with TBI requiring therapeutic craniotomy or craniectomy. Subdural electrodes will be placed for continuous electrocorticography monitoring for seizures and CSDs as a research procedure, with surrogate informed consent obtained preoperatively. The propagation of CSDs relative to structural brain pathology will be mapped using reconstructed CT and electrophysiological cross-correlations. The novel use of multiple subdural strip electrodes in conjunction with brain morphometric segmentation is hypothesised to provide sufficient spatial information to characterise CSD propagation across the cerebral cortex and identify cortical foci giving rise to CSDs. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Hennepin Healthcare Research Institute's ethics committee, HSR 17-4400, 25 October 2017 to present. Study findings will be submitted for publication in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT03321370.

Early detection of ischemic brain injuries by diffusion-weighted imaging after radiofrequency ablation for fetal reduction in monochorionic pregnancies.

BACKGROUND: This study aimed to investigate the additional advantages of magnetic resonance imaging (MRI), particularly diffusion-weighted imaging (DWI) over fetal ultrasound in the detection of acute ischemic cerebral injuries in complicated monochorionic (MC) pregnancies that underwent selective reduction by radiofrequency ablation (RFA). METHODS: This prospective cohort study was conducted on 40 women with complicated MC pregnancies who were treated by RFA. Fetal brain imaging by DWI and conventional MRI was performed either in the early (within 10 days after RFA) or late phase (after 3-6 weeks) in the surviving fetuses to detect both acute and chronic ischemic injuries. The presence of anemia after RFA was also evaluated by Doppler ultrasound. RESULTS: Overall, 13 of the total 43 fetuses (30.23%) demonstrated MRI abnormalities with normal brain ultrasound results including germinal matrix hemorrhage (GMH), extensive cerebral ischemia, and mild ventriculomegaly. Although seven fetuses with GMH eventually survived, fetuses that demonstrated ischemic lesions and ventriculomegaly on MRI died in the uterus. CONCLUSION: The absence of abnormal cerebral lesions or anemia on ultrasound and Doppler exams does not necessarily rule out fetal brain ischemia. Performing early MRI, particularly DWI seems to be a reasonable option for detection of early intracranial ischemic changes and better management of complicated multiple pregnancies which were treated by RFA.