Longitudinal CSF Iron Pathway Proteins in Posthemorrhagic Hydrocephalus: Associations with Ventricle Size and Neurodevelopmental Outcomes.

OBJECTIVE: Iron has been implicated in the pathogenesis of brain injury and hydrocephalus after preterm germinal matrix hemorrhage-intraventricular hemorrhage, however, it is unknown how external or endogenous intraventricular clearance of iron pathway proteins affect the outcome in this group. METHODS: This prospective multicenter cohort included patients with posthemorrhagic hydrocephalus (PHH) who underwent (1) temporary and permanent cerebrospinal fluid (CSF) diversion and (2) Bayley Scales of Infant Development-III testing around 2 years of age. CSF proteins in the iron handling pathway were analyzed longitudinally and compared to ventricle size and neurodevelopmental outcomes. RESULTS: Thirty-seven patients met inclusion criteria with a median estimated gestational age at birth of 25 weeks; 65% were boys. Ventricular CSF levels of hemoglobin, iron, total bilirubin, and ferritin decreased between temporary and permanent CSF diversion with no change in CSF levels of ceruloplasmin, transferrin, haptoglobin, and hepcidin. There was an increase in CSF hemopexin during this interval. Larger ventricle size at permanent CSF diversion was associated with elevated CSF ferritin (p = 0.015) and decreased CSF hemopexin (p = 0.007). CSF levels of proteins at temporary CSF diversion were not associated with outcome, however, higher CSF transferrin at permanent CSF diversion was associated with improved cognitive outcome (p = 0.015). Importantly, longitudinal change in CSF iron pathway proteins, ferritin (decrease), and transferrin (increase) were associated with improved cognitive (p = 0.04) and motor (p = 0.03) scores and improved cognitive (p = 0.04), language (p = 0.035), and motor (p = 0.008) scores, respectively. INTERPRETATION: Longitudinal changes in CSF transferrin (increase) and ferritin (decrease) are associated with improved neurodevelopmental outcomes in neonatal PHH, with implications for understanding the pathogenesis of poor outcomes in PHH. ANN NEUROL 2021;90:217-226.

Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity.

OBJECTIVE: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH. STUDY DESIGN: Preterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared in PHH versus control CSF. Fifty-four of these PHH subjects underwent Bayley Scales of Infant Development-III (Bayley-III) testing at 15-30 months corrected age. Controlling for false discovery rate (FDR) and adjusting for post-menstrual age (PMA) and IVH grade, Pearson's partial correlation coefficients were used to examine relationships between CSF proteins and Bayley-III composite cognitive, language, and motor scores. RESULTS: CSF APP, L1CAM, NCAM-1, and TP were elevated in PHH over control at temporizing surgery. CSF NCAM-1 was associated with Bayley-III motor score (R = -0.422, p = 0.007, FDR Q = 0.089), with modest relationships noted with cognition (R = -0.335, p = 0.030, FDR Q = 0.182) and language (R = -0.314, p = 0.048, FDR Q = 0.194) scores. No relationships were observed between CSF APP, L1CAM, or TP and Bayley-III scores. FOHR at the time of temporization did not correlate with Bayley-III scores, though trends were observed with Bayley-III motor (p = 0.0647 and R = -0.2912) and cognitive scores (p = 0.0506 and R = -0.2966). CONCLUSION: CSF NCAM-1 was associated with neurodevelopment in this multi-institutional PHH cohort. This is the first report relating a specific CSF protein, NCAM-1, to neurodevelopment in PHH. Future work will further investigate a possible role for NCAM-1 as a biomarker of PHH-associated neurological disability.

Comparison of anticoagulation and antiplatelet therapy for treatment of blunt cerebrovascular injury in children <10 years of age: a multicenter retrospective cohort study.

PURPOSE: Blunt cerebrovascular injury (BCVI) is uncommon in the pediatric population. Among the management options is medical management consisting of antithrombotic therapy with either antiplatelets or anticoagulation. There is no consensus on whether administration of antiplatelets or anticoagulation is more appropriate for BCVI in children < 10 years of age. Our goal was to compare radiographic and clinical outcomes based on medical treatment modality for BCVI in children < 10 years. METHODS: Clinical and radiographic data were collected retrospectively for children screened for BCVI with computed tomography angiography at 5 academic pediatric trauma centers. RESULTS: Among 651 patients evaluated with computed tomography angiography to screen for BCVI, 17 patients aged less than 10 years were diagnosed with BCVI (7 grade I, 5 grade II, 1 grade III, 4 grade IV) and received anticoagulation or antiplatelet therapy for 18 total injuries: 11 intracranial carotid artery, 4 extracranial carotid artery, and 3 extracranial vertebral artery injuries. Eleven patients were treated with antiplatelets (10 aspirin, 1 clopidogrel) and 6 with anticoagulation (4 unfractionated heparin, 2 low-molecular-weight heparin, 1 transitioned from the former to the latter). There were no complications secondary to treatment. One patient who received anticoagulation died as a result of the traumatic injuries. In aggregate, children treated with antiplatelet therapy demonstrated healing on 52% of follow-up imaging studies versus 25% in the anticoagulation cohort. CONCLUSION: There were no observed differences in the rate of hemorrhagic complications between anticoagulation and antiplatelet therapy for BCVI in children < 10 years, with a nonsignificantly better rate of healing on follow-up imaging in children who underwent antiplatelet therapy; however, the study cohort was small despite including patients from 5 hospitals.

Intravenous acetaminophen for postoperative supratentorial craniotomy pain: a prospective, randomized, double-blinded, placebo-controlled trial.

OBJECTIVE: Acute pain control after cranial surgery is challenging. Prior research has shown that patients experience inadequate pain control post-craniotomy. The use of oral medications is sometimes delayed because of postoperative nausea, and the use of narcotics can impair the evaluation of brain function and thus are used judiciously. Few nonnarcotic intravenous (IV) analgesics exist. The authors present the results of the first prospective study evaluating the use of IV acetaminophen in patients after elective craniotomy. METHODS: The authors conducted a randomized, double-blinded, placebo-controlled investigation. Adults undergoing elective, supratentorial craniotomies between September 2013 and June 2015 were randomized into two groups. The experimental group received 1000 mg/100 ml IV acetaminophen every 8 hours for 48 hours. The placebo group received 100 ml of 0.9% normal saline on the same schedule. Both groups were also treated with a standardized pain control algorithm. The study was powered to detect a 30% difference in the primary outcome measures: narcotic consumption (morphine equivalents, ME) at 24 and 48 hours after surgery. Patient-reported pain scores immediately postoperatively and 48 hours after surgery were also recorded. RESULTS: A total of 204 patients completed the trial. No significant differences were found in narcotic consumption between groups at either time point (in the treatment and placebo groups, respectively, at 24 hours: 84.3 ME [95% CI 70.2­98.4] and 85.5 ME [95% CI 73­97.9]; and at 48 hours: 123.5 ME [95% CI 102.9­144.2] and 134.2 ME [95% CI 112.1­156.3]). The difference in improvement in patient-reported pain scores between the treatment and placebo groups was significant (p < 0.001). CONCLUSIONS: Patients who received postoperative IV acetaminophen after craniotomy did not have significantly decreased narcotic consumption but did experience significantly lower pain scores after surgery. The drug was well tolerated and safe in this patient population.

Identifying Factors Predictive of Atlantoaxial Fusion Failure in Pediatric Patients: Lessons Learned From a Retrospective Pediatric Craniocervical Society Study.

STUDY DESIGN: Multicenter retrospective cohort study with multivariate analysis. OBJECTIVE: To determine factors predictive of posterior atlantoaxial fusion failure in pediatric patients. SUMMARY OF BACKGROUND DATA: Fusion rates for pediatric posterior atlantoaxial arthrodesis have been reported to be high in single-center studies; however, factors predictive of surgical non-union have not been identified by a multicenter study. METHODS: Clinical and surgical details for all patients who underwent posterior atlantoaxial fusion at seven pediatric spine centers from 1995 to 2014 were retrospectively recorded. The primary outcome was surgical failure, defined as either instrumentation failure or fusion failure seen on either plain x-ray or computed tomography scan. Multiple logistic regression analysis was undertaken to identify clinical and technical factors predictive of surgical failure. RESULTS: One hundred thirty-one patients met the inclusion criteria and were included in the analysis. Successful fusion was seen in 117 (89%) of the patients. Of the 14 (11%) patients with failed fusion, the cause was instrumentation failure in 3 patients (2%) and graft failure in 11 (8%). Multivariate analysis identified Down syndrome as the single factor predictive of fusion failure (odds ratio 14.6, 95% confidence interval [3.7-64.0]). CONCLUSION: This retrospective analysis of a multicenter cohort demonstrates that although posterior pediatric atlantoaxial fusion success rates are generally high, Down syndrome is a risk factor that significantly predicts the possibility of surgical failure. LEVEL OF EVIDENCE: 3.

Management of Penetrating Cerebrovascular Injuries in Pediatric Trauma: A Retrospective Multicenter Study.

BACKGROUND: Blunt cerebrovascular injury is uncommon in the pediatric population; penetrating cerebrovascular injuries are even rarer and are thus poorly understood. OBJECTIVE: To describe the diagnosis and management of penetrating cerebrovascular injuries and describe outcomes of available treatment modalities. METHODS: Clinical and radiographic data were collected retrospectively from a multicenter trauma registry for children screened for cerebrovascular injury during 2003 to 2013 at 4 academic pediatric trauma centers. RESULTS: Among 645 pediatric patients evaluated with computed tomography angiography with blunt cerebrovascular injury, 130 also had a penetrating trauma indication. Seven penetrating cerebrovascular injuries were diagnosed in 7 male patients (mean age 12.4 years, range 12-18 years). Focal neurological deficit and concomitant intracranial injury were each seen in 2 patients. There were 2 intracranial carotid artery injuries, 4 extracranial carotid artery injuries, and 1 vertebral artery injury. The majority of injuries were higher than grade I (5/7; 71%): 2 were grade I, 1 grade II, 2 grade III, and 2 grade IV. The 2 patients with grade III injuries required open surgery, and 1 patient with a grade IV injury underwent endovascular treatment. Two patients suffered immediate stroke secondary to the penetrating cerebrovascular injury. There were no delayed neurological deficits from the penetrating injuries, and no patients died as a result of the injuries. CONCLUSION: This is the largest series of penetrating cerebrovascular trauma in the pediatric literature. Although rare, penetrating cerebrovascular injuries can be high-grade injuries that require urgent recognition and may require aggressive endovascular and/or open surgery for treatment.

Management of posterior fossa tumors and hydrocephalus in children: a review.

OBJECT: Most pediatric patients that present with a posterior fossa tumor have concurrent hydrocephalus. There is significant debate over the best management strategy of hydrocephalus in this situation. The objectives of this paper were to review the pathophysiology model of posterior fossa tumor hydrocephalus, describe the individual risks factors of persistent hydrocephalus, and discuss the current management options. Specifically, the debate over preresection cerebrospinal fluid diversion is discussed. RESULTS: Only 10-40 % demonstrate persistent hydrocephalus after posterior fossa tumor resection. It appears that young age, moderate to severe hydrocephalus, transependymal edema, the presence of cerebral metastases, and tumor pathology (medulloblastoma and ependymoma) on presentation predict postresection or persistent hydrocephalus. The Canadian Preoperative Prediction Rule for Hydrocephalus (CPPRH), a validated prediction model, can be used to stratify patients at point of first contact into high and low risk for persistent hydrocephalus. CONCLUSIONS: A protocol is proposed for managing hydrocephalus that utilizes the CPPRH. Low-risk patients can be monitored conservatively with or without an intraoperative extraventricular drain, while high-risk patients require the use of an intraoperative extraventricular drain, higher postoperative hydrocephalus surveillance, and even consideration for a preoperative endoscopic third ventriculostomy.

Distraction Osteogenesis Technique for the Treatment of Nonsyndromic Sagittal Synostosis.

BACKGROUND: Historically, surgical treatment of children with a delayed presentation of cranial synostosis required complex cranial vault reconstruction. Recently, less invasive options for surgical correction, such as internal distraction osteogenesis, have been explored. In this study, we describe the successful management of delayed presentation of sagittal synostosis using distraction osteogenesis. METHODS: A bicoronal incision was made and 2 large rectangular osteotomies were performed bilaterally, involving the frontal, parietal, temporal and occipital bones. A 2 cm strut of bone over the sagittal sinus was preserved, creating bilateral free-floating bone segments. Two pairs of distractors were placed transversely, along the midline strut of bone, providing lateral distraction of these segments. This placement allowed maximum displacement at the apex of the cranial vault. Distraction was performed differentially at 1 mm per day anteriorly and 2 mm per day posteriorly, for a total of 17 days, allowing for a greater degree of expansion of the posterior vault. The consolidation phase lasted for 10 weeks. The distractors were removed via the same bicoronal incision and cranioplasty was performed to smooth prominent ridging at the margins of the distracted segments. RESULTS: The child's cranial index improved from 0.67 preoperatively to 0.76 postoperatively. The overall vault contour was smooth with no bony defects. There was a significant cosmetic improvement of the child's head shape. No major complications requiring reoperation or rehospitalization were encountered. CONCLUSION: The use of distraction osteogenesis to laterally expand the cranial vault is a useful alternative in the treatment of delayed presentation, nonsyndromic, sagittal synostosis.

The Need for Cost-Effective Neurosurgical Innovation--A Global Surgery Initiative.

The authors discuss the unmet needs for neurosurgical care around the world and some of the innovative work being done to address this need. The growing demonstration of surgical innovation and cost-effective technology represents an opportunity within neurosurgery to achieve the goal of making surgical care more accessible to the global population.

Occipital aneurysmal bone cyst rupture following head trauma: case report.

Aneurysmal bone cysts (ABCs) are benign, expansile, osteolytic lesions that represent 1%-2% of primary bone tumors. Cranial ABCs are even more rare and represent 3%-6% of these unique lesions. The authors describe the case of a 3-year-old girl who presented with an acute posterior fossa epidural hematoma after minor trauma. Imaging workup revealed a previously undiagnosed suboccipital ABC that appeared to have ruptured as a result of her trauma, leading to a life-threatening hemorrhage. To the authors' knowledge, a ruptured ABC has never before been presented in the pediatric literature. In this case report, the authors review the imaging findings, natural history, clinical course, and treatment of these rare lesions.

Pediatric spinal pilomyxoid astrocytoma.

Pediatric spinal pilomyxoid astrocytoma (PMA) is an extremely rare tumor that merits recognition as a specific, unique entity. The authors present the case of an intramedullary PMA in the thoracic spinal cord of an 11-year-old boy who presented with back pain, scoliosis, and multiple lung nodules. The patient underwent T5-11 laminoplasty and near-total resection of the spinal tumor. The final pathological diagnosis was WHO Grade II PMA. The patient did well for 14 months until the tumor progressed both clinically and radiographically. A literature review focusing on the clinical characteristics, histology, and treatment of PMAs provides a better understanding of these rare lesions. Because of the small number of cases optimal treatment guidelines have not been established, but gross-total resection and adjuvant chemotherapy with alkylating agents appear to confer a better long-term prognosis. Pediatric patients with PMAs can remain recurrence free at least 5 years after surgery, although these tumors may disseminate or dedifferentiate into more malignant gliomas. Recognition of intramedullary PMA as a unique entity in children is vital to the development of specific surgical and adjuvant treatment regimens.

Intraventricular fungus ball: a unique manifestation of refractory intracranial candidiasis in an immunocompetent neonate.

The authors report on a case of intracranial candidiasis in an immunocompetent neonate with a ventriculo-peritoneal shunt. The child was known to be colonized with yeast as she had been treated for oral thrush; however, she did not have systemic candidiasis. Despite initial treatment with antifungal medication, intraventricular fungus balls developed that were visible on imaging and confirmed with pathological analysis. Multiple endoscopic intraventricular operations were required for excision of the initial and recurrent fungus balls, multiple fenestrations of loculations and cysts were performed, and ultimately 3 ventriculoperitoneal shunts were placed. The finding of an intraventricular fungus ball is a unique manifestation of intracranial candidiasis, and to the authors' knowledge has not been previously reported in the English literature.