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.

Intraventricular Hemorrhage Clearance in Human Neonatal Cerebrospinal Fluid: Associations With Hydrocephalus.

Background and Purpose- Preterm neonates with intraventricular hemorrhage (IVH) are at risk for posthemorrhagic hydrocephalus and poor neurological outcomes. Iron has been implicated in ventriculomegaly, hippocampal injury, and poor outcomes following IVH. We hypothesized that levels of cerebrospinal fluid blood breakdown products and endogenous iron clearance proteins in neonates with IVH differ from those of neonates with IVH who subsequently develop posthemorrhagic hydrocephalus. Methods- Premature neonates with an estimated gestational age at birth <30 weeks who underwent lumbar puncture for clinical evaluation an average of 2 weeks after birth were evaluated. Groups consisted of controls (n=16), low-grade IVH (grades I-II; n=4), high-grade IVH (grades III-IV; n=6), and posthemorrhagic hydrocephalus (n=9). Control subjects were preterm neonates born at <30 weeks' gestation without brain abnormality or hemorrhage on cranial ultrasound, who underwent lumbar puncture for clinical purposes. Cerebrospinal fluid hemoglobin, total bilirubin, total iron, ferritin, ceruloplasmin, transferrin, haptoglobin, and hemopexin were quantified. Results- Cerebrospinal fluid hemoglobin levels were increased in posthemorrhagic hydrocephalus compared with high-grade IVH (9.45 versus 6.06 µg/mL, P<0.05) and cerebrospinal fluid ferritin levels were increased in posthemorrhagic hydrocephalus compared with controls (511.33 versus 67.08, P<0.01). No significant group differences existed for the other cerebrospinal fluid blood breakdown and iron-handling proteins tested. We observed positive correlations between ventricular enlargement (frontal occipital horn ratio) and ferritin (Pearson r=0.67), hemoglobin (Pearson r=0.68), and total bilirubin (Pearson r=0.69). Conclusions- Neonates with posthemorrhagic hydrocephalus had significantly higher levels of hemoglobin than those with high-grade IVH. Levels of blood breakdown products, hemoglobin, ferritin, and bilirubin correlated with ventricular size. There was no elevation of several iron-scavenging proteins in cerebrospinal fluid in neonates with posthemorrhagic hydrocpehalus, indicative of posthemorrhagic hydrocephalus as a disease state occurring when endogenous iron clearance mechanisms are overwhelmed.

Language-discordant care in pediatric neurosurgery: parent and provider perspectives on challenges and multilevel solutions to reduce disparities.

OBJECTIVE: In the United States, Spanish is the second most spoken language, with nearly 42 million individuals speaking Spanish at home. Spanish speakers have been noted to have higher rates of unfavorable neurosurgical outcomes; however, to the authors' knowledge, no study has explored the experiences of patients, caregivers, and providers receiving or delivering neurosurgical care in language-discordant settings. In this study, the authors sought to identify challenges faced by pediatric neurosurgery providers and Spanish-speaking parents communicating with a language barrier and propose solutions to address those challenges. METHODS: Spanish-speaking parents and pediatric neurosurgery providers were invited to participate in semistructured interviews. Purposeful sampling was used to recruit Spanish-speaking parents whose child had recently undergone neurological surgery at the authors' institution and to identify pediatric neurosurgery clinical team members to interview, including physicians, advanced practice providers, and interpreters. Codes were inductively developed and applied to transcripts by two researchers. Thematic analysis was conducted to identify challenges faced by parents and providers. RESULTS: Twenty individuals were interviewed, including parents (n = 8), advanced practice providers (n = 5), physicians (n = 3), interpreters (n = 2), a social worker (n = 1), and a nurse (n = 1). Three challenges were identified. 1) Compared with English-speaking parents, providers noted that Spanish-speaking parents were less likely to ask questions or raise new concerns. Concurrently, Spanish-speaking parents expressed a desire to better understand their child's future medical needs, care, and development. 2) There is a dearth of high-quality resources available in the Spanish language to supplement patient and parent neurosurgical education. 3) Both parents and providers invariably prefer in-person interpreters; however, their availability is limited. CONCLUSIONS: Three challenges were identified by Spanish-speaking parents of pediatric neurosurgery patients and providers when receiving or delivering care through a language barrier. The authors discuss multilevel solutions that, if deployed, could directly address these shared challenges. Furthermore, optimizing communication may help mitigate the disparities experienced by non-English-speaking Hispanic/Latino individuals when receiving neurosurgical care.

Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: a pilot study.

OBJECTIVE: Macrophages play a critical role in cerebral aneurysm formation and rupture. The purpose of this study is to demonstrate the feasibility and optimal parameters of imaging macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI. METHODS AND RESULTS: Nineteen unruptured aneurysms in 11 patients were imaged using T2*-GE-MRI sequence. Two protocols were used. Protocol A was an infusion of 2.5 mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B was an infusion of 5 mg/kg of ferumoxytol and imaging at day 0 and 3. All images were reviewed independently by 2 neuroradiologists to assess for ferumoxytol-associated loss of MRI signal intensity within aneurysm wall. Aneurysm tissue was harvested for histological analysis. Fifty percent (5/10) of aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls compared to 78% (7/9) of aneurysms in protocol B. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+, demonstrating macrophage infiltration, and Prussian blue, demonstrating uptake of iron particles. Tissue harvested from controls stained positive for CD68 but not Prussian blue. CONCLUSIONS: Imaging with T2*-GE-MRI at 72 hours postinfusion of 5 mg/kg of ferumoxytol establishes a valid and useful approximation of optimal dose and timing parameters for macrophages imaging within aneurysm wall. Further studies are needed to correlate these imaging findings with risk of intracranial aneurysm rupture.

Iron homeostasis and post-hemorrhagic hydrocephalus: a review.

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain development, characterizes our understanding of iron transport in the developing brain, and describes potential mechanisms by which iron overload may cause PHH and brain injury. We also review novel preclinical treatments for IVH that specifically target iron. Understanding iron handling within the brain and central nervous system may provide a basis for preventative, targeted treatments for iron-mediated pathogenesis of GMH-IVH and PHH.

Cerebral aneurysm sac growth as the etiology of recurrence after successful coil embolization.

BACKGROUND AND PURPOSE: Coil compaction is thought to be the main mechanism for recurrence in cerebral aneurysms with previously successful coil embolization. We hypothesize that sac growth may be equally or more important. The objective was to study the relative roles of coil compaction and sac growth as explanations for aneurysm recurrence requiring retreatment in a study population using quantitative 3D image processing methods. METHODS: From July 2009 to December 2010, 175 aneurysms were coiled at the University of Iowa hospitals and clinics. Eight aneurysms had major recurrence requiring retreatment (4.4-12.1 months between procedures; mean: 7.2 months). The 3D structures of the vessel and coil mass were reconstructed using rotational angiography data scanned before and after both initial coil embolization and retreatment. Changes in the sac and coil mass over time were visualized using model registration techniques and quantified using volume calculations. RESULTS: All 8 of the coiled aneurysms with major recurrence had significant aneurysm sac growth (15% to 102% increase in volume), independent of change in coil volume. Five aneurysms with major recurrence had sufficient data for assessment of coil compaction. The coil mass volume decreased in 1 aneurysm (12% compaction by volume), did not change significantly in 1 aneurysm (increased by 1%), and significantly increased in 3 aneurysms (8%, 21%, and 25%) between the first treatment and before the second treatment. CONCLUSIONS: In this study population, aneurysm sac growth, not coil compaction, was the primary mechanism associated with recurrence after initial coil embolization.

Incorporating patient-centered quality-of-life measures for outcome assessment after Chiari malformation type I decompression in a pediatric population: a pilot study.

OBJECTIVE: Optimal management of pediatric Chiari malformation type I (CM-I) is much debated, chiefly due to the lack of validated tools for outcome assessment, with very few tools incorporating patient-centered measures of health-related quality of life (HRQOL). Although posterior fossa decompression (PFD) benefits a subset of patients, prediction of its impact across patients is challenging. The primary aim of this study was to investigate the role of patient-centered HRQOL measures in the assessment and prediction of outcomes after PFD. METHODS: The authors collected HRQOL data from a cohort of 20 pediatric CM-I patients before and after PFD. The surveys included assessments of selected Patient-Reported Outcomes Measurement Information System (PROMIS) health domains and were used to generate the PROMIS preference (PROPr) score, which is a measure of HRQOL. PROMIS is a reliable standardized measure of HRQOL domains such as pain, fatigue, depression, and physical function, which are all relevant to CM-I. The authors then compared the PROPr scores with Chicago Chiari Outcome Scale (CCOS) scores derived from time-matched clinical documentation. Finally, the authors used the PROPr scores as an outcome measure to predict postsurgical HRQOL improvement at 1 year on the basis of patient demographic characteristics, comorbidities, and radiological and physical findings. The Wilcoxon signed-rank test, Mann-Whitney U-test, and Kendall's correlation were used for statistical analysis. RESULTS: Aggregate analysis revealed improvement of pain severity after PFD (p = 0.007) in anatomical patterns characteristic of CM-I. Most PROMIS domain scores trended toward improvement after surgery, with anxiety and pain interference reaching statistical significance (p < 0.002 and p < 0.03, respectively). PROPr scores also significantly improved after PFD (p < 0.008). Of the baseline patient characteristics, preexisting scoliosis was the most accurate negative predictor of HRQOL improvement after PFD (median -0.095 vs 0.106, p < 0.001). A correlation with modest magnitude (Kendall's tau range 0.19-0.47) was detected between the patient-centered measures and CCOS score. CONCLUSIONS: The authors observed moderate improvement of HRQOL, when measured using a modified panel of PROMIS question banks, in this pilot cohort of pediatric CM-I patients after PFD. Further investigations are necessary to validate this tool for children with CM-I and to determine whether these scores correlate with clinical and radiographic findings.

Development of an integrated risk scale for prediction of shunt placement after neonatal intraventricular hemorrhage.

OBJECTIVE: Neonatal intraventricular hemorrhage (IVH) is a major cause of mortality and morbidity, particularly following premature birth. Even after the acute phase, posthemorrhagic hydrocephalus is a long-term complication, frequently requiring permanent ventriculoperitoneal shunt (VPS) placement. Currently, there are no risk classification methods integrating the constellation of clinical data to predict short- and long-term prognosis in neonatal IVH. To address this need, the authors developed a two-part machine learning approach for predicting short- and long-term outcomes after diagnosis of neonatal IVH. Integrating both maternal and neonatal characteristics, they developed a binary classifier to predict short-term mortality risk and a clinical scale to predict the long-term risk of VPS placement. METHODS: Neonates with IVH were identified from the Optum Clinformatics Data Mart administrative claims database. Matched maternal and childbirth characteristics were obtained for all patients. The primary endpoints of interest were short-term (30 day) mortality and long-term VPS placement. Classification of short-term mortality risk was evaluated using 5 different machine learning approaches and the best-performing method was validated using a withheld validation subset. Prediction of long-term shunt risk was performed using a multivariable Cox regression model with stepwise variable selection, which was subsequently converted to an easily applied integer risk scale. RESULTS: A total of 5926 neonates with IVH were identified. Most patients were born before 32 weeks' gestation (67.2%) and with low birth weight (81.2%). Empirical 30-day mortality risk was 10.9% across all IVH grades and highest among grade IV IVH (34.3%). Among the neonates who survived > 30 days, actuarial 12-month postdiagnosis risk of shunt placement was 5.4% across all IVH grades and 31.3% for grade IV IVH. The optimal short-term risk classifier was a random forest model achieving an area under the receiver operating characteristic curve of 0.882 with important predictors ranging from gestational age to diverse comorbid medical conditions. Selected features for long-term shunt risk stratification were IVH grade, respiratory distress syndrome, disseminated intravascular coagulation, and maternal preeclampsia or eclampsia. An integer risk scale, termed the Shunt Prediction After IVH in Neonates (SPAIN) scale, was developed from these 4 features, which, evaluated on withheld cases, demonstrated improved risk stratification compared with IVH grade alone (Harrell's concordance index 0.869 vs 0.852). CONCLUSIONS: In a large cohort of neonates with IVH, the authors developed a two-pronged, integrated, risk classification approach to anticipate short-term mortality and long-term shunt risk. The application of such approaches may improve the prognostication of outcomes and identification of higher-risk individuals who warrant careful surveillance and early intervention.

Elevated cerebrospinal fluid iron and ferritin associated with early severe ventriculomegaly in preterm posthemorrhagic hydrocephalus.

OBJECTIVE: Posthemorrhagic hydrocephalus (PHH) following preterm intraventricular hemorrhage (IVH) is among the most severe sequelae of extreme prematurity and a significant contributor to preterm morbidity and mortality. The authors have previously shown hemoglobin and ferritin to be elevated in the lumbar puncture cerebrospinal fluid (CSF) of neonates with PHH. Herein, they evaluated CSF from serial ventricular taps to determine whether neonates with PHH following severe initial ventriculomegaly had higher initial levels and prolonged clearance of CSF hemoglobin and hemoglobin degradation products compared to those in neonates with PHH following moderate initial ventriculomegaly. METHODS: In this observational cohort study, CSF samples were obtained from serial ventricular taps in premature neonates with severe IVH and subsequent PHH. CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein were quantified using ELISA. Ventriculomegaly on cranial imaging was assessed using the frontal occipital horn ratio (FOHR) and was categorized as severe (FOHR > 0.6) or moderate (FOHR ≤ 0.6). RESULTS: Ventricular tap CSF hemoglobin (mean) and ferritin (initial and mean) were higher in neonates with severe versus moderate initial ventriculomegaly. CSF hemoglobin, ferritin, total iron, total bilirubin, and total protein decreased in a nonlinear fashion over the weeks following severe IVH. Significantly higher levels of CSF ferritin and total iron were observed in the early weeks following IVH in neonates with severe initial ventriculomegaly than in those with initial moderate ventriculomegaly. CONCLUSIONS: Among preterm neonates with PHH following severe IVH, elevated CSF hemoglobin, ferritin, and iron were associated with more severe early ventricular enlargement (FOHR > 0.6 vs ≤ 0.6 at first ventricular tap).

Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture.

BACKGROUND AND PURPOSE: Chronic inflammation is postulated as an important phenomenon in intracranial aneurysm wall pathophysiology. This study was conducted to determine if aspirin use impacts the occurrence of intracranial aneurysm rupture. METHODS: Subjects enrolled in the International Study of Unruptured Intracranial Aneurysms (ISUIA) were selected from the prospective untreated cohort (n=1691) in a nested case-control study. Cases were subjects who subsequently had a proven aneurysmal subarachnoid hemorrhage during a 5-year follow-up period. Four control subjects were matched to each case by site and size of aneurysm (58 cases, 213 control subjects). Frequency of aspirin use was determined at baseline interview. Aspirin frequency groups were analyzed for risk of aneurysmal hemorrhage. Bivariable and multivariable analyses were performed using conditional logistic regression. RESULTS: A trend of a protective effect for risk of unruptured intracranial aneurysm rupture was observed. Patients who used aspirin 3× weekly to daily had an OR for hemorrhage of 0.40 (95% CI, 0.18-0.87); reference group, no use of aspirin), patients in the "< once a month" group had an OR of 0.80 (95% CI, 0.31-2.05), and patients in the "> once a month to 2×/week" group had an OR of 0.87 (95% CI, 0.27-2.81; P=0.025). In multivariable risk factor analyses, patients who used aspirin 3 times weekly to daily had a significantly lower odds of hemorrhage (adjusted OR, 0.27; 95% CI, 0.11-0.67; P=0.03) compared with those who never take aspirin. CONCLUSIONS: Frequent aspirin use may confer a protective effect for risk of intracranial aneurysm rupture. Future investigation in animal models and clinical studies is needed.

Concurrent Venous Stenting of the Transverse and Occipito-Marginal Sinuses: An Analogy with Parallel Hemodynamic Circuits.

Nonthrombotic intracranial venous occlusive disease (NIVOD) has been implicated in the pathophysiology of idiopathic intracranial hypertension (IIH) and various non-IIH headache syndromes. Endovascular stenting of stenotic, dominant transverse sinuses (TSs) may reduce trans-stenosis pressure gradients, decrease intracranial pressure, and alleviate symptoms in a subset of NIVOD patients. We present a case in which concurrent stenting of the occipito-marginal sinus obliterated the residual trans-stenosis pressure gradient across an initially stented dominant TS. We hypothesize that this observation may be explained using an electric-hydraulic analogy, and that this patient's dominant TS and occipito-marginal sinus may be modeled as a parallel hemodynamic circuit. Neurointerventionalists should be aware of parallel hemodynamic drainage patterns and consider manometry and possibly additional stenting of stenotic, parallel venous outflow pathways if TS stenting alone fails to obliterate the trans-stenosis pressure gradient.

Trends in intracranial monitoring for pediatric medically intractable epilepsy: 2000-2012.

OBJECTIVE: To retrospectively examine nationwide trends in intracranial monitoring (ICM) for pediatric medically intractable epilepsy (MIE) from 2000 to 2012. METHODS: The Healthcare Cost and Utilization Project Kids' Inpatient Database was analyzed to identify admissions with ICD-9-CM codes corresponding to MIE and ICM from 2000 to 2012, inclusive. Associations between independent variables and outcomes were tested using χ2 test or Fisher exact test. A multivariate logistic regression analysis of variables associated with ICM was completed using stepwise selection. The Cochran-Armitage test was used to test for trend of a variable over the study period. RESULTS: The number of ICM procedures increased over the study period; however, secondary to large increases in the number of MIE admissions, the rate of ICM declined from 5.39% in 2000 to 2.56% in 2012 (p < 0.001). Despite this decline, ICM increasingly resulted in resective epilepsy procedures. In 2000, only 45.18% of ICM cases led to resective epilepsy surgery, which increased to 75.83% by 2012 (p < 0.001). ICM complication rates were comparable to, if not lower than, standard resective surgery. Disparities in access to ICM exist, with African American individuals and those with Medicaid significantly less likely to undergo ICM. CONCLUSION: In this nationwide characterization of pediatric ICM trends, we identified a slight, significant downward trend in the rate of utilization of ICM for MIE. This was secondary to substantial increases in the number of hospital admissions for MIE. Reasons for this large increase and why it has not led to increased rates of ICM warrant further investigation.

Pediatric meningiomas: 65-year experience at a single institution.

OBJECTIVE Meningiomas are relatively common, typically benign neoplasms in adults; however, they are relatively rare in the pediatric population. Pediatric meningiomas behave very differently from their adult counterparts, tending to have more malignant histological subtypes and recur more frequently. The authors of this paper investigate the risk factors, pathological subtypes, and recurrence rates of pediatric meningiomas. METHODS A retrospective chart review was conducted at the University of Iowa to identify patients 20 years old and younger with meningiomas in the period from 1948 to 2015. RESULTS Sixty-seven meningiomas in 39 patients were identified. Eight patients had neurofibromatosis, 2 had a family history of meningioma, and 3 had prior radiation exposure. Twelve (31%) of the 39 patients had WHO Grade II or III lesions, and 15 (38%) had recurrent lesions after resection. CONCLUSIONS Pediatric meningiomas should be considered for early treatment and diligent follow-up.

An anteromedial approach to the temporal horn to avoid injury to the optic radiation fibers and uncinate fasciculus: anatomical and technical note.

OBJECT: The aim of this study was to define an anteromedial approach to the temporal horn via a transsylvian approach to avoid injury to the optic radiation fibers as well as the uncinate fasciculus. This route was compared with standard surgical approaches to the temporal horn, and their relationship to the optic radiation and uncinate fasciculus was reviewed. METHODS: Three cadaveric brain specimens were prepared with freezing and thawing cycles according to the Klingler technique. Dissection was performed in a lateral-to-medial fashion with the help of wooden spatulas. Photographs were taken through the operating microscope at every level of the dissection. The dissection was continued until the optic radiation was encountered. Particular attention was paid to the relationship of the uncinate fasciculus with the optic radiation. An anteromedial transsylvian approach was defined to enter the temporal horn without injuring the optic radiation or the uncinate fasciculus. CONCLUSIONS: A transsylvian anteromedial approach through the pyriform cortex at the level of the anterior and superior surface of the uncus enables a safe entry into the temporal horn without injury to the optic radiation fibers or the main part of the uncinate fasciculus.

Intradiploic occipital pseudomeningocele in a patient with remote history of surgical treatment of Chiari malformation.

An intradiploic CSF pseudocyst is a rare entity that has been described in association with trauma, as a sequela of untreated hydrocephalus, or occasionally as a congenital finding in older adults. The authors present the case of a woman with a remote history of a posterior fossa intradural procedure, in which she underwent Chiari malformation decompression, Silastic substitute-assisted duraplasty, and occipitocervical fusion; she presented 19 years later with recurrent symptoms of Chiari malformation. She was found to have an occipital intradiploic pseudomeningocele, arising within her dorsal occipitocervical fusion mass and resulting in dorsal hindbrain compression. She underwent a posterior fossa decompression and revision of her failed duraplasty, and she had a good recovery. This case demonstrates intradiploic CSF pseudomeningocele as a rare potential delayed complication of an intradural procedure for the treatment of Chiari malformation with occipitocervical fusion.

Age-related differences in unruptured intracranial aneurysms: 1-year outcomes.

OBJECT: The aim of this study was to determine age-related differences in short-term (1-year) outcomes in patients with unruptured intracranial aneurysms (UIAs). METHODS: Four thousand fifty-nine patients prospectively enrolled in the International Study of Unruptured Intracranial Aneurysms were categorized into 3 groups by age at enrollment: < 50, 50-65, and > 65 years old. Outcomes assessed at 1 year included aneurysm rupture rates, combined morbidity and mortality from aneurysm procedure or hemorrhage, and all-cause mortality. Periprocedural morbidity, in-hospital morbidity, and poor neurological outcome on discharge (Rankin scale score of 3 or greater) were assessed in surgically and endovascularly treated groups. Univariate and multivariate associations of each outcome with age were tested. RESULTS: The risk of aneurysmal hemorrhage did not increase significantly with age. Procedural and in-hospital morbidity and mortality increased with age in patients treated with surgery, but remained relatively constant with increasing age with endovascular treatment. Poor neurological outcome from aneurysm- or procedure-related morbidity and mortality did not differ between management groups for patients 65 years old and younger, but was significantly higher in the surgical group for patients older than 65 years: 19.0% (95% confidence interval [CI] 13.9%-24.4%), compared with 8.0% (95% CI 2.3%-13.6%) in the endovascular group and 4.2% (95% CI 2.3%-6.2%) in the observation group. All-cause mortality increased steadily with increasing age, but differed between treatment groups only in patients < 50 years of age, with the surgical group showing a survival advantage at 1 year. CONCLUSIONS: Surgical treatment of UIAs appears to be safe, prevents 1-year hemorrhage, and may confer a survival benefit in patients < 50 years of age. However, surgery poses a significant risk of morbidity and death in patients > 65 years of age. Risk of endovascular treatment does not appear to increase with age. Risks and benefits of treatment in older patients should be carefully considered, and if treatment is deemed necessary for patients older than 65 years, endovascular treatment may be the best option.

Long-term incidence and risk factors for development of spinal deformity following resection of pediatric intramedullary spinal cord tumors.

OBJECT: Spinal deformity in pediatric patients with intramedullary spinal cord tumors (IMSCTs) may be either due to neurogenic disability or due to secondary effects of spinal decompression. It is associated with functional decline and impairment in health-related quality-of-life measures. The authors sought to identify the long-term incidence of spinal deformity in individuals who had undergone surgery for IMSCTs as pediatric patients and the risk factors and overall outcomes in this population. METHODS: Treatment records for pediatric patients (age < 21 years) who underwent surgical treatment for histology-proven primary IMSCTs between 1975 and 2010 were reviewed. All patients were evaluated in consultation with the pediatric orthopedics service. Clinical records were reviewed for baseline and follow-up imaging studies, surgical fusion treatment, and long-term skeletal and disease outcomes. RESULTS: The authors identified 55 patients (30 males and 25 females) who were treated for pediatric IMSCTs between January 1975 and January 2010. The mean duration of follow-up (± SEM) was 11.4 ± 1.3 years (median 9.3 years, range 0.2-37.2 years). Preoperative skeletal deformity was diagnosed in 11 (20%) of the 55 patients, and new-onset postoperative deformity was noted in 9 (16%). Conservative management with observation or external bracing was sufficient in 8 (40%) of these 20 cases. Surgical fusion was necessary in 11 (55%). Posterior surgical fusion was sufficient in 6 (55%) of these 11 cases, while combined anterior and posterior fusion was undertaken in 5 (45%). Univariate and multivariate analysis of clinical and surgical treatment variables indicated that preoperative kyphoscoliosis (p = 0.0032) and laminectomy/laminoplasty at more than 4 levels (p = 0.05) were independently associated with development of spinal deformity that necessitated surgical fusion. Functional scores and 10-year disease survival outcomes were similar between the 2 groups. CONCLUSIONS: Long-term follow-up is essential to monitor for delayed development of spinal deformity, and regular surveillance imaging is recommended for patients with underlying deformity. The authors' extended follow-up highlights the risk factors associated with development of spinal deformity in patients treated for pediatric IMSCTs. Surgical fusion allows patients who develop progressive deformity to achieve long-term functional and survival outcomes comparable to those of patients who do not develop progressive deformity.

Risk of hemorrhagic complication associated with ventriculoperitoneal shunt placement in aneurysmal subarachnoid hemorrhage patients on dual antiplatelet therapy.

OBJECT: The use of an intracranial stent requires dual antiplatelet therapy to avoid in-stent thrombosis. In this study, the authors sought to investigate whether the use of dual antiplatelet therapy is a risk factor for hemorrhagic complications in patients undergoing permanent ventriculoperitoneal (VP) shunt for hydrocephalus following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients were given 325 mg acetylsalicylic acid and 600 mg clopidogrel during the coil/stent procedure, and they were maintained on dual antiplatelet therapy with acetylsalicylic acid 325 mg daily and clopidogrel 75 mg daily during hospitalization and for 6 weeks posttreatment. Patients underwent placement of VP shunt at a later time during initial hospitalization, usually between 7 and 21 days following aSAH. Postoperative CT scans obtained in each study patient were reviewed for hemorrhages related to placement of the VP shunt. RESULTS: A total of 206 patients were admitted to the University of Iowa Hospitals and Clinics with aSAH between July 2009 and October 2010. Thirty-seven of these patients were treated with a VP shunt for persistent hydrocephalus. Twelve patients (32%) had previously undergone stent-assisted coiling and were on dual antiplatelet therapy with acetylsalicylic acid and clopidogrel. The remaining 25 patients (68%) had undergone surgical clipping or aneurysm coiling and were not receiving antiplatelet therapy at the time of surgery. Four cases (10.8%) of new intracranial hemorrhages associated with VP shunt placement were observed. All 4 hemorrhages (33%) occurred in patients on dual antiplatelet therapy for stent-assisted coiling. No new intracranial hemorrhages were observed in patients not receiving dual antiplatelet therapy. The difference in hemorrhagic complications between the 2 groups was statistically significant (4 [33%] of 12 vs 0 of 25, p = 0.0075]). All 4 hemorrhages occurred along the tract of the ventricular catheter. Only 1 hemorrhage (1 [8.3%] of 12) was clinically significant as it resulted in occlusion of the proximal shunt catheter and required revision of the VP shunt. The patient did not suffer any permanent morbidity related to the hemorrhage. The remaining 3 hemorrhages were not clinically significant. CONCLUSIONS: This small clinical series suggests that placement of a VP shunt in patients on dual antiplatelet therapy may be associated with an increased, but low, rate of symptomatic intracranial hemorrhage. It appears that in patients who are poor candidates for open surgical clipping and have aneurysms amenable to stent-assisted coiling, the risk of symptomatic hemorrhage may be an acceptable trade-off for avoiding risks associated with discontinuation of antiplatelet therapy. The authors' results are preliminary, however, and require confirmation in larger studies.

Acute postoperative neurological deterioration associated with surgery for ruptured intracranial aneurysm: incidence, predictors, and outcomes.

OBJECT: Subarachnoid hemorrhage (SAH) results in significant morbidity and mortality, even among patients who reach medical attention in good neurological condition. Many patients have neurological decline in the perioperative period, which contributes to long-term outcomes. The focus of this study is to characterize the incidence of, characteristics predictive of, and outcomes associated with acute postoperative neurological deterioration in patients undergoing surgery for ruptured intracranial aneurysm. METHODS: The Intraoperative Hypothermia for Aneurysm Surgery Trial (IHAST) was a multicenter randomized clinical trial that enrolled 1001 patients and assesssed the efficacy of hypothermia as neuroprotection during surgery to secure a ruptured intracranial aneurysm. All patients had a radiographically confirmed SAH, were classified as World Federation of Neurosurgical Societies (WFNS) Grade I-III immediately prior to surgery, and underwent surgery to secure the ruptured aneurysm within 14 days of SAH. Neurological assessment with the National Institutes of Health Stroke Scale (NIHSS) was performed preoperatively, at 24 and 72 hours postoperatively, and at time of discharge. The primary outcome variable was a dichotomized scoring based on an IHAST version of the Glasgow Outcome Scale (GOS) in which a score of 1 represents a good outcome and a score > 1 a poor outcome, as assessed at 90-days' follow-up. Data from IHAST were analyzed for occurrence of a postoperative neurological deterioration. Preoperative and intraoperative variables were assessed for associations with occurrence of postoperative neurological deterioration. Differences in baseline, intraoperative, and postoperative variables and in outcomes between patients with and without postoperative neurological deterioration were compared with Fisher exact tests. The Wilcoxon rank-sum test was used to compare variables reported as means. Multiple logistic regression was used to adjust for covariates associated with occurrence of postoperative deficit. RESULTS: Acute postoperative neurological deterioration was observed in 42.6% of the patients. New focal motor deficit accounted for 65% of postoperative neurological deterioration, while 60% was accounted for using the NIHSS total score change and 51% by Glasgow Coma Scale score change. Factors significantly associated with occurrence of postoperative neurological deterioration included: age, Fisher grade on admission, occurrence of a procedure prior to aneurysm surgery (ventriculostomy), timing of surgery, systolic blood pressure during surgery, ST segment depression during surgery, history of abnormality in cardiac valve function, use of intentional hypotension during surgery, duration of anterior cerebral artery occlusion, intraoperative blood loss, and difficulty of aneurysm exposure. Of the 426 patients with postoperative neurological deterioration at 24 hours after surgery, only 46.2% had a good outcome (GOS score of 1) at 3 months, while 77.7% of those without postoperative neurological deterioration at 24 hours had a good outcome (p < 0.05). CONCLUSIONS: Neurological injury incurred perioperatively or in the acute postoperative period accounts for a large percentage of poor outcomes in patients with good admission WFNS grades undergoing surgery for aneurysmal SAH. Avoiding surgical factors associated with postoperative neurological deterioration and directing investigative efforts at developing improved neuroprotection for use in aneurysm surgery may significantly improve long-term neurological outcomes in patients with SAH.