Biographies of international women leaders in neurosurgery.

We received so many biographies of women neurosurgery leaders for this issue that only a selection could be condensed here. In all of them, the essence of a leader shines through. Many are included as "first" of their country or color or other achievement. All of them are included as outstanding-in clinical, academic, and organized neurosurgery. Two defining features are tenacity and service. When faced with shocking discrimination, or numbing indifference, they ignored it or fought valiantly. When choosing their life's work, they chose service, often of the most neglected-those with pain, trauma, and disability. These women inspire and point the way to a time when the term "women leaders" as an exception is unnecessary.-Katharine J. Drummond, MD, on behalf of this month's topic editors.

Migration of a ventriculo-peritoneal shunt catheter into a back incision of a patient with previous spinal fusion.

INTRODUCTION: This case examines a unique, longitudinal presentation of an abandoned, migrating VP shunt which presents as multiple complications, including a weeping abscess in the patients back. We believe that the latter complication was potentially caused by the wound from the patient's previous history of spinal fusion surgery. CASE PRESENTATION: The patient presents with an associated type 2 Chiari malformation, hydrocephalus, and a previous history of posterior spinal fusion (T4-L5 anterior fusion and T2-L5 posterior fusion) at age 11. The patient had undergone shunt revisions in early adolescence as well. At 22, the patient is admitted into emergency care due to recurrent infections caused by a migrating VP shunt. Due to complications in corrective surgery at the time, the shunt was forced to be abandoned. This resulted in the most recent presentation of a weeping abscess at the patient's spinal fusion surgery wound; the culprit was the abandoned, migrating VP shunt.. MANAGEMENT/OUTCOME: An initial course of broad-spectrum antibiotics was started. However, the abscess continued to recur. Eventually, the catheter was surgically removed, a tailored antibiotic regiment was started, and a 6-month patient follow-up was performed. The patient is no longer symptomatic and off of antibiotics. DISCUSSION: In abandoned VP shunts, migration into a non-sterile cavity dictates prompt removal, especially after symptoms of infection present. Additionally, careful monitoring for signs of peritonitis or other symptoms for a dedicated period of time is necessary. To the authors' best knowledge, this is the first case of an occult shunt migration through the patient's back that presented with a weeping abscess.

Apparent diffusion coefficient mapping in medulloblastoma predicts non-infiltrative surgical planes.

INTRODUCTION: An appropriate surgical approach for posterior fossa lesions is to start tumor removal from areas with a defined plane to where tumor is infiltrating the brainstem or peduncles. This surgical approach minimizes risk of damage to eloquent areas. Although magnetic resonance imaging (MRI) is the current standard preoperative imaging obtained for diagnosis and surgical planning of pediatric posterior fossa tumors, it offers limited information on the infiltrative planes between tumor and normal structures in patients with medulloblastomas. Because medulloblastomas demonstrate diffusion restriction on apparent diffusion coefficient map (ADC map) sequences, we investigated the role of ADC map in predicting infiltrative and non-infiltrative planes along the brain stem and/or cerebellar peduncles by medulloblastomas prior to surgery. METHODS: Thirty-four pediatric patients with pathologically confirmed medulloblastomas underwent surgical resection at our facility from 2004 to 2012. An experienced pediatric neuroradiologist reviewed the brain MRIs/ADC map, assessing the planes between the tumor and cerebellar peduncles/brain stem. An independent evaluator documented surgical findings from operative reports for comparison to the radiographic findings. The radiographic findings were statistically compared to the documented intraoperative findings to determine predictive value of the test in identifying tumor infiltration of the brain stem cerebellar peduncles. RESULTS: Twenty-six patients had preoperative ADC mapping completed and thereby, met inclusion criteria. Mean age at time of surgery was 8.3 ± 4.6 years. Positive predictive value of ADC maps to predict tumor invasion of the brain stem and cerebellar peduncles ranged from 69 to 88 %; negative predictive values ranged from 70 to 89 %. Sensitivity approached 93 % while specificity approached 78 %. CONCLUSIONS: ADC maps are valuable in predicting the infiltrative and non-infiltrative planes along the tumor and brain stem interface in medulloblastomas. Inclusion and evaluation of ADC maps in preoperative evaluation can assist in surgical resection planning in patients with medulloblastoma.

Desmoplastic infantile ganglioglioma with associated giant aneurysm­case report.

Desmoplastic infantile ganglioglioma (DIG) and supratentorial giant cerebral aneurysm are each extremely rare entities in infants. Here, we present the case of an 8-day old boy who had both of these conditions concurrently. To our knowledge, there is no previous case reported of a patient with coexisting DIG and giant aneurysm.

Single-cell RNA sequencing reveals Immune Education promotes T cell survival in mice subjected to the cecal ligation and puncture sepsis model.

Background: Individual T cell responses vary significantly based on the microenvironment present at the time of immune response and on prior induced T cell memory. While the cecal ligation and puncture (CLP) model is the most commonly used murine sepsis model, the contribution of diverse T cell responses has not been explored. We defined T cell subset responses to CLP using single-cell RNA sequencing and examined the effects of prior induced T cell memory (Immune Education) on these responses. We hypothesized that Immune Education prior to CLP would alter T cell responses at the single cell level at a single, early post-CLP time point. Methods: Splenic T cells were isolated from C57BL/6 mice. Four cohorts were studied: Control, Immune-Educated, CLP, and Immune-Educated CLP. At age 8 weeks, Immune-Educated and Immune-Educated CLP mice received anti-CD3ϵ antibody; Control and CLP mice were administered an isotype control. CLP (two punctures with a 22-gauge needle) was performed at 12-13 weeks of life. Mice were sacrificed at baseline or 24-hours post-CLP. Unsupervised clustering of the transcriptome library identified six distinct T cell subsets: quiescent naïve CD4+, primed naïve CD4+, memory CD4+, naïve CD8+, activated CD8+, and CD8+ cytotoxic T cell subsets. T cell subset specific gene set enrichment analysis and Hurdle analysis for differentially expressed genes (DEGs) were performed. Results: T cell responses to CLP were not uniform - subsets of activated and suppressed T cells were identified. Immune Education augmented specific T cell subsets and led to genomic signatures favoring T cell survival in unoperated and CLP mice. Additionally, the combination of Immune Education and CLP effected the expression of genes related to T cell activity in ways that differed from CLP alone. Validating our finding that IL7R pathway markers were upregulated in Immune-Educated CLP mice, we found that Immune Education increased T cell surface IL7R expression in post-CLP mice. Conclusion: Immune Education enhanced the expression of genes associated with T cell survival in unoperated and CLP mice. Induction of memory T cell compartments via Immune Education combined with CLP may increase the model's concordance to human sepsis.

Pure endoscopic removal of pineal region tumors.

PURPOSE: Endoscopic resection of pineal tumors using an endoscope with a mounted rigid suction that allows bimanual handling of the tumor for resection. This contrasts to the established method of biopsy of pineal tumors through intraventricular approach. METHODS: Two patients, one with a cystic lesion in the pineal region and one with a large pineal tumor, were operated in sitting position through a subtorcular approach. Endoscope was held in the left hand with suction tip extending beyond the tip through its instrument channel. Regular microsurgical instrumentation/CUSA/Nico Aspirator was used with the right hand for dissection, cutting, and removing the tumor under endoscopic vision. RESULT: Surgeon comfort was superior to when microscope is used in sitting position. Complete resection was achieved in all cases. CONCLUSION: The two-handed endoscopic technique using a mounted suction on the endoscope as described is a safe and effective strategy for resecting pineal region tumors.

A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus.

BACKGROUND: Implantation of ventricular catheters (VCs) to drain cerebrospinal fluid (CSF) is a standard approach to treat hydrocephalus. VCs fail frequently due to tissue obstructing the lumen via the drainage holes. Mechanisms driving obstruction are poorly understood. This study aimed to characterize the histological features of VC obstructions and identify links to clinical factors. METHODS: 343 VCs with relevant clinical data were collected from five centers. Each hole on the VCs was classified by degree of tissue obstruction after macroscopic analysis. A subgroup of 54 samples was analyzed using immunofluorescent labelling, histology and immunohistochemistry. RESULTS: 61.5% of the 343 VCs analyzed had tissue aggregates occluding at least one hole (n = 211) however the vast majority of the holes (70%) showed no tissue aggregates. Mean age at which patients with occluded VCs had their first surgeries (3.25 yrs) was lower than in patients with non-occluded VCs (5.29 yrs, p < 0.02). Mean length of time of implantation of occluded VCs, 33.22 months was greater than for non-occluded VCs, 23.8 months (p = 0.02). Patients with myelomeningocele had a greater probability of having an occluded VC (p = 0.0426). VCs with occlusions had greater numbers of macrophages and astrocytes in comparison to non-occluded VCs (p < 0.01). Microglia comprised only 2-6% of the VC-obstructing tissue aggregates. Histologic analysis showed choroid plexus occlusion in 24%, vascularized glial tissue occlusion in 24%, prevalent lymphocytic inflammation in 29%, and foreign body giant cell reactions in 5% and no ependyma. CONCLUSION: Our data show that age of the first surgery and length of time a VC is implanted are factors that influence the degree of VC obstruction. The tissue aggregates obstructing VCs are composed predominantly of astrocytes and macrophages; microglia have a relatively small presence.

Cerebral anomalies and Chiari type 1 malformation.

OBJECTIVE: To analyze the association of diverse cerebral anomalies in a series of pediatric patients with cerebellar tonsillar ectopia. METHODS: We reviewed the medical records of 60 children diagnosed with Chiari type 1 malformation (CM1), of these, 20 patients (11 boys and 9 girls; mean age 7.2 years, range 2-16 years) had an associated cerebral anomaly. Symptoms of tonsillar ectopia evolved over a mean of 12 months (range 3 months to 4 years). Syringomyelia was present in 5 cases. All patients underwent a posterior fossa decompression. RESULTS: Disclosed anomalies included: congenital hydrocephalus (n = 11), cervicomedullary kinking (n = 5), focal cerebral heterotopia with epilepsy (n = 4), partial agenesis of the corpus callosum (n = 4), hypoplastic brain stem (n = 2), holoprosencephaly (n = 1), and subcortical dysplasia in the context of neurofibromatosis type 1 (n = 1). Other malformations included: subcortical hamartoma associated with neurofibromatosis type 1, craniofacial dysmorphism secondary to Noonan syndrome, congenital occipital plagiocephaly, os odontoideum, craniofacial cleft, juvenile rheumathoid arthritis with platybasia, and osteogenesis imperfecta with bathrocephaly and scoliosis. CONCLUSION: Craniocerebral anomalies in children treated for CM1 may be found consistently. The association of hydrocephalus, which was the most common anomaly in this cohort, with cerebellar tonsillar ectopia may contribute to a poor outcome in regard to tonsillar herniation symptoms.

Eosinophil activation in the cerebrospinal fluid of children with shunt obstruction.

OBJECTIVE: To determine if eosinophils are activated to release the cationic proteins, eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) in shunt obstruction, and to find out if these proteins are associated with ventriculoperitoneal shunt failure. PATIENTS AND METHODS: This was a prospective observational study carried out in a 20-bed tertiary pediatric intensive care unit. Patients studied were children aged 0-18 years with suspected ventriculoperitoneal shunt malfunction requiring shunt revision. No interventions were performed. Cerebrospinal fluid (CSF) was analyzed for cell count and EDN and ECP concentrations. Patients were prospectively followed for 6 months to evaluate shunt failure. RESULTS: In a 2-month period, 56 shunt revisions were performed on 56 children. Three children had culture-proven infection. Eosinophilia, defined as ≥ 5% eosinophils in the CSF, was present in 9 out of 53 children (17%). The 3 patients with infection did not have eosinophilia and were excluded from further analysis. Patients with CSF eosinophilia had higher concentrations of ECP (1.38 ± 0.66 vs. 0.41 ± 0.15 ng/ml; p = 0.013) and EDN (16.94 ± 5.83 vs. 4.69 ± 1.33 ng/ml; p = 0.011). Patients with CSF eosinophilia did not have more ventriculoperitoneal shunt revisions within 6 months (6 of 9) compared to those who did not have eosinophilia (21 of 44; p = 0.50). However, patients with higher levels of ECP in the CSF required more shunt revisions within 6 months of their surgeries (p < 0.05). CONCLUSIONS: In patients with malfunctioning ventriculoperitoneal shunts, CSF eosinophils are activated and release ECP and EDN. The presence of ECP is associated with a shorter shunt life.

Characterization of a multicenter pediatric-hydrocephalus shunt biobank.

BACKGROUND: Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank. METHODS: To date, four hospital centers have contributed various components of failed shunts and CSF from patients diagnosed with hydrocephalus before adulthood. The hardware samples are transported in paraformaldehyde and transferred to phosphate-buffered saline with sodium azide upon deposit into the biobank. Once in the bank, they are then available for study. Informed consent is obtained by the local center before corresponding clinical data are entered into a REDCap database. Data such as hydrocephalus etiology and details of shunt revision history. All data are entered under a coded identifier. RESULTS: 293 shunt samples were collected from 228 pediatric patients starting from May 2015 to September 2019. We saw a significant difference in the number of revisions per patient between centers (Kruskal-Wallis H test, p value < 0.001). The leading etiology at all centers was post-hemorrhagic hydrocephalus, a fisher's exact test showed there to be statistically significant differences in etiology between center (p = 0.01). Regression showed age (p < 0.01), race (p = 0.038) and hospital-center (p < 0.001) to explain significant variance in the number of revisions. Our model accounted for 31.9% of the variance in revisions. Generalized linear modeling showed hydrocephalus etiology (p < 0.001), age (p < 0.001), weight and physician (p < 0.001) to impact the number of ventricular obstructions. CONCLUSION: The retrospective analysis identified that differences exist between currently enrolled centers, although further work is needed before clinically actionable recommendations can be made. Moreover, the variables collected from this chart review explain a meaningful amount of variance in the number of revision surgeries. Future work will expand on the contribution of different site-specific and patient-specific factors to identify potential cause and effect relationships.

Value of overnight monitoring of intracranial pressure in hydrocephalic children.

OBJECTIVE: Exaggerated nocturnal intracranial pressure (ICP) dynamics are commonly observed in hydrocephalic children with a compromise of CSF compensatory reserve capacity. Successful shunting restores this cerebrospinal reserve. We used ICP overnight monitoring combined with positional maneuvers in complex hydrocephalic children with a suspected shunt malfunction for the assessment of shunt function. METHODS: In 32 hydrocephalic children, we performed 65 computerized overnight recordings and 25 positional maneuvers. Baseline ICP was considered abnormal if it exceeded the operating pressure of the shunt by more than 2.5 mm Hg. The maximum ICP (normal = <25 mm Hg), RAP coefficient (the correlation coefficient between pulse amplitude and mean intracranial pressure, which indicates pressure volume compensatory reserve; normal = <0.6), magnitude of slow waves (SLOW) and ICP pulse amplitude (AMP) were calculated for each night. RESULTS: Using baseline ICP, maximum ICP and RAP, 19 recordings were classified as 'normal' (group 1), 13 as 'questionable' (group 2), and 33 as 'pathological' (group 3) indicating shunt dysfunction or active hydrocephalus. ICP, AMP, RAP and SLOW were significantly different between groups and significantly elevated in group 3 compared to group 1. Positional tests identified shunt overdrainage in 5 of 25 occasions. In patients of group 1, who underwent revision, shunts turned out to be functional. All patients of group 3 eventually underwent shunt revision with improvement of symptoms thereafter. CONCLUSION: Computerized ICP monitoring can benefit the assessment of shunt function, and can accurately characterize the status of CSF compensation in shunted children with a complex presentation.

The role of lumboperitoneal shunts in managing chronic hydrocephalus with slit ventricles.

OBJECTIVELumboperitoneal (LP) shunts have a role not only in pseudotumor cerebri, but also in patients with slit-like ventricles who are treated with CSF shunting on a chronic basis. Hesitation to utilize LP shunts is based on previous conventional beliefs including the tendency for overdrainage, difficulties accessing the shunt to tap or revise, and risk of progressive cerebellar tonsillar herniation. The authors hypothesized that the use of horizontal-vertical (HV) valves may reduce the risk of these complications, particularly overdrainage and development of Chiari malformation.METHODSAll pediatric cases involving patients treated with an LP shunt at the Children's Hospital of Michigan were reviewed in this retrospective case series. A total of 143 patients with hydrocephalus were treated with LP shunts from 1997-2015 (follow-up range 8 months-8 years, median 4.2 years). Patients with pseudotumor cerebri underwent placement of an LP shunt as a primary procedure. In patients with slit ventricles from chronically treated hydrocephalus or repeated shunt malfunctions from proximal catheter obstruction, a lumbar drain was inserted to assess candidacy for conversion to an LP shunt. In patients who tolerated the lumbar drain and demonstrated communication of the ventricles with the spinal cisterns, treatment was converted to an LP shunt. All patients included in the series had undergone initial shunt placement between birth and age 16 years.RESULTSIn 30% of patients (n = 43), LP shunts were placed as the initial shunt treatment; in 70% (n = 100), treatment was converted to LP shunts from ventriculoperitoneal (VP) shunts. The patients' age at insertion of or conversion to an LP shunt ranged from 1 to 43 years (median 8.5 years). Of the patients with clear pre-LP and post-LP shunt follow-up imaging, none were found to develop an acquired Chiari malformation. In patients with pre-existing tonsillar ectopia, no progression was noted on follow-up MRIs of the brain in these patients after LP shunt insertion. In our LP shunt case series, no patient presented with acute deterioration from shunt malfunction.CONCLUSIONSConversion to an LP shunt may minimize acute deterioration from shunt malfunction and decrease morbidity of repeated procedures in patients with chronically shunt-treated hydrocephalus and small ventricles. In comparison to previously published case series of LP shunt treatment, the use of LP shunts in conjunction with HV valves may decrease the overall risk of cerebellar tonsillar herniation. The use of an LP shunt may be an alternative in the management of slit ventricles when VP shunting repeatedly fails.

Delayed lateral rectus palsy following resection of a pineal cyst in sitting position: direct or indirect compressive phenomenon?

A rare case of delayed lateral rectus palsy in a patient following resection of a pineal lesion in the sitting position is presented. Postoperative pneumocephalus is common following craniospinal surgical intervention in the sitting position. The sixth cranial nerve is frequently injured because of its prolonged intracranial course. A 13-year-old girl was evaluated for unremitting headaches. No focal deficits were demonstrated on neurological examination. Magnetic resonance imaging revealed a cystlike pineal region mass with peripheral enhancement following intravenous contrast administration. A supracerebellar infratentorial craniotomy was performed in the sitting position, and complete resection of the lesion was achieved. Her postoperative course was complicated by sixth nerve palsy on the third postoperative day. Her symptoms improved with conservative management. The occurrence of sixth cranial nerve palsy secondary to pneumocephalus is a rare entity. Even rarer is the report of this anomaly following craniotomy in the sitting position. This patient's symptoms manifested in a delayed fashion. Although uncommon, this complication should be considered in patients undergoing cranial or spinal surgical interventions in this position.

Effect of molding helmets on intracranial pressure and head shape in nonsurgically treated sagittal craniosynostosis patients.

OBJECTIVE Cranial vault expansion is performed in pediatric patients with craniosynostosis to improve head shape. Another argument for performing total cranial vault reconstruction is the potential reduction in the harmful effects of elevated intracranial pressure (ICP) that are associated with craniosynostosis. Alternatively, molding helmets have been shown to improve the cranial index (CI) in patients with sagittal synostosis without surgery. However, it is unknown if the use of molding helmets without surgery contributes to adverse changes in ICP. The effect of molding helmets on ICP and CI in patients with sagittal synostosis was investigated. METHODS A prospective cohort study of 24 pediatric patients with sagittal synostosis who planned to undergo total cranial reconstruction was performed from 2011 to 2014 at the Children's Hospital of Michigan. A preoperative molding helmet was used in 13 patients, and no molding helmet was used in 11 patients. End-tidal carbon dioxide, patient positioning, level of sedation, type of anesthetic, and the monitoring site at the time of intraoperative recording were regulated and standardized to establish the accuracy of the ICP readings. CI and head circumference were monitored for each patient. RESULTS The mean duration of the preoperative use of the molding helmet was 17 weeks (range 7-37 weeks). Under controlled settings, the average intraoperative ICP was 7.2 mm Hg (range 2-18 mm Hg) for patients treated with a preoperative molding helmet and 9.5 mm Hg (range 2-22 mm Hg) for patients with no preoperative molding helmet. ICP was not significantly different between the 2 groups, suggesting that the use of a molding helmet in this population is safe. The average CI at the time of helmet placement was 0.70 (range 0.67-0.73), and this improved to an average of 0.74 (range 0.69-0.79) after using the molding helmet for a mean of 17 weeks. CONCLUSIONS ICPs were not significantly different with the use of a preoperative molding helmet, refuting the prevailing thought that molding helmets would be detrimental in children who have craniosynostosis. The use of molding helmet in this population of patients improves head shape and does not adversely affect ICP.

Periventricular rigidity in long-term shunt-treated hydrocephalus.

OBJECT: The failure of ventricles to enlarge after acute shunt malfunction in long-term shunt-dependent patients is generally attributed to the presence of periventricular rigidity resulting from gliosis. The aim of this study was to test the hypothesis that periventricular rigidity is present in these patients. METHODS: Fifteen pediatric patients who presented with acute shunt malfunction were studied; slit ventricles were detected in all of these patients. Pressure measurements were recorded simultaneously in both the ventricle and the brain parenchyma during shunt revision and then repeated after bolus infusion of fluid into the ventricle. The mean intraventricular pressure (IVP) at presentation was 24.1 mm Hg (standard deviation 10 mm Hg). The mean baseline IVP after drainage of cerebrospinal fluid but prior to the infusion was 7.5 +/- 4.3 mm Hg. There was no significant difference in the increase in the IVP and the intraparenchymal pressure (IPP) after bolus infusion into the ventricle (3.6 +/- 2.4 mm Hg and 3.3 +/- 2.1 mm Hg, respectively; p = 0.39). The mean pressure volume index was 24.1 ml (standard error of the mean 4.6 ml). CONCLUSIONS: The profile of the changes in IVP and IPP indicates that the periventricular wall does not restrict ventricular enlargement following shunt malfunction in long-term shunt-dependent patients.

The role of lumbar shunts in the management of slit ventricles: does the slit-ventricle syndrome exist?

OBJECT: Slit-ventricle syndrome (SVS) is a confusing description of presentations in patients with chronic shunt-treated hydrocephalus. These patients are prone to acute deterioration with recurrent malfunction. The authors describe the clinical profile and management outcome of using lumboperitoneal (LP) shunts in this population of patients. METHODS: Thirty-three patients with slit ventricles and recurrent malfunctions were converted to LP shunts (mean age 12 years). The initial ventricular shunt was placed at a mean age of 16.5 months. Ten patients had failed endoscopic third ventriculostomies prior to placement of their LP shunt. At a previous presentation, in 11 patients suspected to have SVS following revision of the shunt, intracranial pressure normalized after insertion of a contralateral shunt, suggesting that their ventricles were isolated. The rate of infection and malfunction was compared before and after conversion to an LP shunt. Twenty-seven patients were successfully converted to LP shunts. Four of the 11 patients with isolated ventricles required ventricular shunts in addition to the LP shunt. During a mean follow-up period of 16.7 months, the malfunction rate per patient decreased from 4.81 for ventriculoperitoneal shunts, prior to conversion to 1.48 after conversion to LP shunts, a statistically significant reduction (p < 0.000). No significant difference was found in the rate of shunt infections (7.1% for VP shunts and 9.6% for LP shunts, p = 0.44). No patient presented with acute symptoms following malfunction of an LP shunt or suffered from a Chiari I malformation. CONCLUSIONS: Conversion to an LP shunt is a safe and effective procedure in patients prone to rapid decompensation and recurrent shunt malfunctions from small, slitlike ventricles. The term SVS is confusing. The condition is a manifestation of an unrecognized slitlike isolated ventricle and should be abandoned.