Recommendation for the Enrollment of Hydrocephalus Patients in Children\u27s Special Health Care Services

Recommendation for the Enrollment of Hydrocephalus Patients in Children\u27s Special Health Care Services Background: Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is surgical shunting of cerebrospinal fluid. These shunts fail at a high rate. The relationship between clinical decision making and shunt failure is poorly understood and multifactorial. Treatment paradigms have changed little since the 1980s. In order to investigate factors that affect outcomes, we have established the Wayne State University shunt biobank. Methods: Children\u27s Hospital of Michigan is one of the participating centers in our biobank and has enrolled 73 patients from whom we have collected 115 shunt samples and 40 CSF samples. Samples were directly obtained from the OR. CSF samples were kept cold until they were spun down and put on liquid nitrogen. The shunt samples were fixed in PFA and stored in PBS+ azide. Clinical data was taken from electronic medical records and maintained in a REDCap database under coded identifiers. Regression analysis was performed to determine factors affecting number of revisions. Results: Patient age and Medicaid usage were found to be significant predictors of the number revisions; patient weight and the median income of the family\u27s zip code were not significant predictors. The number of revisions also significantly varied by type of shunt system used. Conclusion: Many studies have used median income of a patient\u27s zip code as a stand in for socioeconomic status, our study found Medicaid enrollment to be a more significant predictor than income. This variable is commonly available in patient EMRs and merits further investigation for its usage in larger cohorts. Moreover, given that the Michigan Department of Health and Human Services has a free program to provide specialist care to children with a number of congenital conditions, among which hydrocephalus is included, it is our recommendation that hospital centers make efforts to enroll their patients in this program as it was associated with better outcomes than Medicaid. Unsurprisingly age was a very significant predictor of the number of shunt failures. The relationship between number of shunt revisions and shunt system type needs further examination to yield prognostic insight, as most patients are only placed on non-standard shunt systems after experiencing multiple failures with the standard ventriculoperitoneal shunt

The effect of A1 and A2 reactive astrocyte expression on hydrocephalus shunt failure

BACKGROUND: The composition of tissue obstructing neuroprosthetic devices is largely composed of inflammatory cells with a significant astrocyte component. In a first-of-its-kind study, we profile the astrocyte phenotypes present on hydrocephalus shunts. METHODS: qPCR and RNA in-situ hybridization were used to quantify pro-inflammatory (A1) and anti-inflammatory (A2) reactive astrocyte phenotypes by analyzing C3 and EMP1 genes, respectively. Additionally, CSF cytokine levels were quantified using ELISA. In an in vitro model of astrocyte growth on shunts, different cytokines were used to prevent the activation of resting astrocytes into the A1 and A2 phenotypes. Obstructed and non-obstructed shunts were characterized based on the degree of actual tissue blockage on the shunt surface instead of clinical diagnosis. RESULTS: The results showed a heterogeneous population of A1 and A2 reactive astrocytes on the shunts with obstructed shunts having a significantly higher proportion of A2 astrocytes compared to non-obstructed shunts. In addition, the pro-A2 cytokine IL-6 inducing proliferation of astrocytes was found at higher concentrations among CSF from obstructed samples. Consequently, in the in vitro model of astrocyte growth on shunts, cytokine neutralizing antibodies were used to prevent activation of resting astrocytes into the A1 and A2 phenotypes which resulted in a significant reduction in both A1 and A2 growth. CONCLUSIONS: Therefore, targeting cytokines involved with astrocyte A1 and A2 activation is a promising intervention aimed to prevent shunt obstruction

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 \u3c 0.001). The leading etiology at all centers was post-hemorrhagic hydrocephalus, a fisher\u27s exact test showed there to be statistically significant differences in etiology between center (p = 0.01). Regression showed age (p \u3c 0.01), race (p = 0.038) and hospital-center (p \u3c 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 \u3c 0.001), age (p \u3c 0.001), weight and physician (p \u3c 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

Radiation exposure, emergency department usage, and the impact of parental health literacy on a cohort of pediatric hydrocephalus patients in Detroit

Hydrocephalus is a significantly morbid long-term disease. While working with patients for another study we became aware of significant radiation exposure and emergency department usage in this patient population. For this study we quantified this usage; additionally, in an IRB approved study we collected health literacy data from the patients’ parents to see if it was correlated with either of these measures. A survey was sent to the 129 families for whom contact information was available. Complete data from a cohort of 110 patients was used. A survey response rate of 8% was obtained. Patients averaged 12.96 (±16.02 SD) emergency room visits, 18.73 (± 21.35 SD) CT-head scans, and 52.48 (±52.68 SD) head x-rays. This is equivalent to an average radiation dose of 37.99 mSv. The average parent respondent had earnings between $75,000-99,999, a master’s degree, and considered themselves experts in hydrocephalus and shunt malfunctions. As a group, health literacy was rated as poor on a validated health literacy instrument. Given the small number of responses we will take extreme caution in interpreting the relationship between emergency department usage rates and health literacy scores. In conclusion, our study demonstrates that hydrocephalus patients have high emergency department usage rates, are exposed to clinically significant amounts of radiation, and have parents who overestimate their own health literacy. Future educational interventions could target improving parental health literacy to see if a corresponding decrease in emergency department visits can be obtained

Additional file 1 of The effect of A1 and A2 reactive astrocyte expression on hydrocephalus shunt failure

Additional file 1: Fig. S1. Microglia/macrophage and astrocyte reactions following neuroprosthetic device implantation. Injury transforms microglia into an M1- and M2-like phenotype and astrocytes into an A1- and A2-type, correspondingly. Astrocytes and microglia work together to initiate either a neuroinflammatory or neuroprotective response after injury through the release of cytokines or neurotrophic factors that can lead to neuronal death or survival. The cytokine pathway is the most important measurable outcome for inflammatory cascades. Inflammatory cells at the brain-device interface communicate via cytokines to activate and recruit other inflammatory cells to the interface. Cytokine stimulation is the gateway for other gene products to be over- or under-expressed in the cascade, resulting in device failure. Therefore, the cytokine pathway acts as a starting point for mechanistic, thorough investigation of inflammation and device failure. Table S1. Ct values for patients with non-obstructed and obstructed shunts

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