Cost-effectiveness analysis of endoscopic third ventriculostomy

Journal ArticleOBJECTIVE: Endoscopic third ventriculostomy (ETV) is currently the principal alternative to cerebrospinal fluid shunt placement in the management of pediatric hydrocephalus. Cost-effectiveness analysis can help determine the optimal strategy for integrating these different approaches. METHODS: All patients (n = 28) who underwent ETV at British Columbia's Children's Hospital between 1989 and 1998 were matched for age, pathogenesis, and number of previous shunt procedures, with patients treated with cerebrospinal fluid shunts. To perform a cost-effectiveness analysis, hydrocephalus-related resource consumption and outcome (determined as the number of hydrocephalus treatment-free days during follow-up) were then retrospectively identified. Cost data were linked to resource use to provide a total cost for all resources used. Costs and outcomes were discounted annually at 5% by standard economic analysis methods. RESULTS: Twenty-four of 28 ETV patients had obstructive hydrocephalus. Over equivalent follow-up periods (median, 35 mo), the ETV success rate (defined by need for reoperation) was 54%.One hydrocephalus-related death and one hemiparesis occurred in the ETV group. No permanent procedure-related morbidity or mortality was seen in the shunt group. The cost/effect ratios for the two groups were similar. The additional incremental resource use by the shunt group included six readmissions and eight reoperations. ETV mean costs per patient were $10,570 ±$7628, versus $10,922 ±$8722 for the shunt group (Canadian dollars for the year 2000). Costs accrued more quickly for the shunt group as time passed. The additional incremental outcome benefit to the endoscopy group was 86 treatment-free days (3.07 d per patient [95% confidence interval, -7.56 to 13.70 d]). Neither of these differences was statistically significant. CONCLUSION: In this matched cohort, ETV was not significantly less costly or more effective over a median 35 months of follow-up, with a 54% initial ETV success rate, even before the additional morbidity and mortality encountered were taken into account. The time course for the accrued costs suggests that a larger cohort, longer follow-up, or higher success rates are needed to demonstrate the cost-effectiveness of this therapy

Predicting shunt failure on the basis of clinical symptoms and signs in children

Journal ArticleObject. In evaluating pediatric patients for shunt malfunction, predictive values for symptoms and signs are important in deciding which patients should undergo an imaging study, whereas determining clinical findings that correlate with a low probability of shunt failure could simplify management. Methods. Data obtained during the recently completed Pediatric Shunt Design Trial (PSDT) were analyzed. Predictive values were calculated for symptoms and signs of shunt failure. To refine predictive capability, a shunt score based on a cluster of signs and symptoms was derived and validated using multivariate methods. Four hundred thirty-one patient encounters after recent shunt insertions were analyzed. For encounters that took place within 5 months after shunt insertion (early encounters), predictive values for symptoms and signs included the following: nausea and vomiting (positive predictive value [PPV] 79%, likelihood ratio [LR] 10.4), irritability (PPV 78%, LR 9.8), decreased level of consciousness (LOC) (PPV 100%), erythema (PPV 100%), and bulging fontanelle (PPV 92%, LR 33.1). Between 9 months and 2 years after shunt insertion (late encounters), only loss of developmental milestones (PPV 83%, LR 36.7) and decreased LOC (PPV 100%) were strongly associated with shunt failure. However, the absence of a symptom or sign still left a 15 to 29% (early encounter group) or 9 to 13% (late encounter group) chance of shunt failure. Using the shunt score developed for early encounters, which sums from 1 to 3 points according to the specific symptoms or signs present, patients with scores of 0, 1, 2, and 3 or greater had shunt failure rates of 4%, 50%, 75%, and 100%, respectively. Using the shunt score derived from late encounters, patients with scores of 0, 1, and 2 or greater had shunt failure rates of 8%, 38%, and 100%, respectively. Conclusions. In children, certain symptoms and signs that occur during the first several months following shunt insertion are strongly associated with shunt failure; however, the individual absence of these symptoms and signs offers the clinician only a limited ability to rule out a shunt malfunction. Combining them in a weighted scoring system improves the ability to predict shunt failure based on clinical findings

Management of shunt infections: a multicenter pilot study

Journal ArticleObject. Approximately 10% of cerebrospinal fluid (CSF) shunt operations are associated with infection and require removal or externalization of the shunt, in-hospital treatment with antibiotic agents, and insertion of a new shunt. In a previous survey, the authors identified substantial variation in the duration of antibiotic therapy as well as the duration of hospital stay. The present multicenter pilot study was undertaken to evaluate current strategies in the treatment of shunt infection. Methods. Patients were enrolled in the study if they had a successful treatment of a CSF shunt infection proved by culture of a CSF specimen. Details of their care and the incidence of culture-proved reinfection were recorded. Seventy patients from 10 centers were followed up for 1 year after their CSF shunt infection. The initial management of the infection was shunt externalization in 17 patients, shunt removal and external ventricular drain insertion in 50, and antibiotic treatment alone in three. Reinfection occurred in 18 patients (26%). Twelve of the 18 reinfections were caused by the same organism and six were due to new organisms. The treatment time varied from 4 to 47 days, with a mean of 17.4 days for those who later experienced a reinfection compared with 16.2 days for those who did not. The most common organism (Staphylococcus epidermidis, 34 patients) was associated with a reinfection rate of 29% and a mean treatment time of 12.8 days for those who suffered reinfection and 12.5 days for those who did not. Conclusions. Reinfection after treatment of a CSF shunt infection is alarmingly common. According to the data available, the incidence of reinfection does not appear to be related to the duration of antibiotic therapy

Activation of epiplexus macrophages in hydrocephalus caused by subarachnoid hemorrhage and thrombin

AimsWe have found that hydrocephalus development in spontaneously hypertensive rats was associated with activation of epiplexus cells. The current study examined whether epiplexus cell activation occurs in a rat subarachnoid hemorrhage (SAH), whether activation would be greater in a subset of rats that developed hydrocephalus and the potential role of thrombin in epiplexus cell activation.MethodsThere were two parts in this study. First, an endovascular perforation was performed in rats to induce SAH. Second, rats received an intraventricular infusion of either thrombin or saline. Magnetic resonance imaging was used to measure the ventricular volumes. Immunofluorescence and immunohistochemistry were used to study epiplexus cell activation.ResultsIba‐1, OX‐6, and CD68 were expressed in the epiplexus cells of the choroid plexus in sham‐operated rats. SAH increased Iba‐1 and CD68 immunoreactivity in epiplexus cells in addition to an increase in Iba‐1‐positive cell soma size. Those effects were greater in rats that developed hydrocephalus. Intraventricular thrombin mimicked the effects of SAH on epiplexus cell activation and hydrocephalus.ConclusionThis study supports the concept that epiplexus cell activation is associated with hydrocephalus development. Epiplexus cell activation may be in response to thrombin production after hemorrhage, and it may be a therapeutic target.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151813/1/cns13203_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151813/2/cns13203.pd

The Role of CD 133+ Cells in a Recurrent Embryonal Tumor with Abundant Neuropil and True Rosettes ( ETANTR )

Embryonal tumor with abundant neuropil and true rosettes ( ETANTR ) is a recently described embryonal neoplasm of the central nervous system, consisting of a well‐circumscribed embryonal tumor of infancy with mixed features of ependymoblastoma (multilayer ependymoblastic rosettes and pseudorosettes) and neuroblastoma (neuroblastic rosettes) in the presence of neuropil‐like islands. We present the case of a young child with a very aggressive tumor that rapidly recurred after gross total resection, chemotherapy and radiation. Prominent vascular sclerosis and circumscribed tumor led to the diagnosis of malignant astroblastoma; however, rapid recurrence and progression of this large tumor after gross total resection prompted review of the original pathology. ETANTR is histologically distinct with focal glial fibrillary acid protein ( GFAP ) and synaptophysin expression in the presence of neuronal and ependymoblastic rosettes with focal neuropil islands. These architectural features, combined with unique chromosome 19q13.42 amplification, confirmed the diagnosis. In this report, we describe tumor stem cell ( TSC ) marker CD 133, CD 15 and nestin alterations in ETANTR before and after chemotherapy. We found that TSC marker CD 133 was richly expressed after chemotherapy in recurrent ETANTR , while CD 15 is depleted compared with that expressed in the original tumor, suggesting that CD 133+ cells likely survived initial treatment, further contributing to formation of the recurrent tumor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102077/1/bpa12079.pd

Neurosurgical Comments on 5 Cases of Increased Intracranial Pressure

Increased cranial pressurePapilledema has a very high positive predictive value for raised ICP. The differential diagnosis includes compressive and ischemic optic neuropathies, papillitis, central retinal vein occlusion, vasculitis, as well as congenital abnormalities of the retina. Venous pulsations, central venous pressure and optic nerve sheath size have also been used to gauge intracranial pressure.Headache associated with cranial nerve palsies.N/APapilledema; Cranial nerve palsiesSurgery1. Arseni C, Marentsis, M. Tumors of the Lower Spinal Cord Associated with Increased Intracranial Pressure and Papilledema. Journal of Neurosurgery, 1967. 27:p.105-110. 2. Caviness, J.A., et al. Hydrocephalus as a possible early symptom in a child with a spinal cord tumor Pediatr Neurol, 1998. 18(2): p.169-71. 3. Firsching, R., et al. Venous ophthalmodynamometry: a noninvasive method for assessment of intracranial pressure. J Neurosurg, 2000. 93(1):p. 33-6. 4. Garton, H.J., J.R. Kestle, and J.M. Drake, Predicting shunt failure on the basis of clinical symptoms and signs in children. J Neurosurg, 2001. 94(2):p. 202-10. 5. Hansen, H.C. and K. Helmke, Validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests. J Neurosurg, 1997. 87(1):p. 34-40. 6. Haroun, R., et al. Current opinions for the treatment of syringomyelia and chiari malformations: survey of the pediatric session of the american association of neurological surgeons. Pediatr Neurosurg, 2000. 33(6):p. 311-7. 7. Leblanc, R., et al., Diffuse craniospinal seeding from a benign fourth ventricle choroid plexus papilloma. Case report. J Neurosurg, 1998. 88(4):p. 757-60. 8. Levin, B.E., The clinical significance of spontaneous pulsations of the retinal vein. Arch Neurol, 1978. 35(1):p.37-40. 9. McKissock, W., J. Taylor, and W. Bloom, Extradural hematoma: Observation in 125 cases. Lancet, 1960. 2:p.167-72. 10. Meadows, J., et al., Asymptomatic Chiari Type I malformations identified on magnetic resonance imaging. Neurosurg, 2000. 92(6):p. 920-6. 11. Oldfield, E.H., et al. Pathophysiology of syringomyelia associated with Chiari I malformation of the cerebellar tonsils. Implications for diagnosis and treatment. J Neurosurg, 1994. 80(1):p. 3-15. 12. Pollock, B.E. and J. Huston, 3rd, Natural history of asymptomatic colloid cysts of the third ventricle. J Neurosurg, 1999. 91(3):p. 364-9. 13. Pollock, B.E., S.A. Schreiner, and J. Huston, 3rd, A theory on the natural history of colloid cysts of the third ventricle. Neurosurgery, 2000. 46(5):p.1077-81; discussion 1081-3. 14. Rifkinson-Mann, S., J.H. Wisoff, and F. Epstein, The association of hydrocephalus with intramedullary spinal cord tumors: a series of 25 patients. Neurosurgery, 1990. 27(5):p.749-54; discussion 754. 15. Valencak, J., et al., Evidence of therapeutic efficacy of CCNU in recurrent choroid plexus papilloma. J Neurooncol, 2000. 49(3):p.263-8

Hidrocefalia

La hidrocefalia no es un padecimiento extra\uf1o en la pr\ue1ctica pedi\ue1trica general. Cabe esperar que un pediatra general atienda dos a cinco ni\uf1os con derivaci\uf3n de l\uedquido cefalorraqu\ueddeo (LCR). En este art\uedculo se revisa detalladamente la hidrocefalia poshemorr\ue1gica

Molecular characterization reveals NF1 deletions and FGFR1‐activating mutations in a pediatric spinal oligodendroglioma

Pediatric spinal oligodendrogliomas are rare and aggressive tumors. They do not share the same molecular features of adult oligodendroglioma, and no previous reports have examined the molecular features of pediatric spinal oligodendroglioma. We present the case of a child with a recurrent spinal anaplastic oligodendroglioma. We performed whole exome (paired tumor and germline DNA) and transcriptome (tumor RNA) sequencing, which revealed somatic mutations in NF1 and FGFR1. These data allowed us to explore potential personalized therapies for this patient and expose molecular drivers that may be involved in similar cases.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136755/1/pbc26346_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136755/2/pbc26346.pd

Delayed Minocycline Treatment Ameliorates Hydrocephalus Development and Choroid Plexus Inflammation in Spontaneously Hypertensive Rats

Hydrocephalus is a complicated disorder that affects both adult and pediatric populations. The mechanism of hydrocephalus development, especially when there is no mass lesion present causing an obstructive, is poorly understood. Prior studies have demonstrated that spontaneously hypertensive rats (SHRs) develop hydrocephalus by week 7, which was attenuated with minocycline. The aim of this study was to determine sex differences in hydrocephalus development and to examine the effect of minocycline administration after hydrocephalus onset. Male and female Wistar–Kyoto rats (WKYs) and SHRs underwent magnetic resonance imaging at weeks 7 and 9 to determine ventricular volume. Choroid plexus epiplexus cell activation, cognitive deficits, white matter atrophy, and hippocampal neuronal loss were examined at week 9. In the second phase of the experiment, male SHRs (7 weeks old) were treated with either saline or minocycline (20 mg/kg) for 14 days, and similar radiologic, histologic, and behavior tests were performed. Hydrocephalus was present at week 7 and increased at week 9 in both male and female SHRs, which was associated with greater epiplexus cell activation than WKYs. Male SHRs had greater ventricular volume and epiplexus cell activation compared to female SHRs. Minocycline administration improved cognitive function, white matter atrophy, and hippocampal neuronal cell loss. In conclusion, while both male and female SHRs developed hydrocephalus and epiplexus cell activation by week 9, it was more severe in males. Delayed minocycline treatment alleviated hydrocephalus, epiplexus macrophage activation, brain pathology, and cognitive impairment in male SHRs