Association between synthetic sealants and increased complication rates in posterior fossa decompression with duraplasty for Chiari malformations regardless of graft type.

OBJECTIVE: Dural sealants are commonly used in posterior fossa decompression with duraplasty (PFDD) for Chiari malformation type I (CMI). Prior evidence suggests that combining certain sealants with some graft material is associated with an increased rate of complications. In 2018, the authors noted an increased rate of symptomatic pseudomeningocele and aseptic meningitis after PFDD in CMI patients. The authors utilized retrospective and prospective analyses to test the hypothesis that complication rates increase with the use or combination of certain sealants and grafts. METHODS: The analysis was split into 2 periods. The authors retrospectively reviewed patients who underwent PFDD for CMI at their center between August 12, 2011, and December 31, 2018. The authors then eliminated use of DuraSeal on the basis of the retrospective analysis and prospectively examined complication rates from January 1, 2019, to August 4, 2021. The authors defined a complication as symptomatic pseudomeningocele, bacterial or aseptic meningitis, cerebrospinal fluid leak, subdural hygroma, hydrocephalus, surgical site infection, or wound dehiscence. RESULTS: From 2011 to 2018, complications occurred in 24.5% of 110 patients. Sealant choice was correlated with complication rates: no sealant (0%), Tisseel (6%), and DuraSeal (15.3%) (p < 0.001). No difference in complication rate was noted on the basis of choice of graft material (p = 0.844). After eliminating DuraSeal, the authors followed 40 patients who underwent PFDD after 2018. The complication rate decreased to 12.5%. All complications after 2018 were associated with Tisseel. CONCLUSIONS: At the authors' single center, use of sealants in PFDD surgery for CMI, especially DuraSeal, was correlated with a higher complication rate. Eliminating DuraSeal led to a significant decrease in the rate of symptomatic pseudomeningocele and aseptic meningitis.

Neurosurgery Research and Education Foundation funding conversion to National Institutes of Health funding.

OBJECTIVE: The Neurosurgery Research and Education Foundation (NREF) provides research support for in-training and early career neurosurgeon-scientists. To define the impact of this funding, the authors assessed the success of NREF awardees in obtaining subsequent National Institutes of Health (NIH) funding. METHODS: NREF in-training (Research Fellowship [RF] for residents) and early career awards/awardees (Van Wagenen Fellowship [VW] and Young Clinician Investigator [YCI] award for neurosurgery faculty) were analyzed. NIH funding was defined by individual awardees using the NIH Research Portfolio Online Reporting tool (1985-2014). RESULTS: Between 1985 and 2014, 207 unique awardees were supported by 218 NREF awards ($9.84 million [M] in funding), including 117 RF ($6.02 M), 32 VW ($1.68 M), and 69 YCI ($2.65 M) awards. Subspecialty funding included neuro-oncology (79 awards; 36% of RF, VW, and YCI awards), functional (53 awards; 24%), vascular (37 awards; 17%), spine (22 awards; 10%), pediatrics (18 awards; 8%), trauma/critical care (5 awards; 2%), and peripheral nerve (4 awards; 2%). These awardees went on to receive $353.90 M in NIH funding that resulted in an overall NREF/NIH funding ratio of 36.0:1 (in dollars). YCI awardees most frequently obtained later NIH funding (65%; $287.27 M), followed by VW (56%; $41.10 M) and RF (31%; $106.59 M) awardees. YCI awardees had the highest NREF/NIH funding ratio (108.6:1), followed by VW (24.4:1) and RF (17.7:1) awardees. Subspecialty awardees who went on to obtain NIH funding included vascular (19 awardees; 51% of vascular NREF awards), neuro-oncology (40 awardees; 51%), pediatrics (9 awardees; 50%), functional (25 awardees; 47%), peripheral nerve (1 awardees; 25%), trauma/critical care (2 awardees; 20%), and spine (2 awardees; 9%) awardees. Subspecialty NREF/NIH funding ratios were 56.2:1 for vascular, 53.0:1 for neuro-oncology, 47.6:1 for pediatrics, 34.1:1 for functional, 22.2:1 for trauma/critical care, 9.5:1 for peripheral nerve, and 0.4:1 for spine. Individuals with 2 NREF awards achieved a higher NREF/NIH funding ratio (83.3:1) compared to those with 1 award (29.1:1). CONCLUSIONS: In-training and early career NREF grant awardees are an excellent investment, as a significant portion of these awardees go on to obtain NIH funding. Moreover, there is a potent multiplicative impact of NREF funding converted to NIH funding that is related to award type and subspecialty.

Comparison of Perioperative Outcomes and Parental Satisfaction Outcomes of Strip Craniectomy with Postoperative Helmet versus Spring-Mediated Remodeling in Sagittal Craniosynostosis.

INTRODUCTION: We sought to compare outcomes and parental satisfaction between 2 approaches for sagittal craniosynostosis: strip craniectomy with spring-mediated skull remodeling (SMSR) and strip craniectomy with postoperative helmet (SCH). METHODS: Perioperative and outcome data for SMSR or SCH patients between September 2010 and July 2019 were retrospectively reviewed. A telephone survey was administered to parents of children who underwent both procedures. RESULTS: A total of 62 children were treated for sagittal craniosynostosis by either SMSR (n = 45) or SCH (n = 17). The SCH group had a lower estimated blood loss (27 vs. 47.06 mL, p = 0.021) and age at surgery (13.0 vs. 19.8 weeks) than the SMSR group. Three patients underwent early springs removal due to trauma or dislodgement, all of whom converted to helmeting. Of the 62 children initially identified, 59 were determined to have an adequate follow-up time to assess long-term outcomes. The mean follow-up time was 30.1 months (n = 16) in the SCH group and 32.0 months in the SMSR group (n = 43, p = 0.39). Two patients in the SCH group and one in the SMSR group converted to open cranial vault reconstruction. Thirty parents agreed to respond to the satisfaction survey (8 SCH, 22 SMSR) based on a Likert scale of responses (0 being most dissatisfied possible, 4 most satisfied possible). Average satisfaction was 3.86/4.0 in the SCH group and 3.45/4.0 in the SMSR group. No parents in the SCH group would change to SMSR, while 3 of the 22 SMSR survey responders would have changed to SCH. CONCLUSIONS: Perioperative outcomes and average parental satisfaction were similar in both groups. Importance of helmet wear compliance and risk of spring dislodgement should be discussed with parents.

Safety and efficacy of brainstem biopsy in children and young adults.

OBJECTIVE: Biopsies of brainstem lesions are performed to establish a diagnosis in the setting of an atypical clinical or radiological presentation, or to facilitate molecular studies. A better understanding of the safety and diagnostic yield of brainstem biopsies would help guide appropriate patient selection. METHODS: All patients who underwent biopsy of a brainstem lesion during the period from January 2011 to June 2019 were reviewed. Demographic, radiological, surgical, and outcome data were collected. RESULTS: A total of 58 patients underwent 65 brainstem biopsies during the study period. Overall, the median age was 7.6 years (IQR 3.9-14.2 years). Twenty-two of the 65 biopsies (34%) were open, 42 (65%) were stereotactic, and 1 was endoscopic. In 3 cases (5%), a ventriculoperitoneal shunt was placed, and in 9 cases (14%), a posterior fossa decompression was performed during the same operative session as the biopsy. An intraoperative MRI (iMRI) was performed in 28 cases (43%). In 3 of these cases (11%), the biopsy was off target and additional samples were obtained during the same procedure. New neurological deficits were noted in 5 cases (8%), including sensory deficits, ophthalmoparesis/nystagmus, facial weakness, and hearing loss; these deficits persisted in 2 cases and were transient in 3 cases. A pseudomeningocele occurred in 1 patient; no patients developed a CSF leak or infection. In 8 cases (13%) an additional procedure was needed to obtain a diagnosis. CONCLUSIONS: Brainstem biopsies are safe and effective. Target selection and approach should be a collaborative effort. iMRI can be used to assess biopsy accuracy in real time, thereby allowing any adjustment if necessary.

Creation of a comprehensive training and career development approach to increase the number of neurosurgeons supported by National Institutes of Health funding.

OBJECTIVE: To increase the number of independent National Institutes of Health (NIH)-funded neurosurgeons and to enhance neurosurgery research, the National Institute of Neurological Disorders and Stroke (NINDS) developed two national comprehensive programs (R25 [established 2009] for residents/fellows and K12 [2013] for early-career neurosurgical faculty) in consultation with neurosurgical leaders and academic departments to support in-training and early-career neurosurgeons. The authors assessed the effectiveness of these NINDS-initiated programs to increase the number of independent NIH-funded neurosurgeon-scientists and grow NIH neurosurgery research funding. METHODS: NIH funding data for faculty and clinical department funding were derived from the NIH, academic departments, and Blue Ridge Institute of Medical Research databases from 2006 to 2019. RESULTS: Between 2009 and 2019, the NINDS R25 funded 87 neurosurgical residents. Fifty-three (61%) have completed the award and training, and 39 (74%) are in academic practice. Compared to neurosurgeons who did not receive R25 funding, R25 awardees were twice as successful (64% vs 31%) in obtaining K-series awards and received the K-series award in a significantly shorter period of time after training (25.2 ± 10.1 months vs 53.9 ± 23.0 months; p < 0.004). Between 2013 and 2019, the NINDS K12 has supported 19 neurosurgeons. Thirteen (68%) have finished their K12 support and all (100%) have applied for federal funding. Eleven (85%) have obtained major individual NIH grant support. Since the establishment of these two programs, the number of unique neurosurgeons supported by either individual (R01 or DP-series) or collaborative (U- or P-series) NIH grants increased from 36 to 82 (a 2.3-fold increase). Overall, NIH funding to clinical neurological surgery departments between 2006 and 2019 increased from $66.9 million to $157.3 million (a 2.2-fold increase). CONCLUSIONS: Targeted research education and career development programs initiated by the NINDS led to a rapid and dramatic increase in the number of NIH-funded neurosurgeon-scientists and total NIH neurosurgery department funding.

Sublaminar polyester bands as a salvage fixation method in the cervical spine: novel application in two patients.

Pedicle and lateral mass screws are the most common means of rigid fixation in posterior cervical spine fusions. Various other techniques such as translaminar screw placement, paravertebral foramen screw fixation, sublaminar and spinous process wiring, cement augmentation, and others have been developed for primary fixation or as salvage methods. Use of these techniques can be limited by a prior history of osteotomies, poor bone density, destruction of the bone-screw interface, and unfavorable vascular and osseous anatomy.Here, the authors report on the novel application of cervical sublaminar polyester bands as an adjunct salvage method or additional fixation point used with traditional methods in the revision of prior constructs. While sublaminar polyester bands have been used for decades in pediatric scoliosis surgery in the thoracolumbar spine, they have yet to be utilized as a method of fixation in the cervical spine. In both cases described here, sublaminar banding proved crucial for fixation points where traditional fixation techniques would have been less than ideal. Further study is required to determine the full application of sublaminar polyester bands in the cervical spine as well as its outcomes.

Management of hydrocephalus in infants with severe hemophilia A: report of 2 cases.

The authors report on the clinical course of two infants with severe hemophilia A (HA) and concomitant progressive hydrocephalus that required management with a ventriculoperitoneal shunt. The first child, with known HA, presented with a spontaneous intracranial hemorrhage and acquired hydrocephalus. He underwent cerebrospinal fluid diversion with a temporary external ventricular drain, followed by placement of a ventriculoperitoneal shunt. The second child had hydrocephalus secondary to a Dandy-Walker malformation and was diagnosed with severe HA during preoperative evaluation. He underwent placement of a ventriculoperitoneal shunt after progression of the hydrocephalus. The authors also review the treatment of hydrocephalus in patients with HA and describe the perioperative protocols used in their two cases. Treatment of hydrocephalus in infants with HA requires unique perioperative management to avoid complications.

Maternal embryonic leucine zipper kinase: key kinase for stem cell phenotype in glioma and other cancers.

Maternal embryonic leucine zipper kinase (MELK) is a member of the snf1/AMPK family of protein serine/threonine kinases that has recently gained significant attention in the stem cell and cancer biology field. Recent studies suggest that activation of this kinase is tightly associated with extended survival and accelerated proliferation of cancer stem cells (CSC) in various organs. Overexpression of MELK has been noted in various cancers, including colon, breast, ovaries, pancreas, prostate, and brain, making the inhibition of MELK an attractive therapeutic strategy for a variety of cancers. In the experimental cancer models, depletion of MELK by RNA interference or small molecule inhibitors induces apoptotic cell death of CSCs derived from glioblastoma multiforme and breast cancer, both in vitro and in vivo. Mechanism of action of MELK includes, yet may not be restricted to, direct binding and activation of the oncogenic transcription factors c-JUN and FOXM1 in cancer cells but not in the normal counterparts. Following these preclinical studies, the phase I clinical trial for advanced cancers with OTSSP167 started in 2013, as the first-in-class MELK inhibitor. This review summarizes the current molecular understanding of MELK and the recent preclinical studies about MELK as a cancer therapeutic target.