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James T. Rutka

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Joshua K. Schaffzin, Katherine Simon, Beverly L. Connelly and Francesco T. Mangano

OBJECTIVE

Surgical site infections (SSIs) are costly to patients and the health care system. Pediatric neurosurgery SSI risk factors are not well defined. Intraoperative protocols have reduced, but have not eliminated, SSIs. The effect of preoperative intervention is unknown. Using quality improvement methods, a preoperative SSI prevention protocol for pediatric neurosurgical patients was implemented to assess its effect on SSI rate.

METHODS

Patients who underwent a scheduled neurosurgical procedure between January 2014 and December 2015 were included. Published evidence and provider consensus were used to guide preoperative protocol development. The Model for Improvement was used to test interventions. Intraoperative and postoperative management was not standardized or modified systematically. Staff, family, and overall adherence was measured as all-or-nothing. In addition, SSI rates among eligible procedures were measured before and after protocol implementation.

RESULTS

Within 4 months, overall protocol adherence increased from 51.3% to a sustained 85.7%. SSI rates decreased from 2.9 per 100 procedures preintervention to 0.62 infections postintervention (p = 0.003). An approximate 79% reduction in SSI risk was identified (risk ratio 0.21, 95% CI 0.08–0.56; p = 0.001).

CONCLUSIONS

Clinical staff and families successfully collaborated on a standardized preoperative protocol for pediatric neurosurgical patients. Standardization of the preoperative phase of care alone reduced SSI rates. Attention to the preoperative in addition to the intraoperative and postoperative phases of care may lead to further reduction in SSI rates.

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Marci Madera, Alvin Crawford and Francesco T. Mangano

✓ Larsen syndrome is a rare genetic disorder of the connective tissue that is characterized by multiple joint dislocations, distinctive deformities of the hands and feet, characteristic facial features, kyphoscoliosis, and segmentation anomalies of the vertebrae. Diverse treatment options, including conservative observation and surgical correction, have been reported for patients who present with cervical spine pathophysiology. Differences in surgical approaches, timing of the correction, and pre- or postoperative bracing have been reported. According to the authors, the present case is the first report of a pediatric patient with Larsen syndrome in whom an asymptomatic cervical instability was treated before neurological deterioration with synchronous anterior decompression and fixation, posterior fusion and fixation, and halo placement. A review of the literature on similar patients reveals the variety of practices associated with a diagnosis of Larsen syndrome.

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Dean A. Hertzler II, John J. DePowell, Charles B. Stevenson and Francesco T. Mangano

Tethered cord syndrome (TCS) is a clinical condition of various origins that arises from tension on the spinal cord. Radiographic findings may include the conus medullaris in a lower than normal position, fatty infiltration of the filum terminale, lipomyelomeningocele, myelomeningocele, myelocystocele, meningocele, split cord malformations, dermal sinus, anorectal malformations, and intraspinal tumors. The clinical constellation of signs and symptoms associated with TCS may include dermatologic, urological, gastrointestinal, neurological, and orthopedic findings. The current review focuses on TCS by age group of the more common causes of the condition, including myelomeningocele, lipomyelomeningocele, as well as the adult presentation of occult TCS. Pertinent review of the neuroembryology and normal anatomical position of the conus medullaris is included.

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James L. Leach, Reem Awwad, Hansel M. Greiner, Jennifer J. Vannest, Lili Miles and Francesco T. Mangano

OBJECTIVE

Diagnostic criteria for hippocampal malrotation (HIMAL) on brain MRI typically include a rounded hippocampus, vertical collateral sulcus, and architectural blurring. Relationship to epileptogenesis remains speculative, and usefulness for surgical guidance is unknown. The study was performed to determine the prevalence of hippocampal rotational anomalies in a cohort of pediatric patients with intractable epilepsy undergoing evaluation for surgery and to determine the significance of this finding in the context of surgical planning.

METHODS

Forty-eight surgically treated children with intractable epilepsy were compared with matched healthy subjects; reviewers were blinded to surgical side. Each temporal lobe was evaluated for rounded hippocampus, blurring, vertical collateral sulcus, wide choroidal fissure, enlarged temporal horn, low fornix, hippocampal signal, and findings of hippocampal sclerosis. A mesial temporal lobe (MTL) score was calculated by summing the number of features, and the collateral sulcus angle (CSA) was measured in each temporal lobe. Surgical side, pathological diagnosis, and imaging findings elsewhere in the brain were tabulated. Presence of HIMAL, associated imaging features, and MTL score were compared between sides, between epilepsy and control groups, in relationship to side of surgery, and in relationship to postoperative outcome.

RESULTS

Only 3 epilepsy patients (6.2%) and no controls exhibited all 3 features of HIMAL (p = 0.12). Eight of 48 (16.7%) epilepsy versus 2 of 48 (4.6%) control subjects had both a rounded hippocampus and vertical collateral sulcus (suggesting HIMAL) (p = 0.045). In control and epilepsy subjects, most findings were more prevalent on the left, and the left CSA was more vertical (p < 0.0001). Epilepsy subjects had higher MTL scores (z = −2.95, p = 0.002) and more acute CSAs (p = 0.04) than controls. Only lateralizing raw MTL score had a significant association with surgical side (p = 0.03, OR 7.33); however, this was not significant when hippocampal sclerosis cases were excluded. HIMAL findings were more prevalent and MTL scores were higher in patients with resections involving the temporal lobes. On group analysis, HIMAL findings did not predict eventual surgical side and did not predict outcome, although the numbers are small. In 4 patients the abnormally rotated hippocampus was resected and showed hippocampal sclerosis and/or dysplastic changes on histopathology. All of these patients had a good outcome after surgery.

CONCLUSIONS

While increased in prevalence in children with intractable epilepsy, imaging findings of HIMAL did not have preoperative lateralizing utility in this group. Findings of HIMAL (including round hippocampus, architectural blurring, and vertical collateral sulcus) did not predict outcome after surgery, although the small number of patients with these findings limits evaluation. In the small number of patients in which the malrotated hippocampus was removed, outcome was good. Further research is needed to continue to define this association in children with intractable epilepsy, focusing on a temporal lobe cohort.

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Francesco T. Mangano and Matthew D. Smyth

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A. Scott Emmert, Shawn M. Vuong, Crystal Shula, Diana Lindquist, Weihong Yuan, Yueh-Chiang Hu, Francesco T. Mangano and June Goto

OBJECTIVE

Emergence of CRISPR/Cas9 genome editing provides a robust method for gene targeting in a variety of cell types, including fertilized rat embryos. The authors used this method to generate a transgenic rat L1cam knockout model of X-linked hydrocephalus (XLH) with human genetic etiology. The object of this study was to use diffusion tensor imaging (DTI) in studying perivascular white matter tract injury in the rat model and to characterize its pathological definition in histology.

METHODS

Two guide RNAs designed to disrupt exon 4 of the L1cam gene on the X chromosome were injected into Sprague-Dawley rat embryos. Following embryo transfer into pseudopregnant females, rats were born and their DNA was sequenced for evidence of L1cam mutation. The mutant and control wild-type rats were monitored for growth and hydrocephalus phenotypes. Their macro- and microbrain structures were studied with T2-weighted MRI, DTI, immunohistochemistry, and transmission electron microscopy (TEM).

RESULTS

The authors successfully obtained 2 independent L1cam knockout alleles and 1 missense mutant allele. Hemizygous male mutants from all 3 alleles developed hydrocephalus and delayed development. Significant reductions in fractional anisotropy and axial diffusivity were observed in the corpus callosum, external capsule, and internal capsule at 3 months of age. The mutant rats did not show reactive gliosis by then but exhibited hypomyelination and increased extracellular fluid in the corpus callosum.

CONCLUSIONS

The CRISPR/Cas9-mediated genome editing system can be harnessed to efficiently disrupt the L1cam gene in rats for creation of a larger XLH animal model than previously available. This study provides evidence that the early pathology of the periventricular white matter tracts in hydrocephalus can be detected in DTI. Furthermore, TEM-based morphometric analysis of the corpus callosum elucidates the underlying cytopathological changes accompanying hydrocephalus-derived variations in DTI. The CRISPR/Cas9 system offers opportunities to explore novel surgical and imaging techniques on larger mammalian models.

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James M. Johnston Jr., Francesco T. Mangano, Jeffrey G. Ojemann, Tae Sung Park, Edwin Trevathan and Matthew D. Smyth

Object

The purpose of this study was to better define the incidence of complications associated with placement of subdural electrodes for localization of seizure foci and functional mapping in children.

Methods

The authors retrospectively reviewed the records of 112 consecutive patients (53 boys, 59 girls; mean age 10.9 years, range 10 months–21.7 years) with medically intractable epilepsy who underwent invasive monitoring at the Pediatric Epilepsy Center at St. Louis Children’s Hospital between January 1994 and July 2005. There were 122 implantation procedures (85 grids and strips, 32 strips only, five grids only, four with additional depth electrodes), with a mean monitoring period of 7.1 days (range 2–21 days). Operative complications included the need for repeated surgery for additional electrode placement (5.7%); wound infection (2.4%); cerebrospinal fluid leak (1.6%); and subdural hematoma, symptomatic pneumocephalus, bone flap osteomyelitis, and strip electrode fracture requiring operative retrieval (one patient [0.8%] each). There were four cases of transient neurological deficit (3.3%) and no permanent deficit or death associated with invasive monitoring.

Conclusions

Placement of subdural grid and strip electrodes for invasive video electroencephalographic monitoring is generally well tolerated in the pediatric population. The authors found that aggressive initial electrode coverage was not associated with higher rates of blood transfusion or perioperative complications, and reduced the frequency of repeated operations for placement of supplemental electrodes.

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Ellen L. Air, Yashar M. Ghomri, Rachana Tyagi, Andrew W. Grande, Kerry Crone and Francesco T. Mangano

Object

Vagal nerve stimulators (VNSs) have been used successfully to treat medically refractory epilepsy. Although their efficacy is well established, appropriate management of infections is less clearly defined. In the authors' experience, patients who have gained a benefit from VNS implantation have been reluctant to have the device removed. The authors therefore sought conservative management options to salvage infected VNS systems.

Methods

The authors performed a retrospective review of 191 (93 female and 98 male) consecutive patients in whom VNS systems were placed between 2000 and 2007.

Results

They identified 10 infections (5.2%). In 9 of 10 patients the cultured organism was Staphylococcus aureus. Three (30%) of 10 patients underwent early removal (within 1 month) of the VNS as the initial treatment. The remaining 7 patients were initially treated with antibiotics. Two (28.6%) of these patients were successfully treated using antibiotics without VNS removal. Patients in whom conservative treatment failed were given cephalexin as first-line antibiotic treatment. All patients recovered completely regardless of treatment regimen.

Conclusions

This study confirms the low rate of infection associated with VNS placement and suggests that, in the case of infection, treatment without removal is a viable option. However, the authors' data suggest that oral antibiotics are not the best first-line therapy.

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Weihong Yuan, Scott K. Holland, Blaise V. Jones, Kerry Crone and Francesco T. Mangano

Object

Diffusion tensor (DT) imaging was used in children with supratentorial tumors to evaluate the anisotropic diffusion properties between different tumor grades and between tumors and adjacent and contralateral white matter.

Methods

In this retrospective review, the authors review the cases of 16 children (age range 1–18 years) who presented to their institution with supratentorial tumors and were treated between 2004 and 2007. Eleven patients had low-grade and 5 had high-grade tumors. Fractional anisotropy (FA), mean diffusivity, and axial (λ) and radial (λ) eigenvalues within selected regions were studied. Mitotic index, necrosis, and vascularity of the tumors were compared with DT imaging parameters.

Results

The mean diffusivity was significantly higher in low-grade than in high-grade tumors (p = 0.04); the 2 tumor grades also significantly differed for both λ (p < 0.05) and λ (p < 0.05). Mean diffusivity values in low-grade tumors were significantly higher than in adjacent normal-appearing white matter (NAWM; p = 0.0004) and contralateral NAWM (p = 0.0001). In both low- and high-grade tumors, the FA was significantly lower than in NAWM (p < 0.0001 and p < 0.03, respectively) and contralateral NAWM (p < 0.0001 and p < 0.003, respectively). Tumor cellularity highly correlated with mean diffusivity and λand λ.

Conclusions

Diffusion tensor imaging is a useful tool in the evaluation of supratentorial tumors in children. The mean diffusivity appears to be a significant marker in differentiating tumors grades. Findings related to λ and λ within tumor groups and between tumors and NAWM may be an indirect manifestation of the combined effects of axonal injury, demyelination, and tumor mass within the cranial compartment.