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Ian F. Pollack, Sameer Agnihotri and Alberto Broniscer

Brain tumors are the most common solid tumors in children, and, unfortunately, many subtypes continue to have a suboptimal long-term outcome. During the last several years, however, remarkable advances in our understanding of the molecular underpinnings of these tumors have occurred as a result of high-resolution genomic, epigenetic, and transcriptomic profiling, which have provided insights for improved tumor categorization and molecularly directed therapies. While tumors such as medulloblastomas have been historically grouped into standard- and high-risk categories, it is now recognized that these tumors encompass four or more molecular subsets with distinct clinical and molecular characteristics. Likewise, high-grade glioma, which for decades was considered a single high-risk entity, is now known to comprise multiple subsets of tumors that differ in terms of patient age, tumor location, and prognosis. The situation is even more complex for ependymoma, for which at least nine subsets of tumors have been described. Conversely, the majority of pilocytic astrocytomas appear to result from genetic changes that alter a single, therapeutically targetable molecular pathway. Accordingly, the present era is one in which treatment is evolving from the historical standard of radiation and conventional chemotherapy to a more nuanced approach in which these modalities are applied in a risk-adapted framework and molecularly targeted therapies are implemented to augment or, in some cases, replace conventional therapy. Herein, the authors review advances in the categorization and treatment of several of the more common pediatric brain tumors and discuss current and future directions in tumor management that hold significant promise for patients with these challenging tumors.

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Giulia Cossu, Mahmoud Messerer and Roy Thomas Daniel

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R. Michael Scott and Edward R. Smith

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Tryggve Lundar, Bernt Johan Due-Tønnessen, Radek Frič, Bård Krossnes, Petter Brandal, Einar Stensvold and Paulina Due-Tønnessen

OBJECTIVE

The authors conducted a study to delineate the long-term results of the surgical treatment of pediatric pleomorphic xanthoastrocytomas (PXAs).

METHODS

All consecutive children and adolescents (0–20 years) who underwent primary tumor resection for a PXA during the years 1972–2015 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily living were scored according to the Barthel Index.

RESULTS

Of the 12 patients, 8 patients were in the 1st decade of life and 4 in the 2nd. The male/female ratio was 6:6. No patient was lost to follow-up. One patient presented with severe progressive tumor disease and died within 3 months after repeated resection. Another child died 3 days following a second surgical procedure involving gross-total resection (GTR) 8 years after the initial operation. The other 10 patients were alive at the latest follow-up when they reached the median age of 34 years (range 11–60 years). The median follow-up duration was 22 years (range 2–41 years). Barthel Index score was 100 in all 10 survivors. A total 18 tumor resections were performed. Five patients underwent a second tumor resection after MRI/CT confirmed recurrent tumor disease, from 6 months up to 17 years after the initial operation. Only one of our patients received adjuvant therapy: a 19-year-old male who underwent resection (GTR) for a right-sided temporal tumor in 1976. This particular tumor was originally classified as astrocytoma WHO grade IV, and postoperative radiotherapy (54 Gy) was given. The histology was reclassified to that of a PXA. Seven of 8 children whose primary tumor resection was performed more than 20 years ago are alive as of this writing—i.e., 88% observed 20-year survival. These are long-term survivors with good clinical function and all are in full- or part-time work.

CONCLUSIONS

Pediatric patients with PXA can be treated with resection alone with rewarding results. Recurrences are not uncommon, but repeated surgery is well tolerated and should be considered in low-grade cases before adjuvant therapy is implemented. Follow-up including repeated MRI is important during the first postoperative years, since individual patients may have a more aggressive tumor course.

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Prospective multicenter studies in pediatric hydrocephalus

JNSPG 75th Anniversary Invited Review Article

John R. W. Kestle and Jay Riva-Cambrin

Prospective multicenter clinical research studies in pediatric hydrocephalus are relatively rare. They cover a broad spectrum of hydrocephalus topics, including management of intraventricular hemorrhage in premature infants, shunt techniques and equipment, shunt outcomes, endoscopic treatment of hydrocephalus, and prevention and treatment of infection. The research methodologies include randomized trials, cohort studies, and registry-based studies. This review describes prospective multicenter studies in pediatric hydrocephalus since 1990. Many studies have included all forms of hydrocephalus and used device or procedure failure as the primary outcome. Although such studies have yielded useful findings, they might miss important treatment effects in specific subgroups. As multicenter study networks grow, larger patient numbers will allow studies with more focused entry criteria based on known and evolving prognostic factors. In addition, increased use of patient-centered outcomes such as neurodevelopmental assessment and quality of life should be measured and emphasized in study results. Well-planned multicenter clinical studies can significantly affect the care of children with hydrocephalus and will continue to have an important role in improving care for these children and their families.

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Abhaya V. Kulkarni and Ruth Donnelly

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Maggie Bellew, Rachel J. Mandela and Paul D. Chumas

OBJECTIVE

The aim of this study was to ascertain whether age at surgery has an impact on later neurodevelopmental outcomes for children with sagittal synostosis (SS).

METHODS

The developmental outcome data from patients who had surgery for SS and who attended their routine preoperative, 6–7 months postoperative, and 5-year-old developmental assessments (yielding general quotients [GQs]) (n = 50), 10-year-old IQ assessment (n = 54), and 15-year-old IQ assessment (n = 23) were examined, comparing whether they had surgery at < 7 months, 7 to < 12 months, or ≥ 12 months).

RESULTS

There was no significant effect for age at surgery for GQ at 5 years of age, but there was a significant effect (p = 0.0001) for those undergoing surgery at < 7 months in terms of preoperative gross locomotor deficit that resolved by 6–7 months postoperatively (increase of 22.1 points), and had further improved by 5 years of age (total increase of 29.4 points). This effect was lessened when surgery was performed later (total increase of 7.3 points when surgery was performed at ≥ 12 months). At 10 years of age, 1-way ANOVA showed a significant difference in Full Scale IQ (FSIQ) score (p = 0.013), with the highest mean FSIQ being obtained when surgery was performed at < 7 months of age (score 107.0), followed by surgery at 7 to < 12 months (score 94.4), and the lowest when surgery was performed at ≥ 12 months (score 93.6). One-way ANOVA for the Performance IQ (PIQ) was very similar (p = 0.012), with PIQ scores of 101.4, 91.4, and 87.3, respectively. One-way ANOVA for Verbal IQ (VIQ) was again significant (p = 0.05), with VIQ scores of 111.3, 98.9, and 100.4, respectively. At 15 years, 1-way ANOVA showed a significant difference in PIQ (p = 0.006), with the highest mean PIQ being obtained when surgery was performed at < 7 months (score 104.8), followed by surgery at 7 to < 12 months (score 90.0), and the lowest when surgery was at performed at ≥ 12 months of age (score 85.3). There were no significant results for FSIQ and VIQ, although there was a similar trend for better outcomes with early surgery.

CONCLUSIONS

The findings of this study add to the literature that suggests that early surgery for SS may result in improved neurodevelopmental outcomes, with surgery optimally undertaken when patients are < 7 months of age, and with those undergoing surgery at ≥ 12 months performing the least well. These results also have potential implications for ensuring early diagnosis and referral and for the type of surgery offered. Further research is needed to control for confounding factors and to identify the mechanism by which late surgery may be associated with poorer neurodevelopmental outcomes.

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Ryan N. Moran, Tracey Covassin and Jessica Wallace

OBJECTIVE

Migraine history has recently been identified as a risk factor for concussion and recovery. The authors performed a cross-sectional study examining baseline outcome measures on newly developed and implemented concussion assessment tools in pediatrics. The purpose of this study was to examine the effects of premorbid, diagnosed migraine headaches as a risk factor on vestibular and oculomotor baseline assessment in pediatric athletes.

METHODS

Pediatric athletes between the ages of 8 and 14 years with a diagnosed history of migraine headache (n = 28) and matched controls without a history of diagnosed migraine headache (n = 28) were administered a baseline concussion assessment battery, consisting of the Vestibular/Ocular Motor Screening (VOMS), near point of convergence (NPC), and the King-Devick (K-D) tests. Between-groups comparisons were performed for vestibular symptoms and provocation scores on the VOMS (smooth pursuit, saccades, convergence, vestibular/ocular reflex, visual motion sensitivity), NPC (average distance), and K-D (time).

RESULTS

Individuals diagnosed with migraine headaches reported greater VOMS smooth pursuit scores (p = 0.02), convergence scores (p = 0.04), vestibular ocular reflex scores (p value range 0.002–0.04), and visual motion sensitivity scores (p = 0.009). Differences were also observed on K-D oculomotor performance with worse times in those diagnosed with migraine headache (p = 0.02). No differences were reported on NPC distance (p = 0.06) or headache symptom reporting (p = 0.07) prior to the VOMS assessment.

CONCLUSIONS

Pediatric athletes diagnosed with migraine headaches reported higher baseline symptom provocation scores on the VOMS. Athletes with migraine headaches also performed worse on the K-D test, further illustrating the influence of premorbid migraine headaches as a risk factor for elevated concussion assessment outcomes at baseline. Special consideration may be warranted for post-concussion assessment in athletes with migraine headaches.

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Julia D. Sharma, Kiran K. Seunarine, Muhammad Zubair Tahir and Martin M. Tisdall

OBJECTIVE

The aim of this study was to compare the accuracy of optical frameless neuronavigation (ON) and robot-assisted (RA) stereoelectroencephalography (SEEG) electrode placement in children, and to identify factors that might increase the risk of misplacement.

METHODS

The authors undertook a retrospective review of all children who underwent SEEG at their institution. Twenty children were identified who underwent stereotactic placement of a total of 218 electrodes. Six procedures were performed using ON and 14 were placed using a robotic assistant. Placement error was calculated at cortical entry and at the target by calculating the Euclidean distance between the electrode and the planned cortical entry and target points. The Mann-Whitney U-test was used to compare the results for ON and RA placement accuracy. For each electrode placed using robotic assistance, extracranial soft-tissue thickness, bone thickness, and intracranial length were measured. Entry angle of electrode to bone was calculated using stereotactic coordinates. A stepwise linear regression model was used to test for variables that significantly influenced placement error.

RESULTS

Between 8 and 17 electrodes (median 10 electrodes) were placed per patient. Median target point localization error was 4.5 mm (interquartile range [IQR] 2.8–6.1 mm) for ON and 1.07 mm (IQR 0.71–1.59) for RA placement. Median entry point localization error was 5.5 mm (IQR 4.0–6.4) for ON and 0.71 mm (IQR 0.47–1.03) for RA placement. The difference in accuracy between Stealth-guided (ON) and RA placement was highly significant for both cortical entry point and target (p < 0.0001 for both). Increased soft-tissue thickness and intracranial length reduced accuracy at the target. Increased soft-tissue thickness, bone thickness, and younger age reduced accuracy at entry. There were no complications.

CONCLUSIONS

RA stereotactic electrode placement is highly accurate and is significantly more accurate than ON. Larger safety margins away from vascular structures should be used when placing deep electrodes in young children and for trajectories that pass through thicker soft tissues such as the temporal region.