Refractory epilepsy in children with brain tumors. The urgency of neurosurgery

Central nervous system tumors represent the most common solid tumors in children and are a leading cause of cancer-related fatalities in this age group.

Genomics of medulloblastoma, ependymoma, and diffuse intrinsic pontine glioma (diffuse midline glioma, with H3-K27M mutation), have refined, if not redefined, the diagnostic classification and therapeutic stratification of patients with these tumors. They detail the substantial genetic heterogeneity across each disease type and, importantly, link genotypic information to clinical course. The most aggressive, treatment-resistant (and also treatment-sensitive) forms within each disease entity are identified, and their potentially actionable targets.

Molecularly based classification of pediatric brain tumors provides a critical framework for the more precise stratification and treatment of children with brain tumors 1).


High-grade pediatric brain tumors display higher CBF in Arterial Spin Labeling than do low-grade tumors, and they may be accurately graded by using presented values. CBF is correlated with tumor microvascular density 2).

Treatment

Malignant disease of the CNS is the primary etiology for deaths resulting from cancer in the pediatric population. It has been well documented that outcomes of pediatric neurosurgery rely on the extent of tumor resection. Therefore, techniques that improve surgical results have significant clinical implications. Intraoperative ultrasound (IOUS) offers real-time surgical guidance and a more accurate means for detecting residual tumor that is inconspicuous to the naked eye.

Outcome

Thirty day mortality is increasingly a reference metric regarding surgical outcomes.

Data estimate a 30-day mortality rate of 1.4-2.7% after craniotomy for pediatric central nervous system tumor. No detailed analysis of short-term mortality following a diagnostic neurosurgical procedure (e.g., resection or tissue biopsy) for tumor in the US pediatric population has been conducted.

The Surveillance, Epidemiology and End Results (SEER) data sets identified patients ≤ 21 years who underwent a diagnostic neurosurgical procedure for primary intracranial tumor from 2004 to 2011. One- and two-month mortality was estimated. Standard statistical methods estimated associations between independent variables and mortality.

A total of 5533 patients met criteria for inclusion. Death occurred within the calendar month of surgery in 64 patients (1.16%) and by the conclusion of the calendar month following surgery in 95 patients (1.72%). Within the first calendar month, patients < 1 year of age (n = 318) had a risk of death of 5.66%, while those from 1 to 21 years (n = 5215) had a risk of 0.88% (p < 0.0001). By the end of the calendar month following surgery, patients < 1 year (n = 318) had a risk of death of 7.23%, while those from 1 to 21 years (n = 5215) had a risk of 1.38% (p < 0.0001). Children < 1 year at diagnosis were more likely to harbor a high-grade lesion than older children (OR 1.9, 95% CI 1.5-2.4).

In the SEER data sets, the risk of death within 30 days of a diagnostic neurosurgical procedure for a primary pediatric brain tumor is between 1.16% and 1.72%, consistent with contemporary data from European populations. The risk of mortality in infants is considerably higher, between 5.66% and 7.23%, and they harbor more aggressive lesions 3).

Case series

2016

27 patients with drug resistant epilepsy and brain tumor, aged up to 19 years at the time of surgery, were studied between 1996 and 2013 and followed up for at least one year. The mean interval between the onset of seizures and the diagnosis of the tumor was 3.6 years, and from diagnosis to the surgery, 18 months. The location of the tumor was in the temporal lobe in 16, with ganglioglioma and dysembryoplastic neuroepithelial tumors being the most frequent. Among the patients, 92.5% and 90.4% were seizure-free in the first and fifth year after surgery, respectively. Twelve of 16 children were successful in becoming drug-free, with complete withdrawal by 3.2 years. Surgery proved to be potentially curative and safe in these cases, suggesting that the tumor diagnosis and surgery cannot be postponed 4).


1) Vitanza NA, Cho YJ. Advances in the biology and treatment of pediatric central nervous system tumors. Curr Opin Pediatr. 2016 Feb;28(1):34-9. doi: 10.1097/MOP.0000000000000309. PubMed PMID: 26709691.
2) Dangouloff-Ros V, Deroulers C, Foissac F, Badoual M, Shotar E, Grévent D, Calmon R, Pagès M, Grill J, Dufour C, Blauwblomme T, Puget S, Zerah M, Sainte-Rose C, Brunelle F, Varlet P, Boddaert N. Arterial Spin Labeling to Predict Brain Tumor Grading in Children: Correlations between Histopathologic Vascular Density and Perfusion MR Imaging. Radiology. 2016 Nov;281(2):553-566. PubMed PMID: 27257950.
3) Hankinson TC, Dudley RW, Torok MR, Patibandla MR, Dorris K, Poonia S, Wilkinson CC, Bruny JL, Handler MH, Liu AK. Short-term mortality following surgical procedures for the diagnosis of pediatric brain tumors: outcome analysis in 5533 children from SEER, 2004-2011. J Neurosurg Pediatr. 2016 Mar;17(3):289-97. doi: 10.3171/2015.7.PEDS15224. Epub 2015 Nov 20. PubMed PMID: 26588456.
4) Bernardino MR, Funayama C, Hamad AP, Machado H, Sakamoto A, Thome U, Terra VC, Santos AC. Refractory epilepsy in children with brain tumors. The urgency of neurosurgery. Arq Neuropsiquiatr. 2016 Dec;74(12):1008-1013. doi: 10.1590/0004-282×20160157. PubMed PMID: 27992000.

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