Pediatric Severe Traumatic Brain Injury

Pediatric Severe Traumatic Brain Injury

see Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition.

New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. The intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available 1).

Greenan et al., used database research to evaluate admission clinical and CT scan characteristics for use as a decision tool to help clinicians caring for children with very severe traumatic brain injury. It may help clinicians identify children who can benefit the most from aggressive medical and surgical intervention 2).


Sarnaik et al., failed to detect mortality differences across age strata in children with severe TBI. We have discerned novel associations between age and various markers of injury-unrelated to AHT-that may lead to testable hypotheses in the future 3).

References

1)

Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR, Davis-O’Reilly C, Hart EL, Bell MJ, Bratton SL, Grant GA, Kissoon N, Reuter-Rice KE, Vavilala MS, Wainwright MS. Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines, Executive Summary. Pediatr Crit Care Med. 2019 Mar;20(3):280-289. doi: 10.1097/PCC.0000000000001736. PubMed PMID: 30830016.
2)

Greenan K, Taylor SL, Fulkerson D, Shahlaie K, Gerndt C, Krueger EM, Zwienenberg M. Selection of children with ultra-severe traumatic brain injury for neurosurgical intervention. J Neurosurg Pediatr. 2019 Apr 5:1-10. doi: 10.3171/2019.1.PEDS18293. [Epub ahead of print] PubMed PMID: 30952132.
3)

Sarnaik A, Ferguson NM, O’Meara AMI, Agrawal S, Deep A, Buttram S, Bell MJ, Wisniewski SR, Luther JF, Hartman AL, Vavilala MS; Investigators of the ADAPT Trial. Age and Mortality in Pediatric Severe Traumatic Brain Injury: Results from an International Study. Neurocrit Care. 2018 Jun;28(3):302-313. doi: 10.1007/s12028-017-0480-x. PubMed PMID: 29476389.

Pediatric Neurosurgery (Neurosurgery by Example)

Pediatric Neurosurgery (Neurosurgery by Example)

Price:$109.25

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Part of the Neurosurgery by Example series, this volume on pediatric neurosurgery presents exemplary cases in which renowned authors guide readers through the assessment and planning, decision making, surgical procedure, after care, and complication management of common and uncommon disorders. As pediatric neurosurgery approximates the anatomical and pathophysiological breadth of all specialty areas of adult neurosurgery, the cases provided are exemplary of those that are more relevant to, and seen in higher frequency, in pediatrics. The cases also demonstrate presentation and management appropriate for pediatrics, as both are distinct in pediatric compared to adult neurosurgery.

Each chapter also contains ‘pivot points’ that illuminate changes required to manage patients in alternate or atypical situations, and pearls for accurate diagnosis, successful treatment, and effective complication management. Containing a focused review of medical evidence and expected outcomes, Pediatric Neurosurgery is appropriate for neurosurgeons who wish to learn more about a subspecialty, and those preparing for the American Board of Neurological Surgery oral examination.

Pediatric glioblastoma

Glioblastoma in children, when compared with adults, is relatively rare.

Despite this rarity, it is apparent from the limited number of publications that pediatric glioblastoma is quite distinct from their adult counterparts. The differences pertain to the molecular genetics, effectiveness of the adjuvant therapies, and possibly the prognosis after treatment. With a plethora of path-breaking translational research coming through in recent times, a host of new information is now available on pediatric glioblastomas that holds great promise as far as the future treatment options are concerned 1)

In contrast to adult GBM, few molecular prognostic markers for the pediatric counterpart have been established.


Some anaplastic pleomorphic xanthoastrocytomas (PXA) were reported to have extremely poor prognosis which showed a type of pediatric glioblastoma (GBM) molecular profile. Recent integrated molecular classification for primary central nervous system tumors proposed some differences between histological and molecular features. Herein, in a genome-wide molecular analysis, Nakamura et al., showed an extreme aggressive anaplastic PXA that resulted in a pediatric GBM molecular profile. A full implementation of the molecular approach is the key to predict prognosis and decide the treatment strategy for anaplastic PXA 2).


Korshunov et al. investigated the prognostic significance of genomic and epigenetic alterations through molecular analysis of 202 pedGBM (1-18 years) with comprehensive clinical annotation. Routinely prepared formalin-fixed paraffin-embedded tumor samples were assessed for genome-wide DNA methylation profiles, with known candidate genes screened for alterations via direct sequencing or FISH. Unexpectedly, a subset of histologically diagnosed GBM (n = 40, 20 %) displayed methylation profiles similar to those of either low-grade gliomas or pleomorphic xanthoastrocytomas (PXA). These tumors showed a markedly better prognosis, with molecularly PXA-like tumors frequently harboring BRAF V600E mutations and 9p21 (CDKN2A) homozygous deletion. The remaining 162 tumors with pedGBM molecular signatures comprised four subgroups: H3.3 G34-mutant (15 %), H3.3/H3.1 K27-mutant (43 %), IDH1-mutant (6 %), and H3/IDH wild-type (wt) GBM (36 %). These subgroups were associated with specific cytogenetic aberrations, MGMT methylation patterns and clinical outcomes. Analysis of follow-up data identified a set of biomarkers feasible for use in risk stratification: pedGBM with any oncogene amplification and/or K27M mutation (n = 124) represents a particularly unfavorable group, with 3-year overall survival (OS) of 5 %, whereas tumors without these markers (n = 38) define a more favorable group (3-year OS ~70 %).Combined with the lower grade-like lesions, almost 40 % of pedGBM cases had distinct molecular features associated with a more favorable outcome. This refined prognostication method for pedGBM using a molecular risk algorithm may allow for improved therapeutic choices and better planning of clinical trial stratification for this otherwise devastating disease 3)

Treatment

Total resection and receiving chemotherapy adjuvant to radiation or chemoradiation (CRT) are most closely associated with improved progression free survival (PFS) and overall survival (OS). For higher risk incompletely resected patients, temozolomide use and treatment intensification with concurrent CRT, adjuvant chemotherapy, and higher radiation dose were associated with improved outcomes 4).

Bevacizumab and irinotecan are a promising regimen for pediatric cases of recurrent glioblastoma after gross-total resection, although the optimal treatment schedule must be determined on a patient-by-patient basis 5).

Case reports

A rare case of primary pediatric glioblastoma multiforme in a 7-year-old girl with Turner’s syndrome is reported, and various aspects regarding clinical and pathophysiological issues have been discussed. Although Turner’s syndrome is not one of the congenital chromosomal abnormalities which demand routine CNS screening, neurological assessment may be of value in those with relevant clinical findings 6).

1)

Das KK, Kumar R. Pediatric Glioblastoma. In: De Vleeschouwer S, editor. Glioblastoma [Internet]. Brisbane (AU): Codon Publications; 2017 Sep 27. Chapter 15. Available from http://www.ncbi.nlm.nih.gov/books/NBK469983/ PubMed PMID: 29251872.
2)

Nakamura T, Fukuoka K, Nakano Y, Yamasaki K, Matsushita Y, Yamashita S, Ikeda J, Udaka N, Tanoshima R, Shiba N, Tateishi K, Yamanaka S, Yamamoto T, Hirato J, Ichimura K. Genome-wide DNA methylation profiling shows molecular heterogeneity of anaplastic pleomorphic xanthoastrocytoma. Cancer Sci. 2019 Jan 4. doi: 10.1111/cas.13903. [Epub ahead of print] PubMed PMID: 30609203.
3)

Korshunov A, Ryzhova M, Hovestadt V, Bender S, Sturm D, Capper D, Meyer J, Schrimpf D, Kool M, Northcott PA, Zheludkova O, Milde T, Witt O, Kulozik AE, Reifenberger G, Jabado N, Perry A, Lichter P, von Deimling A, Pfister SM, Jones DT. Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers. Acta Neuropathol. 2015 Mar 10. [Epub ahead of print] PubMed PMID: 25752754.
4)

Walston S, Hamstra DA, Oh K, Woods G, Guiou M, Olshefski RS, Chakravarti A, Williams TM. A multi-institutional experience in pediatric high-grade glioma. Front Oncol. 2015 Feb 18;5:28. doi: 10.3389/fonc.2015.00028. eCollection 2015. PubMed PMID: 25741472; PubMed Central PMCID: PMC4332307.
5)

Umeda K, Shibata H, Saida S, Hiramatsu H, Arakawa Y, Mizowaki T, Nishiuchi R, Adachi S, Heike T, Watanabe K. Long-term efficacy of bevacizumab and irinotecan in recurrent pediatric glioblastoma. Pediatr Int. 2015 Feb;57(1):169-71. doi: 10.1111/ped.12414. PubMed PMID: 25711258.
6)

Hanaei S, Habibi Z, Nejat F, Sayarifard F, Vasei M. Pediatric Glioblastoma Multiforme in Association with Turner’s Syndrome: A Case Report. Pediatr Neurosurg. 2015 Feb 25. [Epub ahead of print] PubMed PMID: 25720952.
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