Elsevier

Journal of Clinical Neuroscience

Volume 72, February 2020, Pages 15-19
Journal of Clinical Neuroscience

Review article
Diffuse intrinsic pontine gliomas: Diagnostic approach and treatment strategies

https://doi.org/10.1016/j.jocn.2019.12.001Get rights and content

Highlights

Abstract

Diffuse intrinsic pontine gliomas (DIPG) are high grade gliomas of the brainstem with fatal outcomes. Radiation is known to be partially effective to control the immediate flare but relapse is frequent. There has been ongoing research to study the role of molecular subgroups and identification of specific targets but this is not possible with histopathological diagnosis alone. The authors’ objective is to highlight the need for and discuss ongoing molecular research. There is an inherent need for the availability of tumor tissue to be able to conduct research studies. The authors advocate the use of neuronavigation assisted stereotactic technique for tumor biopsy. The technique is feasible with a predefined surgical trajectory. After obtaining tissue diagnosis further work can be performed to isolate and identify histone protein genetic mutations and methylation changes responsible for DIPG molecular subgrouping. Moreover, convection enhanced delivery of therapeutic agents is being developed for better instillation of future drug agents. Despite identification of genetic/epigenetic mutations, growth factors, receptors, and tissue biomarkers, the oncogenesis of DIPG remains elusive. The authors’ effort to provide a comprehensive review on DIPG to better understand the disease, need for tissue diagnosis, described surgical technique, and need for pre-clinical and clinical future research is novel.

Introduction

Diffuse intrinsic pontine gliomas (DIPG) are highly infiltrative gliomas of the brainstem and are the leading cause of death in children [1]. Historically speaking DIPG account for 10 to 20% of all pediatric brain tumors and the typical age of onset is between 6 and 9 years of age [2]. The presentation is usually with an acute onset of neurological symptoms and signs based on the exact location and the extent of the tumor spread. However, the typical presentation is a classic triad of long tract signs with motor weakness, cranial neuropathies, and cerebellar signs [3]. Interestingly, an abducens nerve palsy is considered as a sensitive predictor for the diagnosis in very young children [4]. Since, being locally infiltrative, the symptoms and signs are primarily based on the focal compression or spread along the fiber tracts. Rarely, the signs of raised intracranial pressure due to non-communicating hydrocephalus are observed only if the there is dorsal infiltrative spread in the floor of 4th ventricle. The studied median survival is around 10 months while, overall survival (OS) is 30% at 1 year and around 1% up to 5 years [5], [2], [6].

The diagnosis is primarily based on history, neurological examination and brain imaging which comprises of an initial head CT scan without contrast followed by an MRI brain with and without contrast. On head CT scan it appears as a hypodense brain stem lesion. However, on MRI it appears T1 hypo intense but T2 hyperintense. Rarely, it takes up gadolinium contrast enhancement or it can be quite irregular in enhancement due to the preservation of the blood brain barrier [7], [8]. The preservation of the blood brain barrier is a challenge to the migration of the different chemotherapeutic regimens which provide some success in other pediatric gliomas. However, these agents have failed in the treatment of DIPG [8]. Therefore, this anatomical barrier has led to more molecular and genetic studies to better understand the tumor behavior so that additional routes of drug delivery can be established. The purpose of this review is to better understand the tumor behavior, current diagnostic approach, advances in research and treatment, and outline current challenges in the arrest/cure of DIPG.

Section snippets

Methods and results

Due to the diffusely infiltrative nature of the tumor, these patients are not surgical candidates for the tumor resection. Additionally, there is an inherent risk of morbidity and mortality due to the location of tumor in the brain stem with any approach taken. Nonetheless, there is a need for definitive tumor tissue for genetic and molecular studies for the guiding treatment. Therefore, an acceptable way to approach these tumors is with stereotactically guided biopsies through the relatively

Discussion

The treatment of DIPG unlike other high grade gliomas is solely dependent on the identification of the genetic markers, and molecular biology for more specifically targeted therapies. Biopsy tissue help guide these advancements. Stereotactic biopsy is therefore very valuable in the diagnostic pursuits of these patients. In a meta-analysis of 735 patients, the primary outcome measure of overall diagnostic success was up to 96%, and the procedure-related complications was 0.6% [11]. However,

Conclusion

DIPG is a devastating disease with lasting traumatising effects to the patients, parents, and the families. Despite expertise in the neurosurgical techniques, and decades of endless research as well as pre-clinical and clinical trials, little improvement has been seen in the natural course of the disease. Improvement in the navigational system has enabled us for better use of stereotactic biopsy with less complications. The availability of tissue specimen is not only helpful for the

Financial disclosure

There are no funding sources to report for this study.

Acknowledgement

None.

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