Review articleDiffuse intrinsic pontine gliomas: Diagnostic approach and treatment strategies
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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