Brainstem Gliomas/ Diffuse Midline Gliomas/ Diffuse Pontine Gliomas.pptx

diffuse midline gliomas are high grade gliomas and typically involve pediatric population, carry poor prognosis and limited treatment options. this powerpoint carries detailed description of clinical features, diagnosis, management of diffuse pontine gliomas.

1. Diffuse Midline Gliomas Presented By: Dr. Rahul Jain SR-2 Neurosurgery Moderated by: Dr V. C. Jha Dr Nitish Kumar Dr Gaurav Verma

2. Introduction Diffuse midline gliomas are primary central nervous system (CNS ) tumors . This means they begin in the brain or spinal cord. Diffuse midline glioma is a rare subtype of glial tumors . Diffuse midline glioma (DMG), previously called diffuse intrinsic pontine glioma (DIPG), is a high-grade malignant pediatric tumor originating in the midline of the brain.

3. Often occurs during middle childhood, with an incidence of 0.8 in 100,000 children per year at a median age of 6–7 years old in the United States. In children, involvement tends to be in brainstem (formerly called brainstem glioma), pons ( formerly called diffuse infiltrating pontine glioma [DIPG]), or bithalamic ; males > feamles . In adolescents or adults, they occur unilaterally in the thalamus or in the spinal cord .

4. DMG is still uncurable and is the leading cause of pediatric brain tumor -related deaths In the latest 5th edition of the WHO classification, the nomenclature of DMG H3 K27M-mutant has been changed to DMG H3 K27-altered. It is classified as WHO grade IV regardless of histological findings, and the prognosis is known to be poor. Leptomeningeal involvement was found in 40% in autopsy series. People with gene changes that can be passed down through families, such as Li- Fraumeni syndrome and neurofibromatosis type I, are at increased risk for developing a diffuse midline glioma

5. Definition – diffuse glioma centered in a midline structure of the CNS (e.g., thalamus, brainstem, cerebellum, or spinal cord) harboring a recurrent lysine-to-methionine missense mutation (p.K27M) involving codon 27 in one of the histone H3 genes ( H3F3A, H3F3B, HIST1H3B, or HIST1H3C ). Any diffuse gliomas located within midline structures of the CNS harboring a histone H3 K27M mutation are assigned as WHO grade IV irrespective of having high-grade histologic features . Subtypes :- diffuse midline glioma, H3.3 K27–mutant diffuse midline glioma, H3.1 or H3.2 K27–mutant diffuse midline glioma, H3-wildtype with EZHIP overexpression diffuse midline glioma, EGFR-mutant

6. Clinical features Diffuse midline gliomas are fast-growing tumors and can spread to other areas of the CNS through cerebrospinal fluid (CSF ). Depending on the tumor’s location Double vision Problems swallowing Weakness on one or both sides of the body Loss of balance  Due to hydrocephalus (nausea, vomiting, headache, blurring of vision)

7. In the spine may have: Progressive weakness Numbness Problems with bowel and bladder control Patients typically present with a short course with brainstem findings (triad: multiple cranial nerve palsies, long tract signs and ataxia) or obstructive hydrocephalus. Evidence of thalamic involvement includes signs of increased ICP, motor weakness (e.g., hemiparesis), and gait disturbance .

8. Genomic Understanding

9. The presence of the H3K27M mutation is associated with a significant decrease (by 2.3 years) in overall survival as compared to other pHGGs . H3 K27M-mutant diffuse midline gliomas uniformly lack the IDH1 p.R132 or IDH2 p.R172 mutation that genetically characterizes diffuse lower-grade gliomas within the cerebral hemispheres of young adults . H3 K27M-mutant diffuse midline gliomas do not typically harbor TERT promoter mutation or EGFR amplification that characterizes most IDH wild-type glioblastomas within the cerebral hemispheres of older adults.

10. Diagnostic criteria for diffuse midline glioma, H3 K27M-altered

11. Evaluation H igh rate of leptomeningeal spread, imaging of the entire neuraxis is recommended. Current trends favor obtaining a biopsy in most cases. Biopsy confirms H3 K27M-mutation and can determine if there is MGMT promoter gene methylation .

12. Imaging Pontine lesions enlarge the pons, which is low intensity on T1 and increased intensity on T2 . Enhancement is minimal. Compression of the 4th ventricle may produce hydrocephalus. Encasement of the basilar artery is common. There may be an exophytic component.

13. Treatment The first treatment for diffuse midline glioma is surgery, if possible. The goal of surgery is to obtain tissue to determine the tumor type and to remove as much tumor as possible without causing more symptoms for the person.  The brainstem, thalamus, and spinal cord are sensitive locations in the CNS and surgery in these areas can cause serious loss of function.

14. The negative prognostic implications and the increasing trials for novel therapies have prompted neurosurgeons and oncologists to advocate for biopsy of these lesions. The standard of care includes radiation and chemotherapy . However, there is no standard chemotherapy regimen, and each plan should be tailored to each patient.

15. Prognosis Even with current therapies, 2-year survival is < 10 %. Prognosis is better for subtypes involving H3.1 or H3.2 K27-mutation or EZHIP overexpression than the H3.3 K27 mutation. Median survival in the literature ranges between 9.1 and 19.6 months. However , studies have shown that despite its dismal prognosis , median survival for diffuse midline gliomas is still better compared with high-grade IDH wild-type tumors ( 17.6 months versus 7.7 months ).

16. References Greenberg’s Handbook of Neurosurgery 10 th ed Youmans and winn’s neurological surgery 8 th ed cancer.gov/rare-brain-spine- tumor / tumors /diffuse-midline-gliomas Jovanovich et al.: Diffuse midline glioma future therapeutics. https :// doi.org/10.1093/noajnl/vdad040