Brainstem gliomas are a group of primary brain tumors that arise from glial (helper) cells in the brainstem part of the brain. Brainstem gliomas are most frequent and aggressive in children. They are responsible for 10 to 20% of all central nervous system tumors in children. Contrary to the previously held notion, pediatric brainstem gliomas are found to have a different set of mutations than their adult counterparts. These mutations are responsible for their aggressive nature. This aggressive nature of tumors leads to another problem; they cannot be surgically removed due to their proximity to vital parts of the brain, making brainstem gliomas hard to treat. Brainstem gliomas are known to have a short survival period and high mortality rates. The progression is so rapid that, on average, there is only a lag period of one month between the presentation of symptoms and the diagnosis.
Types
The heterogeneous nature of brainstem gliomas requires them to be classified based on their anatomical location. Following are some of the common types of brainstem gliomas according to their location on the brainstem:
1. Diffuse intrinsic pontine glioma (DIPG): DIPG is the most common and aggressive form of brainstem gliomas. They constitute about 80% of all brainstem tumors. DIPG appears as a striking diffuse enlargement of the brainstem on magnetic resonance imaging (MRI). 2. Exophytic medullary glioma: They are low-grade astrocytomas with a median survival of 5 years. They constitute about 10% of all brainstem tumors and arise from the cervicomedullary junction or the floor of the fourth ventricle. 3. Tectal glioma: These tumors are relatively benign. They are low-grade astrocytomas in nature arising from the retroaqueductal region of the midbrain. Their mean age at diagnosis is 7 to 10 years. They account for less than 5% of all brainstem gliomas.
Global perspective
According to an estimate, brainstem gliomas make up 4.2 % of all gliomas. This ratio rises to 20% in children. In adults, they account for only 2% of all intracranial tumors. The aggressive nature of these tumors is evident by the fact that, on average, children affected by brainstem gliomas survive for only 1 year.
Indian perspective
A study published in 2009, reviewed a total of 656 Indian patients with primary brain tumors and found that 18 of these cases had brainstem gliomas. In India, the median age of diagnosis of primary brain tumors is slightly lower than the global average, but pediatric brainstem gliomas have similar age of diagnosis as the rest of the world.
Signs and symptoms
Brainstem gliomas show long tract symptoms and those arising from cranial nerve damage. These symptoms include:
Ataxia (uncoordinated movements)
Diplopia (double vision)
Weakness of a leg or arm
Unsteady gait
Dysphagia (difficulty swallowing)
Dysarthria (speech difficulty)
Headache
Drowsiness
Nausea
Vomiting
Hydrocephalus (accumulation of fluid in brain cavities; occurs in 10% of patients)
Some rare symptoms are:
Pathological laughter
Irritability
Seizures
Upbeat nystagmus (abnormal and involuntary eye movements)
Post-treatment morbidities are unknown in the majority of the cases due to the very short survival rate of the patients.
Diagnosis
The median age of diagnosis of DIPG in children is 6 to 7 years. MRI is the standard imaging modality for the diagnosis of these tumors. Sometimes an intravenous contrast medium is given to enhance the clarity and provide delineated details. Molecular characterization of brainstem gliomas is difficult due to the lack of biopsies. In some cases where biopsy is possible, the gliomas were found to be an astrocytoma. In pediatric cases, other factors such as age, symptoms, and progression of the tumor are considered in addition to the location of the tumor. Sometimes additional advanced imaging modalities such as MR spectroscopy (MRS) and perfusion or diffusion-weighted MRI are also utilized to get a better idea of the tumor behavior.
Treatment
Diffuse intrinsic: In most primary brain tumors, surgical resection is considered the gold standard of management when the tumor is behaving aggressively but in the case of diffuse brainstem gliomas, the tumor can be present so close to vital parts of the brain that surgery is not a safe option. Even a biopsy can cause neurological symptoms; thereby, imaging is performed for diagnosis. The option for most patients is external beam radiation therapy (RT). The total dose of 60 Gy is administered in fractions over a period of 6 weeks. So far chemotherapy has been found to be ineffective. Similarly, most clinical trials looking into the efficacy of targeted therapy for brainstem gliomas have shown disappointing results.
Posterior exophytic gliomas: The mainstay of treatment is the surgical resection of the tumor.
Focal tectal gliomas: In most cases, the tumor is not malignant but when intracranial pressure is increased, shunt placement or neuroendoscopic third ventriculostomy are considered suitable options.
Quality of life
Child life specialists help improve the quality of life of a child suffering from brainstem glioma. All of the aforementioned symptoms can be managed individually through pharmacological or non-pharmacological methods. These include:
Certain medications such as corticosteroids and analgesics can help relieve the pain. Dexamethasone is the most important of these steroids. It is helpful in managing some symptoms of raised intracranial pressure but has its side effects.
Hydrocephalus and resulting symptoms can be relieved through surgery.
Alternative methods of communication are helpful for patients who have completely lost or have diminished ability of speech. Similarly, nasogastric tube feeding is often recommended for patients who cannot swallow their food properly and are at risk of malnutrition or aspiration pneumonia.
Support groups are there to help parents with the anxiety and depression that follows the diagnosis of this devastating cancer in their child. Taken together, these strategies can improve the quality of life of the patients and their caregivers. New research on the optimal use of existing interventions and the effectiveness of novel therapeutics will further increase the quality of life of patients affected by brainstem glioma.
