What is Diffuse Intrinsic Pontine Glioma?
Diffuse intrinsic pontine glioma (DIPG) is a aggressive type of brain tumor. It mostly affects children, with around 200 to 300 new cases each year in the United States. Unfortunately, most patients live less than a year after diagnosis. Initial treatment normally involves radiation therapy, because it’s not usually possible to remove the tumor with surgery. However, the benefits of radiation are often temporary, and no drug treatments have been successful. Over the years, many attempts have been made to find better treatments through clinical trials, but so far, these have not succeeded in improving patient outcomes.
What Causes Diffuse Intrinsic Pontine Glioma?
The growth of a certain type of brain tumor might be connected to how the brain grows and develops. Research suggests that specific cells present in high amounts during brain development might play a role in causing this disease. This idea is backed up by the fact that this kind of tumor mainly shows up in children between the ages of 5 and 10 when the brain is very active in its growth. It’s rare to see this tumor in adults.
Scientists have identified a particular type of cell related to this condition in a specific part of the brain that’s very active during middle childhood, the same time when this tumor usually appears. Interestingly, these specific cells are not found in the midbrain, an area where this type of tumors are rarely identified.
Recent breakthroughs in understanding this disease at a molecular level have found a specific mutation, called H3K27M, in about 80% of these tumors. Because of this discovery, the World Health Organization categorized this tumor as a ‘diffuse midline glioma H3K27M-mutant’, which is a highly severe type of brain tumor in 2016.
Risk Factors and Frequency for Diffuse Intrinsic Pontine Glioma
Brainstem gliomas are a type of brain tumor that affects around 300 children in the United States every year. They are the leading cause of death among children with brain tumors. The most common brainstem glioma is called DIPG, which makes up 80% of all cases. There are typically 1 to 2 new cases of DIPG for every 100,000 people each year.
- These tumors most commonly occur in children between 6 to 9 years old.
- They are slightly more common in boys than in girls.
- Among all types of brain tumors in children, brainstem gliomas make up 20%.
Signs and Symptoms of Diffuse Intrinsic Pontine Glioma
Diffuse intrinsic pontine glioma (DIPG) in children tends to progress quickly, often showing symptoms within a month before reaching out for medical help. These symptoms are caused by issues with parts of the brainstem called the pons, leading to various health problems. Double vision is usually the first symptom due to a condition known as abducens nerve palsy. When there is damage to the part of the brain that controls facial movements, it can cause facial weakness or even paralysis. If the nerve pathways, which control voluntary movement, are impacted, it can result in weakness and overly active reflexes. Problems with the connections between the cerebellum and pons can lead to poor coordination and balance, as well as slurred speech.
About half of children with DIPG will experience a common trio of symptoms: abnormal nerve pathway signs, cerebellum-related signs, and issues with the cranial nerves. In fewer than 10% of cases, DIPG also causes a condition called hydrocephalus where fluid builds up in the brain. If left untreated, it can evolve into coma and result in death.
- Double vision
- Facial weakness or paralysis
- Weakness and overly active reflexes
- Poor coordination and balance
- Slurred speech
Testing for Diffuse Intrinsic Pontine Glioma
If a doctor suspects that a patient has a DIPG, which is a type of brain tumor, the best way to examine this is by using a magnetic resonance imaging (MRI) scan of the brain, with and without contrast. This type of scan usually shows an increased signal in more than half of the ventral pons, the part of the brain where DIPG tumors are commonly found. This increased signal can be seen on a particular type of MRI scan called a T2 FLAIR MRI sequence.
It’s important to note that the tumor itself will not show any changes when a contrast solution is used, meaning it won’t ‘light up’ on the scan. However, small areas of dying tissue, called necrosis, might show some enhancement. The amount of diffusion or spread of the tumor that is shown on the MRI images can sometimes help doctors predict a patient’s expected survival time.
Using MRI, doctors can also check for the spread of the tumor to other parts of the brain. An MRI of the entire spine is also recommended to make sure that the tumor hasn’t spread there. If the patient doesn’t have a buildup of fluid in the brain, known as hydrocephalus, doctors can also perform a lumbar puncture. This procedure involves removing some of the fluid around the brain and spine, known as cerebrospinal fluid, to check for tumor cells or certain DNA mutations that are associated with this type of tumor.
Treatment Options for Diffuse Intrinsic Pontine Glioma
Steroids, like dexamethasone, are often given to patients to keep neurological symptoms under control until more definitive treatments such as a neurosurgical biopsy or radiation therapy can be performed. However, steroids should be used for a short duration if possible to prevent long-term complications. Steroids help stabilize the barrier between the blood and the brain, but can interfere with the effectiveness of other treatments and may actually decrease patient survival in certain types of severe brain tumors. Fewer than 10% of patients with a certain type of brain tumor known as DIPG develop a condition known as hydrocephalus, where fluid collects in the brain, and need additional procedures to manage it.
Securing a sample of the tumor tissue is vital for both treating the patient and advancing research. However, obtaining a biopsy has traditionally been challenging due to the brain’s complex anatomy. Thankfully, advancements in technology have made a procedure known as a stereotactic biopsy a safe and less invasive method of obtaining a tissue sample with a low risk of complications. This method of biopsy has been shown to be a safe and effective method for diagnosing DIPG.
Once a diagnosis has been established, radiation therapy is often the next step in treatment. Despite continued advancements in radiation and cancer research, the survival outcomes for children with DIPG have not considerably improved over the past couple of decades. Regularly split radiotherapy remains the primary treatment for children with DIPG. However, another form of treatment described as hypofractionated radiotherapy has shown promising results. This form of therapy typically consists of fewer, higher doses of radiation and may be better tolerated in younger children. Possible options for when the tumor progresses include re-radiation. Radiation-enhancing drugs, however, do not seem to boost survival rates.
There have been various clinical trials looking at other treatment options, such as stem cell transplantation and a variety of chemotherapy drugs. These are undergoing continued evaluation, though no significant increase in survival rates for children with DIPGs has been reported with these treatments. Potential advancements, such as convection-enhanced drug delivery systems, show promise in improving treatment options. This method directly targets tumor cells, especially where they meet normal brain cells. Another new treatment approach is adjuvant multimodal immunotherapy, which consists of repeated vaccination cycles and therapy involving immune cell death. Initial results have shown improved overall survival, but more research is needed.
What else can Diffuse Intrinsic Pontine Glioma be?
- Gliomas in the midbrain (the middle part of the brain)
- Gliomas in the cervicomedullary area (where the brainstem meets the spinal cord)
- Pilocytic astrocytoma (a slow-growing brain tumor)
- Cavernous malformation (a cluster of tiny blood vessels in the brain)
- Demyelinating disease (disorder causing nerve damage in the brain)
- Infectious diseases that can affect the brain
What to expect with Diffuse Intrinsic Pontine Glioma
The outlook for DPIG, a type of brain tumor, is unfortunately very poor as there are no proven effective treatments. This form of tumor is the leading cause of death from brain tumors in children. Typically, children diagnosed with DPIG are under seven years old. On average, they tend to live for about nine months after diagnosis, with only 10% surviving more than two years.
Compared to other pediatric brain cancers like glioblastoma, DPIG has the worst prognosis, which means those affected by it have the shortest survival time.
Possible Complications When Diagnosed with Diffuse Intrinsic Pontine Glioma
There are several complications that can occur from various medical conditions. These include:
- Facial paralysis
- Difficulty swallowing, also known as dysphagia
- Respiratory insufficiency, which is difficulty breathing
- Hemiparesis, which is weakness on one side of the body
- Deep vein thrombosis, a condition where a blood clot forms in a deep vein
- Hydrocephalus, commonly known as “water on the brain”
- Radiation necrosis, a condition caused by radiation therapy that destroys healthy brain tissue
- Brain herniation, a potentially deadly side effect of very high pressure within the skull
- Coma, a state of unconsciousness lasting for a prolonged period
- Surgical complications, which include intracranial hemorrhage (bleeding inside the skull), edema (swelling), seizures, and cranial nerve injury (damage to the nerves in the brain)
Preventing Diffuse Intrinsic Pontine Glioma
People who have DIPG, along with their families, should fully understand their condition and what to expect in terms of the disease’s progression to set realistic expectations. The point at which the disease is detected can greatly affect how the family copes with the situation. This is why it is crucial to involve mental health professionals such as psychologists and family therapists early on.
It’s important for parents to know exactly what they may face after treatments, including physical disabilities and general health conditions. They should be well trained on how to handle these situations, like providing nutrition through a nasogastric tube, managing a urinary catheter, dealing with the potential of their loved one being bedbound, and preventing bedsores. This thorough training can be valuable in managing these tough situations.
