What is Neuronal Brain Tumors?
Neuronal brain tumors are a rare type of brain tumor that grows from nerve cells in the brain, also known as neurons. These tumors can consist solely of neuron cells, or they can be made up of both neuron and glial cells, a type of supporting cell in the nervous system. The latter type is known as glioneuronal tumors.
In 2021, the World Health Organization listed 14 specific types of these tumors. Among them, tumors that are only made up of neuron cells include types such as gangliocytoma, central neurocytoma, and cerebellar liponeurocytoma. The mixed glioneuronal group includes tumors like ganglioglioma and desmoplastic infantile astrocytoma.
Generally, these tumors are usually not highly aggressive, meaning they grow slowly and don’t often spread to other parts of the body. Symptoms often include seizures, but other signs can include headaches, vomiting, balance and coordination problems, and specific neurological issues, depending on the location of the tumor in the brain. A lot of these tumors are often found in the temporal lobe, an area of the brain often responsible for seizures.
However, these tumors can occur anywhere within the upper (supratentorial) and lower (infratentorial) parts of the brain. The recent classification of new tumor types helps doctors recognize, diagnose, and treat these conditions more accurately.
What Causes Neuronal Brain Tumors?
It’s not entirely clear what causes certain types of brain tumors to develop. However, research into the genetics of these tumors is helping us get a better understanding. Scientists have identified two main groups of these tumors, each linked to different genetic changes or mutations that mess up the normal functions of cells.
The first group of these tumors is linked to changes in a gene pathway known as the MAPK pathway, which is involved in the growth of cells. Specific changes in the BRAF gene, a part of this pathway, have been found in these tumors. In medical terms, these changes are known as ‘fusion mutations’ and ‘single nucleotide missense mutations’. These changes are usually detected in two types of tumors, gangliocytoma and ganglioglioma, and these changes lead to uncontrolled cell growth.
The second group is linked to changes in genes known as FGFR genes, which are located further up in the MAPK pathway. These changes often occur in a type of tumor called DNET, but have also been found in neurocytoma and RGNT tumors. Interestingly, these groups of tumors can help us also tell apart different types of tumors. The tumors in the group with the BRAF gene mutation tend to resemble astrocytes (a type of brain cell), whereas the ones in the FGFR gene mutation group tend to resemble oligodendroglia (another type of brain cell).
Apart from these groups, scientists have identified new types of tumors, such as MGTs, which are similar to DNET but usually occur in a part of the brain known as the septum pellucidum. They are associated with a change in the PDGFR gene, not the FGFR gene.
Another type, PGNTs, also show unique genetic changes. They often show a fusion change between two genes, SLC44A1 and PRKCA. These changes result in a new gene named SLC44A1-PRKCA. Even though PRKCA is involved in the MAPK pathway, these tumors don’t have the BRAF gene changes that other similar tumors have.
A certain type of tumor called Dysplastic cerebellar gangliocytoma is associated with a condition known as Cowden syndrome. Cowden syndrome often leads to different types of growths throughout the body, and this tumor is one of them. These tumors are linked to changes in a gene called PTEN, which is involved in the mTOR pathway, another important pathway that regulates cell growth.
It’s key to note that not all tumor samples will have these specific genetic changes, and that there may be other changes linked to these tumors that have not yet been detected. The rarity of these tumor types makes it difficult to identify all the genetic changes that may contribute to their development. Doctors and scientists continue their efforts to better understand these genetic changes, and this understanding can help improve treatments in the future.
Risk Factors and Frequency for Neuronal Brain Tumors
This type of brain tumor is rare, making up only about 0.5 to 2% of all primary brain and spinal cord tumors. The most common types in this group are called ganglioglioma and DNET. However, there are many other types, some of which are newly classified and not well-studied yet, such as MVNT, DGONC, MGT, and more. These are generally found in children and young adults. It’s not very common to diagnose these tumors in people over 30 years old.
- This group of brain tumors is rare, accounting for only 0.5 to 2% of all main brain and spinal cord tumors.
- The majority of these tumors are ganglioglioma and DNET.
- There are several newly classified and lesser-known types such as MVNT, DGONC, MGT, and others.
- These tumors primarily affect children and young adults.
- A diagnosis in people older than 30 years is rare.
Signs and Symptoms of Neuronal Brain Tumors
Patients with a brain tumor made of neurons or glial cells can have a wide variety of symptoms. Doctors need to know their patient’s full seizure history, whether they’ve been assessed for seizures before, and if anyone in their family has a history of seizures. They also need to know about other symptoms, like headaches, nausea, vomiting, balance issues, weakness, changes in sensation, eyesight problems, and more. It’s also important to know about any other illnesses the patient has had and any medications they are currently taking or have taken in the past.
Next, a thorough physical exam should be conducted, with a special focus on the nervous system. This includes looking for changes in mental state, problems with vision, issues with the cranial nerves, neurological issues, disruptions in motor skills or sensation, problems with the cerebellum, and swelling of the optic nerve.
Most of the time, the physical exam results are normal. However, sometimes patients might come in with a severe change in mental state and a condition called obtundation, which indicates a sudden blockage of the flow of cerebrospinal fluid. This can happen with brain tumors like central neurocytoma or a seizure.
Patients who have tumors in the lower back part of the brain might show signs of cerebellum problems during the exam, like unsteady movement, a positive Romberg sign, and others. There may also be changes in sensation or weakness, but these are rare. This is because these tumors typically grow slowly and the brain can adapt to their presence. Frequent neurological evaluations are necessary for patients who have just had a seizure or those with a sudden change in status due to a rapid buildup of cerebrospinal fluid.
Testing for Neuronal Brain Tumors
If a doctor suspects that you might have a certain type of brain tumor known as a neuronal or glioneuronal tumor, they will first ask you about your medical history and examine you. Some patients with these tumors may need urgent care if they show signs of severe neurological changes, trouble breathing, or circulatory problems. This could involve treatments to help you breathe, such as intubation and resuscitation. However, most people with these tumors have seizures and symptoms of increased pressure inside their skull, such as headaches.
Doctors have a variety of tests at their disposal to identify and help decide on treatment for these tumors.
CT Scan: A CT scan can quickly show any urgent changes in the brain, like hemorrhage or hydrocephalus (excess fluid in the brain), which might need quick surgical intervention. CT scans can also pick up other signs that suggest the presence of a tumor, such as generally dense or shadowy spots in the brain images, or calcification, which is a buildup of calcium in the tumor. However, the CT scan may not show calcification in most neuronal and glioneuronal tumors.
MRI: An MRI is the main test used to look at these types of tumors. This test uses several special “sequences” or techniques to examine different aspects of the tumor and its surroundings. These techniques can highlight edema (swelling), hemorrhage (bleeding), angiogenesis (creation of new blood vessels), and other features that help to provide a more complete picture of the tumor. Advanced MRI approaches can further detail the nature of the tumor.
Different types of neuronal and glioneuronal brain tumors show up differently on MRIs. For example, a tumor type called gangliocytoma may appear as hyperintense (bright), while another tumor type called a Central neurocytoma might display a unique ‘soap-bubble’ appearance on an MRI.
EEG (Electroencephalography): Because these tumors often cause seizures, you could undergo EEG, a noninvasive test that records the electrical signals in your brain. This can help the doctor understand more about the seizures. In some situations, they may use a more invasive type of EEG, involving small electrodes placed on or under the surface of your brain.
WADA Test: If there’s a risk that surgery could affect your language abilities, a WADA test might be done. This test helps determine which side of your brain controls your language. Although functional MRI can also do this, WADA testing is typically more accurate.
In order to decide on the best course of action for care, doctors, surgeons, radiologists, pathologists, and other professionals will discuss the case together in what are known as interprofessional conferences. These meetings aim to build a thorough and effective treatment plan for patients.
Treatment Options for Neuronal Brain Tumors
If you have a tumor that isn’t causing any symptoms or causing only mild symptoms, and it was discovered while having imaging tests for another reason, it’s acceptable to monitor the tumor with regular check-ups and neuroimaging. This is due to these kinds of tumors generally being low-grade, meaning they’re slow-growing and less likely to spread. However, should the tumor’s appearance change in the scans, or you start experiencing new neurological symptoms, it’s crucial to consider treatment options.
When it comes to seizures related to tumors, anti-seizure medications are often prescribed. The specific medication used can vary, and it’s usual for doctors to try different ones to see which works best. However, it’s important to know that these tumors often don’t respond fully to medications alone and may require surgical treatment.
For symptomatic neuronal and glioneuronal tumors, which are specific types of brain tumors, the first choice of treatment is usually surgical removal. This typically involves an operation called a craniotomy. In urgent cases, such as when the tumor causes acute obstructive hydrocephalus (a sudden blockage of cerebrospinal fluid), immediate surgery is crucial to avoid permanent brain damage or even death. However, these emergency situations are unusual with this group of tumors, and most surgeries can be planned in consultation with your treating team.
Gross total resection, the complete removal of the tumor, is the usual goal of surgery, although in some cases, leaving a small part of the tumor can still be beneficial. This is especially the case with a certain type of tumor called LEATs. For higher-grade tumors, complete removal appears to be more important, as it can improve survival rates.
Minimally invasive surgical techniques are becoming more common for treating large tumors located within the fluid-filled spaces in the brain (ventricles). One such technique is called laser interstitial thermal therapy (LITT), which uses light energy to destroy the tumor. This option may become more prevalent in the future, particularly for tumors located in intricate areas of the brain.
For low-grade tumors, the role of radiotherapy, a type of cancer treatment that uses high doses of radiation to kill cancer cells, is limited. However, for higher-grade tumors, radiation may be needed after surgery. This can improve survival rates, particularly if some of the tumor remains following surgery or if the tumor has recurred.
Chemotherapy, which uses drugs to destroy cancer cells, and immunotherapy, which uses treatments to help your immune system fight cancer, are typically reserved for grade 2 and 3 tumors. This is similar to radiation therapy. These treatments have shown encouraging results, but their exact role is still being defined, particularly for this group of tumors due to their rarity.
As always, the specifics of treatment depend on several factors including the location, type, and grade of the tumor, and your general health and personal preferences.
What else can Neuronal Brain Tumors be?
When trying to diagnose brain tumors that emerge from neurons and glial cells, doctors have to consider a broad range of possibilities. This is because these tumors can be quite diverse in nature. They can appear similar to other primary tumors in the central nervous system, especially the low-grade ones.
Here is a list of conditions that doctors need to consider:
- Diffuse astrocytoma – a type of brain tumor that grows slowly
- Pilomyxoid astrocytoma – a rare type of brain cancer that occurs primarily in children
- Pleomorphic xanthoastrocytoma – a rare kind of tumor, generally benign and found usually in children and young adults
- Pilocytic astrocytoma – a typically slow-growing brain tumor found more often in children and adolescents
- Oligodendroglioma – a rare, slow-growing type of brain tumor
- Lymphoma – a type of cancer that originates in the cells of the immune system
- Ependymoma – a type of tumor that arises from cells lining the brain’s fluid-filled ventricles
- Intraventricular tumors such as subependymal giant cell astrocytoma (SEGA), meningioma, choroid plexus papilloma or even cancer that has spread (metastasized) from a tumor in another part of the body
- Dural-based tumors such as meningioma or metastases that originate in the membrane that covers the brain and spinal cord (dura mater)
- Cerebritis – an inflammation of the brain
Understanding these possibilities is necessary to ensure an accurate diagnosis.
What to expect with Neuronal Brain Tumors
Most of the information we have about tumors related to ganglioglioma and DNET (a type of brain tumor) is because these are the most common tumors of their kind. The main symptom for these tumors is seizures, so researchers are particularly interested in understanding how surgery can help control these seizures. A study reviewed seizure outcomes in 26 patients who had seizures linked to these types of brain tumors.
In this study, it was observed that patients who were diagnosed early, were younger, and had a specific type of seizure known as focal partial seizure, had better outcomes after surgery. Notably, it was found that early surgical intervention resulted in better long-term seizure control. The extent of the tumor removal during surgery might also be crucial. A review of previous research including 1181 patients found that 79% of patients who had all of their tumor removed were free of seizures, compared to just 43% of those who had only part of their tumor removed.
Interestingly, the study also found that patients who had their entire tumor plus a little bit of the surrounding tissue removed experienced even better results with 87% of them becoming seizure-free after surgery. It seems that removing the surrounding abnormal tissue during tumor removal can also be beneficial. Similar results have been seen in children with seizures caused by these brain tumors. It’s particularly important to diagnose and treat these brain tumors promptly in children because shorter seizure duration has been linked to better cognitive (thinking and learning) outcomes in children.
One specific concern for a type of tumor known as central neurocytoma is the need to manage a condition called hydrocephalus (a condition where fluid builds up in the brain) over a long time with CSF shunting (a process to remove excess fluid). The complete removal of these tumors seems to be associated with lower rates of fluid buildup in the brain.
However, anaplastic ganglioglioma, another type of tumor, has been observed to have the worst prognosis in this group, with a median survival time of just over two years despite aggressive treatment.
Predicting outcomes for many of the other tumors in this group can be challenging due to their infrequency. But most tend to be benign (non-cancerous) when examined under a microscope and have a low WHO grading, suggesting favorable long-term survival. The primary focus is managing the symptoms related to the tumors, often through surgery.
Possible Complications When Diagnosed with Neuronal Brain Tumors
The complications arising from brain tumors called neuronal and glioneuronal can vary depending on the type of treatment received. For instance, anti-epileptic medicines commonly cause side effects like feeling irritable, experiencing dizziness, sleepiness, blurred vision, coordination difficulties, extreme tiredness, and weight gain.
More severe side effects are possible too and can include severe skin reactions and birth defects in babies if the medicine is taken during pregnancy. Complications might also stem from surgery to remove the tumor. These could include getting an infection, bleeding inside or outside the skull, buildup of cerebrospinal fluid in the brain after surgery causing swelling (hydrocephalus), new neurological problems, seizures that continue after surgery, damage to the surrounding brain structures such as nerves or blood vessels, swelling of the brain, and, in the worst case, death.
Common side effects:
- Irritability
- Dizziness
- Drowsiness
- Blurred vision
- Difficulty with coordination
- Generalized fatigue
- Weight gain
- Severe skin reactions
- Congenital disabilities if taken during pregnancy
- Infection after surgery
- Intracranial and extracranial bleeding
- Postoperative hydrocephalus
- New neurological deficit
- Lack of seizure control
- Injury to nearby cranial nerves or blood vessels
- Cerebral edema and brain swelling
- Death
Preventing Neuronal Brain Tumors
For patients suffering from epilepsy related to tumor, it’s crucial to understand the measures to prevent seizures and how to avoid any injuries that might happen during a seizure. Family members also need to be informed about recognizing a seizure when it happens and what steps need to be taken afterward. Furthermore, if patients with brain tumors notice any new symptoms related to the nervous system, this could indicate changes to the tumor and their healthcare provider should be contacted immediately.
