Glioma causes, stages, diagnosis and treatment methods

Glioma is a type of tumor that originates in the brain cells and is one of the most common tumors found in the central nervous system. Although its symptoms can vary from person to person, early diagnosis and proper management of the disease are crucial factors in improving treatment outcomes. With advancements in medicine, there are now various therapeutic approaches that can help reduce the effects of the tumor, such as surgery, chemotherapy, radiation therapy, and targeted drugs. However, despite progress in treatment, many challenges remain for patients during their treatment journey, including side effects that may impact their quality of life. In this guide, we will provide comprehensive information about glioma, its causes, symptoms, diagnostic methods, and available treatment options, helping us better understand the disease and how to manage it.

Glioma is a type of tumor that originates from glial cells, which are the cells that support and protect nerve cells in the central nervous system. These tumors typically start in the brain or spinal cord (primary brain tumor), and while they can spread within the central nervous system, they are usually confined to the brain.

Prevalence of Glioma: Gliomas account for about 25% of primary brain tumors and central nervous system tumors in general, with 81% being malignant. Glioblastoma is the most common subtype, making up around 58% of cases. Gliomas are the most common malignant brain tumors, affecting approximately 3.23 people per 100,000. While gliomas are more common in older individuals, some subtypes, such as pilocytic astrocytoma, are more frequently seen in children.

Causes and Risk Factors for Glioma:

1. Genetic Mutations: Genetic mutations are changes in the DNA of cells. If mutations occur in the genes that control cell growth or natural cell death, this may lead to the development of a glioma. Some genetic mutations may be present from birth (inherited), while others may occur over time due to external factors.

2. Genetic Factors: In some families, there may be a genetic predisposition to gliomas. If someone in the family has a glioma, it could increase the likelihood of other family members developing the disease. Certain inherited diseases, such as neurofibromatosis, can also increase the risk of glioma.

3. Radiation Exposure: Long-term or high-dose radiation exposure can increase the risk of developing gliomas. This includes radiation exposure from cancer treatments or from radiation sources in the workplace. Childhood radiation exposure may also increase the risk of glioma later in life.

4. Environmental Factors: Some studies suggest that exposure to certain chemicals or environmental factors might play a role in increasing the risk of gliomas, such as chemicals found in workplaces or pollution.

5. Hormonal Factors: Some studies suggest hormonal changes could be linked to glioma growth, but this remains under investigation.

6. Brain Injuries: Severe brain injuries, such as those resulting from accidents or fractures causing bleeding in the brain, may be linked to a higher risk of glioma. However, there is not enough strong evidence to confirm this connection.

7. Unknown Factors: In some cases, no clear cause for glioma development can be identified, and this is often the case. Gliomas can develop suddenly without any previous medical history.

Types of Glioma:

1. Astrocytoma: This is the most common type of glioma, originating from "astrocytes" – star-shaped cells. This type ranges in severity from benign to malignant. It can be in its early stages or develop into a malignant tumor. In advanced stages, it becomes difficult to treat.

2. Oligodendroglioma: This tumor originates from "oligodendrocytes," cells that help coat and protect nerve fibers. These tumors can be benign or malignant and are generally less aggressive than other types.

3. Glioblastoma Multiforme: One of the most aggressive and fastest-growing gliomas, glioblastoma combines characteristics of both astrocytoma and oligodendroglioma. This tumor grows rapidly and is challenging to treat, often diagnosed at an advanced stage.

4. Ependymoma: A rarer type of glioma that occurs in areas of the brain and spinal cord responsible for producing cerebrospinal fluid. It tends to appear in the spinal cord or around the brain’s ventricles.

5. Pilocytic Astrocytoma: A less aggressive type of astrocytoma, typically found in children or young adults. It grows slowly and is generally treatable.

Tumor Grade Description:

Grade 1: These tumors are made up of slow-growing cells and are the least malignant. They are associated with the highest survival rates.

Grade 2: These tumors consist of relatively slow-growing cells but are still capable of invading normal tissue. Over time, these tumors can become malignant.

Grade 3: These tumors contain actively proliferating cells that invade normal brain tissue. Even if surgically removed, these tumors tend to progress to a higher grade.

Grade 4: These tumors are composed of rapidly multiplying cells and are abnormal in structure. They are the most malignant types of tumors (often referred to as brain cancer); they can also form new blood vessels to continue growing and invade surrounding neural tissue.

Low-grade gliomas (such as Grade 2) may progress to a higher, more dangerous grade over time. In addition to classifying the malignancy grade (or aggressiveness) of the tumor, gliomas are also classified based on the type of cells from which they originate.

Astrocytic Cells: These star-shaped cells play a crucial role in nourishing nerve cells and maintaining the chemical balance in the brain. Two types of tumors can arise from astrocytic cells:

• Astrocytoma: The most common type of glioma, often occurring in the brain, though sometimes it can appear in the spinal cord.
• Glioblastoma: The most malignant and rapidly invading type of astrocytoma (Grade 4), glioblastoma is the most common primary brain tumor among adults and is also referred to as "multiforme" glioblastoma or brain cancer.

Ependymal Cells: These cells line the cavities of the brain and spinal cord and produce cerebrospinal fluid (CSF), which protects the central nervous system and helps in transporting nutrients and waste.

• Ependymoma: A rare type of glioma, most commonly seen in children. In adults, these tumors are typically found in the spinal cord, but in children, they are more likely to occur at the brain’s base. Cancerous cells can spread through CSF to other parts of the brain or spinal cord.

Oligodendrocyte Cells: These brain cells produce myelin, which is the substance that covers the nerve fibers (the "wires" that connect brain cells) to speed up the transmission of electrical signals.

• Oligodendroglioma: A rare glioma type, representing about 10% of primary brain tumors. Adults are more prone to this type, and it is diagnosed more often in men than in women.

Mixed Gliomas: These tumors are composed of a variety of glioma cell types, such as astrocytic or oligodendrocyte cells. More than one type of cell may be present in the tumor, but generally, one type of glioma cell predominates in the tumor.

Recovery Prognosis:

The prognosis for recovery from gliomas largely depends on the tumor’s grade, size, and location. Other important factors include the patient’s age, mental and functional status, and the extent to which surgery can remove the tumor.

Prognosis by Tumor Grade:

1. Grade 1 (Pilocytic Astrocytoma): These tumors generally have an excellent prognosis. Studies show that the 5-year survival rate is around 95%.

2. Grade 2 (Astrocytoma, Oligodendroglioma, Mixed Astrocytoma and Oligodendroglioma): These tumors are harder to predict, as they can develop into Grade 3 or Grade 4 tumors even with treatment. The infiltrative nature of Grade 2 tumors (and also Grade 3 and 4) increases the likelihood of recurrence.

3. Grade 3 (Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Mixed Anaplastic Astrocytoma and Oligodendroglioma): These tumors are more aggressive and have a high probability of recurrence. Some patients may live longer after tumor resection through surgery and adjunct therapies like radiation and chemotherapy.

4. Grade 4 (Glioblastoma Multiforme): These tumors are the most aggressive, and the maximum survival period tends to be 1 to 2 years.

How Is Glioma Diagnosed?

1. Medical History and Physical Examination: The first step is for the doctor to inquire about the symptoms you're experiencing. If you have persistent headaches, balance issues, muscle weakness, or seizures, the doctor will ask about your medical history and any similar conditions in your family. A physical examination is then performed to check for any abnormal neurological signs, such as weakness in limbs or issues with coordination and movement.

2. CT Scan (Computed Tomography): A CT scan is one of the first diagnostic tests done to detect brain tumors. It uses X-rays to create cross-sectional images of the brain. While it can identify the presence of a tumor, it may not always be sufficient to determine the exact type of tumor.

3. MRI (Magnetic Resonance Imaging): MRI is a more detailed test compared to CT scans. It uses a strong magnetic field and radio waves to produce highly detailed images of the brain. MRI is better at showing the size and location of the tumor. There is a type of MRI called "contrast MRI," where a contrast dye is injected into a vein to help distinguish the tumor more clearly.

4. Functional MRI (fMRI): This advanced MRI type is used to identify the areas of the brain involved in specific activities like movement or speech. It helps to precisely locate the tumor and preserves important brain areas during treatment.

5. PET Scan (Positron Emission Tomography): PET scans use low radiation to measure the chemical activity in the brain. Gliomas tend to show up on PET scans because of the high cellular activity in the tumor area. While PET scans aren't typically used for initial diagnosis, they are valuable for assessing tumor spread once it is confirmed.

6. Biopsy: In most cases, a definitive diagnosis of glioma requires a tissue sample from the tumor. A biopsy is performed through a minor surgical procedure, where a sample is taken from the tumor and examined under a microscope. In some cases, a less invasive biopsy can be done using a needle guided by imaging.

7. Genetic Testing: After obtaining the sample, doctors may conduct genetic testing to study any genetic changes in the cells. This helps in identifying the tumor type more precisely and selecting the most suitable treatment.

8. Other Tests: If the doctor suspects additional concerns or needs precise clarification, they may request other tests such as a cerebrospinal fluid (CSF) analysis (which involves taking a sample of the fluid surrounding the brain and spinal cord) or neurological tests to assess nerve function.

9. Final Diagnosis: After gathering all test results, the doctor can accurately diagnose the type of glioma. This is critical for determining the best treatment approach, whether surgical, radiation, chemotherapy, or a combination of these.

Symptoms of Glioma

1. Persistent Headaches: This is one of the most common symptoms of gliomas. The headaches are usually very severe and may occur at specific times of the day, such as in the morning or at night. They may also be accompanied by nausea and vomiting, especially if the tumor is pressing on certain areas of the brain, such as the region responsible for coordination or balance.

2. Seizures: Seizures are common in people with gliomas. They occur due to disturbed electrical activity in the brain caused by the tumor. Seizures can vary from person to person and may range from mild, like small twitches, to severe seizures.

3. Weakness or Numbness in Limbs: A glioma may affect the nerves responsible for movement and sensation in certain parts of the body. This can result in weakness or numbness in the arms or legs, typically on one side of the body (the side affected by the tumor).

4. Balance and Walking Issues: If the tumor is located in the area of the brain responsible for balance (such as the cerebellum), the person may have difficulty walking or maintaining balance. Movements may become uncoordinated, and the person may feel dizzy and have difficulty moving normally.

5. Vision or Hearing Changes: A tumor affecting the area of the brain responsible for vision (such as the occipital lobes) may cause vision problems, such as partial loss of the visual field or blurred vision. If the tumor presses on the parts responsible for hearing, the person may experience partial or complete hearing loss.

6. Changes in Personality or Behavior: Gliomas affecting the areas of the brain responsible for thinking and personality (such as the frontal lobe) can lead to changes in personality or behavior. The person may display mood disturbances, emotional changes, or even a loss of decision-making ability.

7. Memory and Concentration Problems: A glioma affecting the frontal or temporal lobes may cause difficulty with memory or concentration. The person may struggle to remember recent events or focus on daily tasks.

8. Nausea and Vomiting: Due to pressure on specific areas of the brain responsible for controlling nausea and vomiting (such as the brainstem), the person may experience persistent nausea or vomiting, especially in the morning.

9. Speech and Swallowing Changes: If the tumor affects areas responsible for speech or swallowing, the person may have difficulty pronouncing words correctly or swallowing food.

10. Increased Intracranial Pressure: The tumor may cause increased pressure inside the skull, leading to symptoms such as:

• Confusion
• Dizziness
• Difficulty breathing
• Movement disorders

11. Hydrocephalus (Increased Fluid Pressure in the Brain): The tumor may cause a blockage in the pathways of cerebrospinal fluid, leading to fluid buildup in the brain and increased intracranial pressure. This can cause symptoms such as severe headaches, nausea, and vomiting.

Groups at Higher Risk for the Disease

• People with a Family History of Gliomas: If a family member has been diagnosed with a glioma or other brain tumors, this increases the likelihood of other family members developing a glioma.

People with Certain Genetic Diseases:

1. Neurofibromatosis: This is a genetic disorder that increases the likelihood of developing gliomas. Individuals with this condition are more prone to brain and spinal cord tumors.

2. Li-Fraumeni Syndrome: This genetic disorder causes problems with the genes that repair cells, increasing the risk of various tumors, including gliomas.

People Exposed to Radiation:

1. Radiation Therapy: People who have undergone radiation therapy for cancer, especially if the treatment was directed at the brain, have a higher risk of developing gliomas.

2. Chronic Radiation Exposure: Workers in nuclear power plants or those working in the medical radiology field may have a higher risk due to continuous radiation exposure.

People with Weakened Immune Systems:

• Individuals with weakened immune systems, whether due to conditions like HIV or from immunosuppressive medications (e.g., in organ transplant cases), are more susceptible to various types of tumors, including gliomas.

People Aged 45 to 70:

• Gliomas are more common in individuals between the ages of 45 and 70. As people age, the likelihood of genetic mutations in cells increases, which raises the risk of glioma development.

Men More Than Women:

• Studies show that men are more likely to develop gliomas than women, though the difference is not significant. The causes may be related to hormonal or environmental factors.

People with Brain Injuries:

• Individuals who have sustained severe brain injuries from accidents or falls may have a higher risk of developing gliomas. Although the connection between brain injuries and gliomas is not strong, some studies suggest that injuries may increase the risk.

People with a History of Certain Neurological Diseases:

• People with chronic neurological diseases like multiple sclerosis (MS) may be at a greater risk of developing gliomas later in life.

Exposure to Certain Chemicals:

• People exposed to certain chemicals or environmental pollutants in their workplaces, such as industrial chemicals or environmental toxins, may have an increased risk of gliomas. However, this is still under investigation and study.

Treatment Options for Gliomas

The treatment of gliomas depends on the type, size, location, and grade of the tumor. Typically, surgery is the first step in treatment, followed by radiation and chemotherapy, especially for high-grade tumors.

Observation

In some cases, if the tumor is relatively benign, small, or located in a very dangerous area (where surgery could cause damage to brain functions), the doctor may opt for observation and follow-up rather than immediate intervention.

Surgery

Surgery is usually the first treatment option. The goal is to remove as much of the tumor as possible while avoiding damage to healthy brain tissue. For low-grade gliomas, surgery may be sufficient if the tumor is not highly aggressive. However, for more aggressive tumors like glioblastomas, surgery is not always enough because the tumor invades surrounding tissue, making complete removal difficult.

Radiation Therapy

After surgery, radiation therapy is often the second step, especially for high-grade tumors. Fractionated radiation therapy is the most common, where the patient receives small doses over several sessions. Modern techniques, such as intensity-modulated radiation therapy (IMRT), allow for more precise targeting of the tumor while preserving healthy tissue.

Radiation does not remove the tumor but can shrink it or prevent its growth. Ongoing monitoring through regular follow-ups is necessary to check if the tumor starts growing again.

Chemotherapy

Chemotherapy uses drugs to kill tumor cells and is typically used alongside surgery and radiation, especially for high-grade gliomas. Drugs such as Temozolomide (Temodar) and Bevacizumab (Avastin) have shown good results in slowing the growth of glioblastomas. Temozolomide is usually taken in pill form and helps the tumor respond better to radiation. Avastin works by preventing the formation of new blood vessels that supply the tumor with nutrients.

Immunotherapy

Immunotherapy uses antibodies that target cancer cells. This can involve using toxic materials, drugs, or radiation to destroy cancer cells. There are also vaccines containing tumor cells, which help the immune system target and destroy the tumor cells more effectively.

Side Effects of Glioma Treatment

1. Surgical Side Effects: Surgery is a common treatment for gliomas, but it may cause some side effects due to tumor removal, including:

   • Infection: In rare cases, infection may occur at the surgical site, but this is uncommon if proper sterilization protocols are followed.
   • Swelling and Bleeding: Brain swelling or bleeding may occur after surgery.
   • Temporary or Permanent Neurological Issues: Issues like weakness in limbs, loss of sensation, speech or movement difficulties, or vision problems.
   • Memory and Concentration Changes: Patients may experience difficulty concentrating or memory problems due to brain impact.

2. Side Effects of Chemotherapy: Chemotherapy uses potent drugs to kill cancer cells, but it can also affect healthy cells. Some side effects include:

   • Fatigue: Chemotherapy can cause severe fatigue, making daily activities challenging.
   • Nausea and Vomiting: Common side effects, but there are medications to help manage these symptoms.
   • Hair Loss: Chemotherapy can affect healthy hair cells, leading to hair loss.
   • Weakened Immune System: Chemotherapy can suppress the immune system, increasing the risk of infections.
   • Appetite Issues: Patients may lose their appetite or have difficulty eating due to nausea or changes in taste.
   • Anemia: A decrease in red blood cells can cause dizziness and general weakness.
   • Skin Problems: Some chemotherapy drugs may cause dry skin or irritation.

3. Side Effects of Radiation Therapy: Radiation therapy uses high-energy radiation to destroy cancer cells, but it can cause side effects, including:

   • Fatigue: A common side effect causing general tiredness and exhaustion.
   • Skin Changes: Irritation or redness in the area of treatment.
   • Nausea: Especially if the treatment is directed toward the brain.
   • Temporary Hair Loss: Hair loss in the treated area may occur.
   • Neurological Issues: Some patients may experience memory or concentration difficulties.
   • Increased Intracranial Pressure: Radiation may sometimes increase pressure inside the skull, leading to headaches and nausea.

4. Side Effects of Targeted Therapy: Targeted therapy uses drugs that specifically target cancer cells, and side effects may include:

   • Skin Issues: Rashes or dry skin.
   • High Blood Pressure: Some targeted drugs may cause elevated blood pressure.
   • Fatigue: Generalized tiredness and fatigue.
   • Joint Pain: Some patients experience pain in the joints.
   • Liver Problems: Targeted drugs may affect liver function, requiring regular liver tests.

5. Side Effects of Immunotherapy: Immunotherapy stimulates the immune system to attack cancer cells, but it can also cause side effects, including:

   • Skin Reactions: Rashes or skin irritation.
   • Gastrointestinal Issues: Such as diarrhea or nausea.
   • Fever: Some patients may develop a fever.
   • Fatigue: Fatigue is common during immunotherapy.
   • Muscle and Joint Pain: Some patients report muscle and joint aches during treatment.

6. General Side Effects:

   • Anxiety and Depression: Some patients may experience feelings of anxiety or depression due to treatment and health complications.
   • Sleep Problems: Issues such as insomnia or difficulty sleeping due to pain or anxiety.
   • Memory and Concentration Problems: Different treatments may impact focus and memory.

The doctor who treats gliomas is typically an oncologist, specifically a neuro-oncologist. In addition, they may collaborate with a multidisciplinary team that includes:

• Neurosurgeon: A specialist who performs surgeries to remove the tumor.
• Neurologists: To monitor the condition of the nerves and brain functions after treatment.
• Radiation Oncologist: To manage and oversee radiation therapy.
• Medical Oncologist: If chemotherapy is required, they would manage the chemotherapy treatment.
• Immunologists: If immunotherapy is being used, these specialists manage the treatment.
• Rehabilitation Doctors: To provide support post-surgery or after other treatments, such as physical therapy or psychological counseling.