What are the other Names for this Condition? (Also known as/Synonyms)

• Benign Subependymoma
• Subependymal Glioma

What is Subependymoma? (Definition/Background Information)

• A Subependymoma is a type of brain tumor. A brain tumor may be described as a mass of abnormally growing cells arising from the brain tissue (brain parenchyma and meninges) or the spinal cord (central spine). The brain along-with the spinal cord constitute the central nervous system (CNS) of the body
• Broadly, brain tumors are classified as benign (non-cancerous) and malignant. Malignant tumors are cancerous and can spread or metastasize to other regions of the body. They generally exhibit rapid growth and, in some cases, may present symptoms during the early stages of development
• The World Health Organization (WHO) classifies central nervous system tumors according to their grade and histological subtypes. A tumor subtype is determined by a pathologist after examining a tissue biopsy of the tumor under the microscope. This WHO classification system is used by healthcare professionals all over the world in diagnosing and treating these tumors
• Ependymoma is a slow-growing glioma of the brain and spinal cord arising from ependymal cells. The ependymal cells line the walls of the ventricles. Ependymomas are commonly observed in children and young adults; although, a much wider age group of individuals may be affected. Per WHO, the tumor forms a part of group called “ependymal tumors”
• Subependymoma may be described as an uncommon subtype of ependymoma. A vast majority of these slow-growing tumors are found attached to the ventricular walls of the brain. The ventricles of the brain are a network of cavities within the brain tissues that produce and transport cerebrospinal fluid (CSF) within the central nervous system. The ventricles and the CSF that they hold together, act as a shock absorber for the brain protecting it from head injuries
• Subependymoma is a benign tumor that is usually observed in middle-aged and older adults. It is a WHO grade I brain tumor, meaning that is designated as “low-grade”. Grade I tumors are the most benign of the tumors. They are slow-growing and are not known to infiltrate into the surrounding tissues. They offer a very high chance for surgery to be curative; and thus, have the best prognosis among all brain tumors with long-term survival being noted
• The cause of formation of Subependymoma is not well-established. It is reported that a combination of several factors may play a role in their formation, including genetic, environmental, and lifestyle-related. The risk factors may include the presence of certain genetic disorders, exposure to ionized radiation, viral infections, and even head trauma
• In many individuals, Subependymoma is not known to present any symptoms. The signs and symptoms usually arise from large-sized tumors that cause obstruction of CSF flow in the ventricles, resulting in headaches, nausea and vomiting, gait instability, and poor muscle coordination. Obstructive hydrocephalus is also associated with loss of balance, dizziness, memory loss, dementia, and seizures. Complications may develop during/from the treatment too
• The treatment modalities may include surgery and radiation therapy; in many cases, radiotherapy is recommended following a surgical removal of the tumor. The prognosis for individuals with Subependymomas depend on a wide variety of factors, including the size of the tumor, age and overall health status of the individual. In most cases, the prognosis is excellent, since it is a benign low-grade tumor (grade I). Among all ependymal tumors, Subependymomas have the best prognosis

Who gets Subependymoma? (Age and Sex Distribution)

• Ependymomas constitute approximately 3-10% of all primary tumors of the central nervous system; around 8% of all ependymomas are Subependymomas
• Individuals of a wide age range are affected, although these tumors are only occasionally diagnosed in children. Most cases are noted during middle-age and old age
• Males have a slightly higher risk of developing these tumors than females
• Worldwide, individuals of all racial and ethnic groups may be affected; Caucasians are at a greater risk for developing this form of brain tumor

What are the Risk Factors for Subependymoma? (Predisposing Factors)

The risk factors for the development of Subependymomas are mostly unknown.

• Some ependymomas are observed in the background of a familial genetic condition called neurofibromatosis type 2 (NF2)
• Some research shows that smoking during pregnancy may increase the risk for the child developing some forms of ependymomas

In general, the following factors may increase one’s risk for central nervous system tumors:

• Advancing age is an important risk factor; although, some tumors are common among children
• In general, males are at a higher risk for brain tumors than females
• Positive family history: It is reported that certain genetic (hereditary) factors are responsible for the formation of certain brain tumors. Such hereditary conditions include:
  • Li-Fraumeni syndrome
  • Neurofibromatosis type 1 (NF1)
  • Tuberous sclerosis
  • Turcot syndrome
  • Von Hippel-Lindau disease
• Environmental factors such as ionized radiation exposure (both high-dose and low-dose)
• Individuals who have undergone radiation therapy for other cancers involving the head and neck region are at an increased risk
• Viral infections involving pathogens, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), have been implicated
• Exposure to certain chemicals, pesticides, or products, either at work or at home
• Some reports indicate that the use of mobile phones may increase one’s risk due to exposure to electromagnetic waves. However, the scientific research community is presently divided on this factor
• Head injuries
• History of seizures
• Hormonal factors: Studies have shown a correlation between hormones and some types of brain tumors
• Intake of N-nitroso compounds, either in one’s diet (such as cured meat) or via vitamin supplements may increase one’s risk

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Subependymoma? (Etiology)

The exact cause of development of Subependymoma is not well-understood. Research scientists believe that the cause may involve a combination of several factors including genetic, environmental, and occupational factors.

In general, it is known that cancers form when normal, healthy cells begin transforming into abnormal cells - these cancer cells grow and divide uncontrollably (and lose their ability to die), resulting in the formation of a mass or a tumor.

What are the Signs and Symptoms of Subependymoma?

The signs and symptoms of central nervous system tumors may be significantly different from one individual to another. It may be mild or severe, depending on several factors. The onset of symptoms and speed of progression of the tumor can vary. In many individuals, tumors that grow slowly and remain asymptomatic, are only diagnosed during certain radiological imaging studies of the head and neck region, which are performed for unrelated health conditions. In many cases, Subependymomas are discovered incidentally.

The signs and symptoms primarily depend on the location and size of the Subependymoma. This tumor may develop in any part of the brain or spinal cord; although predominantly, involvement of the ventricular system of the brain is noted.

• 50-60% of the tumors involve the fourth ventricles
• And, 30-40% of them develop in the lateral ventricles
• Rarely, tumors involve the cervical spine

In many individuals, the tumors are well-defined and less than 2 cm in size at presentation/diagnosis. Hence, usually, no signs and symptoms are reported. Asymptomatic tumors usually involve the brain; generally, more symptoms are observed in spinal cord tumors.

Due to tumor involvement of the brain ventricles, obstruction of the free flow of cerebrospinal fluid (CSF) may take place leading to increased intracranial pressure, which may result in a set of associated symptoms.

The signs and symptoms of a Subependymoma may include:

• Increased intracranial pressure due to obstruction of CSF drainage, resulting in nausea, vomiting, headaches, and seizures
• Obstruction of the CSF also leads to increased size of the head and associated complications, a condition termed as obstructive hydrocephalus
• Headaches that may be persistent and increasing in intensity; it is observed in 90% of the individuals
• Numbness and tingling sensation
• Visual impairment such as blurred vision, double vision or poor eyesight
• Muscle weakness; loss of strength in the arms of legs, usually on one side of the body
• Fatigue and lethargy
• Lack of coordination; unsteadiness and loss of balance (vertigo)
• Ringing in the ears
• Hearing impairment or hearing loss
• Speech problems
• Dizziness and fainting
• Tremors
• Confusion
• Changes in one’s behavior; personality changes
• Mental impairment
• Memory loss

In case of spinal cord involvement, the following may be noted:

• Itching of skin around the tumor site
• Neck pain
• Numbness and tingling sensation
• Weakness of the body or lower extremities; loss of strength in the arms of legs
• Pain in the arms and legs, depending on the nerves that are compressed by the tumor
• Severe cases may result in loss of bowel and bladder control; typically observed in lower spine ependymomas
• Sexual dysfunction is also observed in many cases

Large tumors cause significant signs and symptoms. Most of the tumors are single; but occasionally, multiple tumors can be detected growing simultaneously in the brain or spinal cord region, particularly in individuals with genetic disorders. The associated symptoms of the underlying condition, if any present, may be noted.

How is Subependymoma Diagnosed?

Subependymomas, especially those involving the brain, may remain undiagnosed for prolonged periods, because they are slow-growing and generally asymptomatic. The tumors are detected when there is a sudden worsening of the symptoms prompting the healthcare provider to perform radiological studies of the brain and/or spinal cord.

The diagnosis of Subependymoma may involve the following tests and examinations:

• Complete physical examination with thorough evaluation of the individual’s medical history (including family history of any genetic disorder)
• Assessment of the presenting signs and symptoms
• Visual field tests; tests to assess visual acuity
• Neurological, motor skills, and cognitive assessment:
  • Checking intellectual ability, memory, mental health and function, language skills, judgment and reasoning, coordination and balance, reflexes, sensory perceptions (space, sight, hearing, touch)
  • The healthcare provider/neurologist may use the Karnofsky Performance Scale in order to assess the neurological functioning of the individual’s central nervous system (CNS)
• Electroencephalography (EEG)
• Electromyography with nerve conductivity tests
• Imaging studies that may be performed include:
  • X-ray of head and neck
  • Computerized tomography (CT) scan of the head and neck region; CT with contrast - the scans may reveal calcifications
  • Magnetic resonance imaging (MRI) scan of the central nervous system (brain and spine); MRI with contrast agents such as gadolinium
  • Cerebral angiographic studies or MR angiography: An angiogram involves injecting dye into the bloodstream, which makes the blood vessels to appear visually on X-rays. The X-ray may show a tumor in the brain or the blood vessels leading into the tumor
  • Magnetic resonance spectroscopy: This radiological technique is used to study the chemical profile of the tumor. It is often performed with and compared to corresponding MRI scan images of the affected region
  • Positron emission tomography (PET scan): A PET scan is a nuclear medicine imaging technique that uses three-dimensional images to show how tissue and organs are functioning. It may be performed to detect any malignancy, and if there is a metastasis (spread) of the tumor to other regions
• Cerebrospinal fluid analysis, where a spinal tap or lumbar puncture procedure may be performed: This diagnostic test is used to remove a sample of cerebrospinal fluid (CSF) from the spaces in and around the brain and spinal cord. The sample is removed from the lower spinal cord using a thin needle, and it is then checked for the presence of cancer cells
• Molecular testing to detect genetic defects or chromosomal abnormalities, if necessary

Tissue biopsy: A biopsy of the affected region is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy sample under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy sample under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis.

There are two ways to perform a biopsy:

• First, a biopsy can be performed as part of a surgical procedure to remove the brain tumor
• Second, a stereotactic needle biopsy can be performed when the tumor is deep within the brain or located in a sensitive area. In this procedure, the surgeon drills a small hole (called a burr hole) into the skull. A thin needle, guided by CT or MRI scanning, is then inserted through the hole to help in the removal of tissue

A differential diagnosis to eliminate other conditions or tumor types may be considered, before arriving at a definitive diagnosis. These include:

• Cavernous malformations
• Central neurocytoma
• Choroid plexus papilloma
• Ependymoma
• Hemangioblastoma
• Metastatic tumors to the brain or spinal cord
• Subependymal giant-cell astrocytoma (SGCA)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Subependymoma?

The possible complications associated with Subependymoma include:

• Emotional and mental stress for both the patients and the caretakers, due to the diagnosis and treatment of a brain tumor
• Large undetected tumors can severely affect brain function and be disabling or even life-threatening, due to mass effect/compression of brain tissue
• Large tumors may also press against the skull (or other) bones causing it to expand, causing severe complications
• Trouble with concentration
• Severe loss of memory
• Severe intellectual disability; dementia including personality changes causing a reduced quality of life
• Severely affected physical and mental health may lead to the overall quality of life being greatly reduced
• Peritumoral brain edema (PTBE): Presence of fluid around the tumor region in the brain resulting in severe symptoms and complications
• Complications due to an underlying genetic disorder, if any present

Complications may arise from surgery, radiation therapy, chemotherapy, or other treatment modalities. These may lead to long-term side effects, particularly in children and older adults.

Surgical complications:

• Damage to the muscles, vital nerves, and blood vessels, during surgery to remove the tumor; injury to unaffected brain tissue during surgery
• Post-surgical infection at the wound site is a potential complication
• Sometimes, removing the tumor can worsen the signs and symptoms in some individuals
• In very few cases, the recurrence of Subependymoma after surgery is observed. The risk for recurrence is generally low

Chemotherapy side effects depend on the type of chemotherapy medication used and may include:

• Nausea and vomiting
• Hair loss
• Mouth sores
• Loss of appetite
• Diarrhea
• Fatigue
• Increased risk for infections
• Easy bruising
• Infertility

Radiation therapy can cause short-term side effects. It depends on the type used and may include:

• Nausea and vomiting
• Hair loss
• Dryness of mouth; loss of taste
• Headaches
• Fatigue
• Skin color changes; usually darkening of skin on the face and neck may be noted
• Speech and hearing difficulties
• Memory issues
• Seizures

Many children treated with radiation to large areas of the brain are affected by learning disabilities and decreased intellect. These detrimental effects are often worse in the following cases:

• Younger children
• Patients, who have had large doses of radiation
• Patients, who have had radiation to large areas of the brain

Radiation can also damage the hormone-producing hypothalamus and pituitary gland, retarding a child’s growth. It can also lead to a weakening of the muscles close to the spine.

Long-term side effects of radiation therapy (seen after 6 months or beyond) may include loss of memory, impaired brain function, and appearance of symptoms that mimic stroke. Radiation and chemotherapy may increase the chance of developing other brain and spinal cord tumors/cancers.

How is Subependymoma Treated?

The treatment modality for central nervous system tumor is chosen, depending on the type, size, location, and stage of the tumor, tumor growth rate, age and health status of the individual. Often, a multidisciplinary team of specialists including neurologists, oncologists, surgeons, radiation therapy experts, and other healthcare professionals are involved in managing the condition.

The treatment measures for Subependymoma may include:

• Symptomatic treatment may involve the use of antiseizure medications, painkillers, steroids (to reduce inflammation), and administration of anti-depressants
• Placement of ventriculoperitoneal (VP) shunt: It is an invasive procedure that involves the use of a medical device called a VP shunt. The device is placed in the ventricles of the brain to treat hydrocephalus, and thus helps relieve excess CSF pressure on the brain

Surgical treatment: Surgery to remove the entire tumor or just part of the tumor depends on several factors including the risk assessment by a neurosurgeon, with respect to the potential injury to nearby brain tissues. It is also considered based on the location, size, and overall health of the individual. A complete removal of the tumor can result in a cure in many patients. Although, in many cases, removal of the tumor offers a lot of surgical challenges to the healthcare providers, due to the complexity of the tumor site involved.

The following surgical techniques may be employed:

• Craniotomy: It is a surgical procedure wherein a tiny hole is created in the cranium to access and remove the tumor. The main goal of surgery is to remove as much tumor as possible without damaging the surrounding brain tissue
• In some individuals, the tumor is partially removed, so as not to cause brain damage, resulting in unwanted additional symptoms. A partial removal is usually considered in slow-growing grade I benign tumors
• Microsurgery: The surgery is performed using microsurgical techniques, which can help minimize damage to the accompanying nerve. Since the tumor mostly affects the covering around the nerves, it can be completely removed without affecting the nerve in most cases. The following techniques may be employed:
  • Subtotal removal; when the tumor is incompletely removed
  • Near total removal; when most of the tumor is removed and there is very little tumor remnants
  • Total tumor removal; when the tumor is removed completely
• Osteoplastic laminotomy: It is a minimally-invasive procedure to treat spinal cord tumors. The technique also helps minimize post-operative complications and provides increased spinal stability. If necessary, osteoplastic laminotomy may be followed up by a spinal column reconstruction procedure
• Laminectomy: An invasive procedure that is performed to relieve compression on the spinal cord or spinal nerves, caused by the tumors, by widening the spinal canal through removal of the laminae (part of the vertebra)
• In some cases, embolization of the tumor may be performed, in order to shrink the tumor size, before major invasive procedures are undertaken. In embolization, the blood supply to the tumor is cut-off, resulting in its shrinkage. This also helps reduce blood loss during a surgical resection
• Radiosurgery may be used for individuals who cannot undergo surgery or have recurrent tumors
• Post-operative care is important: One must maintain minimum activity levels, until the surgical wound heals

Surgical procedures to remove brain tumors carry risks, including infection, possible damage to healthy brain tissue, swelling, or possible fluid build-up in the brain.

Radiation therapy: There are a variety of radiation therapy methods that can be used to treat the tumors. Radiation therapy is performed either after removal of the tumor (to destroy any remaining meningioma cells), or in individuals where surgical removal procedure is not an option. Radiation therapy is helpful to reduce the rate of recurrence. It is especially recommended for individuals where the tumor is removed partially.

• Healthcare providers usually recommend that both adults and children receive radiation therapy, mostly regardless of the fact whether the tumor was fully removed or not
• Localized tumors are treated with localized radiation, while tumors that have spread outside the region are treated with full brain and spine radiation and extra radiation (called a boost), applied to the location where the tumor originated

The types of radiation therapy include:

• Standard external radiation beam therapy using a beam of high-energy X-rays; it is the most common form of radiation therapy used to treat cancers
• 3-dimensional conformal radiation therapy, where 3-d images of the tumor are created using radiological imaging scans to help design appropriate radiation therapy beam size and angles
• Intensity modulated radiotherapy (IMRT): It is a procedure that uses computer-controlled linear accelerators to deliver precise radiation to a malignant tumor
• Stereotactic radiosurgery using Gamma Knife or CyberKnife technique. It is usually reserved for use in ependymomas that have grown back after typical radiation therapy
• Proton radiation therapy: It is a form of external beam therapy using high-energy proton beams to destroy the tumor cells
• Fractionated radiation therapy: It is a good option for individuals whose tumors are too large for radiosurgery, or if the tumor is in a sensitive location. In this therapy, small doses of radiation are administered for a certain set period

Some individuals may experience a few side effects, while others may experience none. These may include fatigue, headaches, hair loss, and scalp irritation. Radiation therapy beams may affect the pituitary gland causing it to dysfunction (bringing about hormonal changes in the body).

Chemotherapy: The response of the tumor to chemotherapy is an important consideration while using this treatment modality. Chemotherapy may not be recommended as a treatment option for treating some tumors.

• It may be beneficial in individuals diagnosed with higher grade tumors. Whether to use chemotherapy as a treatment modality is determined by healthcare provider on case-by-case basis
• Chemotherapy may be administered for those tumors that cannot be effectively treated by surgery or radiation therapy. The administration of some drugs may slow the rate of growth of the tumor

The following chemotherapy agents and methods have been used in higher grade tumors with varying beneficial results:

• Immunotherapy to stimulate an affected individual’s immune system
• Somatostatin analogs which prevent the release of growth hormones
• Hydroxyurea, epidermal growth factor receptor inhibitors, platelet-derived growth factor receptor inhibitors, and vascular endothelial growth factor inhibitors

There are side effects for chemotherapy, which depends upon the type and dose of drugs administered. The common chemotherapy side effects include nausea, vomiting, hair loss, loss of appetite, headache, fever, chills, and weakness. Platinum-based chemotherapeutic drugs, such as cisplatin, as well as radiation, delivered close to the ears, often result in hearing loss.

Clinical trials: In certain advanced stage tumors, there may be some newer treatment options, currently on clinical trials, which can be considered for some patients depending on their respective risk factors. Physicians may recommend standard or experimental chemotherapy, as part of a clinical trial in tumors that grow back after radiation therapy.

Regular observation and periodic checkups to monitor the condition is strongly recommended following treatment. In order to avoid a relapse, or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, healthcare recommendations post-treatment, etc. should be well-documented and follow-up measures initiated.

How can Subependymoma be Prevented?

Presently, there are no specific methods or guidelines to prevent the formation of Subependymoma type. However, if it is associated with a genetic disorder, the following points may be considered:

• Genetic counseling and testing: If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Regular health check-ups might help those individuals with a history of the condition in the immediate family and help diagnose the tumor early

In general, the factors that may help reduce the incidence of brain tumor may include:

• Reducing exposure to ionizing radiation
• Avoiding cigarette smoke inhalation
• Weight loss, in case one is obese or overweight; maintaining a good BMI
• Availing early treatment for infections
• Using safety gear including wearing helmets when playing sports or while riding two-wheelers
• Wearing seatbelts while driving automobiles to minimize the risk for head/body injury

According to the U.S. Preventive Services Task Force (USPSTF), currently there is no standard testing protocols available for brain tumor.

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Subependymoma? (Outcomes/Resolutions)

The prognosis of Subependymoma may vary considerably from one individual to another and is dependent on a set of factors. In a vast majority of cases, the prognosis of individuals with the tumor is excellent, since it is a benign and slow-growing tumor with low recurrence rates. However, some may have disabilities following treatment (surgery), which may be short-term.

• The key prognostic indicators are the age of the individual, location of the tumor, and possibility of complete surgical resection of the tumor
• Individuals treated with both surgery and radiation, have a better prognosis, than those who have had surgery alone
• Individuals with spinal ependymomas usually have better prognoses, since the location of the tumor often allows for a complete excision of the tumor

In general, the prognosis may depend upon several factors, which include:

• Tumor histology or grade of the tumor: The lower the grade, the better is the prognosis
• Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
• Age of the individual: Older individuals generally have poorer prognosis than younger individuals
• Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
• The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
• Location of the tumor is an important prognostic factor: Tumors at certain sites involving the central nervous system are more difficult to surgically excise and remove. They can also cause considerable neurological damage at certain sites in the brain and/or spinal cord. Tumors located near vital structures of the brain have poor prognosis
• Tumors that are slow-growing have better prognosis than rapidly-growing tumors
• Presence of certain genetic abnormalities may result in a rapid progression of tumor growth and development
• Sporadic tumors have generally better prognosis than syndromic tumors; tumors in a background of genetic disorders/syndromes may have additional complications
• The ease of accessibility and surgical resectability of the tumor (meaning, if the primary tumor can be removed completely). This is an important prognostic factor
• Extent of residual tumor in the body following a surgical resection: A complete surgical excision with entire tumor removal presents the best outcome. In some cases, large portions of the tumor may be removed; or, only a small portion for tissue biopsy
• Individuals with bulky disease may have a poorer prognosis
• Involvement of other vital organs may complicate the condition
• Metastatic spread: Spread of the malignancy to other body sites portrays a poorer prognosis
• Whether the tumor is occurring for the first time or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur 
• Response to treatment and absence of post-operative complications: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
• Progression of the condition makes the outcome worse
• Functional neurologic status based on neurological evaluation of the patient: A higher score on the Karnofsky Performance Scale may indicate more favorable outcomes

An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment.

Additional and Relevant Useful Information for Subependymoma:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/cancer/