Ependymoma: Key Facts on Symptoms, Risks & Care

Ependymomas are tumors that develop from glial cells in the central nervous system (CNS). They typically form in the ependymal lining of the ventricles, which are spaces in the brain filled with cerebrospinal fluid. Less commonly, these tumors can develop within the brain parenchyma or even outside the CNS. They affect children more commonly than young adults.¹ Amora EA, Alkherayf F. Ependymoma. StatPearls [Internet]: StatPearls Publishing; 2023. Ependymomas appear in 5.2% of childhood CNS brain tumors and 5.2% of all brain tumors in people younger than 20. Ependymomas represent 1.9% of all tumors in adult patients. These tumors may also follow racial disparity. The incidence rate of ependymomas is 0.27 per 100,000 in African Americans while 0.40 per 100,000 in whites.²Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncology. 2016;18(7):902-13.

Ependymomas are tricky because they look similar under a microscope but have important genetic differences (genetic heterogeneity). These genetic variations affect how the tumors grow, respond to treatment, and impact the patient’s outlook.³Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncology. 2016;18(7):902-13.

Types of Ependymomas

The World Health Organization (WHO) classification of CNS tumors is the standard ependymoma classification system. WHO classifies ependymomas into Grades I to III based on their growth rate, behavior, and appearance under a microscope.

Grade I:

Grade I ependymomas include slow-growing and benign neoplasms. This grade consists of both myxopapillary ependymomas and subependymomas. Each type has different locations in the body, plus distinct symptoms and images on scans.

Myxopapillary Ependymomas

They are common in adults, mainly males. They grow in the lower spinal cord, exclusively at cauda equine, filum terminale, and conus medullaris. The uncommon locations include brain parenchyma, lateral ventricle, and cervical and thoracic spinal cord. These patients experience chronic back pain. MRI scans often show a sharp, sausage-shaped mass enhanced by gadolinium contrast.⁴Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncology. 2016;18(7):902-13.

Subependymomas

They typically attach to the ventricle wall. The most commonly involved ventricle is the fourth ventricle, followed by the lateral ventricles according to frequency. They appear as sharp demarcated nodular masses that are non-enhancing on the MRI scans. These ependymomas can be asymptomatic. They can be accidentally discovered at autopsy or during MRI. However, these patients may experience increased intracranial pressure due to ventricular obstruction.⁵Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncology. 2016;18(7):902-13.

Grade II:

These are called classic ependymomas. These tumors are more cellular and form papillary structures. These cells are regularly arranged and present a clear cytoplasm. They most commonly appear in children and adults.⁶ Amora EA, Alkherayf F. Ependymoma. StatPearls [Internet]: StatPearls Publishing; 2023.

Grade III:

They are anaplastic ependymomas. They often grow near the base of the brain and then spread to other parts of the brain. They present abundant mitotic cells along with psuedopalisading necrosis. The anaplastic ependymomas can recur after treatment.⁷ Amora EA, Alkherayf F. Ependymoma. StatPearls [Internet]: StatPearls Publishing; 2023.

Genetic Subtypes of Ependymomas

Ependymomas are divided into three subtypes based on genetic differences:

• Posterior Fossa Ependymomas: Found at the back of the brain.
• Supratentorial Ependymomas: Located in the upper part of the brain, often linked to RELA gene fusion.
• Spinal Ependymomas: Occur in the spinal cord and are often associated with NF2 mutations.

Etiology of Ependymomas

The leading cause of the ependymomas is not known. However, research indicates that several genetic abnormalities in large genomic regions correlate with the formation of ependymomas. These tumors may correlate with distinct oncogenic products and molecular subgroups.⁸Mack SC, Taylor MD. The genetic and epigenetic basis of ependymoma. Child’s Nervous System. 2009;25:1195-201. For instance, individuals with neurofibromatosis type 2 (NF2) are at higher risk of developing spinal ependymomas due to mutations in the NF2 gene.

Symptoms/Clinical Manifestations 

The symptoms depend on the location of the tumor in the CNS. The specific symptoms appear with the development of the tumor. Since these tumors often grow slowly, symptoms may take months to develop and become noticeable. As the tumor enlarges, it can press against the skull or spinal cord, leading to increased pressure and neurological problems.

Brain Ependymomas

When a tumor grows in the brain, it can increase pressure inside the skull, leading to:

• Headaches
• Vision changes (such as blurred or double vision)
• Nausea and vomiting
• Weakness in certain parts of the body
• Numbness or tingling sensations
• Confusion and difficulty concentrating
• Sleepiness
• Problems with memory, thinking, and speech⁹Acquaye AA, Vera E, Gilbert MR, Armstrong TS. Clinical presentation and outcomes for adult ependymoma patients. Cancer. 2017;123(3):494-501.

Spinal Ependymomas

Tumors in the spinal cord can cause:

• Persistent pain along the spine or nerve pathways
• Numbness or tingling in the arms, legs, or trunk
• Muscle weakness in the arms or legs
• Difficulty controlling bowel or bladder function
• Fatigue and reduced energy levels¹⁰Walbert T, Mendoza TR, Vera-Bolaños E, Acquaye A, Gilbert MR, Armstrong TS. Symptoms and socio-economic impact of ependymoma on adult patients: results of the Adult Ependymoma Outcomes Project 2. Journal of neuro-oncology. 2015;121:341-8.

Other Possible Symptoms

In some cases, patients may also experience:

• Seizures
• Changes in personality or mood
• Sexual dysfunction¹¹Acquaye AA, Vera E, Gilbert MR, Armstrong TS. Clinical presentation and outcomes for adult ependymoma patients. Cancer. 2017;123(3):494-501.

Diagnosis of Ependymomas

If you or your child has symptoms that suggest an ependymoma, rush to your healthcare provider. The providers will ask about the symptoms (when they started and how often you are experiencing them). They will also have a look at your personal and family medical history. They will do a physical exam and recommend further tests to confirm the diagnosis.

Neurological Exam:

In neurological examination, the provider will check your hearing, vision, coordination, balance, reflexes, and strengths. If there is any problem in one or more areas simultaneously, it will provide clues about having a tumor. The problematic areas will indicate the part of the brain or spinal cord affected by the tumor.

Imaging Techniques:

Computed tomography and magnetic resonance imaging are the most widely used imaging techniques to diagnose tumors.

CT Scan

CT scans provide cross-sectional brain images to detect tumors and show their location and size. A CT scan can better depict the calcification of the tumor commonly observed in subependymomas.

MRI

MRI uses a computer, radio waves, and a magnet to take a series of detailed pictures of the areas of the body. Healthcare providers use large magnets to collect spinal cord and brain images. MRI scans provide highly detailed images using a strong magnetic field and radio waves. Ependymomas often appear as heterogeneous masses on T1, T2, and post-contrast MRI.

Diffusion Weighted Images (DWI)

DWI is an MRI technique that uses water molecule diffusion to create images. It helps differentiate pilocytic astrocytomas, ependymomas, and medulloblastomas in the posterior fossa.

Perfusion MRI

Perfusion MRI measures the blood flow in the tissues. It displays high blood volume values.

MR Spectroscopy

It is a non-invasive imaging technique that measures the concentration of metabolites. It is often used in conjunction with the MRI, revealing a reduced N-acetyl aspartate and elevated choline in the patient’s tissues.¹²Rudà R, Bruno F, Pellerino A, Soffietti R. Ependymoma: evaluation and management updates. Current Oncology Reports. 2022;24(8):985-93.

Spinal Tap:

The spinal tap is also known as a lumbar puncture. A spinal tap involves inserting a needle into the lower spine to collect cerebrospinal fluid (CSF). This test checks for tumor cells and abnormal protein levels, particularly in cases where the tumor may have spread.

Biopsy:

A biopsy is performed to confirm the diagnosis if imaging suggests a tumor. In most cases, a stereotactic biopsy is done, where a small hole (burr hole) is made in the skull to extract a tissue sample. A pathologist examines the sample under a microscope to determine if cancer cells are present and assess the tumor’s grade.

Treatment & Management

Surgery is typically the mainstay treatment for ependymomas. However, other therapies are also considered.

Surgery

Surgery is the most common treatment of tumors.¹³McGuire CS, Sainani KL, Fisher PG. Incidence patterns for ependymoma: a surveillance, epidemiology, and end results study. Journal of neurosurgery. 2009;110(4):725-9. The neurosurgeon removes the tumor while taking care of the healthy tissue. However, in some cases, ependymoma is present near the sensitive brain tissues, which makes this process too risky. If surgery succeeds in removing the entire tumor, the patient may not require any additional treatment. AN MRI is often performed after the surgery to find out the remains of the tumor. Healthcare providers often perform a second surgery to clear the remains of the tumor as much as possible.

The other treatment and management options include adjuvant therapies.

Chemotherapy

The healthcare provider advises you to take medicine to kill the tumor cells. It is an optional treatment when the tumor grows back, even after surgery. You may also need chemotherapy if the tumor spreads to the areas of the body, which is rare in ependymomas. That’s why the role of chemotherapy in treating ependymomas is not well defined.¹⁴Brandes AA, Cavallo G, Reni M, Tosoni A, Nicolardi L, Scopece L, et al. A multicenter retrospective study of chemotherapy for recurrent intracranial ependymal tumors in adults by the Gruppo Italiano Cooperativo di Neuro‐Oncologia. Cancer. 2005;104(1):143-8. Some chemotherapy agents, such as cisplatin and etoposide, are commonly used in pediatric protocols, but chemotherapy is not a standard treatment for all ependymoma patients.

Radiation Therapy

The radiation oncologist uses strong radiation energy to destroy or shrink the tumor cells. During this procedure, the machine directs energy beams to a specific point of the tumor cells. Surgeons often recommend radiation therapy to prevent cancerous tumors from recurring and when surgeons fail to attempt a complete tumor removal during the surgical procedure. In some cases, proton beam therapy is used to reduce radiation exposure to healthy brain structures.¹⁵Leeper H, Felicella MM, Walbert T. Recent advances in the classification and treatment of ependymomas. Current treatment options in oncology. 2017;18:1-13.

Targeted Therapy

This therapy includes drugs or other substances to target specific cells to attack the cancer cells and stop them from growing. Targeted therapy for ependymoma remains an experimental approach. Certain molecular subtypes, such as RELA fusion-positive supratentorial ependymomas, are being studied to determine whether targeted treatments may be effective. However, as of now, there are no FDA-approved targeted therapies specifically for ependymomas.¹⁶Merchant TE, Fouladi M. Ependymoma: new therapeutic approaches including radiation and chemotherapy. Journal of neuro-oncology. 2005;75:287-99.

Prognosis

The prognosis of pediatric patients varies depending on the type of treatment, location, and pathological classification. Ependymomas that fall within grade III are related to worse outcomes than grade II ependymomas. Patients with complete resection often present a better outcome and overall survival than patients with incomplete or partial resection. Among the different groups, the infratentorial ependymomas have excellent prognosis even without treatment. On the other hand, supratentorial ependymomas present a higher histological grade and lower survival rate after treatment with surgery and adjuvant therapy.¹⁷Leeper H, Felicella MM, Walbert T. Recent advances in the classification and treatment of ependymomas. Current treatment options in oncology. 2017;18:1-13.

Complications After Surgery

Recurrence of the tumor is the most common complication after surgery. The regrowth occurs usually at the same spot as the first. Long-term survivors of CNS tumors present a vast diversity of complications. These complications include:

• Cognitive limitations
• Neurological deficits
• Endocrine abnormalities
• Growth abnormalities
• Secondary malignancies
• Sensorineural hearing loss

Many patients present long-term complications. These complications include:

• Disturbed sleep
• Fatigue
• Pain
• Numbness and tingling

Prevention of Ependymomas

The common cause of ependymoma is unknown, so there is no way to prevent it. However, the following are some preventive measures:

• Visit your healthcare provider if you develop any symptoms that can suspect ependymomas.
• If it is diagnosed earlier, its treatment can be easier.
• People should receive counseling regarding ependymomas. Anticipatory counseling can benefit patients.
• Palliative care can benefit people with CNS tumors. The palliative should be anticipatory. It should cover a wide spectrum of needs that patients face during ependymomas.

Ependymomas versus Medulloblastoma

Both Ependymoma and medulloblastoma are tumors of children with several similarities in them. However, the key differences between the two are described in the table below.

Final Review

Ependymomas are rare tumors that originate in the brain or spinal cord. They start when the cells (ependymal cells) grow without control. Risk factors may increase the likelihood of developing ependymoma. Their clinical presentation relies on the patient’s age and the location of the tumor. After confirmation of the tumor through neuroimaging referral, neurosurgery is necessary for their removal. However, the surgery may lead to neurological deficits. The patients may need physical, speech, or occupational therapies to overcome these deficits to overcome these deficits. However, in several cases, the neurological defects are permanent. Palliative care is necessary for the patients. Despite developing the new classification and increasing understanding of pediatric and adult ependymomas, treatment and management are still challenging. Rush to your healthcare provider for effective treatment if you experience any symptoms related to the ependymoma.

Refrences

• 1
  Amora EA, Alkherayf F. Ependymoma. StatPearls [Internet]: StatPearls Publishing; 2023.
• 2
  Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncology. 2016;18(7):902-13.
• 3
  Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncology. 2016;18(7):902-13.
• 4
  Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncology. 2016;18(7):902-13.
• 5
  Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro-oncology. 2016;18(7):902-13.
• 6
  Amora EA, Alkherayf F. Ependymoma. StatPearls [Internet]: StatPearls Publishing; 2023.
• 7
  Amora EA, Alkherayf F. Ependymoma. StatPearls [Internet]: StatPearls Publishing; 2023.
• 8
  Mack SC, Taylor MD. The genetic and epigenetic basis of ependymoma. Child’s Nervous System. 2009;25:1195-201.
• 9
  Acquaye AA, Vera E, Gilbert MR, Armstrong TS. Clinical presentation and outcomes for adult ependymoma patients. Cancer. 2017;123(3):494-501.
• 10
  Walbert T, Mendoza TR, Vera-Bolaños E, Acquaye A, Gilbert MR, Armstrong TS. Symptoms and socio-economic impact of ependymoma on adult patients: results of the Adult Ependymoma Outcomes Project 2. Journal of neuro-oncology. 2015;121:341-8.
• 11
  Acquaye AA, Vera E, Gilbert MR, Armstrong TS. Clinical presentation and outcomes for adult ependymoma patients. Cancer. 2017;123(3):494-501.
• 12
  Rudà R, Bruno F, Pellerino A, Soffietti R. Ependymoma: evaluation and management updates. Current Oncology Reports. 2022;24(8):985-93.
• 13
  McGuire CS, Sainani KL, Fisher PG. Incidence patterns for ependymoma: a surveillance, epidemiology, and end results study. Journal of neurosurgery. 2009;110(4):725-9.
• 14
  Brandes AA, Cavallo G, Reni M, Tosoni A, Nicolardi L, Scopece L, et al. A multicenter retrospective study of chemotherapy for recurrent intracranial ependymal tumors in adults by the Gruppo Italiano Cooperativo di Neuro‐Oncologia. Cancer. 2005;104(1):143-8.
• 15
  Leeper H, Felicella MM, Walbert T. Recent advances in the classification and treatment of ependymomas. Current treatment options in oncology. 2017;18:1-13.
• 16
  Merchant TE, Fouladi M. Ependymoma: new therapeutic approaches including radiation and chemotherapy. Journal of neuro-oncology. 2005;75:287-99.
• 17
  Leeper H, Felicella MM, Walbert T. Recent advances in the classification and treatment of ependymomas. Current treatment options in oncology. 2017;18:1-13.