Ependymoma: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Ependymoma is a glial tumor arising from ependymal cells that line the ventricular system and central canal of the spinal cord. It accounts for approximately 5–10% of all pediatric intracranial tumors and 3% of adult brain tumors, with approximately 1,500 new US cases per year. The WHO 2021 classification has transformed ependymoma into a molecularly defined entity, recognizing distinct subgroups across three anatomic compartments: supratentorial (ST-RELA-fused, high-risk; ST-YAP1-fused, favorable), posterior fossa (PFA, young children, poor prognosis; PFB, older children and adults, good prognosis), and spinal (excellent prognosis with complete resection). Ependymoma occurs across all age groups: pediatric posterior fossa disease predominates in children aged 1–5, while spinal ependymoma is more common in adults aged 30–50. Gross total resection remains the single most important prognostic factor across all subtypes and locations.

NF2 (neurofibromatosis type 2) gene mutations are strongly associated with spinal ependymomas in adults, including myxopapillary ependymoma of the conus medullaris and filum terminale, occurring in the context of NF2 syndrome or as sporadic events. Supratentorial ependymomas harbor RELA fusions (C11orf95-RELA or ZBTB20-RELA, poor prognosis) or YAP1 fusions (favorable prognosis, typically in infants). Posterior fossa group PFA ependymoma shows a hypermethylated CpG island methylator phenotype, lacks recurrent somatic mutations, affects young children (under 5 years), and has the worst prognosis among spinal or posterior fossa ependymomas. Posterior fossa PFB affects older children and adults with near-normal karyotype and better prognosis. No established environmental or lifestyle risk factors have been confirmed for ependymoma.

Symptoms depend on tumor location and CSF flow obstruction. Posterior fossa ependymomas cause obstructive hydrocephalus manifesting as headache (worse in the morning), nausea, and vomiting, along with cerebellar signs: ataxia, gait instability, dysmetria, and nystagmus. Cranial nerve dysfunction (diplopia from abducens palsy, facial palsy, or dysphagia) indicates brainstem extension, common in posterior fossa ependymoma. Supratentorial ependymomas present with focal neurological deficits (hemiparesis, visual field loss, aphasia) and new-onset seizures depending on the cortical or subcortical location involved. Spinal ependymomas cause progressive back or neck pain, sensory disturbances below the lesion level, progressive limb weakness, and eventually bladder or bowel dysfunction from spinal cord compression.

MRI of the entire brain and spinal cord with gadolinium contrast is mandatory before surgery to characterize the primary tumor and detect leptomeningeal dissemination (present in approximately 10% of intracranial ependymomas at diagnosis). Posterior fossa ependymoma typically appears as a T2-hyperintense mass in the fourth ventricle, often extending through foramina of Luschka and Magendie. Histopathology identifies characteristic perivascular pseudorosettes and true ependymal canal rosettes. GFAP and EMA immunohistochemistry is positive. Molecular profiling — RELA and YAP1 fusions by FISH or RNA sequencing, 1q gain (adverse prognostic marker), CDKN2A/B homozygous deletion — is required for WHO 2021 integrated diagnosis. DNA methylation array provides definitive molecular classification. CSF cytology and postoperative spine MRI complete staging.

Maximal safe surgical resection is the primary treatment for all ependymoma subtypes; gross total resection is the strongest independent prognostic factor. For incomplete resection with residual visible tumor, second-look surgery is routinely pursued before radiation. In children over 1–3 years, focal conformal radiotherapy (54–59.4 Gy in 1.8 Gy fractions) to the tumor bed plus a 1–2 cm margin is administered after surgery — even after complete resection for posterior fossa PFA disease. Proton beam therapy is preferred for pediatric posterior fossa and supratentorial tumors to minimize radiation dose to the developing hypothalamus, cochlea, and contralateral brain. In infants under 3 years of age, chemotherapy-first strategies (carboplatin, etoposide, cyclophosphamide) are used to delay radiation until older. Re-irradiation using stereotactic radiotherapy or proton beam is used for selected local recurrences. Bevacizumab, temozolomide, or clinical trial agents are options for progressive or recurrent disease.

Prognosis varies markedly by molecular subtype and location. Pediatric intracranial ependymoma: overall 5-year progression-free survival approximately 55–60%; 5-year overall survival approximately 75%. Spinal ependymoma: greater than 90% 5-year survival with complete resection — the most favorable location. RELA-fusion supratentorial ependymoma: 5-year survival approximately 50% with frequent recurrence. Posterior fossa PFB: 5-year survival approximately 80–90%. Posterior fossa PFA: 5-year OS approximately 70%, though recurrence is common. Gross total resection is the strongest independent favorable prognostic factor. 1q gain and CDKN2A/B deletion are adverse molecular prognostic markers. The prognosis for Ependymoma: Causes, Symptoms, Diagnosis and Treatment varies depending on severity at diagnosis, the patient's overall health, and how promptly treatment is initiated. With early diagnosis and appropriate management, many patients achieve good outcomes and maintain quality of life. Regular follow-up with healthcare providers is essential to monitor progress, adjust treatment as needed, and detect any complications early. Adherence to prescribed treatments and lifestyle modifications significantly improves long-term prognosis.

No preventive strategies exist for sporadic ependymoma, as the molecular alterations (RELA fusions, NF2 mutations, CpG island methylation) occur as sporadic or germline events not linked to known environmental exposures. Patients with NF2 syndrome (germline NF2 mutations) have a significantly elevated risk of spinal ependymoma and should be enrolled in a dedicated NF2 surveillance program with annual spinal MRI beginning in adolescence. Genetic counseling and cascade family testing is appropriate for confirmed NF2 families. Radiation exposure should be minimized in children receiving cranial treatment for other conditions. For all pediatric ependymoma patients, long-term multidisciplinary follow-up — including neuropsychological assessment, endocrine evaluation, and audiological monitoring — is essential to detect and manage treatment-related late effects.

Seek urgent neurological evaluation for any child or adult with progressive or persistent early-morning headaches combined with nausea or vomiting, which may indicate raised intracranial pressure. New gait instability, coordination problems, or frequent unexplained falls in a child require prompt neuroimaging. Adults with progressive back or neck pain, particularly when accompanied by new numbness, tingling, weakness in arms or legs, or any change in bladder or bowel function, should be evaluated promptly for possible spinal ependymoma. New-onset seizures always require urgent neurological investigation. Double vision, facial weakness, or difficulty swallowing suggest brainstem involvement and require emergency evaluation. Children who have completed treatment for ependymoma should adhere strictly to all scheduled surveillance MRI appointments, as early detection of recurrence offers additional treatment options.