Subependymoma

Subependymoma is a slow growing, well circumscribed ependymal tumour of grade 1, found mostly in the fourth ventricle and lateral ventricles, and often discovered by chance. Most are cured or controlled by observation or resection, and prognosis is excellent.

It forms under 1% of intracranial tumours, with a peak age in the 40s to 60s and a male predominance of about 2 to 1. Tumours are commonly found at autopsy. The fourth ventricle is the commonest site, followed by the lateral ventricles, septum pellucidum and spinal cord (cervical).

No risk factor is established. Familial and syndromic cases are rare.

Pathophysiology. Tumour cells cluster in a dense fibrillary matrix with microcysts, and mitoses are rare. They express GFAP and S100, and there is no recurrent genetic driver. Methylation profiling separates subependymoma from other ependymal tumours.

Behaviour. Growth is very slow, with local recurrence in a small minority after subtotal resection. Mixed subependymoma and ependymoma exist and behave as the ependymoma component dictates.

• Most patients are asymptomatic and diagnosed by imaging for another reason.
• Symptomatic tumours present with obstructive hydrocephalus: headache, vomiting, gait disturbance, papilloedema, drowsiness.
• Fourth ventricular tumours: vertigo, ataxia, nystagmus and lower cranial nerve signs.
• Rarely intratumoural haemorrhage, seizures, or myelopathy for cervical tumours.

Red flags.

• Acute hydrocephalus with falling consciousness.
• Sudden onset severe headache (haemorrhage).

• MRI of the brain with gadolinium: well defined intraventricular nodule, isointense to hypointense on T1 and hyperintense on T2, with little or no enhancement and little oedema. CT may show calcification.
• MRI of the spine in symptomatic patients, to exclude other ependymal tumours and dissemination.
• Histology: clusters of uniform nuclei in a fibrillary matrix and microcysts, with a Ki-67 index under 1% to 2%. GFAP positive.
• Ophthalmological and vestibular assessment for symptomatic tumours.

Differential diagnosis.

• Ependymoma (supratentorial or posterior fossa)
• Choroid plexus papilloma, central neurocytoma and pilocytic astrocytoma
• Subependymal giant cell astrocytoma (tuberous sclerosis)
• Metastasis and haemangioblastoma

Observation. Asymptomatic tumours of small size are observed with MRI every 6 to 12 months for 2 years and then every 1 to 2 years.

Surgery. Resection for symptomatic or growing tumours, with hydrocephalus treated first (endoscopic third ventriculostomy or an external drain) when the patient is deteriorating. Gross total resection is curative. Brainstem and floor of the fourth ventricle may limit completeness.

Radiotherapy. Not given after gross total resection. Focal radiotherapy or stereotactic radiosurgery is considered for progressive residual disease.

Peri-operative corticosteroid.

• Corticosteroid for symptomatic oedema: dexamethasone 4 mg orally or IV once or twice daily for mild symptoms and up to 4 mg four times daily for marked oedema or raised intracranial pressure, for the shortest period, tapered over 1 to 2 weeks once symptoms settle; maximum 16 mg daily; monitoring: glucose, blood pressure, mood and sleep, gastric symptoms (gastric protection when combined with other risk factors), opportunistic infection, myopathy; adjustment: use the lowest effective dose, avoid prolonged courses because of myopathy, osteoporosis and infection, use lower doses in hepatic impairment

Monitoring. MRI 3 months after surgery, then every 6 to 12 months for 5 years and then every 2 to 3 years. Hydrocephalus and neurological review.

Referral and escalation.

• Neurosurgical referral for any symptomatic or growing tumour.
• Emergency admission for acute hydrocephalus.

Special groups.

• Older adults with incidental tumours: observation unless symptoms or hydrocephalus develop.
• Pregnancy: observation until delivery when stable, and emergency surgery for hydrocephalus.