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Overview of Intracranial Tumors


Steven A. Goldman

, MD, PhD, Sana Biotechnology

Last review/revision Jan 2021 | Modified Sep 2022
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Intracranial tumors may involve the brain or other structures (eg, cranial nerves, meninges). The tumors usually develop during early or middle adulthood but may develop at any age; they are becoming more common among older people. Brain tumors are found in about 2% of routine autopsies.

Some tumors are benign, but because the cranial vault allows no room for expansion, even benign tumors can cause serious neurologic dysfunction or death.

Classification of Intracranial Tumors

There are 2 types of brain tumors:

Brain metastases are about 10 times more common than primary tumors.

Pearls & Pitfalls

  • Brain metastases are about 10 times more common than primary brain tumors.


Pathophysiology of Intracranial Tumors

Neurologic dysfunction may result from the following:

A malignant tumor can develop new internal blood vessels, which can bleed or become occluded, resulting in necrosis and neurologic dysfunction that mimics stroke. Bleeding as a complication of metastatic tumors is most likely to occur in patients with melanoma, renal cell carcinoma, choriocarcinoma, or thyroid, lung, or breast cancer.

Benign tumors grow slowly. They may become quite large before causing symptoms, partly because often there is no cerebral edema. Malignant primary tumors grow rapidly but rarely spread beyond the central nervous system (CNS). Death results from local tumor growth and thus can result from benign as well as malignant tumors. Therefore, distinguishing between benign and malignant is prognostically less important for brain tumors than for other tumors.

Symptoms and Signs of Intracranial Tumors

Symptoms caused by primary tumors and metastatic tumors are the same. Many symptoms result from increased intracranial pressure:

  • Headache

  • Deterioration in mental status

  • Focal brain dysfunction

Headache is the most common symptom. Headache may be most intense when patients awake from deep nonrapid eye movement (non-REM) sleep (usually several hours after falling asleep) because hypoventilation, which increases cerebral blood flow and thus intracranial pressure, is usually maximal during non-REM sleep. Headache is also progressive and may be worsened by recumbency or the Valsalva maneuver. When intracranial pressure is very high, the headache may be accompanied by vomiting, sometimes with little nausea preceding it.

Papilledema develops in about 25% of patients with a brain tumor but may be absent even when intracranial pressure is increased. In infants and very young children, increased intracranial pressure may enlarge the head. If intracranial pressure increases sufficiently, brain herniation Brain Herniation Brain herniation occurs when increased intracranial pressure causes the abnormal protrusion of brain tissue through openings in rigid intracranial barriers (eg, tentorial notch). Because the... read more Brain Herniation occurs.

Deterioration in mental status is the 2nd most common symptom. Manifestations include drowsiness, lethargy, personality changes, disordered conduct, and impaired cognition, particularly with malignant brain tumors. Airway reflexes may be impaired.

Focal brain dysfunction causes some symptoms. Focal neurologic deficits, endocrine dysfunction, or focal seizures (sometimes with secondary generalization) may develop depending on the tumor’s location (see table Common Localizing Manifestations of Brain Tumors Common Localizing Manifestations of Primary Brain Tumors Common Localizing Manifestations of Primary Brain Tumors  ). Focal deficits often suggest the tumor’s location. However, sometimes focal deficits do not correspond to the tumor’s location. Such deficits, called false localizing signs, include the following:

  • Unilateral or bilateral lateral rectus palsy (with paresis of eye abduction) due to increased intracranial pressure compressing the 6th cranial nerve

  • Ipsilateral hemiplegia due to compression of the contralateral cerebral peduncle against the tentorium (Kernohan notch)

  • Ipsilateral visual field defect due to ischemia in the contralateral occipital lobe

Diagnosis of Intracranial Tumors

  • T1-weighted MRI with gadolinium or CT with contrast

Early-stage brain tumors are often misdiagnosed. A brain tumor should be considered in patients with any of the following:

  • Progressive focal or global deficits of brain function

  • New seizures

  • Persistent, unexplained, recent-onset headaches, particularly if worsened by sleep

  • Evidence of increased intracranial pressure (eg, papilledema, unexplained vomiting)

  • Pituitary or hypothalamic endocrinopathy

A complete neurologic examination, neuroimaging, and chest x-rays (for a source of metastases) should be done. T1-weighted MRI with gadolinium is the study of choice. CT with contrast agent is an alternative. MRI usually detects low-grade astrocytomas and oligodendrogliomas earlier than CT and shows brain structures near bone (eg, the posterior fossa) more clearly. If whole-brain imaging does not show sufficient detail in the target area (eg, sella turcica, cerebellopontine angle, optic nerve), closely spaced images or other special views of the area are obtained. If neuroimaging is normal but increased intracranial pressure is suspected, idiopathic intracranial hypertension Idiopathic Intracranial Hypertension Idiopathic intracranial hypertension causes increased intracranial pressure without a mass lesion or hydrocephalus, probably by obstructing venous drainage; cerebrospinal fluid composition is... read more should be considered and lumbar puncture Lumbar Puncture (Spinal Tap) Lumbar puncture is used to do the following: Evaluate intracranial pressure and cerebrospinal fluid (CSF) composition (see table Cerebrospinal Fluid Abnormalities in Various Disorders) Therapeutically... read more done.

Radiographic clues to the type of tumor, mainly location (see table Common Localizing Manifestations of Brain Tumors Common Localizing Manifestations of Primary Brain Tumors Common Localizing Manifestations of Primary Brain Tumors  ) and pattern of enhancement on MRI, may be inconclusive; brain biopsy, sometimes excisional biopsy, may be required.

Specialized tests (eg, molecular and genetic tumor markers in blood and CSF) can help in some cases. In patients with AIDS, Epstein-Barr virus titers in CSF typically increase as CNS lymphoma develops.

Treatment of Intracranial Tumors

  • Airway protection

  • Dexamethasone for increased intracranial pressure

  • Mannitol for herniation

  • Definitive therapy with excision, radiation therapy, chemotherapy, or a combination

Brain herniation due to tumors is treated with mannitol 25 to 100 g infused IV, a corticosteroid (eg, dexamethasone 16 mg IV, followed by 4 mg orally or IV every 6 hours), and endotracheal intubation. Hyperventilation to a carbon dioxide partial pressure (PCO2) of 26 to 30 mm Hg can help decrease intracranial pressure temporarily in emergencies. Mass lesions should be surgically decompressed as soon as possible.

Increased intracranial pressure due to tumors but without herniation can be treated with corticosteroids (eg, dexamethasone 4 mg orally every 6 to12 hours or prednisone 30 to 40 mg orally twice a day).

Treatment of the brain tumor depends on pathology and location (for acoustic neuroma, see Acoustic Neuroma Vestibular Schwannoma A vestibular schwannoma, also called an acoustic neuroma, is a Schwann cell–derived tumor of the 8th cranial nerve. Symptoms include unilateral hearing loss. Diagnosis is based on audiology... read more ). Surgical excision should be used for diagnosis (excisional biopsy) and symptom relief. It may cure benign tumors. For tumors infiltrating the brain parenchyma, treatment is multimodal. Radiation therapy is required, and chemotherapy appears to benefit some patients.

Treatment of metastatic tumors includes radiation therapy and sometimes stereotactic radiosurgery. For patients with a single metastasis, surgical excision of the tumor before radiation therapy improves outcome.

End-of-life issues

Cranial Radiation Therapy and Neurotoxicity

Radiation therapy may be directed diffusely to the whole head for diffuse or multicentric tumors or locally for well-demarcated tumors.

Localized brain radiation therapy may be conformal, targeting the tumor with the aim of sparing normal brain tissue, or stereotactic, typically involving gamma knife or proton beam therapy. Gliomas are treated with conformal radiation therapy; a stereotactically directed gamma knife or proton beam therapy is useful for metastases. Current recommendations are to treat ≤ 4 metastatic lesions with stereotactic or other focal radiation interventions and to treat> 4 lesions with whole-brain radiation therapy (1 Treatment reference Intracranial tumors may involve the brain or other structures (eg, cranial nerves, meninges). The tumors usually develop during early or middle adulthood but may develop at any age; they are... read more Treatment reference ). Giving radiation in smaller fractionated daily doses tends to maximize efficacy while minimizing neurotoxicity and damage to normal CNS tissue (see Radiation Exposure and Contamination Acute radiation syndromes (ARS) Acute radiation syndromes (ARS) ).

Degree of neurotoxicity depends on

  • Cumulative radiation dose

  • Individual dose size

  • Duration of therapy

  • Volume of tissue irradiated

  • Individual susceptibility

Because susceptibility varies, prediction of radiation neurotoxicity is imprecise. Symptoms can develop in the first few days (acute) or months of treatment (early-delayed) or several months to years after treatment (late-delayed). Rarely, radiation causes gliomas, meningiomas, or peripheral nerve sheath tumors years after therapy.

Acute radiation neurotoxicity

Typically, acute neurotoxicity involves headache, nausea, vomiting, somnolence, and sometimes worsening focal neurologic signs in children and adults.

Acute neurotoxicity largely results from transient swelling and edema; thus, it is particularly likely if intracranial pressure is already high. Using corticosteroids to lower intracranial pressure can prevent or treat acute toxicity. Acute toxicity lessens with subsequent treatments.

Early-delayed neurotoxicity

In children or adults, early-delayed neurotoxicity can cause encephalopathy, which must be distinguished by MRI or CT from worsening or recurrent brain tumor. It may occur in children who have received prophylactic whole-brain radiation therapy for leukemia; they may develop somnolence, which lessens spontaneously over several days to weeks, possibly more rapidly if corticosteroids are used.

After radiation therapy to the neck or upper thorax, early-delayed neurotoxicity can result in a myelopathy, characterized by spinal symptoms such as Lhermitte sign (an electric shock-like sensation radiating down the back and into the legs when the neck is flexed). This early-delayed myelopathy typically resolves spontaneously.

Late-delayed neurotoxicity

After diffuse or whole-brain radiation therapy, many children and adults develop late-delayed neurotoxicity if they survive long enough. The most common cause in children is diffuse therapy given to prevent leukemia or to treat medulloblastoma. After diffuse therapy, the most common symptom is progressive dementia; adults may also develop an unsteady gait and focal neurologic symptoms. MRI or CT can show cerebral atrophy and often white matter loss.

After localized therapy, neurotoxicity more often involves focal neurologic deficits.

MRI or CT shows a mass that may be enhanced by contrast agent and that may be difficult to distinguish from recurrence of the primary tumor. Excisional biopsy of the mass is diagnostic and often ameliorates symptoms.

Late-delayed myelopathy can develop after radiation therapy for extraspinal tumors (eg, due to Hodgkin lymphoma). It is characterized by progressive paresis and sensory loss, often as a Brown-Séquard syndrome (ipsilateral paresis and proprioceptive sensory loss, with contralateral loss of pain and temperature sensation). Most patients eventually become paraplegic.

Treatment reference

  • 1. Gaspar L, Prabhu R, Hdeib A, et al: Congress of Neurological Surgeons systematic review and evidence-based guidelines on the role of whole brain radiation therapy in adults with newly diagnosed metastatic brain tumors. Neurosurgery 84 (3):E159–E162, 2019. doi: 10.1093/neuros/nyy541

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