intracranial tumors

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 the elderly. 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 these tumors can be serious.

Classification

Some primary intracranial tumors (eg, gliomas, medulloblastomas, ependymomas) originate in brain parenchyma; others (eg, meningiomas, acoustic neuromas, other schwannomas) originate in extraneural structures. Extracranial tumors may metastasize to any intracranial structure or to the skull. In the brain, metastases are about 10 times more common than primary tumors.
Brain Metastases

Type of tumor varies somewhat by site (see Table 1: Intracranial and Spinal Tumors: Common Localizing Manifestations of Brain Tumors ) and patient age (see Table 2: Intracranial and Spinal Tumors: Common Tumors).

Table 1

Common Localizing Manifestations of Brain Tumors

Tumor Site
Findings
Common Primary Tumor Types*

Anterior corpus callosum
Cognitive impairment
Astrocytoma

Oligodendroglioma

Basal ganglia
Hemiparesis (contralateral), movement disorders
Astrocytoma

Brain stem
Unilateral or bilateral motor or sensory loss, cranial nerve deficits (eg, gaze palsies, hearing loss, vertigo, palatal paresis, facial weakness), ataxia, intention tremor, nystagmus
Astrocytoma (most often juvenile pilocytic astrocytoma)

Cerebellopontine angle
Tinnitus and hearing loss (both ipsilateral), vertigo, loss of vestibular response to caloric stimulation

If tumor is large, ataxia, loss of facial sensation and facial weakness (both ipsilateral), possibly other cranial nerve or brain stem deficits
Acoustic neuroma

Meningioma

Schwannoma

Cerebellum
Ataxia, nystagmus, tremor, hydrocephalus with suddenly increased intracranial pressure
Astrocytoma

Ependymoma

Medulloblastoma

2nd cranial (optic) nerve
Loss of vision
Astrocytoma (most often juvenile pilocytic astrocytoma)

5th cranial (trigeminal) nerve
Loss of facial sensation, jaw weakness
Meningioma

Frontal lobe
Generalized or focal (contralateral) seizures, gait disorders, urinary urgency or incontinence, impaired attention and cognition and apathy (particularly if tumor is bilateral), hemiparesis

Expressive aphasia if tumor is in dominant hemisphere

Anosmia if tumor is at base of lobe
Astrocytoma

Oligodendroglioma

Hypothalamus
Eating and drinking disorders (eg, polydipsia), precocious puberty (especially in boys), hypothermia
Astrocytoma

Occipital lobe
Generalized seizures with visual aura, visual hallucinations, hemianopia or quadrantanopia (contralateral)
Astrocytoma

Oligodendroglioma

Parietal lobe
Deficits in position sensation and in 2-point discrimination (contralateral), anosognosia (no recognition of bodily defects), denial of illness, hemianopia (contralateral), generalized or focal seizures, inability to perceive (extinguishing of) a contralateral stimulus when stimuli are applied to both sides of the body (called double simultaneous stimulation)

Receptive aphasia if tumor is in dominant hemisphere
Astrocytoma

Oligodendroglioma

Pineal region
Paresis of upward gaze, ptosis, loss of pupillary light and accommodation reflexes, sometimes hydrocephalus with suddenly increased intracranial pressure
Germ cell tumor

Pineocytoma (rare)

Pituitary or suprasellar region
Endocrinopathies, monocular visual loss, headache without increased intracranial pressure, bitemporal hemianopia
Craniopharyngioma

Pituitary adenoma

Pituitary carcinoma (rare)

Temporal lobe
Complex partial seizures, generalized seizures with or without aura, hemianopia (contralateral), mixed expressive and receptive aphasia or anomia
Astrocytoma

Oligodendroglioma

Thalamus
Sensory impairment (contralateral)
Astrocytoma
*Similar manifestations may result from brain parenchymal metastases or from tumors around the dura (eg, metastatic tumors; meningeal tumors such as meningiomas, sarcomas, or gliomas) or skull lesions (eg, granulomas, hemangiomas, osteitis deformans, osteomas, xanthomas) that compress the underlying brain.

Table 2

Common Tumors

Age Group
Primary
Metastases

Children
Cerebellar astrocytomas and medulloblastomas

Ependymomas

Gliomas of the brain stem or optic nerve

Germinomas

Congenital tumors*
Neuroblastoma (usually epidural)

Leukemia (meningeal)

Adults
Meningiomas

Schwannomas

Primary lymphomas

Gliomas of the cerebral hemispheres, particularly glioblastoma multiforme, anaplastic astrocytoma, low-grade astrocytoma, and oligodendroglioma
Bronchogenic carcinoma

Adenocarcinoma of the breast

Malignant melanoma

Any cancer that has spread to the lungs
*Congenital tumors include craniopharyngiomas, chordomas, germinomas, teratomas, dermoid cysts, angiomas, and hemangioblastomas.

Pathophysiology

Neurologic dysfunction may result from the following:

Invasion and destruction of brain tissue by the tumor

Direct compression of adjacent tissue by the tumor

Increased intracranial pressure (because the tumor occupies space within the skull)

Bleeding within or outside the tumor

Cerebral edema

Obstruction of dural venous sinuses (especially by bone or extradural metastatic tumors)

Obstruction of CSF drainage (occurring early with 3rd-ventricle or posterior fossa tumors)

Obstruction of CSF absorption (eg, when leukemia or carcinoma involves the meninges)

Obstruction of arterial flow

Rarely, paraneoplastic syndromes (see Overview of Cancer: Paraneoplastic Syndromes)

A malignant tumor can develop new internal blood vessels, which can bleed or become occluded, resulting in necrosis and neurologic dysfunction that mimics stroke.

Benign tumors grow slowly. They may become quite large before causing symptoms, partly because often there is no cerebral edema. Malignant tumors grow rapidly but rarely spread beyond the 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

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 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 occurs (see Coma and Impaired Consciousness: Brain herniation.).

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. Generalized seizures may occur, more often with primary than metastatic brain tumors. Impaired consciousness (see Coma and Impaired Consciousness) can result from herniation, brain stem dysfunction, or diffuse bilateral cortical dysfunction. Airway reflexes may be impaired.

Some symptoms result from focal brain dysfunction. Focal neurologic deficits, endocrine dysfunction, or focal seizures (sometimes with secondary generalization) may develop depending on the tumor’s location (see Table 1: Intracranial and Spinal Tumors: Common Localizing Manifestations of 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’s notch)

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

Some tumors cause meningeal inflammation, resulting in subacute or chronic meningitis (see Meningitis).

Diagnosis

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

Similar findings can result from other intracranial masses (eg, abscess, aneurysm, arteriovenous malformation, intracerebral hemorrhage, subdural hematoma, granuloma, parasitic cysts such as neurocysticercosis) or ischemic stroke.

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 (see Headache: Idiopathic Intracranial Hypertension) should be considered and lumbar puncture done.

Radiographic clues to the type of tumor, mainly location (see Table 1: Intracranial and Spinal Tumors: Common Localizing Manifestations of 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; eg, in patients with AIDS, Epstein-Barr virus titers in CSF typically increase as CNS lymphoma develops.

Treatment

Airway protection

Dexamethasone

for increased intracranial pressure

Mannitol

for herniation

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

Patients in a coma or with impaired airway reflexes require endotracheal intubation. 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 po or IV q 6 h), and endotracheal
intubation. Mass lesions should be surgically decompressed as soon as possible.

Increased intracranial pressure due to tumors but without herniation is treated with corticosteroids (eg, dexamethasone

as for herniation above or prednisone

30 to 40 mg po
bid).

Treatment of the brain tumor depends on pathology and location (for acoustic neuroma, see Inner Ear Disorders: Acoustic Neuroma). 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 solitary metastasis, surgical excision of the tumor before radiation therapy improves outcome.

End-of-life issues: If brain tumors are expected to soon be fatal, end-of-life issues should be considered (see The Dying Patient).

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, involving brachytherapy, a gamma knife, or a linear accelerator. In brachytherapy, radioactive stable iodine (125I3) or iridium-192 (192Ir4) is implanted in or near the tumor. Gliomas are treated with conformal radiation therapy; a gamma knife or linear accelerator is useful for metastases. Giving radiation daily tends to maximize efficacy and minimize neurotoxicity damage to normal CNS tissue (see Radiation Exposure and Contamination: 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. It is particularly likely if intracranial pressure is 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 occurs in children who have received prophylactic whole-brain radiation therapy for leukemia; they 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 Lhermitte’s sign (an electric shock-like sensation radiating down the back and into the legs when the neck is flexed). The myelopathy resolves spontaneously.

Late-delayed neurotoxicity: After diffuse 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 main symptom is progressive dementia; adults also develop an unsteady gait. MRI or CT shows cerebral atrophy.

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.

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