A brain tumor, or tumour, is an intracranial solid neoplasm, a tumor (defined as anabnormal growth of cells) within the brain or the

central spinal canal. Brain tumors include all tumors inside the cranium or in the central spinal canal. They are created by an abnormal and uncontrolled cell division, usually in the brain itself, but also inlymphatic tissue, in blood vessels, in the cranial nerves, in the brain envelopes (meninges),skull, pituitary gland, or pineal gland. Within the brain itself, the involved cells may beneurons or glial cells (which include astrocytes, oligodendrocytes, and ependymal cells). Brain tumors may also spread from cancers primarily located in other organs (metastatic tumors). Any brain tumor is inherently serious and life threatening because of its invasive and infiltrative character in the limited space of the intracranial cavity. !owever, brain tumors (even malignant ones) are not invariably fatal, especially lipomas which are inherently benign. Brain tumors or intracranial neoplasms can be cancerous (malignant) or non cancerous (benign)" however, the definitions of malignant or benign neoplasms differs from those commonly used in other types of cancerous or non cancerous neoplasms in the body. #ts threat level depends on the combination of factors like the type of tumor, its location, its si$e and its state of development. Because the brain is well protected by the skull, the early detection of a brain tumor occurs only when diagnostic tools are directed at the intracranial cavity. %sually detection occurs in advanced stages when the presence of the tumor has caused une&plained symptoms. 'rimary (true) brain tumors are commonly located in the posterior cranial fossa in childrenand in the anterior two thirds of the cerebral hemispheres in adults, although they can affect any part of the brain.

(igns and symptoms

)isibility of signs and symptoms of brain tumors mainly depends on two factors* tumor si$e (volume) and tumor location. The moment that symptoms will become apparent, either to the person or people around him (symptom onset) is an important milestone in the course of the diagnosis and treatment of the tumor. The symptom onset + in the timeline of the development of the neoplasm + depends in many cases on the nature of the tumor but in many cases is also related to the change of the neoplasm from ,benign, (i.e. slow growing-late symptom onset) to more malignant (fast growing-early symptom onset).

(ymptoms of solid neoplasms of the brain (primary brain tumors and secondary tumors alike) can be divided in . main categories*

/onse0uences of intracranial hypertension* The symptoms that often occur first are those that are the conse0uences of increased intracranial pressure* 1arge tumors or tumors with e&tensive perifocal swelling (edema) inevitably lead to elevated intracranial pressure (intracranial hypertension), which translates clinically into headaches, vomiting (sometimes without nausea), altered state of consciousness (somnolence, coma), dilation of the pupil on the side of the lesion (anisocoria), papilledema (prominent optic discat the funduscopic eye e&amination). !owever, even small tumors obstructing the passage of cerebrospinal fluid (/(2) may cause early signs of increased intracranial pressure. #ncreased intracranial pressure may result in herniation (i.e. displacement) of certain parts of the brain, such as the cerebellar tonsils or the temporal uncus, resulting in lethal brainstem compression. #n very young children, elevated intracranial pressure may cause an increase in the diameter of the skull and bulging of the fontanelles.

3ysfunction* depending on the tumor location and the damage it may have caused to surrounding brain structures, either through compression or infiltration, any type of focal neurologic symptoms may occur, such as cognitive and behavioral impairment (including impaired 4udgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes,hemiparesis, hypoesthesia, aphasia, ata&ia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis,double vision, di$$iness, but more severe symptoms might occur too such as* paralysis on one side of the body hemiplegia or impairment to swallow . These symptoms are not specific for brain tumors + they may be caused by a large variety of neurologic conditions (e.g. stroke, traumatic brain in4ury). What counts, however, is the location of the lesion and the functional systems (e.g.motor, sensory, visual, etc.) it affects. A bilateral temporal visual field defect (bitemporal hemianopia5due to compression of theoptic chiasm), often associated with endocrine dysfunction5 either hypopituitarism or hyperproduction of pituitary hormones andhyperprolactinemia is suggestive of a pituitary tumor.

#rritation* abnormal fatigue, weariness, absences and tremors, but also epileptic sei$ures.

The above symptoms are true for A11 types of neoplasm of the brain (including secondary tumors). #t is common that a person carriesa primary benign neoplasm for several years and have no visible symptoms at all. 6any present some uncertain and intermittent symptoms like headaches and occasional vomiting or weariness, which can be easily mistaken for gastritis or gastroenteritis. #t might seem strange that despite having a mass in his skull e&ercising pressure on the brain the patient feels no pain, but as anyone who has suffered a concussion can attest, pain is felt on the outside of the skull and not in the brain itself. The brain has no nerve sensors in the meninges (outer surface) with which to feel or transmit pain to the brain7s pain center" it cannot signal pain without a sensory input. That is why secondary symptoms like those described above should alert doctors to the possible diagnosis of a neoplasm of the brain. #n a recent study by the 3utch 8' Association, a list of causes of headaches 9:; was published, that should alert 8'7s to take their diagnosis further than to choose for symptomatic treatment of headaches with simple pain medication (note the occurrence of brain tumors as possible cause)* Alarm signals Possible cause

First headache complaint from person over 50 years old

brain tumor, arteritis temporalis

First migraine attack in person over 40 years old

brain tumor

Headache in person under 6 years old

brain tumor, hydrocephalus

Person over 50 years old ith pain at temples

!iant"cell arteritis

Pregnancy ith unkno n headache

pre"eclampsia

#ncreased headaches after trauma

sub$epidural hematoma

%evere headaches and very high blood pressure

malignant hypertension

&cute severe headache

meningitis, '(& )'erebrovascular accident or stroke*, subarachnoidal hemorrhage

Headache and fever ) ith reduced consciousness*

meningitis

%tiffness of the neck$neurological dysfunction

meningitis, brain tumor

Headache ith signs of elevated intracranial pressure

brain tumor

Focal neurological dysfunction

brain tumor

+arly morning vomiting or vomiting unrelated to headache or other illness

brain tumor

,ehavioral changes or rapid decline in school results

brain tumor

/ause
Aside from e&posure to vinyl chloride or ioni$ing radiation, there are no known environmental factors associated with brain tumors. 6utations and deletions of so called tumor suppressor genes are thought to be the cause of some forms of brain tumors. 'eople with various inherited diseases, such as )on !ippel 1indau syndrome, multiple endocrine neoplasia, neurofibromatosis type < are at high risk of developing brain tumors. Although studies have not shown any link between cell phone radiation and brain tumors,9<; the World !ealth =rgani$ation has classified mobile phone radiation on the #A>/ scale into 8roup <B + possibly carcinogenic. That means that there ,could be

some risk, of carcinogenicity, so additional research into the long term, heavy use of mobile phones needs to be conducted.9.; 9edit;Types Tumors can be benign or malignant, can occur in different parts of the brain, and may or may not be primary tumors. A primary tumor is one that has started in the brain, as opposed to a metastatic tumor, which is something that has spread to the brain from another part of the body. 9?; Tumors may or may not be symptomatic* some tumors are discovered because the patient has symptoms, others show up incidentally on an imaging scan, or at an autopsy. The most common primary brain tumors are*9@;

8liomas (@A.?B) 6eningiomas (<A.CB) 'ituitary adenomas (:@B) Derve sheath tumors (CB)

Pathophysiology

6ain anatomical regions of the vertebrate brain

[edit]Anatomy 2rom the brain Wikipedia article and for the purpose of understanding this article some summary notes about the brain and its different types of organic tissues will be provided. When reading the human brain in the picture on the right, only a few of the areas are really of interest to us. The first type of tissue encountered beneath the skullbone in the intracranial cavity is actually not shown on this picture* the meninges. This is what is inflamed in meningitis. [edit]Meninges !uman brains are surrounded by a system of connective tissue membranes called meningesthat separate the skull from the brain. This three layered covering is composed of (from the outside in) the dura mater (,hard mother,), arachnoid mater (,spidery mother,), and pia mater(,soft mother,). The arachnoid and pia are physically connected and thus often considered as a single layer, the pia arachnoid. Below the arachnoid is the subarachnoid space which contains cerebrospinal fluid, which circulates in the narrow spaces between cells and through cavities called ventricles, and serves to nourish, support, and protect the brain tissue. Blood vessels enter the central nervous system through the perivascular space above the pia mater. The cells in the blood vessel walls are 4oined tightly, forming the blood+brain barrier which protects the brain from to&ins that might enter through the blood. Tumors of the meninges are meningioma and are often benign neoplasms. [edit]Brain

matter

The brains of vertebrates (including humans) are made of very soft tissue, with a te&ture that has been compared to gelatin. 1iving brain tissue is pinkish on the outside and mostly white on the inside, with subtle variations in color. Three separate brain areas make up the ma4ority of brain volume*

telencephalon (cerebral hemispheres or cerebrum) mesencephalon (midbrain) cerebellum

These areas are composed of two broad classes of cells* neurons and glia. These two types are e0ually numerous in the brain as a whole, although glial

cells outnumber neurons roughly ? to : in the cerebral corte&. 8lia come in several types, which perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development. 'rimary tumors of the glial cells are called 8lioma and often are malignant by the time they are diagnosed. [edit]Spinal

cord and other tissues

The pink area in picture is called the pons and is a specific region that consists of myelinated a&ons much like the spinal cord The yellow region is the diencephalon (thalamus and hypothalamus) which consist also of neuron and glial cell tissue with the hypophysis (or pituitary gland) and pineal gland (which is glandular tissue) attached at the bottom" tumors of the pituitary and pineal gland are often benign neoplasms

The tur0uoise region or medulla oblongata is the end of the spinal cord and is composed mainly of neuron tissue enveloped in(chwann cells and meninges tissue. =ur spinal cord is made up of bundles of these a&ons. 8lial cells such as (chwann cells in the periphery or, within the cord itself, oligodendrocytes, wrap themselves around the a&on, thus promoting faster transmission of electrical signals and also providing for general maintenance of the environment surrounding the cord, in part by shuttling different compounds around, responding to in4ury, etc.

[edit]Diagnosis

A posterior fossa tumor leading to mass effect and midline shift

Although there is no specific or singular clinical symptom or sign for any brain tumors, the presence of a combination of symptoms and the lack of corresponding clinical indications of infections or other causes can be an indicator to redirect diagnostic investigation towards the possibility of an intracranial neoplasm. Brain tumors have similar characteristics and obstacles when it comes to diagnosis and therapy with tumors located elsewhere in the body. !owever, create specific issues that follow closely to the properties of the organ they are in. 9E; The diagnosis will often start with an interrogation of the patient to get a clear view of his medical antecedents, and his current symptoms. /linical and laboratory investigations will serve to e&clude infections as the cause of the symptoms. F&aminations in this stage may include the eyes, otolaryngological (or FDT) and-or electrophysiological e&ams. The use ofelectroencephalography (FF8) often plays a role in the diagnosis of brain tumors. (welling, or obstruction of the passage of cerebrospinal fluid (/(2) from the brain may cause (early) signs of increased intracranial pressure which translates clinically into headaches,vomiting, or an altered state of consciousness, and in children changes to the diameter of the skull and bulging of the fontanelles. 6ore comple& symptoms such as endocrine dysfunctions should alarm doctors not to e&clude brain tumors. A bilateral temporal visual field defect (due to compression of the optic chiasm) or dilatation of the pupil, and the occurrence of either slowly evolving or the sudden onset of focal neurologic symptoms, such as cognitive and behavioral impairment (including impaired 4udgment, memory loss, lack of recognition, spatial orientation disorders), personality or emotional changes, hemiparesis,hypoesthesia, aphasia, ata&ia, visual field impairment, impaired sense of smell, impaired hearing, facial paralysis, double vision, or more severe symptoms such as tremors, paralysis on one side of the body hemiplegia, or (epileptic) sei$ures in a patient with a negative history for epilepsy, should raise the possibility of a brain tumor. [edit]Imaging #maging plays a central role in the diagnosis of brain tumors. Farly imaging methods5 invasive and sometimes dangerous5 such aspneumoencephalography and cerebral angiography, have been abandoned in recent times in favor of non invasive,

high resolution techni0ues, such as computed tomography (/T) scans and especially magnetic resonance imaging (6>#). Deoplasms will often show as differently colored masses (also referred to as processes) in /T or 6># results.

Benign brain tumors often show up as hypodense (darker than brain tissue) mass lesions on cranial /T scans. =n 6>#, they appear either hypo (darker than brain tissue) or isointense (same intensity as brain tissue) on T: weighted scans, or hyperintense (brighter than brain tissue) on T< weighted 6>#, although the appearance is variable.

/ontrast agent uptake, sometimes in characteristic patterns, can be demonstrated on either /T or 6># scans in most malignant primary and metastatic brain tumors.

'erifocal edema, or pressure areas, or where the brain tissue has been compressed by an invasive process also appears hyperintense on T< weighted 6>#, they might indicate the presence a diffuse neoplasm (unclear outline)

This is because these tumors disrupt the normal functioning of the blood+brain barrier and lead to an increase in its permeability. !owever it is not possible to diagnose high versus low grade gliomas based on enhancement pattern alone. 8lioblastoma multiforme and anaplastic astrocytoma have been associated9by whom?; with the genetic acute hepatic porphyrias ('/T,A#', !/' and )'), including positive testing associated with drug refractory sei$ures.9citation needed; %ne&plained complications associated with drug treatments with these tumors should alert physicians to an undiagnosed neurological porphyria. The definitive diagnosis of brain tumor can only be confirmed by histological e&amination of tumor tissue samples obtained either by means of brain biopsy or open surgery. The histological e&amination is essential for determining the appropriate treatment and the correct prognosis. This e&amination, performed by a pathologist, typically has three stages* interoperative e&amination of fresh tissue, preliminary microscopic e&amination of prepared tissues, and followup e&amination of prepared tissues after immunohistochemical staining or genetic analysis.

[edit]Pathology

6icrograph of an oligodendroglioma, a type of brain cancer. Brain biopsy. !GF stain.

Tumors have characteristics that allow determination of its malignacy, how it will evolve and it will allow the medical team to determine the management plan. Anaplasia* or dedifferentiation" loss of differentiation of cells and of their orientation to one another and blood vessels, a characteristic of anaplastic tumor tissue. Anaplastic cells have lost total control of their normal functions and many have deteriorated cell structures. Anaplastic cells often have abnormally high nuclear to cytoplasmic ratios, and many are multinucleated. Additionally, the nuclei of anaplastic cells are usually unnaturally shaped or oversi$ed nuclei. /ells can become anaplastic in two ways* neoplastic tumor cells can dedifferentiate to become anaplasias (the dedifferentiation causes the cells to lose all of their normal structure-function), or cancer stem cells can increase in their capacity to multiply (i.e., uncontrollable growth due to failure of differentiation). Atypia* is an indication of abnormality of a cell (which may be indicative for malignancy). (ignificance of the abnormality is highly dependent on conte&t. Deoplasia* is the (uncontrolled) division of cells" as such neoplasia is not problematic but its conse0uences are* the uncontrolled division of cells means that the mass of a neoplasm increases in si$e, and in a confined space such as the intracranial cavity this 0uickly becomes problematic because the mass invades the space of the brain pushing it aside, leading to compression of the brain tissue and increased intracranial pressure and destruction of brain parenchyma. #ncreased #ntracranial pressure (#/') may be attributable to the direct mass effect of the tumor, increased blood volume, or increased cerebrospinal fluid (/(2) volume may in turn have secondary symptoms

Decrosis* is the (premature) death of cells, caused by e&ternal factors such as infection, to&in or trauma. Decrotic cells send the wrong chemical signals which prevents phagocytes from disposing of the dead cells, leading to a build up of dead tissue, cell debris and to&ins at or near the site of the necrotic cells 9H; Arterial and venous hypo&ia, or the deprivation of ade0uate o&ygen supply to certain areas of the brain, occurs when a tumor makes use of nearby blood vessels for its supply of blood and the neoplasm enters into competition for nutrients with the surrounding brain tissue. 6ore generally a neoplasm may cause release of metabolic end products (e.g., free radicals, altered electrolytes, neurotransmitters), and release and recruitment of cellular mediators (e.g., cytokines) that disrupt normal parenchymal function. [edit]Classification
[edit]Secondary

brain tumors

(econdary tumors of the brain are metastatic tumors that invaded the intracranial sphere from cancers originating in other organs. This means that a cancerous neoplasm has developed in another organ elsewhere in the body and that cancer cells have leaked from that primary tumor and then entered the lymphatic system and blood vessels. These are most common among brain tumors. #n the %nited (tates there are about :HA,AAA new cases every year. 9C; They then circulate through the bloodstream, and are deposited in the brain. There, these cells continue growing and dividing, becoming another invasive neoplasm of the primary cancer7s tissue. (econdary tumors of the brain are very common in the terminal phases of patients with an incurable metastasi$ed cancer" the most common types of cancers that bring about secondary tumors of the brain are lung cancer, breast cancer, malignant melanoma, kidney cancer and colon cancer (in decreasing order of fre0uency). (econdary brain tumors are the most common cause of tumors in the intracranial cavity. The skull bone structure can also be sub4ect to a neoplasm that by its very nature reduces the volume of the intracranial cavity, and can damage the brain.
[edit]By

behavior

Brain tumors or intracranial neoplasms can be cancerous (malignant) or non cancerous (benign). !owever, the definitions of malignant or benign neoplasms differs from those commonly used in other types of cancerous or non cancerous neoplasms in the body. #n cancers elsewhere in the body, three malignant properties differentiate benign tumors

from malignant forms of cancer* benign tumors are self limited and do not invade or metastasi$e. /haracteristics of malignant tumors include*

uncontrolled mitosis (growth by division beyond the normal limits) anaplasia* the cells in the neoplasm have an obviously different form (in si$e and shape). Anaplastic cells display markedpleomorphism. The cell nuclei are characteristically e&tremely hyperchromatic (darkly stained) and enlarged" the nucleus might have the same si$e as the cytoplasm of the cell (nuclear cytoplasmic ratio may approach :*:, instead of the normal :*? or :*E ratio).8iant cells + considerably larger than their neighbors + may form and possess either one enormous nucleus or several nuclei (syncytia). Anaplastic nuclei are variable and bi$arre in si$e and shape.

invasion or infiltration (medical literature uses these terms as synonymous e0uivalents. !owever, for clarity, the articles that follow adhere to a convention that they mean slightly different things" this convention is not followed outside these articles)*

#nvasion or invasiveness is the spatial e&pansion of the tumor through uncontrolled mitosis, in the sense that the neoplasm invades the space occupied by ad4acent tissue, thereby pushing the other tissue aside and eventually compressing the tissue. =ften these tumors are associated with clearly outlined tumors in imaging.

#nfiltration is the behavior of the tumor either to grow (microscopic) tentacles that push into the surrounding tissue (often making the outline of the tumor undefined or diffuse) or to have tumor cells ,seeded, into the tissue beyond the circumference of the tumorous mass" this does not mean that an infiltrative tumor does not take up space or does not compress the surrounding tissue as it grows, but an infiltrating neoplasm makes it difficult to say where the tumor ends and the healthy tissue starts.

metastasis (spread to other locations in the body via lymph or blood).

=f the above malignant characteristics, some elements do not apply to primary neoplasms of the brain*

'rimary brain tumors rarely metastasi$e to other organs" some forms of primary brain tumors can metastasi$e but will not spread outside the intracranial cavity or the central spinal canal. 3ue to the blood+brain barrier cancerous cells of a primary neoplasm cannot enter the bloodstream and get carried to another location in the body. (=ccasional isolated

case reports suggest spread of certain brain tumors outside the central nervous system, e.g. bone metastasis of glioblastoma multiforme.9I;)

'rimary brain tumors generally are invasive (i.e. they will e&pand spatially and intrude into the space occupied by other brain tissue and compress those brain tissues), however some of the more malignant primary brain tumors will infiltrate the surrounding tissue.

=f numerous grading systems in use for the classification of tumor of the central nervous system, the World !ealth =rgani$ation (W!=) grading system is commonly used for astrocytoma. Fstablished in :II. in an effort to eliminate confusion regarding diagnoses, the W!= system established a four tiered histologic grading guideline for astrocytomas that assigns a grade from : to ?, with : being the least aggressive and ? being the most aggressive. [edit]Treatment When a brain tumor is diagnosed, a medical team will be formed to assess the treatment options presented by the leading surgeon to the patient and his-her family. 8iven the location of primary solid neoplasms of the brain in most cases a ,do nothing, option is usually not presented. Deurosurgeons take the time to observe the evolution of the neoplasm before proposing a management plan to the patient and his-her relatives. These various types of treatment are available depending on neoplasm type and location and may be combined to give the best chances of survival*

surgery* complete or partial resection of the tumor with the ob4ective of removing as many tumor cells as possible radiotherapy* the most commonly used treatment for brain tumors" the tumor is irradiated with beta, & rays or gamma rays.

chemotherapy* is a treatment option for cancer, however it is seldom used to treat brain tumors as the blood and brain barrier prevents the drugs from reaching the cancerous cells. /hemotherapy can be thought of as a poison that prevents the growth and division of all cells in the body including cancerous cells. Thus the significant side effects associated and e&perienced by patients undergoing chemotherapy.

A variety of e&perimental therapies are available through clinical trials9:A;

(urvival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the e&tent of surgical tumor removal and other factors specific to each case.9::; [edit]Surgery The primary and most desired course of action described in medical literature is surgical removal (resection) via craniotomy. 6inimally invasive techni0ues are being studied but are far from being common practice. The prime remediating ob4ective of surgery is to remove as many tumor cells as possible, with complete removal being the best outcome and cytoreduction (,debulking,) of the tumor otherwise. #n some cases access to the tumor is impossible and impedes or prohibits surgery. 6any meningiomas, with the e&ception of some tumors located at the skull base, can be successfully removed surgically. 6ostpituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base (trans nasal, trans sphenoidal approach). 1arge pituitary adenomas re0uire a craniotomy (opening of the skull) for their removal. >adiotherapy, including stereotactic approaches, is reserved for inoperable cases. (everal current research studies aim to improve the surgical removal of brain tumors by labeling tumor cells with @ aminolevulinic acidthat causes them to fluoresce. 9:<; 'ostoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors. >adiotherapy may also be administered in cases of ,low grade, gliomas, when a significant tumor burden reduction could not be achieved surgically. Any person undergoing brain surgery may suffer from epileptic sei$ures. (ei$ures can vary from absences to severe tonic clonic attacks. 6edication is prescribed and administered to minimi$e or eliminate the occurrence of sei$ures. 6ultiple metastatic tumors are generally treated with radiotherapy and chemotherapy rather than surgery and the prognosis in such cases is determined by the primary tumor, but is generally poor. [edit]

adiation therapy

The goal of radiation therapy is to selectively kill tumor cells while leaving normal brain tissue unharmed. #n standard e&ternal beam radiation therapy, multiple treatments of standard dose ,fractions, of radiation are applied to the brain. This process is repeated

for a total of :A to .A treatments, depending on the type of tumor. This additional treatment provides some patients with improved outcomes and longer survival rates. >adiosurgery is a treatment method that uses computeri$ed calculations to focus radiation at the site of the tumor while minimi$ing the radiation dose to the surrounding brain. >adiosurgery may be an ad4unct to other treatments, or it may represent the primary treatment techni0ue for some tumors. >adiotherapy may be used following, or in some cases in place of, resection of the tumor. 2orms of radiotherapy used for brain cancer include e&ternal beam radiation therapy, brachytherapy, and in more difficult cases, stereotactic radiosurgery, such as 8amma knife,/yberknife or Dovalis T& radiosurgery.9:.; >adiotherapy is the most common treatment for secondary brain tumors. The amount of radiotherapy depends on the si$e of the area of the brain affected by cancer. /onventional e&ternal beam 7whole brain radiotherapy treatment7 (WB>T) or 7whole brain irradiation7 may be suggested if there is a risk that other secondary tumors will develop in the future.9:?; (tereotactic radiotherapy is usually recommended in cases involving fewer than three small secondary brain tumors. #n <AAC a study published by the %niversity of Te&as 6. 3. Anderson /ancer /enter indicated that cancer patients who receive stereotactic radiosurgery ((>() and whole brain radiation therapy (WB>T) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with (>( alone.9:@;9:E; [edit]Chemotherapy 'atients undergoing chemotherapy are administered drugs designed to kill tumor cells. Although chemotherapy may improve overall survival in patients with the most malignant primary brain tumors, it does so in only about <A percent of patients. /hemotherapy is often used in young children instead of radiation, as radiation may have negative effects on the developing brain. The decision to prescribe this treatment is based on a patientJs overall health, type of tumor, and e&tent of the cancer. The to&icity and many side effects of the drugs, and the uncertain outcome of chemotherapy in brain tumors puts this treatment further down the line of treatment options with surgery and radiation therapy preferred. %/1A Deuro =ncology publishes real time survival data for patients with a diagnosis of glioblastoma multiforme. They are the only institution in the %nited (tates that displays

how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high grade glioma tumors. 9:H; [edit]!ther A shunt is used not as a cure but to relieve symptoms by reducing hydrocephalus caused by blockage of cerebrospinal fluid.9:C; >esearchers are presently investigating a number of promising new treatments including gene therapy, highly focused radiation therapy, immunotherapy and novel chemotherapies. A variety of new treatments are being made available on an investigational basis at centers speciali$ing in brain tumor therapies. [edit]Prognosis The prognosis of brain cancer varies based on the type of cancer. 6edulloblastoma has a good prognosis with chemotherapy, radiotherapy, and surgical resection while glioblastoma multiforme has a median survival of only :< months even with aggressivechemoradiotherapy and surgery. Brainstem gliomas have the poorest prognosis of any form of brain cancer, with most patients dying within one year, even with therapy that typically consists of radiation to the tumor along with corticosteroids. !owever, one type of brainstem glioma, a focal 9:I; seems open to e&ceptional prognosis and long term survival has fre0uently been reported. [edit]"lioblastoma

multiforme

Main article: Glioblastoma multiforme

8lioblastoma multiforme is the deadliest and most common form of malignant brain tumor. Fven when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical e&cision is used, median survival is only :<+:H months. (tandard therapy for glioblastoma multiforme consists of ma&imal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer, then by chemotherapy. 6ost patients with glioblastoma take a corticosteroid, typicallyde&amethasone, during their illness to palliate symptoms. F&perimental treatments include gamma knife radiosurgery,9<A; boron neutron capture therapy and gene transfer.9<:; [edit]!ligodendrogliomas
Main article: Oligodendroglioma

=ligodendroglioma is an incurable but slowly progressive malignant brain tumor. They can be treated with surgical resection,chemotherapy, and-or radiotherapy. 2or suspected low grade oligodendrogliomas in select patients, some neuro oncologists opt for a course of watchful waiting, with only symptomatic therapy. Tumors with the :p-:I0 co deletion have been found to be especially chemosensitive, and one source reports oligodendrogliomas to be ,among the most chemosensitive of human solid malignancies,.9<<; A median survival of up to :E.H years has been reported for low grade oligodendrogliomas.9<.; [edit]#pidemiology The incidence of low grade astrocytoma has not been shown to vary significantly with nationality. !owever, studies e&amining the incidence of malignant /D( tumors have shown some variation with national origin. (ince some high grade lesions arise from low grade tumors, these trends are worth mentioning. (pecifically, the incidence of /D( tumors in the %nited (tates, #srael, and the Dordic countries is relatively high, while Kapan and Asian countries have a lower incidence. These differences probably reflect some biological differences as well as differences in pathologic diagnosis and reporting.
9<?;

Worldwide data on incidence of cancer can be found at the W!= (World !ealth =rganisation) and is handled by the A#>/ (Agency for #nteranctional >esearch on /ancer) located in 2rance.9<@; 2igures for incidences of cancers of the brain show a significant difference between more and less developed countries (the less developed countries have lower incidences of tumors of the brain) this could be e&plained by undiagnosed tumor related deaths (patients in e&treme poor situations do not get diagnosed, simply because they do not have access to the modern diagnostic facilities re0uired to diagnose a brain tumor) and by deaths caused by other poverty related causes that preempt a patient7s life before tumors develop or tumors become life threatening. Devertheless studies9which?; suggest that certain forms of primary brain tumors are more prevalent among certain groups of the population. [edit]$nited

%ingdom

2rom the British national statistics data about new diagnoses of malignant neoplasms of the brain for the year <AAH (in absolute figures and in rates per :AA,AAA) 9<E;*

All 10 15 20 25 30 35 40 50 Measur Se DA Und 1 5 45 55 60 65 70 75 80 age 85+ es x SR er 1 4 9 49 59 64 69 74 79 84 s 14 19 24 29 34 39 44 54

M Absolut e figures F

2,13 7 1

34 40 31 37 33 48 61 87

10 116. 14 242 264 258 237 193 128 73 0 1 2

1,59 7 8

42 39 37 28 25 37 50 42 73 87

99 140 191 166 169 158 111 97

Rates M 7.7 8.5 2.1 per 100,00 0 in abita F 5.3 6.2 2.2 nts

2. 2. 15. 18. 24. 25. 26. 26. 21. 2.0 2.1 1.9 2.8 3.7 4.6 5.1 6.6 9.3 8 7 7 6 0 8 7 6 2

3. 2. 12. 14. 16. 17. 15. 12. 2.5 1.7 1.5 2.2 3.0 2.2 3.7 4.9 6.3 8.8 6 8 9 3 2 1 1 8

[edit]$nited

States

#n the %nited (tates in the year <AA@, it was estimated 9by whom?; there were ?.,CAA new cases of brain tumors (/entral Brain Tumor >egistry of the %nited (tates, 'rimary Brain Tumors in the %nited (tates, (tatistical >eport, <AA@+<AAE), 9<H; which accounted for less than : percent of all cancers, <.? percent of all cancer deaths, 9<C; and <A+<@ percent of pediatric cancers.9<C;9<I; %ltimately, it is estimated there are :.,AAA deaths per year in the %nited (tates alone as a result of brain tumors.9<H; [edit]De&eloping

Countries

While cancer survival rates are increasing in the %nited (tates, children in developing countries are suffering because of the lack of advanced health care systems. 6ore than EA percent of the world7s children with cancer have little or no access to effective therapy, and their survival rates are predictably inferior to those in countries with advanced health care systems.9.A; [edit]

esearch

[edit]'esicular

stomatitis &irus

#n <AAA, researchers at the %niversity of =ttawa, led by Kohn Bell 'h3., discovered that the vesicular stomatitis virus, or )(), can infect and kill cancer cells, without affecting healthy cells if coadministered with interferon.9.:;9.<; The initial discovery of the virus7 oncolytic properties were limited to only a few types of cancer. (everal independent studies have identified many more types susceptible to the virus, including glioblastoma multiforme cancer cells, which account for the ma4ority of brain tumors. #n <AAC, researchers artificially engineered strains of )() that were less cytoto&ic to normal cells. This advance allows administration of the virus without coadministration with interferon. /onse0uently administration of the virus can be given intravenously or through theolfactory nerve. #n the research, a human brain tumor was implanted into mice brains. >esearch on virus treatment like this has been conducted for some years, but no other viruses have been shown to be as efficient or specific as the )() mutant strains. 2uture research will focus on the risks of this treatment, before it can be applied to humans. 9..; [edit]

etro&iral replicating &ectors

1ed by 'rof. Dori Lasahara, researchers from %(/, who are now at %/1A, reported in <AA: the first successful e&ample of applying the use of retroviral replicating vectors towards transducing cell lines derived from solid tumors. 9.?; Building on this initial work, the researchers applied the technology to in vivo models of cancer and in <AA@ reported a long term survival benefit in an e&perimental brain tumor animal model. 9.@; (ubse0uently, in preparation for human clinical trials, this technology was further developed by Tocagen, #nc. (Toca @:: G Toca 2/) and is currently under clinical investigation in a 'hase #-## trial for the potential treatment of recurrent high grade glioma including glioblastoma multiforme (8B6) and anaplastic astrocytoma. 9.E; [edit]In

children

A brainstem glioma in four year old. 6>#sagittal, without contrast

#n the %(, about <AAA children and adolescents younger than <A years of age are diagnosed with malignant brain tumors each year. !igher incidence rates were reported in :IC@+I? than in :IH@+C.. There is some debate as to the reasons" one theory is that the trend is the result of improved diagnosis and reporting, since the 4ump occurred at the same time that6>#s became available widely, and there was no coincident 4ump in mortality. The central nervous system (/D() cancer survival rate in children is appro&imately EAB. The rate varies with the type of cancer and the age of onset* younger patients have higher mortality. 9.H; #n children under <, about HAB of brain tumors are medulloblastoma, ependymoma, and low grade glioma. 1ess commonly, and seen usually in infants, are teratoma and atypical teratoid rhabdoid tumor.9.C; 8erm cell tumors, including teratoma, make up 4ust .B of pediatric primary brain tumors, but the worldwide incidence varies significantly. 9.I;
ttp!""en.#i$ipe%ia.org"#i$i"&rain'tu(or"p$! 17!22"14)anuari2013

Brain Neoplasms

Author* K (tephen !uff, 63" /hief Fditor* Barry F Brenner, 63, 'h3, 2A/F' ttp!""e(e%i*ine.(e%s*ape.*o("arti*le"779664+p$ 17!24"14)anuari2013

Bac(ground

Brain tumors may originate from neural elements within the brain, or they may represent spread of distant cancers. 'rimary brain tumors arise from /D( tissue and account for roughly half of all cases of intracranial neoplasms. The remainder of brain neoplasms are caused by metastatic lesions. #n adults, two thirds of primary brain tumors arise from structures above the tentorium (supratentorial), whereas in children, two thirds of brain tumors arise from structures below the tentorium (infratentorial). 8liomas, metastases, meningiomas, pituitary adenomas, and acoustic neuromas account for I@B of all brain tumors. /lassification by tumor cell type is irrelevant to the emergency physician because emergent treatment is the same regardless of the tumor type.

Deoplasms, brain. /T images of several tumor types. (lide courtesy of %6A(( /ontinuing Fducation =ffice.

6any review articles have been written on brain tumors, and this discussion at times draws from the consensus of these reviews. 9:, <, ., ?, @, E, H, C, I; 8lioma has recently been in the news with the diagnosis of this malignant brain tumor in 6ay <AAC in (enator Fdward 6. Lennedy and his death August <@, <AAI. 2or more information on this, see the 6edscape 6edical Dews article and theWeb63 !ealth Dews article.

Pathophysiology
Tumors of the brain produce neurologic manifestations through a number of mechanisms. (mall, critically located tumors may damage specific neural pathways traversing the brain. Tumors can invade, infiltrate, or supplant normal parenchymal tissue, disrupting normal function. Because the brain dwells in the limited volume of the cranial vault, growth of intracranial tumors with accompanying edema may cause increased intracranial pressure. Tumors ad4acent to the third and fourth ventricles may impede the flow of cerebrospinal fluid, leading to obstructive hydrocephalus. #n addition, tumors generate new blood vessels (ie, angiogenesis), disrupting the normal blood brain barrier and promoting edema.

Deoplasms, brain. /olloid cyst of the third ventricle with obstructive hydrocephalus. #mage courtesy of 'eter 2errera, 63.

The cumulative effects of tumor invasion, edema, and hydrocephalus may elevate the intracranial pressure (#/') and impair cerebral perfusion. #ntracranial compartmental rise in #/' may provoke shifting or herniation of tissue under the fal& cerebri, through the tentorium cerebelli, or through the foramen magnum. (low growing tumors, particularly tumors e&panding in the so called silent areas of the brain, such as the frontal lobe, may be associated with a more insidious clinical course. These tumors tend to be larger at detection. 6ost primary brain tumors do not metastasi$e, but if they do metastasi$e, intracranial spread generally precedes distant dissemination. 6etastatic brain tumors from non /D( primary tumors may be the first sign of malignancy, or they may herald a relapse. Donetheless, the signs and symptoms of brain metastases simulate those of primary brain tumors. 1eptomeningeal infiltration may present with dysfunction of multiple cranial nerves.

#pidemiology
)re*uency
United States

Fstimates of the annual incidence rate of primary brain tumors range from H :I.: cases per :AA,AAA population. 6etastatic tumors to the brain are more common with more than <AA,AAA patients per year in the %nited (tates with a new diagnosis of intracranial metastases. An increase in the prevalence of !#) infection corresponds to an increase in the occurrence of primary /D( lymphoma. 'ituitary adenomas are e&ceptionally common, and they are fre0uent incidental findings on autopsy. Autopsy series of patients with systemic cancer show that intracranial metastases are present in :C <?B of patients.
International

The international incidence is not known, but it is thought to parallel that of the %nited (tates.

Mortality+Morbidity

#n the %nited (tates in :III, primary cancers of the central nervous system were the cause of death in appro&imately :.,:AA people. Brain tumors are the second most common cancer in children, comprising :@ <@B of all pediatric malignancies. 'erhaps no other cancer is as feared as brain tumor since severe disability, including paralysis, sei$ures, gait disturbances, and impairment of intellectual capacity may occur.

ace
3ifferences are seen between ethnic groups within the same country, and a . fold difference in incidence has been reported between countries worldwide. 3eveloped countries appear to have the highest rates, but this may reflect better registration systems.

Se,
6eningiomas and pituitary adenomas are slightly more common in women than in men. 6ales are more likely to be diagnosed with brain tumors than females, with a male to female ratio of :.@*:.

Age

Tumors in the posterior fossa predominate in preadolescent children, with the incidence of supratentorial tumors increasing from adolescence to adulthood. 1ow grade gliomas, such as astrocytomas, are more common in younger people than in older people. !igh grade gliomas, such as anaplastic astrocytoma andglioblastoma multiforme, tend to originate in the fourth or fifth decade or beyond. #n children, brain tumors are the most prevalent solid tumor, second only to leukemia as a cause of pediatric cancer. The incidence rate of primary /D( neoplasms is ..E cases per :AA,AAA children each year.

-istory
'resenting complaints of patients with an intracranial neoplasm tend to be similar for primary brain tumors and intracranial metastases. 6anifestations depend on the cause of the symptoms* an increase in #/', direct compression of essential gray or white matter, shifting of intracranial contents, or secondary cerebral ischemia. (ymptoms may be nonspecific and include headache, altered mental status, ata&ia, nausea, vomiting, weakness, and gait disturbance. /D( neoplasms also may manifest as focal sei$ures, fi&ed visual changes, speech deficits, or focal sensory abnormalities. The onset of symptoms usually is insidious, but an acute episode may occur with bleeding into the tumor, or when an intraventricular tumor suddenly occludes the third ventricle. #n one study of children with brain tumors, time from symptom onset to diagnosis of a brain tumor was found to be ... months. !ead tilt, cranial nerve palsies, endocrine and growth abnormalities and reduced visual acuity were associated with a longer symptom

interval. !eadache was the number one symptom e&perienced in more than half of patients.9:A; Although headache is the symptom customarily associated with an intracranial neoplasm, it often is a late complaint. %sually, headache is not an isolated finding. o !eadache is the worst symptom in only one half of patients. o 6ost headaches in patients with brain tumors are nonspecific and resemble tension type headaches.9C, ::, :<; o A change in any patient7s headache pattern may be cause for concern. o Dew onset of headaches in middle aged or older patients is worrisome. o The location of the headache reliably indicates the side of the head affected, but it does not indicate the precise site of the tumor. o !eadaches are more common with posterior fossa tumors. o !eadache is a more fre0uent symptom of intracranial tumor in pediatric patients. o 'revailing inaccurate portrayals of a tumor headache include pain that is worse in the early morning than at other times" vomiting (with or without nausea)" and e&acerbation with )alsalva maneuvers, bending over, or rising from a recumbent position. 6ental status changes, especially memory loss and decreased alertness, may be subtle clues of a frontal lobe tumor. /omplaints may be as mundane as sleeping longer, appearing preoccupied while awake, and apathy. o Temporal lobe neoplasms may lead to depersonali$ation, emotional changes, and behavioral disturbances. o )ision, smell, and other sensory disturbances may be caused by a brain tumor. o An acoustic neuroma may present as intermittent (then progressive) hearing loss, dise0uilibrium, and tinnitus. o (ymptoms of pediatric posterior fossa tumors include increased irritability, unsteadiness, ata&ia, headache, vomiting, and progressive obtundation. o (upratentorial tumors in children are more commonly associated with sei$ures, hemiparesis, visual field cuts, speech difficulties, and intellectual disturbance. o 'ituitary adenomas may be divided into < broad categories* nonfunctional and hypersecretory. Donfunctional pituitary adenomas remain asymptomatic until they are large enough to encroach the optic chiasm and disturb normal vision. 6ost hypersecretory pituitary adenomas secrete prolactin, with affected women noting an amenorrhea galactorrhea syndrome. 6en with prolactin pituitary adenomas more commonly complain of headache, visual problems, and impotence. (ei$ures, focal or generali$ed, may be the earliest e&pression of a brain tumor. o A Kacksonian pattern, ie, one in which a focal sei$ure begins in one e&tremity and then progresses until it becomes generali$ed, is distinctive in suggesting a focal structural lesion of the corte&. o 3epending on the rate of growth of the tumor, sei$ures may be present for months to years before a brain tumor is diagnosed.

o o

Any middle aged or elderly patients presenting with a first sei$ure should have /D( tumor high in the differential diagnosis. 'atients with a brain tumor may present with acute neurologic changes mimicking those associated with stroke.

Physical
Do physical finding or pattern of findings unmistakably identifies a patient with a /D( neoplasm.

Based on their location, intracranial tumors may produce a focal or generali$ed deficit, but signs may be lacking (especially if the tumor is confined to the frontal lobe) or even falsely locali$ing. 'apilledema, which is more prevalent with pediatric brain tumors, reflects an increase in #/' of several days or longer. 'apilledema usually does not cause visual loss. Dot all patients with /D( tumors develop papilledema. 3iplopia may result from displacement or compression of the si&th cranial nerve at the base of the brain. #mpaired upward ga$e, called 'arinaud syndrome, may occur with pineal tumors. Tumors of the occipital lobe specifically may produce homonymous hemianopia

or partial visual field deficits.

glioblastoma with surrounding edema.

Deoplasms, brain. =ccipital lobe

Anosmia may occur with frontal lobe tumors. Brainstem and cerebellar tumors induce cranial nerve palsies, ata&ia, incoordination, nystagmus, pyramidal signs, and sensory deficits on one or both sides of the body. o Three cranial nerves run through the cerebellopontine angle* facial, cochlear, and vestibular. 6asses in these regions may impair the functions of these nerves. o Acoustic neuromas most commonly originate from the vestibular nerve (part of cranial nerve )###).

Causes
Although few factors are une0uivocally associated with an increased risk of brain cancer, some are conse0uential.

6ost /D( neoplasms are thought to arise from individual cell mutations.

A prior history of irradiation to the head for reasons other than treatment of the present tumor may increase the chance of primary brain tumor. A few inherited diseases, such as neurofibromatosis, tuberous sclerosis, multiple endocrine neoplasia (type :), and retinoblastoma, increase the predilection to develop /D( tumors. The most common tumors originating from the cerebellopontine angle are acoustic neuroma and meningioma. 'rimary /D( lymphoma is a relatively fre0uent occurrence in !#) patients. 6etastatic tumors reach the brain via hematogenous dissemination through the arterial system. o 1ung cancer is by far the most common solid tumor disseminating to the brain, followed by breast, melanoma, and colon cancer. o 1ess common sources of metastasis are malignant melanoma,testicular cancer, and renal cell cancer. o 'rostate, uterine, and ovarian cancers are unlikely sources of brain metastasis.

Differential Diagnoses

Fncephalitis Fpidural !ematoma (troke, !emorrhagic (troke, #schemic (ubdural !ematoma

.aboratory Studies
'atients with cancer are predisposed to medical complications, including bleeding disturbances (hyperviscosity), metabolic disorders (hypercalcemia), and production of e&cessive hormones (syndrome of inappropriate antidiuretic hormone secretion). With clinical suspicion of cancer, obtain routine laboratory studies on admission, including a /B/, coagulation studies, and analysis of electrolytes and comprehensive metabolic panel.

Imaging Studies
=btain neuroimaging studies in patients with symptoms suggestive of an intracranial neoplasm (eg, acute mental status changes" new onset sei$ures" focal, motor, or sensory deficits, including gait disturbance" suspicious headache" signs of elevated #/', such as papilledema). Although some tumors e&hibit a characteristic appearance, do not make an une0uivocal diagnosis based solely on radiologic findings. 8enerally, /T is the imaging modality of choice for the F3 physician. #ntravenous contrast material assists in tumor identification. 6ost tumors demonstrate enhancement with contrast material administration. Tumors may appear hypodense, isodense, or hyperdense, or they may have mi&ed density. 6etastases to the brain tend to be multiple, but certain tumors, such as renal cell carcinomas, tend to be solitary metastatic brain lesions.

With increasing availability, 6>#s may supplant /Ts as the imaging procedures of choice. An 6># is most helpful for identifying tumors in the posterior fossa (including acoustic neuromas), hemorrhagic lesions. #t is useful in patients with an allergy to iodinated contrast material or renal insufficiency. 3rawbacks to 6># include incompatibility with certain medical e0uipment, longer imaging times (increased risk of motion artifact), and poor visuali$ation of the subarachnoid space. Deither /T nor 6># can be used to differentiate tumor recurrence from radionecrosis. =n plain skull radiographs, large pituitary adenomas are associated with a large sella turcica.

Procedures

1umbar puncture is not indicated in the F3 in the patient with suspected /D( neoplasms.

Prehospital Care
'rehospital care is supportive and directed to the presenting symptom comple&. 2or e&ample, treat sei$ures in the usual manner. Airway disturbance, breathing difficulty, signs of pronounced elevation in #/', and notable impairment of consciousness may necessitate definitive airway control with endotracheal intubation and, possibly, hyperventilation.

#mergency Department Care

F3 treatment of the patient with an intracerebral neoplasm depends on both the nature of the tumor and the general condition of the patient. 3ecisions regarding surgical resection, initiation of radiation treatment, and chemotherapy are beyond the scope of practice of the F3 physician. /orticosteroids may dramatically reduce signs and symptoms related to cerebral edema. Affected patients may e&perience relief within the first few hours of steroid therapy. o 3e&amethasone is the agent of choice because of its minimal salt retaining properties. >ecommended doses generally range from ? <? mg daily. 2or patients with impaired consciousness or signs of increased intracranial pressure, :A mg #)9?; or :A <? mg #) are recommended as the first dose. (ide effects, notably pro&imal muscle weakness, are dose dependent. =ften, corticosteroids can be tapered or discontinued after definitive therapy. The final dose of steroids should be the lowest necessary to control the patient7s neurologic symptoms. 2or patients with signs or symptoms of impending herniation and airway compromise, consider use of ad4unctive medications for rapid se0uence intubation. These might include lidocaine and medication for rapid onset neuromuscular blockade, with precautions to diminish fasciculations. #nduction agents, such as thiopental, may be used. After definitive control of the airway, consider gentle hyperventilation.

3iscuss the use of mannitol with the appropriate consultant. Although mannitol may reduce transiently lower #/', concern about rebound increases in #/' makes its use problematic.

Consultations
1ocal practice patterns govern re0uests for consultations.

8enerally, care of patients with a brain tumor is multidisciplinary, re0uiring assistance from a neurosurgeon, an oncologist, a radiologist, and an e&pert in radiation therapy. 6anagement varies greatly depending on tumor location, tissue type, and comorbid conditions. (urgical treatment options may include tumor removal or debulking, installation of a ventricular shunt, and placement of radioactive implants.

Medication Summary
'ractice parameters from the American Academy of Deurology discourage prophylactic use of anticonvulsants for sei$ures in patients with newly diagnosed brain tumors and suggest that it is appropriate to taper and discontinue anticonvulsant use postoperatively in patients without sei$ures.9:.; Anticonvulsant use may be reserved for patients with clinical sei$ures, but some physicians prescribe prophylactic anticonvulsants in patients with cortical tumors.

Corticosteroids
Class Summary
(teroids are thought to stabili$e cell membranes and diminish the vasogenic edema associated with tumors.
)iew full drug information

De,amethasone /Decadron0
%sed in treatment of vasogenic cerebral edema" improves endothelial integrity.

-yperosmolar agents
Class Summary
These agents may reduce #/' and cerebral edema by creating an osmotic gradient across an intact blood brain barrier. As water diffuses from the brain into the intravascular compartment, #/' decreases.
)iew full drug information

Mannitol /!smitrol0

6ay reduce subarachnoid space pressure by creating osmotic gradient between cerebrospinal fluid in arachnoid space and plasma. Dot for long term use.

)urther Inpatient Care

2urther inpatient care is comple& and may involve multiple consultants, depending on the tumor type and overall prognosis. 3efinitive diagnosis re0uires tissue biopsy performed by a 0ualified neurosurgeon. Additional neurosurgical options include resection or debulking and placement of a ventricular shunt with obstructive hydrocephalus. The admitting physician should coordinate oncologic or radiation oncology consultations.

)urther !utpatient Care

The patient7s primary physician best manages coordination of consultants, but the responsible neurosurgeon should direct the treatment of specific postoperative complications or care. A common problem confronting the F3 physician is a patient with a known brain neoplasm complaining of a headache or worsening other symptoms. This scenario always raises the possibility of tumor recurrence or worsening cerebral edema. =btain a /T scan or 6># to rule out life threatening events, such as hemorrhage or herniation. >adiation therapy for gliomas usually is performed on an outpatient basis.

Inpatient 1 !utpatient Medications

(teroids or anticonvulsants may be used. 'rovide medications for patient comfort and pain control.

Transfer
Dew occurrence of /D( tumor may re0uire transfer to a facility with appropriate neurosurgical staff. (peak directly to the consultant prior to transfer to address initiation of steroid or anticonvulsant treatment.

Complications
Acute symptoms in a patient with a brain tumor, particularly when signs and symptoms simulate the presentation of a cerebrovascular accident, suggest the possibility of acute hemorrhage into a tumor. Brain neoplasms predisposed to hemorrhage include lung cancer, melanoma, and choriocarcinoma. 1esions near the third ventricle can cause paro&ysmal symptoms of headache, syncope, or mental status change. Additionally, vomiting, ata&ia, memory changes, visual disturbances, or personality changes may occur. Fpisodic increases in #/' secondary to pressure arising from blockage of cerebrospinal fluid outflow cause transient symptoms. (udden death is a reported complication from obstruction of outflow drainage from the third ventricle.

(udden increases in #/' may lead to life threatening brain herniation, which shifts the brain parenchyma in the direction of least resistance* caudally through the foramen magnum (posterior fossa tumors) or transtentorial apertures. (ome pituitary tumors are hormonally active and capable of producing acromegaly or galactorrhea. 'ituitary apople&y, an unusual complication arising from pituitary adenomas, describes hemorrhage into the tumor, leading to headache, deterioration of vision, oculomotor palsies, and shock secondary to acute adrenal insufficiency. Although radiation therapy rarely causes acute to&icity with modern dosing schedules and concomitant use of steroids, subacute or chronic effects may occur. (ubacute encephalopathy occurs E :E weeks after radiation therapy and is characteri$ed by somnolence and headaches. /hronic effects of prolonged radiation treatment tend to be more serious and range from impairment of intellectual capacity to complete incapacity.

Prognosis

Tumor resectability, tumor location, age of the patient, and tumor histology are the primary determinants of survival. Without radiation therapy, the mean life e&pectancy of a patient with brain metastases is : month. >adiation therapy may e&tend survival to ? E months. 'atients with sei$ures secondary to a brain tumor generally e&perience obvious neurologic deterioration over a E month course. 6ost patients with brain metastases die from progression of their primary malignancy rather than from brain damage.

Patient #ducation

2or e&cellent patient education resources, visit e6edicine!ealth7s /ancer /enter. Also, see e6edicine!ealth7s patient education article Brain /ancer.

Brain Cancer Staging

Author* Keffrey D Bruce, 63" /hief Fditor* Kules F !arris, 63 ttp!""e(e%i*ine.(e%s*ape.*o("arti*le"2006770"p$.17!33"14 )anuari 2013

Staging of Brain Cancers

The histologic classification employed by the World !ealth =rgani$ation (W!=) for central nervous system (/D() tumors, shown below, makes use of ? grades. 9:, <;

2-! histologic grading for C3S tumors

Grade I:

1esions with low proliferative potential, a fre0uently discrete nature, and the possibility of cure following surgical resection alone Kuvenile pilocytic astrocytoma, subependymal giant cell astrocytoma

Grade II:

1esions that are generally infiltrating and low in mitotic activity but recur" some tumor types tend to progress to higher grades of malignancy 3iffuse astrocytoma, oligodendroglioma, oligoastrocytoma

Grade III:

1esions with histologic evidence of malignancy, generally in the form of mitotic activity, clearly e&pressed infiltrative capabilities, and anaplasia Anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligoastrocytoma

Grade IV:

1esions that are mitotically active, necrosis prone, and generally associated with a rapid preoperative and postoperative evolution of disease 8lioblastoma

Brain Cancer Treatment Protocols

Author* Keffrey D Bruce, 63" /hief Fditor* Kules F !arris, 63 ttp!""e(e%i*ine.(e%s*ape.*o("arti*le"2005182"p$.17!36"14,anuari2013

Treatment Protocols
(urgical resection is the primary treatment for all tumor grades. The surgical goal is gross total resection, though less aggressive resection is employed for tumor involving elo0uent brain. There is significant divergence of opinion, particularly for grade ## lesions, especially for grade ## astrocytoma. >adiation and chemotherapy dosages vary considerably among institutions. Those below represent successful regimens from recent clinical trials. 3e&amethasone and sei$ure treatment or prophyla&is is commonly appropriate. 9:, <, ., ?, @, E, H,
C, I, :A, ::, :<;

Treatment recommendations based on grade

Grade I (pilocytic astrocytomas):

These lesions are typically uncommon and noninvasive and are considered benign and potentially curable by surgery" when total surgical removal is not possible, radiation therapy or e&pectant management is typically employed

Grade II (low grade infiltrati!e astrocytomas" oligodendroglioma" mi#ed gliomas):

(urgery is recommended for grade ## with ma&imal safe resection %nfavorable prognostic factors include age M ?Ay, astrocytoma histology, largest dimension of tumor N E cm, tumor crossing midline, and presence of neurologic deficit before resection" patients with up to < of these are considered low risk" patients with . or more are high risk9:.; 1ow risk patients should undergo observation, as well as patients who are O ?Ay" high risk patients should be treated with fractionated e&ternal beam radiation therapy or ad4uvant chemotherapy9:.; The standard radiation for low grade astrocytomas is ?@ @? 8y, delivered in :.C to <.A 8y fractions9:.; Ad4uvant therapy includes temo$olomide H@ mg-m<-day on days : <: of <C d cycle9:?;

'ostoperative radiation therapy is often employed for unresectable, residual, or recurrent tumor /hemotherapy is often used for low grade oligodendrogliomas, particularly with :p:I0 deletion, which is a marker for tumor susceptibility to chemotherapy9:, <, .;

Grade III (anaplastic astrocytoma" oligoastrocytoma or oligoastrocytoma):

The standard of care is surgical resection followed by e&ternal beam radiation therapy (EA 8y in .A .@ fractions) and ad4uvant temo$olomide H@ mg-m<-day, usually : :.@h before radiation9E, H, C, I; 'ost+radiation therapy* continue temo$olomide at higher doses of :@A <AA mg-m<-day '= for @d every <Cd or '/) (procarba$ine, lomustine, vincristine)* lomustine (//D%) :.A mg-m< on day : plus procarba$ine H@ mg-m< on days C <: plus vincristine :.? mg-m< on days C and <I" administer every Ewk for up to ? cycles9?, @, E; with deferred radiation therapy

Grade IV (glioblastoma):

The standard of care is surgical resection followed by e&ternal beam radiation therapy (EA 8y in .A .@ fractions) and ad4uvant temo$olomide H@ mg-m<-day, usually : :.@h before radiation9E, H, C, I; 'ost+radiation therapy* continue temo$olomide at higher doses of :@A <AA mg-m<-day '= for @d every <Cd

ecommendations for recurrent tumors

There is no standard therapy for recurrent brain cancer" patients who were spared radiation therapy or chemotherapy commonly undergo these therapies at recurrence" there are numerous agents being used in cases of primary treatment failure, as well as many ongoing clinical trials /urrent avenues available include antiangiogenic agents, tyrosine kinase inhibitors, convection enhanced delivery of chemotherapeutic agents or to&ins, cancer vaccines, and stereotactic radiosurgery