A brain tumor (sometimes referred to as brain cancer) occurs when a group of cells within the brain turn cancerous and grow out of control, creating a mass. There are two main types of tumors: malignant (cancerous) tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and secondary tumors, which most commonly have spread from tumors located outside the brain, known as brain metastasis tumors. All types of brain tumors may produce symptoms that vary depending on the size of the tumor and the part of the brain that is involved. Where symptoms exist, they may include headaches, seizures, problems with vision, vomiting and mental changes. Other symptoms may include difficulty walking, speaking, with sensations, or unconsciousness.
The cause of most brain tumors is unknown, though up to 4% of brain cancers may be caused by CT scan radiation. Uncommon risk factors include exposure to vinyl chloride, Epstein-Barr virus, ionizing radiation, and inherited syndromes such as neurofibromatosis, tuberous sclerosis, and von Hippel-Lindau Disease. Studies on mobile phone exposure have not shown a clear risk. The most common types of primary tumors in adults are meningiomas (usually benign) and astrocytomas such as glioblastomas. In children, the most common type is a malignant medulloblastoma. Diagnosis is usually by medical examination along with computed tomography (CT) or magnetic resonance imaging (MRI). The result is then often confirmed by a biopsy. Based on the finding, the tumors are divided into different grades of severity.
Treatment may include some combination of surgery, radiation therapy and chemotherapy. If seizures occur, anticonvulsant medication may be needed. Dexamethasone and furosemide are medications that may be used to decrease swelling around the tumor. Some tumors grow gradually, requiring only monitoring and possibly needing no further intervention. Treatments that use a person's immune system are being studied. Outcomes for malignant tumors vary considerably depending on the type of tumor and how far it has spread at diagnosis. Although benign tumors only grow in one area, they may still be life-threatening depending on their size and location. Malignant glioblastomas usually have very poor outcomes, while benign meningiomas usually have good outcomes. The average five-year survival rate for all (malignant) brain cancers in the United States is 33%.
Secondary, or metastatic, brain tumors are about four times as common as primary brain tumors, with about half of metastases coming from lung cancer. Primary brain tumors occur in around 250,000 people a year globally, and make up less than 2% of cancers. In children younger than 15, brain tumors are second only to acute lymphoblastic leukemia as the most common form of cancer. In New South Wales, Australia in 2005, the average lifetime economic cost of a case of brain cancer was AU$ 1.9 million, the greatest of any type of cancer.
Signs and symptoms
The signs and symptoms of brain tumors are broad. People may experience symptoms regardless of whether the tumor is benign (not cancerous) or cancerous. Primary and secondary brain tumors present with similar symptoms, depending on the location, size and rate of growth of the tumor. For example, larger tumors in the frontal lobe can cause changes in the ability to think. However, a smaller tumor in an area such as Wernicke's are (small area responsible for language comprehension) can result in a greater loss of function.
Headaches :
Headaches as a result of raised intracranial pressure can be an early symptom of brain cancer. However, isolated headache without other symptoms is rare, and other symptoms including visual abnormalities may occur before headaches become common. Certain warning sign for headache exist which make the headache more likely to be associated headache worsened by Valsalva maneuver, headache causing awakening from with brain cancer. These are defined as "abnormal neurological examination, sleep, new headache in the older population, progressively worsening headache, atypical headache features, or patients who do not fulfill the strict definition of migraine". Other associated signs are headaches that are worse in the morning or that subside after vomiting.
Location-specific symptoms :
The brain is divided into lobes and each lobe or area has its own function. A tumour in any of these lobes may affect the area's performance. The symptoms experienced are often linked to the location of the tumour, but each person may experience something different.
- Frontal lobe: Tumours may contribute to poor reasoning, inappropriate social behavior, personality changes, poor planning, lower inhibition, and decreased production of speech (Broca's area).
- Temporal lobe : Tumours in this lobe may contribute to poor memory, loss of hearing, and difficulty in language comprehension (Wernicke's area is located in this lobe).
- Parietal lobe : Tumours here may result in poor interpretaion of languages, difficulty with speaking, writing, drawing, naming, and recognizing, and poor spatial and visual perception.
- Occipital lobe : Damage to this lobe may result in poor vision or loss of vision.
- Cerebellum : Tumours in this area may cause poor balance, muscle movement, and posture.
- Brain stem : Tumours on the brainstem can cause seizures, endocrine problems, respiratory changes, visual changes, headaches and partial paralysis.
- Leptomeninges : Tumours that spread to the leptomeninges, the lining of the brain, may cause cranial nerve palsies such as facial paralysis, abnormalities of eye movement, abnormalities of facial sensation or swallowing difficulty, depending on which cranial nerves are involved.
A person's personality may be altered due to the tumor damaging lobes of the brain. Since the frontal, temporal, and parietal lobes control inhibition, emotions, mood, judgement, reasoning, and behavior, a tumor in those regions can cause inappropriate social behavior, temper tantrums, laughing at things which merit no laughter, and even psychological symptoms such as depression and anxiety. More research is needed into the effectiveness and safety of medication for depression in people with brain tumors.
Personality changes can have damaging effects such as unemployment, unstable relationships, and a lack of control.
Cause
A known cause of brain cancers is ionizing radiation. Approximately 4% of brain cancers in the general population are caused by CT-scan radiation. For brain cancers that follow a CT scan at lags of 2 years or more, it has been estimated that 40% are attributable to CT-scan radiation. The risk of brain cancer is dose dependent, with the relative risk increasing by 0.8 for each 100 gray of ionizing radiation received. At this dose, approximately 6391 people would have to be exposed to cause 1 case of brain cancer. Ionizing radiation to the head as part of treatment for other cancers is also a risk factor for developing brain cancer.
Mutations and deletions of tumor suppressor ganes, such as P53, are thought to be the cause of some forms of brain tumor. Inherited conditions, such as Von Hippel- Lindau disease, tuberous sclerosis, multiple endorine neoplasia, And neurofibromatosis type 2 carry a high risk for the development of brain tumors. People with celiac disease have a slightly increased risk of developing brain tumors. Smoking may increase the risk, but evidence of this remains unclear.
Although studies have not shown any link between cell-phone or mobile-phone radiation and the occurrence of brain tumors, the World Health Organization has classified mobile-phone radiation on the IARC scale into Group 2B- Possibly carcinogenic. The claim that cell-phone usage may cause brain cancer is likely based on epidemiological studies which observed a slight increase in glioma risk among heavy users of wireless phones. When those studies were conducted, GSM (2G) phones were in use. Modern, third-generation (3G) phones emit, on average, about 1% of the energy emitted by those GSM (2G) phones, and therefore the finding of an association between cell-phone usage and increase risk of brain cancer is not based upon current phone usage.
Pathophysiology
Meninges
Human brains are surrounded by a system of connective tissue membrances called meninges that separate the brain from the skull. This three-layered covering is composed of (from the outside in) the dura mater, arachnoid mater, and pia matter. The arachnoid and pia are physically connected and thus often considered as a single layer, the leptomeninges. Between the arachnoid mater and the pia mater is the subarachnoid space which contains cerebrospinal fluid (CSF). This fluid circulates in the narrow spaces between cells and through the cavities in the brain called ventricles, to 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 joined tightly, forming the blood- brain barrier which protects the brain from toxins that might enter through the blood.
Tumors of the meninges are meningiomas and are often benign. Though not technically a tumor of brain tissue, they are often considered brain tumors since they protrude into the space where the brain is, causing symptoms. Since they are usually slow-growing tumors, meningiomas can be quite large by the time symptoms appear.
Brain matter
The three largest divisions of the brain are the cerebral cortex, cerebellum and the brainstem. These areas are composed of two broad classes of cells : neurons and glia. These two cell types are equally numerous in the brain as a whole, although glial cells outnumber neurons roughly 4 to 1 in the cerebral cortex. Glia come in several types, which perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development. Primary tumors of the glial cells are called gliomas and often are malignant by the time they are diagnosed.
The thalamus and hypothalamus are major divisions of the diencephalon, with the pituitary gland and pineal gland attached at and the bottom; tumors of the pituitary and peneal gland are often benign.
The brainstem lies between the large cerebral cortex and the spinal cord. It is divided into the midbrain, pons and medulla oblongata.
Diagnosis
There are no specific signs or symptoms for brain cancer, but the presence of a combination of symptoms and the lack of alternative causes may indicate a brain tumor. A medical history aids in the diagnosis. Clinical and laboratory investigations will serve to exclude infections as the cause of the symptoms.
Brain tumors, when compared to tumors in other areas of the body, pose a challenge for diagnosis. Commonly, radioactive tracers are uptaken in large volumes in tumors due to the high activity of tumor cells, allowing for radioactive imaging of the tumor. However, most of the brain is separated from the blood by the blood brain barrier (BBB), a membrane that exerts a strict control over what substances are allowed to pass into the brain. Therefore, many tracers that may reach tumors in other areas of the body easily would be unable to reach brain tumors until there was a disruption of the BBB by the tumor. Disruption of the BBB is well imaged via MRI or CT scan, and is therefore ragarded as the main diagnostic indicator for malignant gliomas, meningiomas, and brain metastases.
Imaging
Medical imaging plays a central role in the diagnosis of brain tumors. Early imaging methods- invasive and sometimes dangerous such as pneumoencephalography and cerebral angiography have been replaced by non-invasive, high-resolution techniques, especially magnetic resonance imaging (MRI) and computed tomography (CT) scans. MRI with contrast enhancement is the preferred imaging test in the diagnosis of brain tumors. Glioblastomas usually enhance with contrast on T1 MRI weighted MRI imaging, and on T2 with FLAIR imaging showing hyperintense cerebral edema. Low grade gliomas are usually hypointense on T1 MRI, and hyperintense with T2 with FLAIR MRI. Meningiomas are usually homogenously enhanced with dural thickening on MRI.
Treatment with radiation can lead to treatment induced changes in the brain, including radiation necrosis (death of brain tissue due to radiation treatments) visible on brain imaging and which can be difficult to differentiate from tumor recurrence.
Different Types of MRI Scans
Magnetic Resonance Angiography (MRA) :
looks at the blood vessels in the brain. In the diagnosis of brain tumor, MRAs are typically carried out before surgery to help surgeons get a better understanding of the tumor vasculature. For example, a study was done where surgeons were able to separate benign brain tumors from malignant ones by analyzing the shapes of the blood vessels that were extracted from MRA. Although not required, some MRA may inject contrast agent, gadolinium, into the patient to get an enhanced image.
Magnetic Resonance Spectroscopy (MRS)
measures the metabolic changes or chemical changes inside the tumor. The most common MRS is proton spectroscopy with its frequency measured in parts per million (ppm). Gliomas or malignant brain tumors have different spectra from normal brain tissue in that they have greater choline levels and lower N-acetyl aspartate (NAA) signals. Using MRS in brain tumor diagnosis can help doctors identify the type of tumor and its aggressiveness. For example, benign brain tumors or meningioma have increased alanine levels. It can also help to distinguish brain tumors from scar tissues or dead tissues caused by previous radiation treatment, which does not have increased choline levels that brain tumors have, and from tumor-mimicking lesions such as abscesses or infarcts.
Perfusion Magnetic Resonance Imaging (pMRI)
assess the blood volume and blood flow of different parts of the brain and brain tumors. pMRI requires the injection of contrast agent, usually gadopentetate dimeglumine (Gd-DTPA) into the veins in order to enhance the contrast. pMRI provides a cerebral blood volume map that shows the tumor vascularity and angiogenesis. Brain tumors would require a larger blood supply and thus, would show a high cerebral blood volume on the pMRI map. The vascular morphology and degree of angiogenesis from pMRI help to determine the grade and malignancy of brain tumors. For brain tumor diagnosis, pMRI is useful in determining the best site to perform biopsy and to help reduce sampling error. pMRI is also valuable for after treatment to determine if the abnormal area is a remaining tumor or a scar tissue. For patients that are undergoing anti-angiogenesis cancer therapy, pMRI can give the doctors a better sense of efficacy of the treatment by monitoring tumor cerebral blood volume.
Functional MRI (fMRI)
measures blood flow changes in active parts of the brain while the patient is performing tasks and provides specific locations of the brain that are responsible for certain functions. Before performing a brain tumor surgery on patients, neurosurgeons would use fMRI to avoid damage to structures of the brain that correspond with important brain functions while resecting the tumor at the same time. Preoperative fMRI is important because it is often difficult to distinguish the anatomy near the tumor as it distorts its surrounding regions. Neurosurgeons would use fMRI to plan whether to perform a resection where tumor is surgically removed as much as possible, a biopsy where they take a surgical sampling amount to provide a diagnosis, or to not undergo surgery at all. For example, a neurosurgeon may be opposed to resecting a tumor near the motor cortex as that would affect the patient's movements. Without preoperative fMRI, the neurosurgeon would have to perform an awake-craniotomy where the patient would have to interact during open surgery to see if tumor removal would affect important brain functions.
Diffusion Weighted Imaging (DWI)
a form of MRI that measures random Brownian motion of water molecules along a magnetic field gradient. For brain tumor diagnosis, measurement of apparent diffusion coefficient (ADC) in brain tumors allow doctors to categorize tumor type. Most brain tumors have higher ADC than normal brain tissues and doctors can match the observed ADC of the patient's brain tumor with a list of accepted ADC to identify tumor type. DWI is also useful for treatment and therapy purposes where changes in diffusion can be analyzed in response to drug, radiation, or gene therapy. Successful response results in apoptosis and increase in diffusion while failed treatment results in unchanged diffusion values.
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