Brain Tumor

Introduction:
A brain tumor is an abnormal growth of cells within the brain or inside the skull, which can be cancerous or non-cancerous.

It is defined as any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself, in the cranial nerves, in the brain envelopes, skull, pituitary and pineal gland, or spread from cancers primarily located in other organs.

Primary brain tumors are commonly located in the posterior cranial fossa in children and in the anterior two-thirds of the cerebral hemispheres in adults, although they can affect any part of the brain

Symptoms:

Symptoms of brain tumors may depend on two factors: tumor size and tumor location. The time point of symptom onset in the course of disease correlates in many cases with the nature of the tumor is a frequent reason for seeking medical attention in brain tumor cases.

Large tumors or tumors with extensive perifocal swelling edema inevitably lead to elevated intracranial pressure, which translates clinically into headaches, vomiting, altered state of consciousness, dilatation of the pupil on the side of the lesion, papilledema. However, even small tumors obstructing the passage of cerebrospinal fluid (CSF) may cause early signs of increased intracranial pressure. Increased intracranial pressure may result in herniation of certain parts of the brain, such as the cerebellar tonsils or the temporal uncus, resulting in lethal brainstem compression. In young children, elevated intracranial pressure may cause an increase in the diameter of the skull and bulging of the fontanelles.

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, personality changes, hemiparesis, hypesthesia, aphasia, ataxia, visual field impairment, facial paralysis, double vision, tremor etc. These symptoms are not specific for brain tumors - they may be caused by a large variety of neurologic conditions. What counts, however, is the location of the lesion and the functional systems it affects.

A bilateral temporal visual field defect, often associated with endocrine disfunction—either hypopituitarism or hyperproduction of pituitary hormones and hyperprolactinemia is suggestive of a pituitary tumor.

Diagnosis:

Although there is no specific clinical symptom or sign for brain tumors, slowly progressive focal neurologic signs and signs of elevated intracranial pressure, as well as epilepsy in a patient with a negative history for epilepsy should raise red flags. However, a sudden onset of symptoms, such as an epileptic seizure in a patient with no prior history of epilepsy, sudden intracranial hypertension is also possible.

Glioblastoma multiforme and anaplastic astrocytoma have been associated in case reports on PubMed with the genetic acute hepatic porphyrias, including positive testing associated with drug refractory seizures. Unexplained complications associated with drug treatments with these tumors should alert physicians to an undiagnosed neurological porphyria.

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 abandoned in recent times in favor of non-invasive, high-resolution modalities, such as computed tomography (CT) and especially magnetic resonance imaging (MRI). Benign brain tumors often show up as hypodense mass lesions on cranial CT-scans. On MRI, they appear either hypo- or isointense on T1-weighted scans, or hyperintense on T2-weighted MRI. Perifocal edema also appears hyperintense on T2-weighted MRI. Contrast agent uptake, sometimes in characteristic patterns, can be demonstrated on either CT or MRI-scans in most malignant primary and metastatic brain tumors. This is because these tumors disrupt the normal functioning of the blood-brain barrier and lead to an increase in its permeability.

Electrophysiological exams, such as electroencephalography (EEG) play a marginal role in the diagnosis of brain tumors.

The definitive diagnosis of brain tumor can only be confirmed by histological examination of tumor tissue samples obtained either by means of brain biopsy or open surgery. The histological examination is essential for determining the appropriate treatment and the correct prognosis. This examination, performed by a pathologist, typically has three stages: interoperative examination of fresh tissue, preliminary microscopic examination of prepared tissues, and followup examination of prepared tissues after immunohistochemical staining or genetic analysis.

Another possible diagnosis would be neurofibromatosis which can be in type one or type two.

Treatment and prognosis:

Many meningiomas, with the exception of some tumors located at the skull base, can be successfully removed surgically. In more difficult cases, stereotactic radiosurgery, such as Gamma knife, Cyberknife or Novalis Tx radiosurgery, remains a viable option.

Most pituitary adenomas can be removed surgically, often using a minimally invasive approach through the nasal cavity and skull base. Large pituitary adenomas require a craniotomy for their removal. Radiotherapy, including stereotactic approaches, is reserved for the inoperable cases.

Although there is no generally accepted therapeutic management for primary brain tumors, a surgical attempt at tumor removal or at least cytoreduction is considered in most cases. However, due to the infiltrative nature of these lesions, tumor recurrence, even following an apparently complete surgical removal, is not uncommon. Several current research studies aim to improve the surgical removal of brain tumors by labeling tumor cells with a chemical that causes them to fluoresce. Postoperative radiotherapy and chemotherapy are integral parts of the therapeutic standard for malignant tumors. Radiotherapy may also be administered in cases of "low-grade" gliomas, when a significant tumor burden reduction could not be achieved surgically.

Survival rates in primary brain tumors depend on the type of tumor, age, functional status of the patient, the extent of surgical tumor removal, to mention just a few factors.

UCLA Neuro-Oncology publishes real-time survival data for patients with this diagnosis. They are the only institution in the United States that shows how brain tumor patients are performing on current therapies. They also show a listing of chemotherapy agents used to treat high grade glioma tumors.

Patients with benign gliomas may survive for many years, while survival in most cases of glioblastoma multiforme is limited to a few months after diagnosis if treatment is ignored.

The main treatment option for single metastatic tumors is surgical removal, followed by radiotherapy and/or chemotherapy. Multiple metastatic tumors are generally treated with radiotherapy and chemotherapy. Stereotactic radiosurgery (SRS), such as Gamma Knife, Cyberknife or Novalis Tx, radiosurgery, remains a viable option. However, the prognosis in such cases is determined by the primary tumor, and it is generally poor.

Radiotherapy is the commonest treatment for secondary cancer brain tumours. The amount of radiotherapy depends on the size of the area of the brain affected by cancer. Conventional external beam whole brain radiotherapy treatment (WBRT) or 'whole brain irradiation' may be suggested if there is a risk that other secondary tumours will develop in the future. Stereotactic radiotherapy is usually recommended in cases of under three small secondary brain tumours.

In 2008 a study published by the University of Texas M. D. Anderson Cancer Center indicated that cancer patients who receive stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) for the treatment of metastatic brain tumors have more than twice the risk of developing learning and memory problems than those treated with SRS alone.

A shunt operation is used not as a cure but to relieve the symptoms. The hydrocephalus caused by the blocking drainage of the cerebrospinal fluid can be removed with this operation.

Research to treatment with the vesicular stomatitis virus:

In 2000, researchers at the University of Ottawa, led by John Bell PhD., have discovered that the vesicular stomatitis virus, or VSV, can infect and kill cancer cells, without affecting healthy cells if coadministered with interferon.

The initial discovery of the virus' oncolytic properties were limited to only a few types of cancer. Several independent studies have indentified many more types susceptible to the virus, including glioblastoma multiforme cancer cells, which account for the majority of brain tumors.

In 2008, researchers artificially engineered strains of VSV that were less cytotoxic to normal cells. This advance allows administration of the virus without coadministration with interferon. Consequently administration of the virus can be given intravenously or through the olfactory nerve. In the research, a human brain tumor was implanted into mice brains. The VSV was injected via their tails and within 3 days all tumor cells were either dead or dying.

Research 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 VSV mutant strains. Future research will focus on the risks of this treatment, before it can be applied to humans.