There are various kinds of tumours that can develop within the skull. A primary differentiation is made on the basis of the tissue in which the tumour originated. Thus there are intracerebral tumours and extracerebral tumours. "Intracerebral" means "within the actual brain tissue". "Extracerebral" means "originating from other tissue than brain tissue, but still located within the skull". These tumours can exercise pressure on the brain. An example of an extracerebral tumour is a meningioma, a tumour that originates in the meninges. Intracerebral tumours occur relatively more frequently than extracerebral tumours.

1. Intracerebral tumours

Intracerebral tumours are further differentiated between:

Primary tumours:
Primary tumours are tumours originating in the brain tissue itself. Such tumours often develop from the support cells in the brain tissue, the glia. These brain tumours are called gliomas. This is the most common type of brain tumour. Other, less common brain tumours include ependymomas and medulloblastomas.

Secondary tumours:
A secondary tumour is a dissemination, or metastasis, of a tumour elsewhere in the body. Through the blood, cells of e.g. a breast or lung tumour arrive at the brain, where they grow into a metastasis. These are called brain metastases. This article examines gliomas, which are primary, intracerebral brain tumours.

2. Gliomas

A brain tumour differs from a tumour elsewhere in the body in that it is often not so easy to differentiate between benign and malignant tumours. This also applies to gliomas. The degree of malignancy of a glioma is expressed in degrees of the disease. Gliomas of Grade I or II are low-grade. Gliomas of Grade III or IV are called high-grade. Low-grade gliomas grow slowly. For this reason, they are sometimes termed "relatively benign". However, low-grade gliomas are not clearly differentiated as compared to benign tumours: The tumour cells are located among the healthy tissue cells and cannot be properly differentiated from them. In most cases, such tumours cannot be surgically removed in their entirety. Total removal of the tumour would involve too much damage to healthy tissue. There is therefore a risk that after some time the tumour will grow again. A high-grade glioma quickly behaves like a "true" malignant tumour: Its growth is rapid and uninhibited. As opposed to most malignant tumours occurring elsewhere in the body, gliomas do not metastasise to other organs. Every year, a couple of thousand people are diagnosed with brain tumours in the Netherlands. Low-grade gliomas are more frequently seen in people aged between 20 and 40, while high-grade gliomas are more frequently seen in people aged 40 and over. Nothing is really known as of yet about what causes gliomas; in the last few years there have been indications that anomalies in the genetic material may play a role in their development.

3. Signs and symptoms

The signs that manifest as a consequence of a brain tumour depend very much on the area of the brain in which the tumour is located. The various signs are classified into three groups as follows:

Deficit symptoms:
When a tumour exercises pressure on the surrounding brain tissue, its function is impaired. This translates into deficit symptoms: physical or intellectual function, or both, are partially impaired. For example, a tumour in the area of the nerve cells that govern movement can cause paralysis symptoms. Sometimes these symptoms are so mild that they are not immediately experienced as denoting paralysis. The patient may, for example, notice that he or she has trouble handling a fork or buttoning a shirt. People who are right-handed (and in half of all cases concerning left-handed people), the language and speech centre is located in the left hemisphere, or half, of the cerebrum, the largest portion of the brain. A tumour in this brain hemisphere can bring about language problems as the first noticeable signs. The person will notice that he or she cannot think of certain words or is pronouncing certain words incorrectly. In many patients, a brain tumour will manifest itself in the form of behavioural changes. They behave differently from the way they used to and others expect them to. Some patients react more lethargically, others become more irritable. Frequent mood changes are another sign of this type of impairment. Some patients seem to have greater difficulty understanding certain things.

Epilepsy:
Another sign that can occur with a brain tumour is a "fit". "Fits", or seizures, are an everyday way of expressing what is actually termed "epilepsy". Such seizures are caused by an irritation of the nerve cells in the brain tissue. Such epileptic seizures are often the first sign of a brain tumour. There are several types of seizures. Sometimes they are no more than small jerks of a hand or a short-term "absence"; but the patient can also be struck by sudden loss of consciousness paired with strong jerking of the arms and legs. With these types of seizure it is not unusual that patients may not be able to control their bladder, or that they may bite their tongue. Bystanders witnessing a seizure are often very frightened and may panic. However, these seizures always resolve spontaneously.

Increase in intracranial pressure:
A third group of signs that can indicate a brain tumour involves an increase in the intracranial pressure. We can imagine the cranium, or skull, as an almost completely closed container. In it are located the brain and a certain amount of cerebrospinal fluid and blood. When the content of the skull increases in size, for example due to the presence of a tumour, the pressure inside the cranium also grows. In addition, fluid can accumulate in the brain tissue around the tumour. This accumulation of fluid is called an oedema. Such accumulations of fluid also contribute to an increase in the contents of the skull, intensifying the pressure inside. The intracranial pressure can also increase when a tumour blocks the flow of cerebrospinal fluid around the brain. This then causes a rapid increase in pressure within the skull. This can lead to a number of symptoms. For example, a patient can get an enduring headache. Sometimes the headache is combined with nausea and vomiting. If the pressure increases significantly, the patient can become drowsy. In exceptional cases, the patient can also get blurred vision because of pressure being exercised on the optic nerves. These signs and symptoms can also occur with other conditions that are not brain tumours. If a person has one or more of the abovementioned complaints, it is a good idea to consult one's GP to find out what exactly the matter is. Of course, it should be remembered that complaints such as headaches are very frequent and most of the time are not caused by a brain tumour.

Examination:
On the basis of the patient's symptoms, the GP can presume that a condition of the nervous system may be involved, which will require further investigation. The patient will then be referred to a specialist in this area, that is to a neurologist. At the first examination, this specialist will first ask the patient about his or her symptoms. Then there will be a physical examination, known as a "neurological examination". If the doctor thinks that the symptoms may be connected to the brain tumour, nowadays the next step is always a computer tomogram (CT scan) of the brain. After this examination, an MRI (Magnetic Resonance Imaging) scan can also take place. In some hospitals it is also customary to perform an EEG (ElectroEncephaloGram). Below you will find a more detailed description of the abovementioned examinations.

4. Neurological examination

During the physical examination the doctor evaluates the proper working of bodily functions as well as the patient's speech, vision, balance, strength in the members and the ability to feel sensitivity stimuli. The neurological examination can sometimes give indications concerning the possible presence and location of a brain tumour.

5. Computer tomography (CT scan)

A computer tomography machine is a device that makes it possible to take very detailed photographs through the body on a centimetre by centimetre basis. This is done by combining X-rays and a computer. The machine has an opening through which the patient is slid while lying on a movable platform. Then, a number of photographs are made while the platform moves a little further with each image taken. These photographs give a clear picture of the location, size and extent of a potential brain tumour. After a first series of images, additional photographs may be necessary. For these, the patient will receive an injection of a contrast medium via a vein in the arm. This injection will often cause a slightly hot feeling and, sometimes, nausea. A CT scan causes very little stress for the patient, and in our hospital takes less than one minute!

6.MRI or NMR [Nuclear Magnetic Resonance]

As well as a CT scan, patients in whom a potential brain tumour is suspected will mostly also undergo an MRI. The equipment required for this examination is available in our hospital. Our neuroradiologists enjoy an international reputation. More about this can be found on this website :www.nmr.be . This examination technique uses magnetic fields and radio waves (instead of X-rays). The patient lies in a strong magnetic field. Then, radiofrequency waves are directed at the part of the body to be examined. The body mirrors, or echoes, these radio waves. This process is called resonance. Each of the different sorts of cells that constitute the tissue bounces back the radio waves in a different way. This produces a signal pattern.

The signals are then processed by a computer and transformed into images. This makes it possible to obtain photographs without needing to resort to X-rays. In some cases it is necessary to administer a contrast medium for the examination. The patient experiences no particular sensations during the examination. An MRI takes approximately half an hour. Owing to the use of magnetic fields, this examination is not suitable for patients who have a pacemaker or an implanted hearing aid. People who are claustrophobic can also experience problems with this examination.

7. EEG

An EEG provides the doctor with information about brain function in different parts of the brain. With impaired function, especially when a patient suffers seizures, the EEG results can be abnormal. For this examination, some twenty small metal plates (electrodes) are placed on the patient's head. These electrodes measure low level electric voltages at the scalp. These microvoltages are produced by the electrical flows that connect the nerve cells in the brain to one another. The differences in the electrical voltages emitted are amplified and represented on moving graph paper. This recording process takes 20 to 30 minutes. The entire examination takes 45 to 60 minutes.

8. Further examination

The examinations mentioned earlier are essentially intended to determine whether the problem is a tumour or another brain condition. On the basis of these examinations, doctors can conclude with a significant degree of accuracy whether the patient's symptoms are the result of a brain tumour or not. An examination of the tumour tissue is necessary for a conclusive diagnosis. The removal of a small piece of tissue is called a biopsy. The specialist who performs this procedure is a neurosurgeon, i.e. a surgeon specialising in operations of the nervous system. Another specialist, an anatomic pathologist, then examines the tissue under the microscope. By means of anomalies found in the cells, this specialist can determine the type of the condition. In patients with brain tumours it is possible to perform biopsies under local anaesthesia. Surgeons also use navigation technology (similar to the GPS in your car) with which they can localise the biopsy with a margin of error of only 1 mm.

9. Angiography

Sometimes, an angiography is additionally carried out before a stereotactic biopsy or craniotomy. Angiographies are X-ray examinations that create an image of the blood vessels in the head. On these X-rays the doctor can see where precisely the tumour is located in relation to the blood vessels, and whether they present any anomalies. This examination sometimes also reveals the type of tumour under consideration. At the beginning of the examination, the radiologist will introduce a catheter (a thin tube) into the patient's femoral artery. To do so, he or she will use a special hollow needle through which the catheter is pushed. Through the aorta (the body's largest artery) the catheter is introduced into the carotid artery. When the tip of the catheter is at the correct point of the artery, a contrast medium is injected. This creates a brief, but sometimes unpleasant, sensation of heat in the head. While the contrast medium flows through the blood vessels of the head, a series of photographs is taken in quick succession. This is accompanied by quite a bit of noise from the X-ray machine. The entire examination takes 1 to 1.5 hours.

10. Stereotactic biopsy

Stereotaxy is a method used to determine a specific spot within the brain. This method is primarily used to reach masses or areas in the brain that lie so deep that it would be irresponsible to try to access them by means of heavy surgery through the surrounding soft, easily damaged brain tissue. This procedure uses a three-dimensional coordinates system (with an X, a Y and a Z axis) which is applied over the patient's calvaria by means of a frame before the procedure. In this way, the patient's skull is placed within a three-axis system enabling any imaginable point within the brain to be defined by means of an X-coordinate, a Y-coordinate and a Z-coordinate. As the axes have special markings, it is possible to produce a CT scan or an MRI of the patient's skull and brain, on which the X, Y and Z values can be read. This makes it possible to calculate the (mathematical) position of a specific area within the brain, or of a deep seated brain anomaly (cyst, tumour, etc.).

Cartesian coordinates system

Illustration : Cartesian coordinates system consisting of 3 planes X, Y and Z positioned perpendicularly to one another, into which the brain is fitted. Ordinarily the X plane is horizontal, the Y plane is vertical and runs through the middle of the two brain hemispheres, while the Z plane is also vertical and runs parallel to the face.

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Illustration: This photograph shows the ferrule frame encompassing a skull model sawn open. The axis system is fitted onto the ferrule. The coordinates can be accurately set in millimetres. How the needle turns over the degree quadrant is irrelevant. The calculated target point is the centre of a sphere.

Nowadays the procedure is even more precise and really simple. The doctors make a CT scan or MRI of your head. These images are forwarded to the operating theatre. On these images, the doctor can specify where exactly he or she wishes to carry out the biopsy. The computer leads the doctor to the tumour, without detours and without damaging any brain tissue. Three to five biopsy samples are taken (1 by 3 mm), which is sufficient for the anatomic pathologist to make an accurate diagnosis.

10.1 Applications of stereotaxy

There are a number of reasons why a stereotactic brain intervention can become necessary:

  • To make a diagnosis (diagnostic stereotaxy). This usually means that a deep-lying mass is involved which is not easily accessible for evaluation involving opening up the skull (which requires cutting out a section of the skull for access). In such cases, the purpose of a stereotactic intervention is to gain precise access to the area involving the anomaly with a biopsy needle via a small perforation of the skull. Once at the targeted area, several small pieces of (tumour) tissue are removed and sent to the anatomic pathologist for a tissue diagnosis (usually called a biopsy).
  • For treatment of an anomaly (therapeutic stereotaxy). This is the removal of small, deep lying tumours or cysts, or the introduction of radioactive material for internal irradiation (brachytherapy).
  • To "disconnect" certain parts of the brain (functional stereotaxy). This involves a highly targeted disconnection of areas of the brain that are involved in certain motor, or movement, disorders (like Parkinson's disease or dystonia), or, in rare cases, in psychiatric disorders.
  • To stimulate certain parts of the brain (neuromodulation). This involves the stereotactic positioning of electrodes in the brain, which enable electrical stimulation supporting examination and treatment of certain forms of epilepsy and motor disorders (like Parkinson's disease or dystonia).
  • In connection with tissue implants (neurotransplantation). This application is still at the experimental stage. It aims at implanting donor tissue (certain hormone producing nerve cells) in the brains of patients with Parkinson's disease.

11. Risks involved in the operation

The most important risk involved in a stereotactic procedure is the occurrence of bleeding. Bleeding can occur if a blood vessel in the brain is damaged by the introduction of the biopsy needle or of the electrode. These haemorrhages are usually very small and cause no noticeable symptoms. Sometimes, however, the bleeding is more significant and involves severe (permanent) neurological symptoms or even a fatal outcome.

The risk of infection is quite small in stereotaxy, although a little greater in procedures that require canulas or electrodes (as e.g. in brachytherapy or neurostimulation) to remain in position for several days.

Craniotomy

Craniotomy is the procedure carried out to open the skull. The procedure takes place under anaesthesia. For this operation either the entire head or part of it will be shaved. In a craniotomy, the neurosurgeon makes a small opening in the skull. The remainder of the operation then takes place through that opening. Sometimes, the specialist will only take a small piece of tumour tissue for microscopic examination. In most cases, however, he or she will remove as much tumour tissue as possible. In such cases, the intervention is not purely aimed at obtaining a sample for examination, but is as the same time a form of treatment. The navigation technology described earlier (see video) is used throughout the procedure.

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It is very important to prevent bleeding from occurring after the tumour has been removed. A special sort of tweezers is used to ensure hermetic closure (cauterisation) of the smallest blood vessels.

 

At the end of the operation, the small "trap door" for the opening is replaced in the skull. After the operation, the patient will stay in the Intensive Care Unit for one or more nights. If there are no complications, the patient will often be able to go home within the following couple of weeks. However, longer hospital stays may be necessary if follow-up treatment is required.

12. Treatment

Once the tissue examination has revealed whether there is a glioma or other tumour, the doctors consider whether any (further) treatment would be appropriate, and if so, what type. Their opinion is based on the type of tumour and the patient's age and health condition. Thus, for example, an operation is not possible if the tumour is located very deep in the brain or in a part of the brain that is very important for the patient's functioning.

With low grade gliomas, doctors can decide that it may be better for the patient temporarily to wait and see how things develop. Low-grade gliomas often grow very slowly. This can mean that sometimes the tumour will hardly grow over a number of years. As gliomas do not metastasise, for many patients it makes more sense to wait and see. Naturally, in such cases the patient is carefully monitored. Regular CT scans and MRIs will be required to determine whether the tumour has increased in size. At a certain moment in time further treatment may become necessary.

When the doctors decide that further treatment is possible and constitutes a sensible alternative, the options usually are:

  • Surgery, followed by radiation (radiotherapy)
  • Radiotherapy only
  • Surgery, followed by radiation and chemotherapy

Chemotherapy is treatment with medication that inhibits the division and multiplication of cells (these drugs are called cytostatics), and has to date been applied in brain tumour patients only to a very limited extent. The treatment is very heavy, and to date the results have been very disappointing. For Grade III astrocytoma, temodal is generally considered to be the standard treatment, together with surgery and radiotherapy.

13. Surgery

After the craniotomy described earlier, the neurosurgeon will remove as much tumour tissue as possible. In doing so, he or she will use, among other instruments, a surgical microscope and special equipment to remove the tumour as radically as possible. In practice, however, total removal of the tumour is almost impossible. The problem is that the borderline between tumour tissue and healthy brain tissue can rarely be defined precisely. However, the neurosurgeon cannot remove a large amount of apparently healthy brain tissue to be more certain of having eliminated all the tumour tissue. This would involve serious and unacceptable risks for the patient's function. This is why mostly only part of the tumour can be removed.

After the surgery, radiation therapy may be necessary to remove as much as possible of the remaining tumour cells. In any event, whether or not everything has been taken out is not essential for the further course of the illness.

14. Radiation

Radiation can be used as complementary therapy after surgery or as the sole therapy. This does not make a significant difference as to the type of radiation therapy to be used. Radiation damages tumour cells. They have trouble recovering, so that the result of radiation is the total or partial destruction of the tumour or the remaining tumour cells (the tumour residue). Radiation also affects the surrounding cells. They usually recover satisfactorily.

Radiation can be administered in two ways: as external or internal radiation therapy. For the radiation therapy itself we work with the Radiotherapy Department of the St-Augustinus Hospital in Wilrijk.

15. Uncommon tumours

This section takes a look at less common growths that may appear within the skull. Although they are comparatively rare, every neurosurgeon is regularly confronted with them, as neurosurgery centres generally cover a significant geographical area. Tumours can be classified both according to their type and according to the place in which they occur (location). Usually a differentiation is made between those occurring in the anterior and middle fossa of the skull and those in the posterior fossa. The reason is that the signs and symptoms and the treatment can differ depending on tumour location. Then there are also the tumours in and around the sella turcica (the "Turkish saddle", a saddle-shaped bony structure), such as for example the tumours of the hypophysis, or pituitary gland. In this presentation we will first talk about the different tumours on the basis of their nature, while indicating where they usually occur.

15.1.Craniopharyngioma

Craniopharyngiomas are tumours that grow out of Rathke's pouch, a brain component that transforms into the hypophysis during the development of the unborn child. When the pouch does not close properly during development, a tumour, or actually more of a cyst (a fluid-filled cavity), containing in this case a thick yellowish liquid, can develop in the remaining cleft. Calcifications can also appear. In view of the manner in which this type of tumour develops, it is understandable that it is usually diagnosed in relatively young people. It grows in the area of the sella turcica. The "Turkish saddle" is a cavity in the middle of the skull base, behind the eyes. It contains the hypophysis. Owing to the slow growth of such tumours, the signs and symptoms develop very slowly and insidiously. Most symptoms are the result of pressure: vision deterioration because of pressure on the optic nerve(s), and hormonal disorders due to stress on the hypophysis and/or the hypothalamus above. The condition is best diagnosed with an MRI. Although craniopharyngiomas are relatively benign tumours, the treatment can nonetheless be quite troublesome. Surgery does not always succeed in removing both the tumour and the surrounding capsule entirely, so that new growth (a recurrence) is still possible. For this reason, radiation is virtually always additionally applied after surgery. An alternative is a treatment whereby radioactive material is injected into the cyst to shrink the tumour.

15.2. Medulloblastoma and ependymoma

These two tumours are of different origin and look different under the microscope, but the signs, symptoms and treatment are very similar, which is why they will be discussed together in one and the same section. Medulloblastomas are tumours that occur only in the posterior cranial fossa, which houses the brainstem and the cerebellum. Ependymomas develop from the cells lining the ventricles of the brain; they can also occur in the cerebrum (the main part of the brain) itself. Both these tumours occur mostly in children and young adults. It is not known for certain how they come about, but the tendency to grow this type of tumour is probably congenital (already present at birth). Patients present with the signs and symptoms typical of masses in the posterior fossa: headache (sometimes including nausea and vomiting), double vision, uncertainty in walking and dizziness. Some of these complaints are the result of an obstruction of the drainage of cerebrospinal fluid (liquor), due to pressure on the drainage pathways. This leads to the patient developing hydrocephalus, sometimes also called "water on the brain".

The treatment consists, in the first instance, in tumour surgery; sometimes the hydrocephalus must be treated at the same time with a drain (internal or external). Radiotherapy and possibly also chemotherapy would follow. The patient's age plays an important role in the choice of treatment. In younger patients, tumours tend to grow aggressively. Although generally speaking central nervous system tumours do not usually metastasise, cells of the two types of tumours discussed here can be carried along with circulation of liquor and spread through the system. Post-operative radiation treatment takes this risk into account and for this reason the entire central nervous system, including the spinal cord, is irradiated.

15.3. Plexus papilloma

This is a rare tumour developing in the area called the choroid plexus. This is an elongated tissue consisting of tufts that produce the cerebrospinal fluid. It is housed in the ventricles of the brain. Signs and symptoms are primarily connected with the area in which they occur. The first sign to appear in the posterior fossa is hydrocephalus. The tumour is relatively benign and does not usually recur after removal. Thus, further treatment is not necessary, but the patient should be regularly monitored for several years. There is a malignant form of this tumour, but it is rare. (See video)

15.4. Pineal tumour

The pineal gland, sometimes called "pineapple gland" because of its shape, is a structure that lies behind the third ventricle of the brain. The function of this small "organ" is not clear, but it is presumed, in analogy to other species, that it plays a role in the "biological clock". Tumours that grow in this area quickly close off the connection between the third and fourth ventricles of the brain, a thin canal called aqueduct of Sylvius. This prevents the cerebrospinal fluid from draining, and causes hydrocephalus. Another typical sign is the inability to look upwards. There are different types of pineal tumours. They can be both benign or malignant. Sometimes a biopsy followed by radiation is the best therapy; in other cases surgery is required and chemotherapy may need to follow. Pineal tumour surgery is "heavy" surgery that sometimes needs to include treatment of the hydrocephalus condition.

In conclusion

The tumours described above occur only rarely. No individual neurosurgery centre will have treated significant numbers of patients. This means that there is little in the way of collected experience regarding these conditions; the literature can only report on small series of patients treated over long periods of time. The treatments have changed quite often in the course of the years, which makes it difficult properly to evaluate their efficacy. However, there is significant agreement concerning the process to be followed. There will of course be differences in emphasis between the different centres, e.g. as concerns whether or not chemotherapy is a valid option. These differences usually arise around issues of unproven treatment efficacy. All centres implement convincingly proven therapies.