Dealing with Brain Tumour

this document is still being drafted, to replace the earlier document here.

A primer prepared for OzBrainTumour members

© Dennis Argall 2002
dennis@aplaceof.info

Contents

You may click on blue text in the contents to go to that section.

Introduction

1: What is cancer, what is a brain tumour, where does it come from?
2: Diagnostic and monitoring tools
3: Treatment and Care — overview

Defeating the tumour

4: To destroy and/or remove the tumour cells, to fight the tumour — overview
5: Neurosurgery
6: Radiotherapy
7: Chemotherapy
8: Anti-angiogenics

Dealing with effects on the brain

9: To minimise the effects of the tumour on the brain, in particular, to reduce the swelling it causes, and to reduce the prospect of seizures
10: Dexamethasone
11: Mannitol
12: Dealing with seizure: overview and action stations!
13: Seizure: ambulance and hospital
14: Seizure: medications - Dilantin and others

Other significant medical problems

15: Low white blood cell counts
16: low platelets
17: deep vein thrombosis

Life and happiness

18: to maximise the comfort and quality of life of the patient for as long as possible - overview

19:

[D] if the tumour cannot be defeated, to allow the patient to die with dignity, or as some might prefer to put it, to live with dignity while dying.

Introduction

The annual incidence of brain and other central service system cancers has been, year by year, 1983 to 1998:
937 966 954 1,018 1,060 1,102 1,120 1,121 1,207 1,239 1,216 1,272 1,271 1,307 1,307 1,327

Among these, gliomas are the most common: there are six or seven hundred glioma diagnoses in Australia in a year. This is not the most common kind of cancer. Many doctors have little experience of it.

When it comes to problems and when it comes to treatments, there are similarities between brain tumour and bodily cancer and there are also important differences.

These notes are designed to help someone with a brain tumour and also those caring for and near a person with a brain tumour:
• to understand the issues,
• to cope with treatments and perhaps choose among them,
• to get support of practical kinds and deal with legal and financial issues, and
• to make the most of every day.

There are more than forty different kinds of brain tumour (though some of these very rare) and it is important, in learning about the situation you are addressing, always to have that in mind.

When a doctor looks at scans or at tissue from an operation, she or he is seeking a precise diagnosis, to identify what kind of thing is at work, exactly what the disease is. This is not easy. Some of the most important distinctions in brain tumour pathology were established in the 1990s; some are as yet undiscovered. There continue to be variations in conclusions between even the best pathologists.

The diagnosis is very important, because it defines treatment options and gives some indication of the gravity of the situation.

When a person asks: “How long have I got?” the doctor’s term is prognosis – what is the expected course and duration and outcome of the disease. It is not possible to be precise about prognosis, for anyone, with just about any kind of tumour.

So people often say: “Accept the diagnosis, not the prognosis” - but individuals will each develop their own attitudes, ways of dealing with crisis. The way you have dealt with tough issues in the past, as a person, as a family, will define how you deal with this situation now, unless you plan radical change.

A key distinction is in the grading of the malignant tumour (benign tumours are not graded, by definition they do not evolve). As with other things in medicine, there is a grading from 1 to 4, or rather, in Roman numbers, I, II, III and IV, with IV being the most serious, the most aggressive, the most malignant.

There may be many people out there in normal daily life with low grade tumours, Grade I tumours are not going to be detected normally, almost by definition. If it is the case that people can survive without knowing they have low grade tumours, it follows that Grade IV tumours become the most commonly diagnosed, as they grow quickly and have rapidly increasing symptom impacts. It still may not be easy for a doctor to diagnose at first. It’s not appropriate to send everyone with a headache or sinus pain or sleepiness or mental muddle or blurred vision off for a brain scan immediately. Some symptoms may be subtle, but if the tumour is high grade - highly aggressive, growing fast - symptoms will be hard to relieve and rapidly increasing. You may already be aware of this...

Malignant means growing, spreading and dangerous, the opposite of benign. There are many people out there in ordinary life today, who have had benign tumours removed and no one might know. One said to me: “I had it removed in an operation through my nose ten years ago. It was just a mass. There is a period of my life I can’t remember (this is just an example, symptoms vary greatly), but otherwise I’m fine.” Malignant tumours also have different impacts, depending on whether they are discrete masses, which can be removed, or have diffuse qualities and resistance to treatments, meaning that they go on growing.

All of these variations impact on treatment decisions. In the end, the purpose of life is not to go to medical appointments, there has to be more. With a high grade tumour, if the choice -and it is a choice for the patient - is to fight, then the pace is generally pretty fierce. With a low grade tumour, periodic monitoring needs to allow a person to get on with life, with enough checking just to see that radical change does not escape attention. Treatments do not work for everyone. They need monitoring with scans and meetings with an expert doctor. If a treatment is not working (if the tumour grows, regardless) then that treatment is stopped; treatments themselves cause suffering and some harm, and are not persisted with unnecessarily.

These issues of 'choice' and of 'getting on with life' are important:
• It is important to be well informed in making any decisions about treatment;
• It is important to be aware that a brain tumour can impact on the ability of the patient to make sound decisions and on personality; and
• It is important to discuss things with clarity while ever this is possible. Life is now, tomorrow never comes. Deferring issues in this situation may mean, if the tumour progresses, missing out

Adults caring for adults can do their utmost to seek to understand and support what the brain tumour patient wants to do; the position of the adult caring for a child with a brain tumour is far more difficult. I cared for a wife who had behind here a life of achievement and grown children and could reflect on that happily and could make her own treatment decisions. People caring forand making decisions for children face issues which are weighty and hard. There are a number of parents in this situation on OzBrainTumour, who share experiences.

In the realm of cancer treatments, there are many poisons and risks, and you can only take so much of these. So there are critical treatment choices as to how often, how many, and in what order. As regards treatment for the most aggressive brain tumours, medical science is hampered by lack of understanding of nearly everything. 'New', 'hopeful' treatments are often experimental, real improvements in treatment are rare.

§.....§.....§

So here we are together, in the Australian Brain Tumour Support Group on the internet, OzBrainTumour.

OzBrainTumour was established in November 2000, and had over one hundred members by the middle of 2001. We started out with a group with a 100% survival rate, a small group. 2001 was a year of inspiration and fighting and learning and a year also of savage test and loss of a succession of heroes we loved. Some carers later left the group to their private grief, others stayed, we did not know quite what would happen, what it would mean, whether after our ‘failure’ we would have anything to offer, how well we would be placed to encourage new people, arriving full of hope and determination. We had no wish to poison them with our loss.

I think it is possible to say we have not only survived as a group, but also that we have become a strong and supportive group, with a number of people, from all sorts of backgrounds, who have lost parents, partners, siblings, friends and, grief of all griefs, children, staying here with much advice and experience to offer. I continue to be amazed by the beauty and richness of what people write in the most terrible and testing of times. If we make ourselves stronger here and more aware of life, that's terrific.

But the group is changed from the early innocent days. The future of the group depends on you, on us all.

The group does not belong to anyone in particular, Now that you are a member it belongs to you too. It does not have rules or disciplines, the way discussion proceeds depends on who writes. Each of us has equal right to write, either on a new subject, or in reply to someone who has written. The group is only as good, as meaningful, as it is for you. As the person who founded it and as a 'moderator', there is nothing for me to 'moderate' — people are caring, gracious and generous - but you may also express rage and hurt and anger, if you wish, that's fine. Support means support and if nothing else, we share with each other an experience which others may not readily understand.

In addition to OzBrainTumour, there is a subgroup, OzBTcarerplace, established in April 2002 for those who are or have been in the past carers, to deal with issues they face. Do not underestimate the importance of this. To care for someone requires the carer to be well and it is also important that carers survive.

Here are links to the web sites for the groups:

OzBrainTumour - http://groups.yahoo.com/group/OzBrainTumour/
or use these email addresses:
Post message: OzBrainTumour@yahoogroups.com — after you have joined the group
Subscribe: OzBrainTumour-subscribe@yahoogroups.com
Unsubscribe: OzBrainTumour-unsubscribe@yahoogroups.com

OzBTcarerplace -http://groups.yahoo.com/group/OzBTcarerplace/
or use these email addresses:
Post message: OzBTcarerplace@yahoogroups.com — after you have joined the group
Subscribe: OzBTcarerplace-subscribe@yahoogroups.com
Unsubscribe: OzBTcarerplace-unsubscribe@yahoogroups.com

To access the web sites you need to sign up for Yahoo.groups. Sorry about that, and the flying advertising, but it allows us this space. There are some useful links (or bookmarks) at the web site, and the archive of all our old messages, to which you have access as a member.

I write these notes having cared for my wife Margaret Gray for sixteen months from her diagnosis to her death in September 2001. Like others, I had to learn an awful lot very quickly. Margaret and I wanted others to learn more easily; I continue to share what I learned along the way. Margaret's history can be found here. I am not a doctor but have had a career in research and policy work and am pleased to have time now to continue this support.

This work would not have been possible without the support and encouragement of many and the opportunity to learn from doctors and nurses, especially at the Royal North Shore Hospital in Sydney. There has also been, most importantly, the chance to learn by sharing my learning with that of others over the internet, in several brain tumour support groups, especially the international BRAINTMR group and Brain-Temozolomide. These have been very supportive families, with wonderful friendship, advice and support in the worst of times.

Dennis Argall

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1: What is cancer, what is a brain tumour, where does it come from?

Brain tumour is a form of cancer, cancer patients are treated by oncologists, but brain tumours, because of their location, involve issues distinct from other forms of cancer. Neuro-oncologists specialise in brain tumour.

There is a paper on cancer in Australia published by the Australian Institute of Health and Welfare on the web. Click here for a copy, while online: requires Adobe Acrobat Reader, obtainable free here.

The sad thing is that medical science still does not know what causes cancer, why cells turn tumorous. There are several distinguishing features of tumour cells, but exactly why and in what order cells change to be like this is not settled. Some key factors are:
[1] cells alter the way in which they make energy, they alter their respiration. In healthy organisms, including people, mitochondria in every cell make an abundance of energy and also carbon dioxide from sugar and oxygen. Tumour cells abandon this and make energy from sugar alone in the manner of bacteria, or of all cells before the appearance of mitochondria a billion and a half years ago, so there is something retrograde happening in the cell;
[2] cells undergo mutation, and this mutating process can increase in pace and be very diverse. This is the quality which is most evident as tumours grow and spread. Particularly because of the attention in biology to the human genome, this genetic mutation aspect tends to be the focus of research, though whether the mutation precedes the altered respiration seems not settled, and thus whether gene research will resolve the cancer problem is in my view moot;
[3] cells 'dedifferentiate' and lose their ability to 'differentiate'. Loss of this ability to differentiate in a developed organism produces cells which are not helpful;
[4] tumour cells can - in malignant and aggressive forms - reproduce very rapidly. In medicine various things are graded from I to IV (1 to 4) in order of severity. Tumours are graded I to IV according to degree of malignancy and aggressiveness ('benign' growths are not graded). The pathology of tumours is not simple and even the best institutions do not always agree on the identity and grading of tumour samples.

People generally have some cells making mistakes, pursuing aberrant growth and reproduction patterns, all the time — in the late 1960s, a study of bodies of healthy car accident victims in the United States found 'cancer' in every person over fifty. There are natural regulatory systems which normally allow us to avoid progressive disease by eliminating such problem cells. The mitochondria in healthy cells appear to keep watch and cause a deranged cell to commit a kind of euthanasia, known as apoptosis. Some theories of cancer think in terms of one rogue, mutated cell leading on to millions. On the other hand, given that the mechanism of tumorigenesis (a healthy cell becoming a cancer/tumour cell) is not understood, doctors also recognise that there is likely to be an ongoing process of tumorigenesis - no matter how many tumour cells you kill with treatments, somehow more cells are going the same way.

[5] There is another important piece of information. Tumour cells, as the proliferate, need a lot of blood supply to feed them. They thus develop new blood vessel systems which are messy and very different from normal healthy blood vessel systems. This creation of new blood vessels is called angiogenesis and opens the door to some treatments which try to stop angiogenesis - anti-angiogenesis.

Brain tumours are distinct in that they develop in a very confined space. Operating on the brain is difficult and fraught with risk of complication. Tumours may be in locations of the brain so critical to life that they are deemed 'inoperable'.

There is a blood-brain barrier (see for example http://galileo.physiology.uiowa.edu/animations/bloodgif.htm or http://www.sfn.org/briefings/blood-brain.html ) which means that the world inside the brain is different and transfer of materials between the brain and the rest of the body is limited. Thus:
[6] there is some prospect of tumour cells from other parts of the body entering the brain and producing brain metastases [colloquially 'mets'] — the rise of tumours in a new site anywhere in the body is called metastasis. Tumour cells in places copiously supplied with blood (the lung is a striking example) or in cells of a type which have properties of mobility (e.g. melanoma, in melanocytes) can migrate more easily than some others; but
[7] there is less prospect of tumour cells leaving the brain — though in part this may be because aggressive malignant brain tumours can kill with such speed that migration elsewhere is not an issue. As treatment prospects improve, as more treatments — notably more operations — occur, and survival times increase, metastases outside the brain seem to be arising as an increased prospect;
[8] there are special issues arising with drugs used to kill tumour cells, most seem to have difficulty crossing the blood-brain barrier — dosage needed to cross the blood-brain barrier may be such as to cause substantial side effects and impact severely on quality of life. There is currently one fairly new drug, temozolomide, which behaves better in this respect. There is also a problem recently recognised that some of the chemo drugs used successfully against other cancers are broken down [metabolised] more quickly by the liver, under the influence of drugs the brain tumour patient needs to take to avoid seizure and oppose swelling.

The confined space of the brain means that a tumour which grows rapidly and cannot be removed or stopped will kill by crushing healthy areas of the brain. There arise thus these considerations in dealing with brain tumour:
[9] how to kill the tumour cells - similar issues as with bodily cancers, but as noted above, the problem of getting a drug over the blood-brain barrier AND also
[10] the problem that killing tumour cells causes inflammation and this causes swelling and irritation also of healthy brain cells, again, within confined space;
[11] the pressure and damage within the brain can interfere with any and all things the brain does (thought, emotion, personality, movement, control of organs, speech and hearing, vision, smell, etc, etc), depending on where the tumour or tumours is or are;
[12] the pressure itself, also the effects of tumour infiltration, also the effects of surgery or other treatments may, cause seizures. These are, as in epilepsy, electrical storms of varying severity, which the sufferer may be aware of, or which may render the person unconscious, and not be recalled.

A family doctor may see few brain tumours in the course of a career. The family doctor will be faced from day to day with patients with headaches, seizures, other neurological abnormalities, which can be symptomatic of many things, and it is not therefore an easy task to diagnose brain tumour. This is probably why the most common diagnosis is with Glioblastoma multiforme Grade IV, because it is so aggressive (cells duplicating as swiftly as every 15 hours at times) that its impacts increase rapidly.

Oncologists in general oncology practice see brain tumours as only a small proportion of their case load. There are few neuro-oncologists in Australia, and only in Sydney and Melbourne. Neuro-oncologists, who specialise in brain tumour, are better informed about treatment options and about the subtleties of good treatment. Regrettably, not all general oncologists will admit to a slightness in their knowledge of brain tumour. There is also, away from the main brain tumour treatment centres in Sydney and Melbourne, a deeper pessimism about the prognosis for brain tumour patients, a tendency towards a more conservative approach to treatment, perhaps of 'cost-effectiveness' in not pursuing treatment, rather, providing minimalist therapy, more focus on palliation With the most aggressive of tumours it needs to be understood that there is no established 'cure' and the more aggressive treatments in those capital cities are achieving what may seem only some modest improvements in length of survival and quality of life. Weeks, months, a year or several years for a few; these may be very precious for those who achieve them, but they generally need to be fought for and obtained at cost of many treatments. Whether, for a person in another part of the country, it is worthwhile to disrupt life locally to pursue such possible gains, is a matter for personal judgment.

Palliative care - providing for the comfort of the patient as distinct from therapy, seeking to cure the patient. There has been some slowness to adopt newer brain tumour treatments in some places. This also combines with a negative attitude among some doctors in relation to informing and supporting patients — the news is too grim and the time too short for support groups, according to some.

These other observations can be made:
[13] compared with some bodily cancers, brain tumours tend not to cause pain, brain tumour patients tend just to slip away BUT
[14] along the way, the sufferer and carers must cope with impacts on the nervous system and the mind which can be difficult indeed.

How to get rid of a brain tumour? Much depends on the type of tumour. There are many different kinds. Some benign growths can be removed without significant further consequence. Some benign tumours can be removed by operations via the nose. The most common malignant tumours are astrocytomas, growing in the astrocytes or glial cells, supporting structures in the brain, rather than nerve cells themselves. There is a tendency for malignant tumours at lower grade to return or recur - doctors refer to recurrence - at higher grade. The names of these grades are:

Anaplastic astrocytoma grade I, II and III - AAI, AAII, AAIII
Glioblastoma multiforme grade IV - GBMIV

The terrible and repetitious pattern of these tumours recurring at higher grade means that the preponderance of discussion in this group will be about coping with AAIII and especially GBM IV, the most common of diagnoses. We need, nonetheless, to support people coping with other types of tumour.

IMPORTANT NOTE: It is useful if in writing to the group you can mention, in your signature, the tumour you are dealing with. It is easy otherwise for people who are wanting to be helpful to send you advice which may not in fact be relevant - we tend to write of what we know, not of what the other person is dealing with - unless that person makes clear what the issue is.

One especially important diagnostic distinction is between these AA/GBM tumours and a new class distinguished from them in the 1990s, of oligodendrogliomas - sorry, it took me time to cope with that word, try 'oligo' for short. These oligo tumours are more responsive to chemotherapy; treatment regimes needed for the AA and GBM tumours are not the same as for oligodendrogliomas.

So... be careful with advice you get and advice you give.

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2: Diagnostic and monitoring tools

Suspicion of tumour arises from symptoms. These vary immensely, depending on the part of the brain affected by tumour. If the optic nerve or relevant brain area is affected, vision may be impaired; if parts of the brain controlling motor activity (moving muscles) are involved, some loss of manual skills or movement may develop. There may or may not be seizures, there may or may not be 'neurological signs' (moving eyes in the right direction, walking straight, etc.)

Drowsiness is common, foggy thinking is common, muddle is common, headache is common.

Where possible, an MRI [magnetic resonance imaging] scan is the best way towards diagnosis. But there are few MRI machines and if you are sent by a GP for an MRI scan you pay $500+ and there is no rebate. You can wait to see a neurologist, but…

A CT [computed tomography] scan is easier to access, and attracts rebate, but is not so good for seeing tumours.

The CT scan is a special kind of x-ray machine that is less dangerous than conventional x-rays, because the dose is much smaller. It is good for observing oedema (fluid) or haemorrhage, and thus is the absolute best choice for checking for stroke (blood vessel problem, clot or rupture, etc.) impacting on brain function. Also excellent for finding aneurism (blood vessel expanding, threatening to rupture, causing catastrophic stroke) — you meet people dealing with such problems in a neurosurgery ward.

The MRI machine is not an x-ray device but can identify different states of water in cells, tumour cells being distinctly different from normal cells in that regard. It can be tweaked in different ways to see different things, including oedema, and with the addition of a chemical, gadolinium, via a vein in the arm, contrast in the images can be increased to show tumour very clearly. Sometimes the scan will show black space within the tumour, which is likely to be a 'cyst', a sac of fluid. As tumours grow, some of the areas inside them may be deprived of circulation and cells there die (necrosis) and within that dead area, fluid may accumulate and form a cyst.

A doctor looking at scans is looking for information on the size and shape of the tumour, but also looking to see what it is doing to the brain, the extent to which pressure from the tumour is pushing the brain around, for example deflecting the midline. This latter kind of information may be visible on a CT scan, even if it does not show the tumour itself clearly.

When the scans are put up on the viewer in a doctor's office, in each picture, the right is to the left and vice versa. Think of this in terms of looking at a person, not in terms of your own brain. A doctor looking at a patient sees the patient's left brain to the right.

Precise diagnosis is not possible from any scan, that requires examination by a pathologist of material removed from the brain. But the look at the scans is likely to tell a good neurosurgeon whether he should carry out a modest biopsy, taking a little bit out for study, or whether the lesion, the altered thing, is such that it is smart in any operation to go the whole hog and get out as much as possible, as swiftly as possible.

Note that in assessing prognosis, these things, evident on the scan, are a good guide:
• size of tumour
• extent of midline shift (is the pressure from one side pushing on the other hemisphere, deflecting the midline of the brain, shown as a shift of the midline on the scans)
• whether the tumour has crossed the midline - if it is in both sides of the brain, operation becomes more difficult.
and that the next really big determinant is going to be:
• percentage removed at operation.

One doctor may say 'inoperable' another may say 'operable'. Multiple opinions can be obtained and a good doctor should accept your desire for another opinion — remembering that if a tumour is growing fast, quick decision and action becomes important. There is, however, no imperative to pursue or accept the most 'aggressive' treatment advice.

The MRI is not able to distinguish between live tumour cells and dead tumour cells. A PET [positron emitting tomography] scan can, but not with precision. PET scans involve injection of a radioactive sugar-like solution into a vein; the PET machine then observes metabolism in the brain — live cells metabolise, burn sugar, dead cells do not. Tumour cells voraciously consume sugar, more so than healthy brain cells. BUT: there are only a couple of PET machines in Australia, and there is no rebate. AND while such a scan may show an area of apparent necrosis, not live tumour, it is wise, in the course of disease, to assume that there are always some live cells in such an area —and the number of live cells may increase dramatically quickly.

So the MRI remains the most valued tool. The CT scan will be used a lot in a hospital environment because it's quick and relatively inexpensive and accessible and especially because immediately after an operation the concern is to check for bleeding and for 'angry' reactions, producing oedema. These are environments where the CT scan shines. The MRI may produce upsetting false images if used too soon after procedures, surgery or radiotherapy, which inflame and agitate the brain.

There are no blood tests to establish brain tumour. But there is a need during treatment to carry out blood tests, especially where an anti-seizure medicine is being taken and you need to keep the level of that substance in the blood (the serum level) in the therapeutic range. Also, radiation and chemotherapy impact on bone marrow, and bone marrow produces elements of the blood, which need checking on.

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3: Treatment and Care — overview

Just to repeat, from a previous section, this paragraph:

The confined space of the brain means that a tumour which grows rapidly and cannot be removed or stopped will kill by crushing healthy areas of the brain. There arise thus these considerations in dealing with brain tumour:
[9] how to kill the tumour cells - similar issues as with bodily cancers, but as noted above, the problem of getting a drug over the blood-brain barrier AND also
[10] the problem that killing tumour cells causes inflammation and this causes swelling and irritation also of healthy brain cells, again, within confined space;
[11] the pressure and damage within the brain can interfere with any and all things the brain does (thought, emotion, personality, movement, control of organs, speech and hearing, vision, smell, etc, etc), depending on where the tumour or tumours is or are;
[12] the pressure itself, also the effects of tumour infiltration, also the effects of surgery or other treatments may, cause seizures. These are, as in epilepsy, electrical storms of varying severity, which the sufferer may be aware of, or which may render the person unconscious, and not be recalled.

There are thus broadly four things to be pursued in treatments:
[A] to destroy and/or remove the tumour cells, to fight the tumour
[B] to minimise the effects of the tumour on the brain, in particular, to reduce the swelling it causes, and to reduce the prospect of seizures
[C] to maximise the comfort and quality of life of the patient for as long as possible and
[D] if the tumour cannot be defeated, to allow the patient to die with dignity, or as some might prefer to put it, to live with dignity while dying. Nursing and medical support in this stage is called palliative care, scarcely spoken of, but terribly important in terminal illness.

In all discussion here, note that while there is an order and timing of treatment, based on the experience and knowledge of doctors applied to the individual circumstance, there is an absolute right of the patient to decide whether to accept treatment.

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4: To destroy and/or remove the tumour cells, to fight the tumour — overview

There are basically three conventional areas of possible action, within which there are various options:
• surgery — physically removing tumour
• radiotherapy — bombarding the tumour area with radiation
• chemotherapy — attacking the tumour with poisonous chemicals
• anti-angiogenesis — exploiting the need for tumours to develop blood supply by inhibiting new blood vessel development.

Alongside or in addition to these a number of alternatives are advocated by people outside mainstream medicine. There is some discussion of this at OzBrainTumour. Note that in New South Wales and doubtless elsewhere, it is illegal for anyone other than a registered medical practitioner to claim to 'treat' cancer, though 'relief of symptoms' may be offered.

We are in a difficult situation, alternatives are instantly attractive when confronted by the limited value of conventional treatments. Nonetheless, this primer focuses on coping with the conventional treatments, because it is important to understand in the first instance what is available conventionally.

The most common order of treatments is as above, surgery, radiotherapy and then chemotherapy, at least in the case of AAIII and GBM. In the case of oligodendroglioma, these have greater response to chemotherapy and radiotherapy may be delayed.

A patient always has the right to seek a second opinion, though many patients and carers find it most comfortable to trust a doctor with whom they are dealing. If seeking further opinion in relation to a high grade tumour, be conscious that time may be of the essence.

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5: Neurosurgery

Surgery options depend in the first instance on tumour location:
• Is it a discrete mass, or masses, or is it diffuse in character, on the scans?
• Is it accessible — near a place of surgical entry, or deep within the brain?
• Is it entangled with pieces of the brain whose damage would have catastrophic impact, or would terribly diminish quality of life?

A surgeon will also be looking at the general health and age of the patient. The younger and fitter, the more able to cope with a very invasive operation. To open a brain (craniotomy), to remove material, to make good, put back a plug of skull and sew back over a scalp and skin flap is a process involving perhaps ten people and a minimum of four hours.

A neurosurgeon also is aware of which types of tumour are best operated on, or best left. If you do not understand what considerations are in the surgeon's mind, ask. Generally, doctors become more forthcoming if you are more assertive in seeking information. You may need to make clear that you want to be extensively informed — if indeed you want to be extensively informed.

Some surgeons are more 'aggressive' than others. That's life, it also reflects experience as well as judgments of science and art. Some will be concerned to avoid causing deficits, some will be concerned to 'get the lot.' Getting as much as possible means leaving behind a minimum of tumour cells, maximising the time for regrowth, also making it easier for later treatments — radiotherapy, chemotherapy —to work on a smaller rather than larger number of cells. But getting out as much as possible may mean greater risk of damage to healthy brain cells.

Sometimes second or third operations may be offered. An operation alone is not doing much more than buy a little time, if the tumour is aggressive. A GBM might regrow to two or five centimetres in a couple of months. The point of the operation is not the result of the operation alone, but establishment of a base for radiotherapy (generally only one course possible, there are established maximum lifetime doses) or chemotherapy to work better. From that perspective, if chemotherapy fails and there is no further non-surgical option in sight, a further operation recedes in value.

Be aware that the risks associated with operations increase with each successive operation.

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6: Radiotherapy

There is a transcript of a substantial presentation on radiation therapy by Adjunct Professor Phillip Yuile of Royal North Shore Hospital and Radiation Oncology of Sydney, provided also to new subscribers of OzBrainTumour, and obtainable here.

The fundamental principle in the use of radiation for therapy is the same as the principle at work where people are concerned about radiation in daily life —radiation damages cells, and damages them particularly when they are in the process of dividing. The higher the grade of tumour, the more aggressive the tumour, the more frequently its cells divide and multiply. Brain cells, by contrast, seldom divide and multiply. So targeting the brain with radiation will impact rapidly on the tumour cells, whereas damage to the healthy brain cells may take many years to have obvious effects — the age and general health of the patient and the context of other treatments and irritations to the brain will be relevant to this.

The most common type of radiotherapy used is external beam radiotherapy, in which a target is defined around the tumour site, going beyond the tumour site itself, because in more aggressive tumours there is infiltration and seeding away from the site of visible tumour, and it is important to get at those tumour cells too. The radiotherapy machine fires x-rays at the target from three directions, each day usually for thirty daily treatments. There are some pictures of such a machine here. There are also some machines similar in set up which fire electrons rather than x-rays at the target - electrons having weight, unlike the x-rays, impact near the skin surface only, and so are relevant to problems near the surface, not to the brain.

So that the machine always addresses the target precisely, a mask is made, which the patient wears each day, during treatment - while lying on the treatment table, the sides of the mask are clipped to the table, so that the head is reliably located in the same position each time.

These treatments involve lying down, dressed, on a table, for some minutes. Unless distressed by the mask it is a simple procedure. Some places allow you to bring along a CD or tape to play.

There are also stereotactic radiotherapy, or rather radiosurgery, machines, which target a more sharply defined area by different means. They therefore limit radiation dose as tightly as possible to the target. This is very suitable where such a tightly defined target is all that it is important to target — where it is not a tumour which infiltrates or seeds. This is most valuable in the case, say, of brain metastases from lung cancer. But it is a technology which is not extensively available in Australia. In Australia, linear accelerators (linac machines) are used, and the machines and patient set up look similar to the conventional radiotherapy machines except that rather than aiming from just three points, the radiation source is moved around on a gantry to come from many directions, at all times very precisely aiming radiation at the precisely defined target, with minimal dose to any other area.

The same stereotactic effect is achieved with some other machines. In other countries there is a machine known as the Gamma Knife, which has similar precise targeting effect using 200+ sources of gamma radiation (cobalt 60) at the end of tubes inside a large radiation shielding box, the tubes being focused to aim at the target.

SIDE EFFECTS:

There may be some accumulation of fatigue from the treatment. There can be a sunburn effect on the skin, for which aloe vera or vitamin E may provide relief. Hair will fall out, over a couple of days, several weeks into treatment and you may want to get the remnant hair trimmed as you would wish before that happens, as the scalp becomes tender. Hair will later regrow in low dose target areas, will not regrow in high dose areas. Plan for that.

While the skin is tender, soft scarves are the most comfortable cover. The local Cancer Society office may have a wig hire service, but a wig may not be comfortable until inflammation subsides.

There is also an equivalent of sunburn going on inside the skull and this intracranial inflammation, also caused by the death of tumour cells, can cause swelling and pressure, for which the anti-inflammatory drug dexamethasone is valuable, though this is a terrible substance with other, negative effects and its prescription and dosage need careful management. In this regard, you need to be conscious that the tumour-killing treatments can produce some of the symptoms that tumours themselves produce, because the same processes of inflammation, fluid build up, swelling and pressure are involved, noting also that these things can irritate healthy brain cells and make them inflamed too. This internal aggravation may make it more comfortable also to wear a scarf to protect from cold winds.

The hair fall-out is caused because the radiation damages cells in the process of reproduction, and hair cells are being rapidly reproduced daily, to produce hair growth. Bone marrow is also busy daily producing blood elements. There is quite a lot of bone marrow in the skull, but the risks of serious problems are less from limited target radiotherapy than from chemotherapy — see discussion of side-effects in the next section.

It is important to be aware that there is a maximum lifetime dose of radiation that anyone can be given — indeed there is no 'safe' amount — and therefore, when you have the full course of thirty or so treatments, that is, basically, it; no more later.

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7: Chemotherapy

Chemotherapy drugs are cytotoxic; they kill cells in the process of dividing. Most of these are administered to cancer patients intravenously. They impact on the whole body, and have effects on all frequently dividing cells — tumour cells, certainly, but also hair roots, bone marrow and mucous membranes of the gastrointestinal tract and the urogenital tract. So side effects can be severe, and there are limits to how much of such poisons people can cope with.

There is also a problem with established chemotherapy drugs that they tend not to get across the blood-brain barrier. On top of that, a brain tumour patient is likely to be taking anti-seizure medications which may have the effect of actually metabolising (breaking down) a lot of the drug before it can get to the brain.

Low grade tumours and oligodendrogliomas have a record of response to such drugs better than in GBMIV, where the time gained, if any, may be so short as not to be worthwhile, especially where the drug has a record of diminishing quality of life.

As a result of these combined consideration, chemotherapy has historically not been presented as an option for many brain tumour patients with the more aggressive tumours in Australia, though if you subscribe to internet brain tumour discussion, you will find it is more commonly embarked upon in the United States. Generally speaking there is a reluctance in Australia to subject patients to an intensity of punishing treatment, compared with standard practice in the United States.

Much changed in 2000, when a new drug, temozolomide, marketed as Temodal, came on the market and was added to the schedule of the Pharmaceutical Benefits Scheme, bringing it down from $3000-4000 per month to the price of PBS subsidised subscriptions. Temodal, normally taken for five days every four weeks (5/28), has these advantages:
• it is taken orally, at home
• it dissolves in the stomach, and passes readily over the blood-brain barrier
• it only metabolises into the active cytotoxic agent in an alkaline environment —tumour cells produce masses of lactic acid, leaving an alkaline environment behind in the cell
• this is also an excellent reason NOT to bite the capsule, as saliva is alkaline, whereas the stomach is acid.

Not all doctors or hospitals are familiar with Temodal. It has a good record, though not for all patients, perhaps 30% respond. Once begun, the patient takes it every four weeks, perhaps indefinitely, certainly for some months with scans showing no tumour (some doctors say never stop; some say take a break from the treatment). It is necessary to have blood tests and see a doctor every four weeks, before each Temodal round. Also, normally, a scan to monitor whether the drug is working, every two months. If there is tumour regrowth while taking the drug, it is clearly not working and there is no virtue in persisting with the discomfort involved in taking it.

The discomfort of Temodal arises particularly because it causes nausea. For this you need a powerful anti-nausea drug, most commonly Zofran. These have a combined effect of constipation which may be severe, and requires attention to diet and also use of laxatives.

There is a 'Temodal flare' of symptoms, probably especially in patients for whom the drug is working —if there is a kill of tumour cells, there is inflammation and irritation in the brain. So in a given 28 days, there may be symptoms of one kind or another from say day 3 to day 10; there is virtue in developing a program for rest and ease during that phase, scheduling more active things for the rest of the four weeks.

Blood tests (complete blood count) are required especially to monitor damage by the drug to bone marrow and impacts upon these bone marrow products:
• White blood cell count. White blood cells are at the core of the immune system. The nadir (lowest point) in white blood cell count in the Temodal cycle is day 21, and a count there and at day 28 is important to see that the white blood cell count is on the rise again, otherwise there may be need to lower the Temodal dose and or delay it. There is no point in killing tumour cells only to die of pneumonia.
• Platelets. These are tiny pieces of fibrin, which last in the blood only for several days. They physically block leaks in blood vessels, and so a shortage of them creates a risk of blood vessel leaks. A person with very low platelets will bruise easily and badly, not least when blood samples are drawn. Again, no point in killing tumour cells, only to have a stroke.

There are a number of new drugs for brain tumour in stages of clinical trial at any time, for example, currently, Gleevec. The major events at which reports on such things are presented and specialist doctors confer are:
• the annual meeting of the American Society of Clinical Oncologists, in May
• the annual meeting of the Society for Neuro-Oncology, in November, also in the US.

Clinical trials begin at phase I, where drugs are tested at various levels of dosage, for toxicity. Participation in such a trial is not without risk. Successive levels of trial seek to define value and appropriate dosage. It is not a speedy process, involving large amounts of money, generally drug company money, and it is not made easier by the fact that numbers of brain tumour patients are never larger, and they are, with the higher grade tumours, struggling to survive. There are few trials of new brain tumour drugs in Australia, Temodal was the most recent. Australian neuro-oncologists are likely to focus their interests on drugs which show promise in US trials. Note also that some doses used in treatment in the US are thought savage by some Australian doctors. Always, in hunting treatment options, have regard for quality of life.

Please also look at these notes on a presentation by Dr Helen Wheeler, neuro-oncologist, in February 2001.

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8: Anti-Angiogenics

As tumours develop, they require a blood supply, The blood vessels that support them are very different from normal human blood vessels. There has for some years been the notion that tumour growth might be inhibited by inhibiting the growth of new blood vessels, but this form of treatment has only been taken up in recent years. The development of new blood vessels is called angiogenesis. To oppose that is thus anti-angiogenesis

At the core of the idea is the fact that tumours cannot grow beyond pinhead size without angiogenesis. So the interest is in anti-angiogenics. In western medicine there is one notorious anti-angiogenic drug, sauramide, sold as Thalidomide. Its anti-angiogenic properties were demonstrated in the late 1950s when, in Australia, Canada and the UK, but not in the US, Thalidomide was approved for sale as an anti-nausea drug, to be used in pregnancy. Foetuses must develop new blood vessels, of course. Many babies of mothers taking Thalidomide were born without limbs, because Thalidomide opposed the development of the necessary blood vessels at the critical time.

While Thalidomide has demonstrated considerable value in clinical trials in the US and at the Royal North Shore Hospital in Sydney, it is still a drug with a past, a prohibited substance, unsubsidised and with no drug company interested in the work needing to be done to secure its approval and marketing as a drug because it is out of patent, and thus not profitable.

In a presentation to the Sydney Neuro-Oncology Group's support group's first meeting in February 2001, Dr Helen Wheeler indicated that patients using a combination of Temodal and Thalidomide had done better than patients using either of these drugs alone.

The 5/28 schedule of Temodal (see previous section) is not designed thus for optimal tumour killing capability, it is designed with breaks between treatment rounds to allow the body, particularly the blood count, to recover. Tumours are often able to recover swiftly from the effects of the Temodal. The combination with Thalidomide can be seen as of especial value in minimising tumour growth between Temodal rounds. It remains the case that there is no Pharmaceutical Benefits Scheme subsidy to Thalidomide; the patient pays the full cost, which is at June 2002........

The dosages of Thalidomide used at RNSH are smaller than in the United States. The Australian trials and the US trials seem to have had comparable results; the therapeutic dose is not settled.

There are a number of new anti-angiogenic drugs being trialed in the United States; there is the prospect that some drug company will find a way to modify the Thalidomide molecule sufficiently to allow the new molecule to be patented under a new name, and thus profitable, while retaining the established anti-angiogenic property of Thalidomide.

SIDE EFFECTS.

The lower Australian doses have advantages in reducing side effects. Side effects include:
• sedation — when the drug is commenced there is an immediate powerful sleeping effect, so it needs to be taken at bedtime. This sleep seems recuperative and relatively refreshing, rather than stupefying. This effect may reduce in a week or so, may recur with dosage increases.
• constipation — this is a persistent effect and there is a considerable combined effect during the period when Temodal and Zofran (both also constipating) are taken, so that there is a need for constant laxative doses and effort the clear the gut immediately before the Temodal round, to avoid the gut turning to concrete.
• peripheral nerve damage — Thalidomide is a neurotoxin and sustained larger doses are likely to produce tinglings in hands, feet, arms, etc. This may be reducible by reducing dose.

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9: To minimise the effects of the tumour on the brain; in particular, to reduce the swelling it causes, and to reduce the prospect of seizures: overview

These are two matters generally arising in conversation with doctors and nurses as separate subjects, but most usefully seen as part of the same cloth.

Swelling and pressure in a confined space - destructive: Central to understanding the management of brain tumours is the fact that the brain is a confined space inside the skull - this intracranial space is not flexible as, say, the stomach is, when there is a growth developing. Anything strange produced in the cranium is hard to dispose of, to remove from the brain. Elsewhere in the body this there are efficient systems for removing waste materials, but behind the blood-brain barrier it is more difficult. The accumulation of unwanted stuff in the intracranial space is the source of pressure; pressure causes inflammation, weeping of tissue and swelling. This all makes for a self-reinforcing destructive pressure on the healthy brain. So a brain tumour does its destructive work essentially by crushing the brain.

The metabolism of tumours involves the production of large amounts of lactic acid. So it's not just the mass of the tumour at work, this fluid product increases pressure.

The killing of tumour cells, by radiation or by chemicals, produces a mass of inflammation which adds to the cycle of inflammation, swelling, weeping, pressure buildup.

This has an important consequence in limiting the use of these anti-tumour treatments to times when there is not a burden of preexisting pressure on the brain. What that means in practice is that there is a logic of carrying out an operation before the radiation and chemotherapy, to remove material, to ease pressure, to reduce to a minimum that amount of tumour that has to be treated by radiation and/or chemotherapy… bearing in mind that an operation itself is a great annoyance and irritant to brain tissue, and will cause inflammation and there is a need to give the brain some time, several weeks, to recover from an operation before embarking on other treatments. Also noting that often at diagnosis, scans will show lots of pressure buildup and some days of treatment with dexamethasone (see below) may be needed to reduce the pressure and make the operation safer.

Electrical storms: The activity of nerve cells, including brain cells, involves the transmission of tiny electrical charges across gaps — synapses —between nerve cells. There are also neurotransmitter chemicals involved, substances created to carry the signals, then broken down (reuptake) after the job is done. These are sensitive and delicate processes, of which medical science still has only modest understanding. If these electrical and chemical processes go wrong, there may be seizure, as in epilepsy, if there is an overload of transmission, when, say, a local short-circuit or excess of electrical activity produces something of an electrical storm, either within an area of the brain, or through the whole brain. There are many different types of seizure, defined by different characteristics. The person suffering the seizure may or may not be aware of the seizure, depending on how the areas of the brain involved in consciousness are involved and overwhelmed.

A person with a brain tumour may experience seizure as a first symptom; or may experience seizure for the first time after an operation, or with later disease progression, or not at all. The prospect of seizure arises with the way the tumour pushes the brain around, squeezes it, or the way the brain is interfered with in an operation, or the way bits of necrosis, dead tumour cells, may move and impact on brain cells. As an analogy, consider a force pushing electric wires close to each other, consider rough cutting through a mass of wires which then have to self-repair.

In the management of brain tumour, drugs [a] to control swelling and [b] to limit or prevent seizure are very important. They tend to be prescribed and discussed with patients separately. My concern in this overview is to draw attention to this interlinking — the drug to control swelling, while effective, may prevent the situation with seizure potential from arising; the anti-seizure medicine comes at the problem from the other direction, dampening down the chemical base for seizure. Taking the one kind of drug does not remove the need for the other, if medically prescribed. However, weaning off the drug used to control swelling, and growth of the tumour, increases the risk of seizure. If seizure then strikes, it is easy to say "why has my anti-seizure medication failed?" when that may be an unfair test of the latter drug if swelling and pressure are elevated. Appropriate immediate remedy includes also review of the anti-swelling medication.

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10: Dexamethasone

A person with a brain tumour will be prescribed, promptly after diagnosis and in preparation for an operation, the corticosteroid drug dexamethasone (dex, for short). This is an anti-inflammatory. Our bodies naturally produce corticosteroids daily, in an amount approximately equal to 0.7mg of dexamethasone a day. Dex is about five time stronger than the anti-inflammatory drug prednisone, which in turn is about five times stronger than hydrocortisone. For an indication of the strength of dexamethasone relative to other corticosteroids, see http://www.medmedia.com/meda1/93.htm For an extract from the U.S. Physicians Desk Reference on this drug go to http://home.cyberave.com/~hsquare/pdrfg/pd/monos/decadron.htm

There is no substitute for this drug available. It is not a cure, it does not stop the tumour. Its role is to oppose inflammation and swelling, as discussed in the preceding section. This grants time and comfort for the patient. Also, by reducing pressure, it allows the brain to tolerate radiotherapy or chemotherapy treatments that also cause inflammation.

As an anti-inflammatory, dex also opposes wound healing — wound healing is closely associated with the inflammation reaction. There is thus a particular concern in its use around neurosurgery — it will be appropriate to get the dex dose up to reduce swelling before the operation, then a concern to get it down, to allow healing, after the operation.

While dex is similar to the natural bodily hormone cortisol, its administration — in doses way above normal daily human needs — has some deranging effects. This means that while it is invaluable in tumour management, every effort is made to minimise the dose, or wean the patient right off dex, if possible. Here are some of the side effects:
• in a very small percentage of patients, there is a susceptibility to corticosteroid psychosis. This is recognised but not well studied in medical science. It is not something that creeps up, if you are going to have this problem it will arise promptly. It will be manifest in emotional disturbance or anger or in delusional states, the sufferer believing that some very unreal things are happening. Doctors are not in the habit of warning about this, but it seems important for both the person taking this medicine, and the carer, to be aware that this could happen. Better to know that the drug could be doing such a thing than to feel wounded psychologically by sudden, deviant, out-of-character behaviour;
• raging appetite and weight gain. Lots of people experience this;
• bone and muscle wasting. Elevated corticosteroid doses cause an excess of catabolism, the process by which mineral resources are drawn daily from our muscles and bones, as we do work. If this is sustained, as in long term use of dex, the result is a weakening and reduction of muscle and bone, particularly in the upper legs and arms. Over time, this may give rise to a risk of injury, especially in the context of weight gain;
• other hormonal disturbance. There is a natural cycle of steroidal hormonal production and management, and this disturbance in level in corticosteroids impacts on that balance. There may be a loss of energy and other symptoms as in hypothyroidism or Chronic Fatigue Syndrome. If these symptoms are severe, a thyroid check may be desirable;
• as part of the hormonal disturbance, problems of sugar management may arise, and a person may develop diabetes. Increase thirst and very frequent urination are the most common common symptoms of diabetes onset, and if they should develop, please talk to the doctor.

When a person is given supplements of corticosteroid drugs, including dex, our regulatory systems reduce or shut down our natural production of cortisol. This means that if a person weans off the dex, the adrenals may need some encouragement to be kicked back into action. For this reason, there is a need to proceed the weaning with care through that normal level of human production, around 0.7mg a day. A common practice is not to try to make the dose smaller and smaller then but to alternate days of dose at 0.5mg with days without dose. The half life of dex (the period within which the level of the chemical in the body reduces by one half) is about 35 hours, so doses two day apart will send alarm bells ringing to get things going again. Extremes of fatigue may be experienced; rest to accommodate that, it's worth getting off the drug.

It is important not to abandon taking dex suddenly if a patient is doing well. Too-sudden dose reductions can cause a big surge in inflammation, swelling and pressure, and a rapid return of symptoms. By the same token, when a patient is at a terminal stage of illness, weaning of dex may be inappropriate, there may be a time when swift withdrawal has virtue (see later section).

In advance of an operation, a surgeon may prescribe perhaps 16mg dex a day, in four doses of 4mg [4mg qid]. After the operation, the dose may swiftly drop to 8mg then 4mg, to promote healing, as discussed above. If there is a return of symptoms, the dose may need to go up again. But in general, the ambition is always to lower the dose. The longer the dose has been high, the longer the wean must take. Easy to go to 16mg then back to 4mg in days, but if a patient has been at say 8mg for weeks, dose reductions need to be very gradual, a schedule of many weeks to get back to zero, even though tumour may be stable or gone from scans. A mild increase in symptoms may not mean a need to make a shift to sustained higher dose. A day or so of bigger dose may knock the swelling problem and allow the earlier lower dose to be maintained. This is a matter for medical management; it will help the doctor to have clear advice on whether symptoms are rising or abating at any dose, or in response to dose change. Work with the doctor on this. Give her or him the information to allow good choices of dose. And don't allow the real desire to get off the drug to prevent you from reporting symptoms from which you could be protected with a little more dex. The issue, in fighting a ferocious enemy, is to win days of quality of life, to steal every moment possible from the tumour.

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11: Mannitol

This is not a commonly prescribed substance, but deserves brief mention here. Mannitol can be injected intravenously, to allow fluid escape over the blood brain barrier, for a brief period, for example after radiosurgery, when there is an intense burst of inflammation to be dealt with. It is not a treatment that can be used regularly.

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12: Dealing with seizure: overview and action stations!

A lot of this section is addressed to the carer, as the person whose help is critical when a person is having a seizure.

To witness a person having a seizure may be disturbing. To understand what is happening may help. To understand what to do for a person in seizure is invaluable, and potentially lifesaving. Understand especially that the person watching may find it much more traumatic than the person having the seizure. While you cannot fail to be affected, try to distance yourself enough to watch and learn.

Seizure (having a fit) occurs when there is a surge of electrical activity through the brain, overwhelming control functions of one kind or another, also, in grand mal (aka tonic clonic) seizures, overwhelming consciousness. So in any seizure, there will be involuntary movements, and in the most severe, there will be loss of consciousness, and the person having the seizure then will have no recall of what has happened. In the seizure state, arms and legs may flail, the face be contorted and flushed, spittle flying, beyond the wildest orgasm, there may be lurching and lunging, often in a semi curled position.

A person suffering a seizure may find it embarrassing, even a matter of shame, to lose control in this way, or to have no recollection. How the sufferer copes may depend to a significant extent on how reassuring those around her or him are at the time. It may be helpful to see the event in the context of the brain trying to throw off a problem and settle normally again.

In the onset of any seizure, the person may become excited and passionate in speech and then start not to make sense. Eyes will roll; control of limbs diminishes — the higher brain functions are disabled, the brain stem (the dinosaur brain) is left to cope.

The greatest dangers to a person in seizure are:
• personal injury, from falling down or from thrashing about
• choking or asphyxiation, if there is any regurgitation from the stomach and breathing into the lung of material from the mouth.

There are a couple of important things that follow. If there is a known risk of seizure, especially of tonic clonic seizure, then it is desirable to make the living environment free of sharp objects that could be fallen upon.

If a person begins having a seizure, then there are some sensible things the observer can do:
• DON'T PANIC —the seizure is not destructive in itself, and it is up to you to see you can help and love and accept the involuntary movements and be there to help the person through the event;
• try to remember immediately to look at your watch or a clock —if there is a need to call an ambulance, the ambulance staff and hospital emergency staff will ask: [1] how long did it last [2] whether the person was conscious [3] did the person hit anything, is there any injury; you are a valuable reporter, to assist in later interpretation of the event. In addition, it will help you to know that the event was over in say five minutes, because, especially the first time you go through this, those five minutes will seem much longer;
• do not try to restrain the person from involuntary movements — you won't succeed, you may hurt either or both of you, you may add to the muscle exhaustion of the person in seizure afterwards;
• see that the person is in a situation where they cannot fall or hit anything — if on a bed, either move the person away from the edge, or if that is difficult, be there to prevent falling from the bed; if on the floor, great, just get sharp objects out of the way, or covered by something soft;
• if the person has been eating, or if there is any indication of food rising from the stomach, it is best to try to get the person into what is known in first aid as the 'recovery position', off the back, onto the side, top leg bent up, so that the head can be over to the side and any regurgitated food has a chance to come out of the mouth rather than go back down to the lungs;
• in no circumstance try to hold the mouth open, or put anything in the mouth. Definitely don't try to administer oral medication, it's way too late and you can only cause choking. There is a risk that the tongue will be bitten, but that has to be lived with; your fingers or any mouth guard is likely to be crushed if put in the mouth, with further injury all round.

In essence, you are trying to allow the person to come through the event, without injury, and on his or her own.

YOU MAY WISH TO COPY THE LAST SEVERAL INCHES OF TEXT, AND THE NEXT SEVERAL TOO, INTO A WORD PROCESSOR AND PRINT IT OUT AND KEEP IT SOMEWHERE HANDY. I HAVE KEPT SUCH A PIECE OF PAPER IN THE BEDROOM WITH JUST A CORNER STICKING OUT FROM BEHIND A PICTURE, READY FOR GRABBING — YOU CAN USE REMINDERS IN EMERGENCY.

Or...

There is a useful internet site with information here — http://www.intelihealth.com/IH/ihtIH/WSIHW000/9339/10654.html#what

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13: Seizure: ambulance and hospital

Advice as to when or whether to call an ambulance varies, doctors vary in advice. Act in accordance with your own feelings, if you do not have clear directions from a doctor. There is harm in allowing a seizure to run on by being brave; there is no harm in seeking help. If it seems to you, in the first minute or so, that this seizure may not resolve quickly, call for help. Here is where the cordless or mobile phone becomes invaluable. You can watch over the patient, watch the clock, call the ambulance, call the baby-sitter, the aunt, whoever else is needed to jump in for support.

If the person is out of seizure, sitting, conscious, coherent, when the ambulance team arrive, that's cause for celebration, not apology. If the person has not surfaced or returned to coherence when the ambulance team arrives, be glad you called them when you did.

Here is an important distinction: a 'self-resolving' seizure, one from which the person recovers without assistance, is much less worrisome than a non-self-resolving seizure, where a person remains in status epilepticus.

If an ambulance crew arrives, be ready to tell them:
• when the seizure began (if you haven't a clue as to precise time, relate it to the time of your 000 call, which will have been logged, e.g. "a couple of minutes before I called")
• whether the person has been conscious/unconscious, when last ate/drank, whether coughed up anything during the seizure
• this is a person diagnosed on ... with ...
• these are the current medications
• whether you have been with the person throughout, whether you know if the person hit anything, suffered any injury during the seizure.

THEN you can surrender patient care to the ambulance team, and while they work, you can get yourself organised to go with them. Take everything for your own comfort as well as what you need to tell the triage nurse at the hospital. You, not the ambulance team, need to provide the history to the hospital. Have the scans and medication chart, and also when last doses taken, readily to hand, sort out with the ambulance team how long the seizure lasted. You are going into the hands of an emergency team at a hospital who may never have seen the patient before and you are the one who can help them deal with the whole case properly. They will not know best how to keep medications in therapeutic range unless you tell them exactly what established doses are, and when last doses taken. Help them help you. You want the triage nurse to smile and say to you: "Wow, you give great history!" They will appreciate facts; separate your opinions from facts in giving the history. And be aware that you will be seeing a range of people one after the other, double that if you arrive near a shift change. Don't gush "oh it was awful", ask "do you want history from me?" Proffer notes on history and medications. Know that communications between doctor and nurse teams may be far from perfect, especially if things are under pressure in Emergency; offer briefing to both doctors and nurses. Don't guess whether you are talking to doctor or nurse, introduce yourself, ask who they are. Your appearance of competence and understanding of issues may be rewarded. Plan ahead how you are going to brief, before you get to the hospital. Do this with love, know that calm and perspective help most now, catch your breath, count to 100. Close your eyes for a moment (while sitting :).

In the same period, while the ambulance team is working, make the other calls:- to alert neighbours (shape the neighbourhood gossip: "We are going to be OK, it's just a seizure." "She says it's JUST a seizure, wow!"), family, baby-sitters, employers, etc. Expect to be tied up for some time. Keep in touch with the ambos while you are doing this stuff. Tell them: "I am getting organised to come with you. How long do you expect to be? Do you need anything from me now?"

You are also the person who knows the best way out of your house with a patient on a stretcher or trolley. Ask: "Are you right for getting out of here? There is a lane at the back" — or whatever, you can show one of them exit options, there will be one of the team who will be wanting to figure all that out while the other works on the patient.

If an ambulance team arrives at a person still in status epilepticus, in seizure, they will need first to stabilise the person and stop that. The ambos will probably be travelling with intravenous Valium and will administer that, which will calm and sedate the person. One consequence of this and also of other hospital administered intravenous drugs for the same purpose, see next paragraph, is that the patient will now be affected by the drugs, and there will be a degree of iatrogenic (treatment caused) muddle and sleepiness, which you should not attribute to the tumour or seizure damage until those medications work their way out of the system.

The hospital as well as ambulance team will need to use intravenous drugs because a person in this situation will not be given oral medication for some time, until clear of seizure prospect — that is, until normal swallowing mechanisms are assured and there is reduced prospect of regurgitation. The ambulance team, as noted above, will probably be using Valium, a general purpose benzodiazepine drug. Hospitals will use, from the same drug family:
• clonazepam, which is long tasting, stabilising, but can cause a lot of confusion and needs weaning off;
• midazolam, very swift acting, very short half-life, to knock over a seizure quickly. If a person is having problems with repeated seizures, this may be kept readily on hand and the test may be that if the patient resolves the seizure before the couple of minutes to fetch the 'midaz' then good, no need for the midaz.

There will also be use of intravenous forms of general use anti-seizure medication, especially Dilantin (see below), and this may be used as the first line intravenous injection in hospital UNLESS the patient has been taking Dilantin already and it seems to be failing. Taking intravenous Dilantin can raise serum levels quickly. If you are the person there in the hospital watching the patient, have an eye out for Dilantin overdose symptoms. If the seizure has come about while the patient is taking Dilantin and the hospital is using clonazepam and or midazolam, make sure they also keep the Dilantin level up, don't let them forget that ( speaking from bitter experience).

If you have taken the hospital a list of tablet medications that the patient is taking, keep track of that medication timetable yourself. If the hospital staff are focused on the seizure, you may be the one to say: "She's now four hours overdue for dex, can you do IV dex now?" Look at the medication chart; if the dex is there, good, if it's not there, thrust it gently at the nurse or doctor as you make this comment, talking quietly but seriously, if possible over the top of your reading glasses. When they exclaim "are you a doctor?" you know you may be winning...

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14: Seizure: medications - Dilantin (phenytoin) and others

Not all brain tumour patients will be prescribed anti-seizure medication. It will be prescribed if seizure is an early symptom, or if it occurs after operation of if the doctor thinks seizure very likely. But if it not prescribed and there is no seizure, excellent.

The drug phenytoin, marketed as Dilantin, is a long established, generally very effective and reliable anti-seizure medication.

Some doctors may prescribe a different drug from the start, something with which they are familiar, some patients may have a reaction to Dilantin or it may not be effective and a substitute may be needed from the outset,, some patients may need to be moved to a different drug if after a period of protection from seizure, Dilantin ceases to provide protection. But most patients will start out with Dilantin.

Taking Dilantin over a period of time involves some management. There are a number of interactions with other drugs and substances. For information on Dilantin's interactions, see http://www.parkinsons-information-exchange-network-online.com/drugdb/103.html.

There is in particular an interaction with dexamethasone. When you take dex, the processes of metabolism in the liver which break down Dilantin, rendering it inactive, are speeded up, so an increase in dexamethasone dose may lower serum Dilantin levels. On the one hand, raising the dex dose may have a benefit in reducing prospect of seizure if it reduces swelling significantly (see section 9) — but on the other, if it eats away at the level of Dilantin in the blood, and that serum level is not monitored and maintained, it can lead to seizure.

This need to monitor and adjust 'serum Dilantin' is complicated by the fact that once an effective level of Dilantin is established in the blood, very small dose adjustments can cause significant swings in serum level.

My reading of anecdotal accounts to brain tumour discussion groups suggests that a lot of seizures in brain tumour patients, after diagnosis, arise from poor management of anti-seizure medication. Why risk seizure? — make sure serum levels of anti-seizure medication are kept at a sensible and safe level, by regular testing.

There is also some prospect, unfortunately, that changes in social activity can trigger seizure — excitement, pleasure, upset — so you really do want to try to have the best level of medication protection, rather than avoid pleasure or excitement!

There are some negative effects of Dilantin overdose. The biggest risk of this occurring on a serious scale if a patient is being given emergency treatment with IV Dilantin, say at different hospitals — if you are away from home and regular doctor access, for example, and perhaps the person having seizure problems is transferred between hospitals. If you are travelling away from access to your treating doctor or hospital, make sure you have a piece of paper with your treating doctor's phone number, or the hospital file number, on hand, along with a record of drug treatments. This may sound obsessive, but it is unfair to expect doctors who may be junior and inexperienced, who spend most of their time dealing with road or other trauma in emergency, to have an immediate genius in dealing with a brain tumour seizure circumstance — the carer knows the case and provide a brief.

Leaving aside sudden major change in serum Dilantin level in such a crisis, the serum level can drift up gently in various circumstances. The most readily observed symptoms are drowsiness, vagueness, odd eye movements and red spotty skin rash. Drowsiness can indicate other problems when dealing with brain tumour as well. Worth consulting the doctor in any such circumstances.

There is a good site with useful information on Dilantin overdose here — http://www.nlm.nih.gov/medlineplus/ency/article/002533.htm .

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15: Low white blood cell counts

As discussed above, treatments which impact on bone marrow (radiotherapy to some extent, chemotherapy more seriously) may reduce white blood cell count, by reducing the production of white blood cells. White blood cells are central to the immune system. If there are not enough white blood cells, there is a risk of the body not being able to control bacterial infection. Bacteria are always present in the body. The majority are beneficial, essential to life. Bacteria which threaten life can grow in numbers rapidly in the absence of white blood cells and especially in a person who is weak. A sedentary or bedridden person can succumb swiftly to pneumonia.

A doctor will periodically order a Full Blood Count [FBC] during treatment, especially to check that white blood cells are not falling to dangerously low numbers (the pathology report indicates normal ranges). If the numbers are low, treatment may need to be deferred or dosage reduced. It's a hard choice — deferring or reducing treatment may advantage the tumour, but persisting with treatment which is damaging the immune system rsks swiftly killing the patient.

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16: Low platelets

The Full Blood Count (see previous section) will also indicate platelet numbers. Platelets are also produced in bone marrow. They are tiny pieces of 'fibrin' which last only two or three days in the blood stream. Their purpose is to physically block weaknesses, imperfections, holes in blood vessels, and thus to prevent haemorrhage (blood leaking from blood vessels). A person with low platelets will bruise swiftly and badly; if you have a blood sample taken while platelet numbers are low, it is likely to be immediately evident with substantial bruising around the site of where the needle entered the vein.

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17: Deep vein thrombosis

A substantial proportion of bran tumour patients will develop deep vein thrombosis [DVT] — the same thing as happens to some long distance travellers, the 'Economy Class Syndrome" that comes from sitting in one place far too long.

In brain tumour patients, as well as risks from being bedridden after an operation, there may also be risks arising from the quality of circulation, all cancer patients appear to be at elevated risk of DVT.

Before an operation and for some days after, until mobile, a hospital patient wears 'TEDs'. A correspondent to the BrainTmr discussion group provided this information:
"For all of you info freaks---TED (sic T.E.D) is the brand name of Kendall's
constant non-graduated compression hosiery that provides 21 to 30 mm Hg
compression. T.E.D stands for Thrombo Embolism Deterrent. These are a
distant second in uncomfortableness to having to wear the graduated
compression hose made by Jobst and others. After they get stretched out
they have a preponderance of uses ...tying up tomato plants, emergency fan
belt...." [Lynda, 10 July 2002]

Some hospitals use TEDs which are full length, and which are a great struggle to get into. Royal North Shore Hospital in Sydney uses knee-high TEDs as their research indicates that results are equal for the two lengths, and the shorter stockings are easier keep clean and are more likely to continue to be worn than are the longer and more difficult to manage stockings.

The purpose of the stocking is to prevent pooling of blood in the legs, which can cause blood to form clots (deep vein thromboses) there.This may cause local pain symptoms, but the real risk to health is not in the legs but in the prospect that bits of clots may break away and travel elsewhere to block fine blood vessels and the places where this is most critically a risk are the brain and the lung. In the brain, interruption of blood supply is a cause of stroke, in the lung, pulmonary embolism.

A DVT is identified using a specific type of ultrasound device, with which the length and extent of a DVT can be measured. A DVT may extend a considerable distance, say from below the knee to above the groin . And it becomes more serious if it is bilateral - in veins in both legs, joining in the abdomen.

The medical management of DVT requires medication to prevent further clotting. These medications do not dissolve the clot itself, that is left to bodily mechanisms.

The need is to give patients enough medication for quick protection against further clotting, without overdose. There has been some traditional use of Warfarin, a drug you may be familiar with in rat poisons (give the rat or mouse enough and a bump on the furniture may cause prompt haemorrhage). Warfarin dosage needs careful monitoring and it now seems preferable to give patients Clexane, a low molecular weight heparin, which does not require monitoring. There is some information on Clexane here.

Clinical trials in the United States in 1998 tried giving patients medication before brain operations to try to prevent DVT afterwards; alas the trials were stopped because in reducing clotting they increased the incidence of brain haemorrhaging.