Michael Schumacher’s traumatic brain injury explained

Photo by Mark McArdle

Seven times Formula 1 World Champion and holder of a huge number of driving records, Michael Schumacher is thought of as the greatest F1 driver of all time, a champion among champions. On 29th December last year on a ski slope in the French Alps, Schumacher fell and hit his head on a jagged rock. Witness reports claim that he lost consciousness for about a minute, but that ten minutes later, when the emergency helicopter arrived, he was conscious and alert. Over the next two hours, however, Schumacher’s condition deteriorated and since that day, he has had two head operations and has remained in intensive care under a medically-induced coma.

An epidural haemotoma caused by a fracture in the skull (indicated by the arrow). Image by Hellerhoff.

Traumatic brain injury, or TBI, is quite a vague medical term and simply describes any injury to the brain sustained by a trauma – that is, a serious whack to the head. TBI is the most common brain disorder in young people: while older people are at higher risk from degenerative diseases, young people are more likely to find themselves in car crashes, fights or…ski accidents.

The specific type of TBI that Schumacher is believed to have suffered is an epidural haemotoma (click here for a seriously gory video of a haemotoma clot removal – you have been warned). Between the brain and the skull are a number of protective layers; these are membranes which encapsulate the brain and spinal cord, all of which swim around in cerebrospinal fluid. An epidural haemotoma is a bleed between the tough outermost membrane, called the dura mater, and the skull. Technically this sort of bleed isn’t in the brain itself, but this injury seriously affects the brain due to one important factor: pressure.

Six ways a brain squeezed by a bleed can go. Coning (indicated by number 6) is a last resort but compresses respiratory centres and can be fatal. Image by Rupert Millard.

Since the skull is an almost totally enclosed space, a bleed that grows too big in size could end up pushing, not just on the inside of the skull, but on the brain itself – squeezing it into an ever-decreasing volume. When put under pressure the only way the brain can physically go is down towards the spinal cord, but if this happens, the brainstem at the base of the brain may become compressed. This horrible scenario, known as ‘coning’, has a really high fatality rate, as the brainstem is needed to keep our heart pumping and lungs breathing. So keeping intracranial (in-skull) pressure low after TBI is key.

Doctors have reported that, as well as a haemotoma, Schumacher suffered contusion and oedema. Cerebral contusion is essentially bruising, as you might expect in other parts of the body: tiny blood vessels bleed when they have suffered a serious hit – in this case either from the rock itself, or from the other side of Schumacher’s skull in a ‘rebound’ type impact. Oedema, or swelling, may come as a result of the contusion – like when a bruised knee swells – and again would need to be curbed in order to prevent the pressure inside the skull from rising dangerously.

Illustration by Max Andrews.

So what have the doctors done to treat Michael Schumacher’s condition? Well, firstly, the surgeon Prof. Stephan Chabardes has reportedly performed two operations to remove blood clots from the haemotoma, as well as a craniectomy – removal of part of the skull – in order to relieve the intracranial pressure and prevent coning. Craniectomy has been used for some time to treat both TBI and stroke, but remains somewhat controversial, mainly because of the risks of further bleeds, infections, or herniation of brain tissue through the surgically-made hole in the skull.

The second main strategy in treating Michael Schumacher has been to keep him under an artificial or medically-induced coma. This involves sedating him with strong anaesthetic agents. Propofol, which quietens brain activity by boosting inhibitory GABAA (‘off’) receptor activity and by blocking sodium (‘on’) ion channels in neurons, or barbiturates, which also enhance GABAA receptors, but block excitatory glutamate (‘on’) channels could be used to keep him sedated and to ‘slow’ his brain down. Slowing is achieved through a net reduction in excitatory activity within the brain. Thus, the medically-induced coma not only stops the patient being conscious, through what no doubt would be a painful experience, but also limits the amount of activity-related blood flow, curbs swelling and prevents what’s known as excitotoxicity.

Risk of post-trauma seizures after TBI by the severity of the initial injury. Graph by Delldot (wiki).

Excitotoxicity can occur after TBI, stroke or in patients with epilepsy. It is a term used to describe what happens when brain cells run out of energy or become overloaded with excitatory inputs. In this state cells become overexcited and die, either immediately, or after a delay. Seizures, which can cause excitotoxic cell death, are fairly common after severe TBI and are thought to drive brain damage after the original injury. Seizures after TBI can be worsened by swelling and higher temperatures, so it is likely that Schumacher has been kept a few degrees cooler than his normal body temperature to limit this risk.

Data as interpreted from Laureys S, Owen AM, Schiff ND (2004). “Brain function in coma, vegetative state, and related disorders”. The Lancet Neurology 3 (9): 537–546. Graph by Shin Andy Chung.

If he is still in a medically-induced coma, or is gradually being weaned off the anaesthetic agents, Schumacher may be undergoing physical therapy to move his limbs and joints to prevent muscle wastage, or contracture, which is irreversible muscle shortening. If his condition improves and he is able to move, his limbs will need re-strengthening.

Some conflicting reports suggest that doctors treating Michael Schumacher may have started removing him from his coma. If they are doing this, the full extent of their patient’s rehabilitation needs won’t become clear for some time. While I obviously hope the driving legend makes a full and speedy recovery, it is hugely unlikely that his brain will completely recover all its previous functions. The brain is such a delicate organ and Schumacher’s tragic case only highlights its fragility.

Hugo Lloris in 2012. Photo by Stanislav Vedmid.

Schumacher’s injuries also raise the debate on the guidelines of treating head injuries in sports. Last November, Tottenham’s Hugo Lloris lost consciousness after a hit to his head during a football match, but after waking up was allowed to return to the pitch to finish the game. Lucid intervals, such as the one reported shortly after Schumacher’s fall, can be deceptive and players of contact sports should always be given immediate medical attention after losing consciousness. It’s no news that the cumulative effects on the brain of losing consciousness multiple times – as many boxers do on a regular basis – are to be avoided at all costs.

Every year in the USA, 1.7 million TBIs – more than double the number of heart attacks – contribute to almost a third of all accidental deaths as well as varying levels of lasting disability. While we hold our fingers crossed for Michael Schumacher’s successful rehabilitation, we must also think of the other thousands of people, and their families dealing with the long-term aftermath of serious brain injuries around the world.

 Post by Natasha Bray

Playing at a better future: Could video games improve your life?

Your brain is plastic. No, not like the picture to the right but in the sense that everything which makes us who we are (our thoughts, beliefs and understanding of the world around us) can be subject to change. This change may come from our interactions with the world, as we learn to adapt and live in a changing environment, or the change may come from within, as we make conscious decisions to view the world differently. This natural plasticity helped our ancestors adapt when their environments changed and undoubtedly played an important role in their continued survival. However, a recent media storm has grown around the way brains, especially teenage brains, may be altered in response to societies’ increasing use of technology. This interest has raised concerns surrounding the impact technology, such as social media and video games, could have on the growing brain.

Video games in particular may be thought to bring together a ‘perfect storm’ of attributes primed to alter your brain. Specifically, they provide us with challenges that stretch our abilities but that are also matched to the our current gaming level; thus, are always achievable. This type of challenge makes us feel particularly good, since we feel as though we have earned our own rewards (such as in-game experience points or unlocking a new level of game play) through what we perceive to be hard work. Thus, we feel a sense of accomplishment and our brains are thought to undergo changes which reinforce certain game-related behaviours.

A number of scientific studies have explored the negative effects gaming can have on the developing brain. And, there have been a range of reactive articles exploring the notion of a dystopian future where a generation of emotionally blunted sociopathic adults cruise around heartlessly re-enacting crimes from games such as Grand Theft Auto. However, it is important to understand that many diverse activities lead to changes in brain structure and function and that these changes are not always negative. Indeed, some studies are now beginning to highlight the positive effects games have on development and how games may be designed to improve mental function.

Interestingly, game developers and scientists are now coming together in the hope of tackling depression, a major cause of disability, especially amongst young adults (up to a quarter of young people will have experienced a depressive disorder by the age of 19). Sadly, shortages in trained councillors and the reluctance of some young people to seek traditional help means that fewer than a fifth of young people with depressive disorders will actually receive treatment.

A research group, lead by professor Sally Merry at the University of Auckland, have developed a role playing game (SPARX), based around the principles of cognitive behavioural therapy (CBT), which aims to help young people cope with depressive disorders. SPARX is an interactive first person role playing game which allows the user to design a playable character, who is then charged with restoring ‘balance’ to a fantasy world dominated by GNATs (Gloomy Negative Automatic Thoughts). The game leads the player through a range of interactive levels where they learn different CBT techniques aimed at interrupting and readdressing negative thought patterns. At the beginning and end of each level the user interacts with a ‘guide’ who explains the purpose of the in-game activities, provides education, gauges the players mood and sets them real-life challenges (equivalent to homework). Players’ progress is monitored throughout and young people who are not seen to improve are prompted to seek further help from their referring clinicians (a trailer of SPARX is available at www.sparx.org.nz).

Studies suggest that SPARX significantly reduces depression, hopelessness and anxiety in young gamers and that the game is at least as good as traditional CBT. Game designers have also worked hard to make sure the game is engaging for young people; and this seems to have worked: 60% of players completed the whole game while 86% completed at least 4 levels and the majority of young people stated that they would recommend the game to their friends. This is a pretty impressive statistic, since teenage gamers are notoriously hard to please and a self help fantasy RPG certainly sounds like the kind of thing teens would dismiss as being ‘lame’. The success of this intervention suggests that such games could be a great way to treat patients who do not have access to therapy or who may be reluctant to engage with conventional therapeutic methods.

Ultimately the world of gaming is huge and only getting larger. It is currently estimated that by the age of 21 the average young gamer will have spent around 10,000 hours gaming; this is almost equivalent to the time they will have spent in school! With young adults investing so much of their free time in the gaming world, it’s about time we set about understanding the influence games have on development and perhaps, as SPARX has done, start putting these games to work for us. Just think, if we could harness the pleasure gamers feel when working towards gaming-related goals, we could use this medium not only to educate but perhaps also to encourage people to ‘play’ at the biggest puzzle game around – scientific research. The future seems full of amazing possibilities, so put your game face on and join the fun!

Post by: Sarah Fox

 

First patients enrolled on study aimed to improve outcome following brain injury.

Formed from around 80-90 billion neurons and with a consistency so soft you could cut

A CT of the head years after a traumatic brain injury showing an empty space marked by the arrow were the damage occurred.
A head CT image taken years after a traumatic brain injury, showing an empty space marked by the arrow were the damage occurred.

it with a table knife, the brain is a delicate vulnerable organ. Unfortunately, despite its hard outer shell (the skull), the brain is still susceptible to many forms of damage, both external and internal. Two common forms of brain damage are subarachnoid haemorrhage (SAH – a type of stroke caused by bleeding in and around the brain) and traumatic brain injury (TBI – occurring when an external force causes injury to the brain, i.e. hitting your head). It is not always possible to prevent this type of injury, however, scientists from Edge Therapeutics, Inc are currently working hard to develop life-saving hospital products capable of improving the outcome of patients following SAH and TBI.

Edge Therapeutics are currently enrolling patients on Phase I/II clinical trials for their pipeline drug EG-1962. Despite its inaccessible name, EG-1962 is designed to perform a unique and possibly life-saving function. The drug is designed to treat a state known as delayed cerebral ischemia (DCI). DCI is a complication and major cause of death and disability which occurs in patients within the first two weeks following brain injury. As the name suggests, DCI causes cellular damage through ischaemia (restriction of blood flow to the tissue). This ischaemia can result from a number of mechanisms stemming from the site of brain injury, including cerebral vasospasm (a narrowing of vessels carrying blood), cortical spreading ischaemia (decreased blood flow caused by mass activation of large populations of brain cells) and microthrombembolism (a blockage of blood flow around small, trauma-induced blood clots).

blood
Cerebral angiogram showing the blood vessels in a brain.

EG-1962, also referred to as nimodipine microparticles, is a novel preparation of the FDA-approved drug nimodipine. This preparation encapsulates nimodipine in a biodegradable coating which can be injected directly at the site of injury, releasing nimodipine steadily over a period of 21 days. This new system is thought to be an improvement on the current method of oral delivery, which is more likely to cause nasty side effects (such as low blood pressure and lung complications) and less likely to supply sufficient drug to areas where it is needed.

E. Francois Aldrich, M.D. (an Associate Professor of Neurosurgery at the University of Maryland and the Chief of Cerebrovascular Surgery) stated that he hopes the study will help select on optimal dose of EG-1962, which could potentially prevent DCI, therefore improving the lives of a number of patients suffering from various forms of brain injury.

The current study, dubbed NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage), will enrol up to 96 patients in approximately 20 centres internationally. This study aims to ensure EG-1962 is safe; to discover the most safely effective dose; and to assess whether EG-1962 offers a significant improvement over oral nimodipine. Results are expected in the first half of this year and Dr. R. Loch Macdonald, Chief Scientific Officer at Edge Therapeutics, hopes that these findings will lead to further advances in the clinical development of the drug.

Although a significant number of drugs undergoing Phase I/II trials will fail to progress any further, it is hoped that this treatment or similar preparations may soon be available to reduce the damage caused by DCI.

Post by: Sarah Fox

Science in 2014: What will the future hold?

The new year is usually reserved for looking back and reflecting over what has just gone. But it’s also a good time to look forward into the upcoming year and think about what it may bring.

Science is no exception to this. 2013 has been a remarkable year; we had our first taste of lab-grown meat, the Curiosity Rover found water on Mars and Richard III turned up in a car park. But what will 2014 bring to the world of science?

The Rosetta Spacecraft will hopefully tell us more about comets and the origins of the universe

comet

The Rosetta Spacecraft was launched in 2004 and has been on a 10 year journey towards the comet 67P/Churyumov-Gerasimenko. The spacecraft, which has been in a state of hibernation since July 2011, will wake up on January 20th 2014. It is hoped that Rosetta will begin mapping the comet in August and eventually land a probe on its surface in November, then Rosetta will travel with the comet towards the Sun until December 2015. It is hoped that the information gathered from Rosetta will help to better understand the role comets play in the origins of the universe.

Better diagnostic techniques for cancer

syringe

Last year, laboratory supply giants Qiagen teamed up with the company Exosome Diagnostics to develop a less invasive test for cancer and other diseases, which may one day replace standard tissue biopsies. This technology makes use of tiny spheres of fat called exosomes. Exosomes are formed inside cells, before being released into the body where they travel in fluids such as spinal fluid, urine and blood. The inside of these exosomes can contain many bits of information about the cells they were released from, including genetic material such as RNA and DNA. It is hoped that 2014 will see the implementation of technologies which harvest exosomes from body fluid and use the information they contain for early diagnosis and development of new treatment strategies.

Increased research into three-parent embryos

embryo

Last year, I reported that the Human Fertilisation and Embryology Authority (HFEA) ethics committee were debating whether to allow research into three parent embryos in the UK. The committee found that there was widespread support for the technique and so approved the proposal. This means that the UK is the first country to approve the use of an IVF technique using the DNA from a mother, father and mitochondrial donor. Parliament are now producing draft regulations and the legislation should hopefully be put into place by the end of this year. This means that 2014 could be the start of a journey which may ultimately lead to the eradication of certain inherited diseases from family lines.

Laboratory-grown organs becoming closer to reality

petri dishes

The last few years have seen a big increase in the number of organs successfully grown in the lab and this technology is now providing real benefits for patients as lab-grown organs, including windpipes and bladders, are being used as transplants.

The ability to grow complex organs, such as a liver or pancreas, would be a huge leap forward which could revolutionise transplantation techniques and help cure diseases such as diabetes. In 2013 it was reported that scientists were able to produce tiny livers and mini brains outside of the body. This amazing technology may one day provide the answer to our shortage of transplant donors, while lab-grown organs derived from a patient’s own stem cells may also eliminate the problem of transplant rejection. Although, it is unlikely the coming year will see the development of fully functioning complex lab-grown organs, these techniques have come forward in leaps and bounds and, hopefully, 2014 will bring us another step closer to growing complex organs outside the body.

Of course, this is just the tip of the iceberg. One of the most exciting things about science is that it isn’t always clear what the future holds. We have very little idea really what will be discovered in 2014; I’m looking forward to watching the stories unfold and the discoveries roll in.

Post by: Louise Walker

What do you think 2014 will hold for scientific discovery? Please let us know in the comments below