Some REAL expert reading!

Here’s a reference to an excellent and VERY recent (May 29th issue) review of the what, how, and why of traumatic intracranial hypertension. Online it’s subscribers only, but if this is a subject that interests you, it’s worth trying to get a copy of the article.

Traumatic Intracranial Hypertension

Stocchetti N, Maas A

New England Journal of Medicine, 2014: 370(22); 2121-2130

Oh and if management of near-lethal trauma interests you (I’ll get into some of this in future posts), then check this article in today’s New York Times out:


Some important science on disorders of consciousness – part 2


An MRI scanner

Imagine this: You’ve volunteered for a brain imaging experiment to help study consciousness. You come to the MRI suite, and lie down. The researchers put an IV drip in place, and then infuse a form of glucose that “lights up” the brain areas that are activated at any given moment. So far so good.

You’re told to close your eyes and imagine hitting a tennis ball back and forth with a partner. Sure enough, this consistently activates an area related to preparing the brain for motor activity (called the Supplementary Motor Area, SMA, in yellow below). Then you’re asked to imagine walking around your house, and to visualise all the things you’d see as you navigated like this. And once again, the corresponding area, called the Parahippocampal Gyrus, (PG, in green below) lights up. Here’s roughly what the images look like:


Nothing unusual or unexpected here. But now let’s go a bit further with the technique.

Let’s now take a series of patients (54 to be exact) who have been diagnosed with either vegetative state (remember – that’s eye opening without any signs of conscious interaction with the environment) or a minimally conscious state (awake, but with fluctuating but consistent signs of consciousness), and let’s try the same experiment.

Incredibly, FIVE of these patients  (10%!) could manipulate brain activity in response to the researchers’ requests. These people were, in fact, obeying commands (“think about tennis”, “think about navigating”), but their response wasn’t behavioural, it was . . . metabolic; what’s crucial is that they clearly showed signs of consciousness.

This was an amazing finding, but the investigators took the work further still, and, using a very ingenious trick, what they revealed shocked the world of medicine.

Let’s quickly put you back into the fMRI machine. This time, here’s what I’m going to do. I’m going to ask you a simple, unambiguous question (like, do you have a brother?). I’m going to tell you to think “tennis” for YES, think “navigation” for NO. (Rather like using fMRI activation as a “blink once for yes, twice for no” kind of communication tool.) Turns out this works fine, with 100% accuracy with normal subjects.

I guess you see where I’m going with this. Let’s take one of the patients diagnosed as vegetative but who has shown the ability to “light up” his or her supplemental motor area or parahippocampal gyrus on demand. Let’s do the same thing with him. Let’s ask him or her questions – tennis if yes, navigation if no. What happens? Let me quote the researchers: “. . . for those five questions, the pattern (of activation) produced ALWAYS matched the factually correct answer.” 

I’ll let that soak in for a moment.

These scientists just took a patient who’d been diagnosed as vegetative (and again, I’ll insist that this means NO CONSCIOUSNESS) and not only TALKED TO HIM, but actually got answers!

What are the implications? First of all, this study shows how hard it actually is to make a proper diagnosis of the vegetative state. Until now, this diagnosis relied on confidently stating that there is evidence of absence of consciousness, based on detailed and lengthy observation of the patient’s behavioural responses. But remember, these patients have severely damaged brains; the behavioural repertory of responses that they can show may often be so limited that none will be found. But this study emphasises that absence of (behavioural) evidence is NOT necessarily evidence of absence (of consciousness). The infinitely more sensitive “behavioural” response of metabolic brain activation could allow, in the future, clinicians to make this diagnosis with much more confidence. This obviously has enormous implications in terms of medical and ethical decision-making as concerns any given patient.

More importantly for us, this tool would appear to open up the possibility of actually communicating with some of these patients (a small minority at best, but still . . .). The current procedure is much too cumbersome, difficult, and expensive to use routinely, but it’s not too much of a stretch to imagine a future where helmet-sized mini-MRI machines are placed on the heads of patients with prolonged disorders of consciousness to allow their care team and loved ones to communicate with them.

There is a huge amount of fascinating and useful research being done on consciousness – both normal and disordered. Functional imaging is one of the most powerful tools in this quest for knowledge. As they say, watch this space.

Here’s a link to the original NY Times article about this research. The second contains a video by Liege’s own Steve Laureys (the lead researcher), explaining the technique. And the third is to a pdf of the original article, published in the New England Journal of Medicine.

Some important science on disorders of consciousness – part 1

Well Liège has made it into the news again!

The Coma Science Group here at our hospital, working with other centres,

has published another significant study of persistent disorders of consciousness. It’s worth having a look at this; in a subsequent post we’ll look at another very important paper by these researchers. I’ll also  place these reports into some kind of context in terms of Michael Schumacher’s situation (or more correctly, presumed situation).

First a link to an article about today’s study:

And a link to the article itself:

The background

Remember how we said that the vegetative state is defined as a state where the patient shows signs of wakefulness (notably open eyes) without behavioural responsiveness (as a marker of consciousness or awareness). Because of the emotionally laden and ambiguous nature of the word “vegetative”, some, including the Coma Science Group, prefer to use the term “unresponsive wakefulness syndrome” (henceforth UWS) for this state.

The key in differentiating a patient with unresponsive wakefulness syndrome from a minimally conscious state is the presence in the latter of fluctuating signs of awareness, with consistent but intermittent appropriate responses to stimuli.

Distinguishing these states can be difficult, but is absolutely crucial, medically, socially, ethically and therapeutically. A patient who is genuinely in a UWS, has, by definition, no self awareness. No voices are recognised, no sensation of hunger, none of pain, none of thirst. This is why clinicians caring for patients in a UWS are authorised almost everywhere to withdraw medical support, if and when appropriate, (including food and water – remember this is not cruel because there is no hunger or thirst perceived) from UWS patients. This is not the case once the patient has demonstrated any consciousness at all. Prognostically, as we’ve mentioned previously, persistence of a clinically correctly diagnosed (and that’s the point here) UWS for one year after the inciting trauma pretty much means any meaningful recovery is impossible. On the other hand, a minimally conscious state raises the possibility of continued progress.

Unfortunately, it can sometimes be remarkably difficult to show conclusively what state the patient is in. The problem is double.

First of all, there is the fluctuating nature of awareness. Episodes of interaction can appear randomly, or might be associated with a certain time of day, the presence of certain people, etc. The key is to do sufficient evaluations, sufficiently often, to reliably ascertain what the patient’s best level of awareness is.

Second, let’s remember that these patients have suffered devastating brain damage, whether caused by trauma (as is the case with Michael), infections, massive strokes, global anoxia, etc. This means that these patients will almost always have severe restrictions in their ability to show their responses to external (and internal) stimuli – spastic limbs which preclude reliable movements, visual or auditory deficits, etc.

Because of this, current guidelines for the management of patients with prolonged disorders of consciousness are becoming more and more insistent as to the FREQUENCY and QUALITY of the evaluations that are done. Standardised measurement scales are used, and the training necessary to administer them are well defined. Despite this, doubt remains at the edges between the diagnoses. Help is clearly needed to reliably diagnose the presence of these difficult-to-demonstrate degrees of awareness.

The study published today is an attempt to validate the use of imaging techniques, in addition to clinical evaluation, to help determine whether a patient is or is not AWARE.

The study

Steve’s study looked at the ability of two imaging techniques, FDG PET scanning and fMRI imaging, to help distinguish between UWS and minimally conscious states. FDG PET images show brain areas that are actively using glucose. This is known to correlate with activity in those same areas. FDG PET images show the pattern of brain activity at rest. On the other hand, fMRI images look for use of oxygen in the brain. It is particularly useful to do when asking the subject to do a mental task – whether visualising something, imagining something, or DOING something moving fingers, pressing buttons, etc).

It is also known with high confidence that certain brain areas show normal activity in normally conscious patients, essentially no activity in UWS patients, and intermediate (but significantly reduced) activity in patients who are minimally conscious.

This study looked at the reliability of using activity in these areas to help confirm the diagnosis made clinically, and to help determine the patient’s prognosis.

Briefly, the study showed that FDG PET imaging is highly correlated with a previously validated (and widely if not universally used) clinical scoring scale. Importantly, one third of patients (13 of 41) diagnosed clinically as being in a UWS were shown by FDG PET to have activity in centres associated with awareness. Over the next year, nine of these 13 patients (remember, they were classified clinically as UWS!) had moved “up” to a clinical diagnosis of minimal consciousness or better, while of those with an imaging “confirmation” of UWS had terribly dismal outcomes. Of these 26 patients, 35% were still unconscious after one year . . . and 56% were dead. This shows that these images may well sensitively show the possibility of awareness, and seem to contain the same prognostic information that a clinical diagnosis of minimally conscious state contains. Further the numbers track what I’ve said in previous posts in terms of prognosis.

It is absolutely vital that we understand what the study didn’t show. It did NOT show that these 32% of patients were aware, or conscious. It showed that these patients, who clinically were felt to be unconscious, “had cerebral activity compatible with consciousness” (the authors’ words). But importantly, these patients had significantly better CLINICAL courses subsequently than those in whom PET confirmed an absence of activity compatible with consciousness.

Conclusion: it’s looking like at some point in the not distant future FDG PET imaging may well be a standard test in addition to clinical scoring, to determine whether awareness is or is not present in patients with disorders of consciousness. Remember: 1) it’s not yet fully validated, meaning more research is necessary before making this a standard tool with fully accepted statistical notions of reliability and validity; 2) until it IS validated, it remains a research tool.

Implications for Michael Schumacher

Actually, to the extent that Michael has been reliably shown clinically to have signs of awareness/consciousness (this would appear to be the case based on direct quotes of Sabine Kehm), this type of imaging would have no real utility, as a diagnosis of minimally conscious state would then have been made clinically.  On the other hand, my next post will deal with another paper by our Coma Science Group, one with fascinating clinical and even philosophical implications.



Time Zones and the 2014 F1 Calendar

As fans of Formula 1, you’ve no doubt seen the provisional calendar for 2014. The proposed sequence of 22 races has provoked no shortage of commentary and criticism from the teams and other participants in the championship. While this is usually centered around logistics and costs, there’s another factor that looms large. This factor is, amazingly, based on millions of years of mammalian evolution. Evolution? Really? Let’s take a closer look.


The 2014 schedule will require a significant number of trips across large numbers of time zones. Why is this of concern?


This is where we need to invoke human evolution. You see, our bodies are cyclic. The eternal rhythm of night and day, with the opportunities (think hunter-gatherer) and dangers (think predators) that this presents, has conditioned the fundamental way our bodies function. Almost every bodily system runs on a cycle called a circadian (“almost 24 hours”) rhythm. The most obvious is the sleep-wake cycle, but the concentrations of major hormones, the activity of the cardiovascular system as well as other major functions all follow this roughly 24-hour cycle.


Even if these cycles are largely intrinsic to the body, when we actually measure them we see that in general, they are roughly 25, not 24, hours. This means that without periodic “resynchronization”, the inner clock will drift out of synchronization with the outer world. Not surprisingly, daylight (and more specifically the blue component) serves as the most powerful and efficient synchronizer or “zeitgeber” (“time giver”). There are others, but these would seem to play a secondary role.


Modern air travel allows us to make trips that stretch over 5, 6, even 12 time zones in just a few hours. This means that upon arrival, our inner clock can be totally out of synch with outside reality. You get to your destination in the morning, and your inner clock says it’s midnight. Or perhaps you arrive at night with your body telling you it’s time to wake up. That’s jet lag. Critically, in addition to disturbances in the sleep-wake cycle, other functions are affected, sometimes dramatically. Intellectual function, appetite, mood are all altered by jet lag. If we do nothing, our bodies will resynchronize naturally, especially if we are exposed to natural daylight. In general, it takes about one day per timezone (for trips to the east), and a bit less for trips to the west, to get back in phase.


So now the problem becomes clear. The mechanics, engineers, and of course the drivers all need to be functioning at full efficiency as of Thursday of a race weekend. What about jet lag? How can its negative effects on performance be eliminated, or at least reduced? And are any of these solutions applicable to us? Well there’s good news – and what’s more, there are actually several ways to fight against jet lag.


Obviously if a driver arrives in, say, Australia a week before the race weekend, he or she will have enough time to adjust “naturally” to the new time zone, especially if he (or she) takes in plenty of that wonderful Australian sunshine. Unfortunately this option is only really available to the drivers, and for only a few races in what would appear to be a very crowded and busy calendar. The other team members usually need to be at the factory until the last minute.


On the other hand, Singapore is a special case. The city is exactly six hours ahead (later than) European time. The race, as well as practices and qualifying are also exactly six hours later than their usual (European) time. This means that everyone can stay on “European time”, and not be affected by jet lag at all! Indeed this is the strategy used by the majority of teams. This implies STRICT obedience to the principles: total avoidance of bright light during the hours of European night, and exposure to bright light, rich in blue, during European day. This has been a successfully used technique for what is a unique set of circumstances.


With our current state of knowledge about the causes of jet lag, the most effective way to minimize its impact requires a bit of thought and preparation. When we’re traveling westwards (Montreal, Brazil, Texas, Mexico), it’s best to delay bedtime and awakening for about an hour each day, starting four days or so before leaving. Ideally, exposure to bright blue light (several such lamps are available commercially) for at least 45 minutes during the hours of morning at the destination helps to re-synchronize our internal clock. Next, look at the flight times in terms of the time at your destination. If the flight is during daytime, try to stay awake. If not, get some sleep. Then, if you arrive at night, avoid bright lights, TV, laptop and tablet screens (they’re very rich in blue light, the “morning” signal). Alternately, if you get there in the morning, get out into daylight. Using this kind of system, you should be remarkably fresh remarkably quickly.


If on the other hand the trip is towards the east (Malaysia, China, Singapore, Korea, etc), we basically do the opposite. We go to bed (and wake up) an hour earlier each day, starting four or five days before departure. Blue light exposure is de rigueur as soon as we get up, and we need to avoid light starting at about 6 PM destination time. Same rule for the flight – if it’s during destination night, try to sleep; if during destination day, keep the lights on, use your blue light, and stay awake.


What about melatonin, exercise and diet? All of these play a role, but their practical role hasn’t yet been well defined. This is a very hot research topic for obvious reasons!

 Follow Gary on Twitter : @former_f1doc