Pure Pedantry

So let's talk about this guy. In 1984, Terry Wallis has a car accident where he was thrown from his pickup. He goes into a coma. Despite his family's objections, it would appear he was misdiagnosed as being in a persistent vegetative state rather than a minimally conscious state:

But improvements in the care of patients could be made without putting every patient into a brain scanner, says Schiff. There is currently no system for even a bedside re-examination from 8 weeks after an initial diagnosis, despite the fact that "their whole prognosis might change", he says.

Wallis was frequently classified as being in a permanent vegetative state. Though his family fought for a re-evaluation after seeing many promising signs that he was trying to communicate, their requests were turned down.

"A careful bedside examination at 6 months [after the accident] would have unequivocally said he was not in a vegetative state," says Schiff. There is a much greater chance of a late recovery from a minimally conscious state, he adds, although such recoveries are still rare. "The Wallis case will force the issue," he believes.

What is the difference between a persistent vegetative state and a minimally conscious state? Here are the American Academy of Neurology's criterion for a persistent vegetative state:

-- No evidence of awareness of self or environment and an inability to interact with others;
-- No evidence of sustained, reproducible, purposeful, or voluntary behavioral responses to visual, auditory, tactile, or noxious stimuli;
-- No evidence of language comprehension or expression;
-- Intermittent wakefulness manifested by the presence of sleep-wake cycles;
-- Sufficiently preserved hypothalamic and brainstem autonomic functions to permit survival with medical and nursing care;
-- Bowel and bladder incontinence; and
-- Variably preserved cranial nerve (pupillary, oculocephalic, corneal, vestibulo-ocular, gag) and spinal reflexes.

The criterion for a minimally conscious state are different. Here is a chart comparing the physical signs of each (and another syndrome called locked-in syndrome). (Ed. The original link for this chart is dead. Here is a link to the appropriate paper.)

Click on image below for larger chart:

The key difference, as summarized in a quote from an article about the Terry Schiavo case, is "the difference...between autonomic activity and episodic conscious activity," said Fins.

To emphasize the point, there is a huge area of difference between someone who has essentially only the housekeeping functions in the brain and someone who -- for reasons metabolic or traumatic -- comes in and out of consciousness intermittently. It is very unfortunate that Terry Wallis was misdiagnosed in this case, because the prognosis for individuals with minimally conscious state -- while not fabulous -- is much better than for a persistent vegetative state. I just thought I would get the distinction out of the way early lest people go into a flurry of speculation about how all people in comas now have the possibility of recovery. Terry Wallis had a possibility of recovery because he had a condition that allowed for recovery. Terry Schiavo did not.

But what caused Mr. Wallis to go into a minimally conscious state; what about his disease allowed for the possibility of recovery? I have never looked at his chart, and it is difficult to tell from the article but it looks like he had Diffuse Axonal Injury:

To try and find out what was going on inside Wallis's brain, Nicholas Schiff and colleagues from the Weill Medical College of Cornell University in New York City, used a new brain imaging technique called diffusion tensor imaging (DTI). The system tracks water molecules and so reveals the brain's white matter tracts - akin to a wiring diagram. They combined this with more traditional PET scanning, to show which brain areas were active.

The team's findings suggest that Wallis's brain had, very gradually, developed new pathways and completely novel anatomical structures to re-establish functional connections, compensating for the brain pathways lost in the accident.

They found that new axons - the branches that connect neurons together - seemed to have grown, establishing novel working brain circuits.

Surprisingly, the circuits look nothing like normal brain anatomy. A lot of the damage had been to axons that passed from one side of the brain to the other, torn by the force of the accident. But Schiff says that new connections seem to have grown across around the back of the brain, forming structures that do not exist in normal brains. (Emphasis mine.)

The axons going from one side of the brain to another refers to the corpus callosum, and injuries to the corpus callosal axons is one relatively common problem resulting from torsion in car accidents. Diffuse Axonal Injury results from shearing of the axons when the head is rotated very rapidly. Axons are sort of like the telephone lines that connect neurons to one another. They are processes that neuron cell bodies grow in order to communicate with other neuron cell bodies, sometimes very far away in the body or brain. The corpus callosum is an area in the brain with a great many of these axons that are transversing from one side of the brain to the other.

The fact that this is DAI as opposed to something else may explain why there was recovery in this case. We know that neurons in your brain very rarely divide, but under some circumstances axons can regrow -- provide the neuron cell body is intact. It is possible that if the damage were restricted solely to the axons and you waited long enough, they would just regrow back to their old targets. This appears to be what happened here.

What is extraordinary about this case is that such widespread rewiring is nearly unheard of. The classical belief is that in the central nervous system (CNS) -- as opposed to the peripheral nervous system (PNS) -- regrowth of axons is suppressed by a signaling pathway that is at least partially known (involving proteins like Nogo and Nogo-R). Under this system regrowth of this nature should not occur. Even more than that, it is remarkable that after the axons started growing they managed to find their original targets. The process of axon pathfinding is complicated and involves many signalling molecules that direct the axons to the right place. It is not what I would have expected that those signals would still be present in the brain of an adult.

In any case, it is OK to get excited about cases like this. The human body can do a lot more than we thought. It is important, however, to remember that most evidence suggests that normal brain regeneration is rather limited in scope.