Research news and notes

Transplanted hand recovers function and reactivates the appropriate sensory cortex 

Limb transplantation is still uncommon as the technical challenge is substantial but not insurmountable. The question of recovery of neural function in the transplanted limb is key. It is also important to learn whether the brain can recover from a deafferentation injury induced by the loss of a limb. In a recent issue of Current Biology, Frey et al [3] present a case study of a 54-year-old patient who received a hand transplant 35 years after amputation of the right hand. The patient recovered some palmar sensation 4 months after the transplant. Stimulation of the hand resulted in functional magnetic resonance imaging response within the contralateral sensory cortical area. This response was the same as in control patients. Face stimulation did not intrude into the hand area, which the authors would expect in an amputee. According to this report, the brain appeared to possess the ability to recover from an old deafferentation injury.

There is reason to believe that hand transplants will become more common. I would like to offer a wild speculation: would a limb transplantation work as a treatment of phantom limb pain?

Barbiturates for refractory high intracranial pressure: which drug is better? 

Barbiturate-induced coma is occasionally used as a treatment of increased intracranial pressure that is resistant to usual therapy, but which barbiturate should we use? A recent study by Pérez-Bárcena et al [5] compared the efficacy of thiopental and pentobarbital in 2 groups of patients who had suffered a severe traumatic brain injury. There were 22 patients in each group, recruited over 5 years. One group received pentobarbital and the other thiopental. The patients were collected prospectively and randomized; the baseline clinical characteristics of the patients were the same in both groups, but the pentobarbital group had worse computed tomographic scan appearance. The dosage was also variable. Uncontrollable increases in intracranial pressure occurred in 18 of the 22 patients on pentobarbital and 11 of the 22 patients who received thiopental. The authors attempted to correct for possible asymmetry between the groups, as seen on the computed tomographic scan, by performing a logistic regression analysis; despite the confounding factors, thiopental appeared to be more effective. The side effects appeared similar in both groups. It is difficult to draw conclusions from a single, somewhat compromised study. Nevertheless, this work makes an important point: we must not assume that all drugs in a group are the same. It is not enough to just give the patient “barbiturates” or “steroids,” we must learn which drug in each group works best for a particular condition. We must also not assume that all patients are the same. Even if a medication is found in a large study to “work best” on average for a certain indication, it is still possible that some patients could actually benefit more from a different drug. Such fine-tuning is key to tailored medicine—which is a way to improve outcome through understanding and accounting for individual variability.

Does the use of anticoagulant and antithrombotic medication affect the outcome of traumatic brain injury? 

Anticoagulant and antithrombotic medications are used widely. There is reason to suspect that these drugs increase the risk of mortality or serious morbidity from hemorrhagic brain injury. But do they really? An article by Fortuna et al [2] in the October 2008 issue of Surgery failed to find increased, in-hospital mortality among patients who had used aspirin, clopidogrel, or warfarin before the injury. The authors reviewed 416 cases of patients older than 50, 40% of whom were taking the medications before injury. This observation supports an earlier study [7] that found no adverse effect of preinjury warfarin on the mortality of length of stay of patients who had head injury.

These results appear counterintuitive. It would make sense to assume that anticoagulation results in more bleeding, and therefore, greater brain injury than if coagulation were normal. A 2006 article by Cohen et al [1] looked at the outcome of brain trauma in elderly patients who were anticoagulated with warfarin. The outcome correlated with the patients' international normalized ratio. The higher the international normalized ratio, the worse was the outcome. Maybe the different studies present different aspects of the same problem? None of the studies were prospective, and none looked at detailed neurologic outcome. The controversy is likely to persist at least until a prospective study is performed that looks specifically at progression of intracranial hemorrhage and neurologic injury as key measures of outcome.

How do patients with traumatic brain injury die? 

We have long observed cardiac and pulmonary dysfunction in patients after subarachnoid hemorrhage, although the independent contribution of those medical problems to mortality remains uncertain [6]. Patients who had traumatic brain injury (TBI) also appear to have multiple medical complications as well.

Kemp et al [4] reviewed the charts of all trauma patients who died at a single trauma center over 1 year. Of 135 patients, 54 had isolated TBI. Cardiovascular and respiratory causes contributed to mortality in 51.1% and 34.1% of patients, respectively. Overall, two-thirds of all deaths after severe TBI were attributed to nonneurologic causes. Nonneurologic complications occurred early and were seen even among those with isolated head injuries. It is possible that TBI predisposes the victim to life-threatening medical complications to a greater degree than subarachnoid hemorrhage.