Recently in Trauma Category

Riffing on the seemingly growing trend of former professional athletes providing their brains to the Center for Traumatic Encephalopathy (see here, for example), writers for The Onion report, "Neurologists Implore Professional Athletes to Wait Until They Are Dead to Send in Brains for Research."

The God-bless-em scribblers even went so far as to fact-check the president of the American Academy of Neurology.*

* Although I suspect they used an actor in their accompanying photo to convey a presumptive neurologist's on-the-mark expression of worry, confusion, and mild exasperation.

Former Chicago Bears safety Dave Duerson had "moderately advanced" chronic traumatic encephalopathy (CTE), according to yesterday's press release from Boston University's Center for CTE. Duerson, 50, who committed suicide in February, had, in an unusual move, specifically directed that his brain be studied by the Center. He shot himself in the chest to facilitate the thorough examination of his brain.

Coverage of this story from MedPage Today and the WSJ Health Blog are short on specifics, but the latter indicates that 13 of 14 brains of former NFL players that have been studied so far by the Center showed signs of CTE. Changes in Duerson's brain were located in the frontal and temporal lobes, the amygdala, and the hippocampus, according to reports.

Friday's update

on the clinical status and recovery of Gabrielle Giffords from the NYT. 

Most notable:

• Giffords has recovered sufficient right body strength to "walk with assistance."
• Her vision does not appear to be impaired (suggesting that she doesn't have visual field deficits due to an occipital lobe injury).
• Her personality is re-emerging and appears to be preserved.
• Except for memory of the event, her memory—both antegrade and retrograde—appears to be preserved.
• Her speech is recovering.

Giffords is reportedly repeating words with ease and "is starting to string words together." Although categories of aphasia can be arbitrary and somewhat artificial, the described deficits suggest a transcortical motor aphasia due to some disruption between the supplementary motor area (located in the superior frontal lobe) and the frontal perisylvian speech zone (generally described as being an anterior extension of Broca's area).* This aphasia is frequently associated with right hemiparesis.

The speech deficit is consistent with descriptions of Giffords's brain injury (see here and here) due to a gunshot wound in January.

* Although Giffords's ability to name objects (which can be limited in transcortical motor aphasia) was not described.

While MedPage Today reported yesterday that Gabrielle Giffords remains in a Houston ICU because of a ventricular drain (due to, presumably, obstructive hydrocephalus), the hospital implies today that she will be moved to a rehab center imminently. Clarifying details should be provided this afternoon by the Congresswoman's doctors at Memorial Hermann, who will discuss her condition and progress at a press conference.

When Giffords's ventricular drain was placed is unclear from news sources, but logic and experience suggest that it was inserted either 1) at the time of Giffords's initial brain surgery, immediately after her injury as a prophylactic measure or 2) while she was in the Tucson ICU, because of developing hydrocephalus detected by a routine pressure monitor and/or follow-up brain images. [01/27/11 update: ABC News indicates that the drain was placed sometime last week.]

At Houston, surgeon John Holcomb emphasized to MedPage Today that the drain would either need to be removed or replaced with a permanent shunt before Giffords moved to a rehab facility. The anticipated move suggests that the issue of the shunt has been resolved or is about to be.

On seeming cue, neurosurgeons at the University of Alabama at Birmingham published a retrospective study this month in Neurosurgery of risk factors for conversion to a permanent ventricular shunt after traumatic brain injury (TBI). A minority of 71 TBI patients, about 22%, required a permanent device during hospitalization. The risk of a permanent device was elevated more than 5-fold if a patient had to undergo craniotomy within 48 hours of admission (as Giffords did) or showed bacterial contamination of spinal fluid (which is unknown in Giffords's case). However, the requirement for a permanent shunt did not appear to affect the disposition at discharge. [01/27/11 update: In an interview with one of Giffords's Houston doctors, ABC News reveals that there have been "no signs of infection."]

As far as Giffords's neurologic deficits are concerned, news reports (taken collectively) indicate some type of preserved vision (eg, aversion to shined light per her doctors, possibly watching television per her husband) and flaccid paralysis of her right arm. She is reportedly able to follow commands with her left body (indicating comprehension or a receptive speech capacity), but she has demonstrated no or minimal attempts at speech (suggesting a significant productive speech deficit).

These signs have traditionally been categorized as Broca's or expressive aphasia (in contradistinction to Wernicke's or receptive aphasia); although such a diagnosis is probably far too simplistic—especially without other details about her speech capabilities or disabilities. Moreover, it is really too early to guess at her speech deficits until she has spent considerable time in rehab and has reached a medical plateau.

01/27/11 update: News sources covering yesterday's press conference (like ABC News) report that Giffords ventriculostomy was removed 3 days ago (Monday) and that she was transferred to rehab. Futhermore there have been "no signs of infection," presumably referring to the ventriculostomy. Although not stated explicitly, it is also presumed that Giffords did not require a permanent VP shunt. 

Yesterday's press release and press conference

from the University of Arizona Medical Center provide more clues to the nature of Rep. Giffords's injury. In addition to performing a tracheotomy* and inserting a percutaneous feeding tube on Saturday, neurosurgeon Lemole and other physicians also performed a "minor" 2-hour repair of a right "orbital roof fracture" on Giffords. (Giffords sustained bilateral orbital roof fractures, but the left-sided injury, according to Lemole, did not require surgical repair.)

Lemole said that bone fragments from the right-sided fracture were "pushing down enough on the eye and the contents of the eye socket," so that an oculoplastic surgeon (Lynn Polonski) needed to perform a "quick releasing-and-incision operation" on the day of Giffords's injury. On Saturday, the full extraction procedure was performed, which necessitated a craniotomy (ie, an opening "just above the [right] eyebrow"). Once the bone fragments were removed, a metal mesh was placed in the roof of Giffords's right orbit. Lemole emphasized that, postoperatively, Giffords returned to her preoperative level of consciousness and functioning.

Given the description of orbital roof fractures, it appears that Giffords probably sustained significant injury (via the bullet exit entry wound) to her left (and possibly right) inferior frontal lobes. If previous descriptions of Giffords's brain injury are correct—namely that the bullet did not cross the hemispheric midline—the right-sided orbital injury may merely be collateral damage from the bullet exiting entering her left forehead.

The roof of the orbital socket, largely composed of the orbital plate of the frontal bone (of the skull), is relatively thin and therefore vulnerable in cases of traumatic injury—like a gunshot wound to the head.

Ophthalmologists are encouraged—nay, urged—to weigh in.

* At the press conference, Dr. Randall Friese, who performed the tracheotomy, indicated that Giffords cannot produce audible speech because the tracheostomy that she has in place "does not allow air to get past her vocal cords." But, he added, "she could certainly mouthe words...when she's ready to do that." Friese did indicate, later in the Q&A portion of the conference, that Giffords hasn't attempted speech.

Images of branded orbital meshes or plates in the inferior aspect of the orbit from Synthes.

If reports are true—namely that the bullet that hit Arizona Congresswoman Gabrielle Giffords entered her left forehead, missed her ventricles and language areas, and exited her left occiptal or parietal area*—then the bullet path (confined to the left hemisphere) seems subcortical (ie, below the surface of the brain) and fairly superior (ie, high or close to the top of the head).

Guessing her consequent deficits is probably a fool's task, even for a neurologist, but damage to the visual cortex may have been averted if the bullet exit wound was superior enough. Otherwise, transection of subcortical motor and sensory tracts and injury to the some portion of the frontal cortex by the bullet seem likely. Nevertheless, early reports indicate that Giffords (before a chemical coma was induced) had preserved motor function, along with basic comprehension of simple commands.

Injury-associated brain edema (swelling), which can lead to midline shift and deadly brain herniation, is being addressed (as expected) surgically with removal of a large portion of Giffords's skull and by ventilatory settings and drugs, say news reports.

According to a 2009 review by Maiden on gunshot wounds, the extent of brain damage is dependent on the bullet type, shape, construction, velocity, and mass and the nature of the injured tissue. He also writes, "[B]ullets which display greater yaw [side-to-side movement] will be associated with increased temporary cavitation [of tissue]." Cavitation of the brain could place strain and traction on adjacent tissue; although early brain swelling may make this issue an academic point, I would argue. A ballistics tutorial, including a discussion of yaw and what it means to tissue injury, is provided through the website of the University of Utah Health Sciences Library.

Reports indicate that Giffords was shot in the head with a 9-mm handgun at a range of about 4 feet. The 22-year-old alleged (and apparently seriously troubled) perp shot 19 other people, 6 of whom have died so far.

* It's not entirely clear from news reports whether the bullet entered Giffords's forehead or the back of her head.

From http://www.nlm.nih.gov/visibleproofs/education/medical/index.html: Postmortem image of coronal brain section showing path of a fatal bullet that entered the right temporal area and lodged in left frontal lobe.

Update: According to the LA Times, the bullet entered the back of Giffords's head.

01/12/11 update: Although Dr. G. Michael Lemole, Jr, Giffords's treating neurosurgeon, reports that the congresswoman is scratching her nose—a excellent clinical sign—he does not say (importantly) which hand she used. 

However, according to an MSNBC report, Giffords is moving both of her arms and that she "previously raised two fingers with her left hand and gave a thumbs-up when responding to doctors' verbal commands [emphasis added]." (With a left hemispheric injury, paralysis or paresis of the right arm and/or leg would be expected.) In addition, Dr. Peter Rhee, trauma chief at the University of Arizona, indicated (in a sort of groan-inducing fashion) that Giffords has a "101 percent chance of surviving."

In short, Giffords is extremely lucky in her extreme unluckiness.

The rising interest in brain injury among American football players has spilled over into Sports Illustrated. In the November 1 issue, out today, writer David Epstein profiles a complex study conducted by Purdue researchers, who fitted 11 Indiana highschoolers' helmets with impact sensors. Using the NFL-endorsed ImPACT neurocognitive test and fMRI, the researchers determined, to their surprise, that repetitive nonconcussive* head blows are not without consequence. The visual memory scores of some players who sustained these types of hits,** usually frontal and often exceeding 100 Gs, dropped significantly and appeared to correlate with changes in fMRI brain activity (in the dorsolateral prefrontal cortex).

The disturbing finding: On the sidelines and off the field, these players were clinically asymptomatic, at least by crude measures. They could carry on conversations, did not demonstrate memory impairment, and appeared to be fine by their parents' observations.

The reassuring finding: These players' ImPACT scores returned to baseline off-season.

The remaining uncertainty: No one really knows what the long-term toll of repetitive, nonconcussive, frontal head blows is, season after season. The Purdue researchers hope to follow up their subjects throughout their high school athletic careers and perhaps into college.

In addition to SI coverage, the Purdue study was published in the peer-reviewed Journal of Neurotrauma last month.

fMRI = functional MRI.

* Meaning, not impairing consciousness.

** Frontal head blows can be distinguished from the brainstem-torquing side blows associated with concussion.

No longer a fanciful abstraction, the use of hESC-derived cells in humans has begun in a phase 1 clinical trial. The specific hESC-derived cell line, called GRNOPC1 and licensed to the California-based Geron, will be injected into the spinal cords of patients with subacute thoracic injury. The first enrollee got a shot of 2 million hESC-derived oligodendrocytes yesterday at the Shepherd Center in Atlanta. The story is carried by the LA Times, and Geron's press release can be found here.

The company has selected 6 other medical centers for the trial, including the primary site of Northwestern University in Chicago, which is currently open for enrollment. The trick or trickiness of enrolling patients will be to identify individuals who have sustained complete (ie, grade A) spinal injury at the thoracic level (T3-T10) and are within 1-2 weeks of injury onset. However, the anticipated number of enrollees is small: 10.

The human clinical trial represents the expected quantum step from animal studies of GRNOPC1, which demonstrated improved locomotion in spinally injured rats and histologic evidence of cellular function. The development of epithelial cysts at the sites of cord injury in animals stalled a go-ahead from the FDA in 2009 to begin human trials. But the regulatory hold was lifted in July of this year, after Geron performed additional preclinical studies.

Oligodendrocytes, the myelin-producing cells of the central nervous system, are expected to facilitate signal conduction in a damaged cord. However, hESC-derived cells may also express important neurotrophic factors that promote the survival or regeneration of injured axons.

hESC = human embryonic stem cell.

Transverse section of the thoracic spinal cord from Gray's Anatomy (1918).

Last month, physicians at Bagram Airfield in Afghanistan removed a 14.5-mm explosive round, containing about 5 g of explosive, from the scalp of an Afghan National Army soldier. The 2 1/2-inch round was lodged into the soldier's scalp after he was involved in a roadside bomb attack, revealed a recent Air Force press release. Friday's NYT picked up the story, adding more details.

Seems that the medical staff first believed that the Afghani merely sustained a shrapnel wound to the head; however, on closer inspection, thanks to CT images, the radiologist realized that the foreign object was an explosive round, "primed to go off." Nice pick up.

The discovery, which prompted the bomb squad, led to the evacuation of the operating suite, and the remaining operating personnel had to wear body armor. Electronic monitoring machines also had to be turned off, for fear of triggering the device. Because the bomb squad suspected that the live round probably had an impact detonator in the tip, instructions to the lead surgeon were, "Just don't drop it."

A frontal skull image provided by the Air Force shows the round lodged in the right frontal area of the patient's scalp, evidently resting on the skull.

However, a horizontal CT image shows that the round is lodged between 2 skull fragments in the right frontal area. This image suggests (to me) that the device impacted the head sideways, probably blasting into the Afghani's head from his left and grazing his brow before burying itself under a created skull fragment.

The round was removed successfully, and the Afghan soldier reportedly continues to recover.

Raising a host of questions, from practical to philosophical, English and Belgian investigators showed that some patients with profound disorders of consciousness may be able to communicate—albeit in rudimentary fashion and with the aid of a million-dollar machine. Their functional MRI study of patients in persistent vegetative or "minimally conscious" state is available online today at the NEJM web site.

Among 54 severely disabled patients, investigators found that 5 could "willfully modulate their brain activity," as seen on fMRI pictures, in response to suggested motor imagery. Specifically when these patients were asked to imagine playing tennis, parts of the supplementary motor area reliably lit up. Four of the 5 patients could also respond to suggested spatial imagery, like navigating through a familiar city, by activating the parahippocampal gyrus. Follow-up bedside testing showed "some sign of awareness" in 3 of the 5 patients—suggesting that voluntary behavioral cues were missed before the fMRI assessment or that fMRI training primed these patients to respond behaviorally at the bedside (the former seems more likely).

The investigators then selected 1 patient with reliable fMRI responses to undergo training that correlated the motor imagery with "yes" and the spatial imagery with "no." The patient was then able to use the technique during fMRI to accurately answer yes-no questions, like Is your father's name Alexander? However, back at the bedside, no form of communication could be established with this patient.

All 5 responsive patients had traumatic brain injury without anoxic damage (among 32 in the study population). It is important to note that none of the 16 patients with anoxic brain injury responded (a fact that editorialist Allan Ropper also stresses).* Before fMRI testing, 4 of the responsive patients were diagnosed with vegetative state, including the patient who underwent communication training.

The American Academy of Neurology, the flagship organization for practicing US neurologists, provides the following criteria for the diagnosis of 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
• Variably preserved cranial nerve and spinal reflexes

Minimally conscious state, which acknowledges the intermediate stage between no and some awareness in the severely brain damaged, is defined as follows:

A condition of severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated.

Diagnosis: limited but clearly discernible self or environmental awareness on a reproducible or sustained basis by demonstrating one or more behaviors, including, following simple commands, gesturing yes/no answers to questions, intelligible verbalizations, purposeful behavior, appropriate smiling or crying, reaching for and touching objects, and pursuit eye movements.

Course: may be a transient stage in the recovery after severe head injury or other brain insult or a permanent condition.

Medicolegal cases of Jobes (1987) and Wendland (2002).

Results of this fMRI study suggest that the imaging technique might be useful for distinguishing the 2 conditions (and that, perhaps, the definition of minimally conscious state should include fMRI-dependent findings) and for establishing communication in patients with reproducible fMRI responses.

* Ropper also concludes his NEJM editorial with a groan-inducing pun that should not be reproduced.

Image of Berkeley's fMRI machine from Wikipedia.