TBI linked to increased dementia risk even decades after injury


Voice Analysis Tech Could Diagnose Disease

Researchers enlist smartphones and machine learning to find vocal patterns that might signal post-traumatic stress disorder or even heart disease.

In the near future, smartphone apps and wearables could help diagnose disease with short voice samples.

Charles Marmar has been a psychiatrist for 40 years, but when a combat veteran steps into his office for an evaluation, he still can’t diagnose post-traumatic stress disorder with 100 percent accuracy.

“You would think that if a war fighter came into my office I’d be able to decide if they have PTSD or not. But what if they’re ashamed to tell me about their problems or they don’t want to lose their high-security clearance, or I ask them about their disturbing dreams and they say they’re sleeping well?” says Marmar.

Marmar, who is chairman of the department of psychiatry at New York University’s Langone Medical Center, is hoping to find answers in their speech.

Voice samples are a rich source of information about a person’s health, and researchers think subtle vocal cues may indicate underlying medical conditions or gauge disease risk. In a few years it may be possible to monitor a person’s health remotely—using smartphones and other wearables—by recording short speech samples and analyzing them for disease biomarkers.

For psychiatric disorders like PTSD, there are no blood tests, and people are often embarrassed to talk about their mental health, so these conditions frequently go underdiagnosed. That’s where vocal tests could be useful.

As part of a five-year study, Marmar is collecting voice samples from veterans and analyzing vocal cues like tone, pitch, rhythm, rate, and volume for signs of invisible injuries like PTSD, traumatic brain injury (TBI), and depression. Using machine learning to mine features in the voice, algorithms pick out vocal patterns in people with these conditions and compare them with voice samples from healthy people.

For example, people with mental or cognitive problems may elongate certain sounds, or struggle with pronouncing phrases that require complex facial muscle movements.

Collaborating with researchers at SRI International, a nonprofit research institute in northern California, Marmar has been able to pick out a set of 30 vocal characteristics that seem to be associated with PTSD and TBI from 40,000 total features they’ve extracted from the voices of veterans and control subjects.

In early results presented in 2015, a voice test developed by Marmar and his team was 77 percent accurate at distinguishing between PTSD patients and healthy volunteers in a study of 39 men. More voice recordings have been collected since that study, and Marmar and his colleagues are close to identifying speech patterns that can distinguish between PTSD and TBI.

“Medical and psychiatric diagnosis will be more accurate when we have access to large amounts of biological and psychological data, including speech features,” Marmar says. To date, the U.S. Food and Drug Administration has not approved any speech tests to diagnose disease.

Beyond mental health, the Mayo Clinic is pursuing vocal biomarkers to improve remote health monitoring for heart disease. It’s teaming up with Israeli company Beyond Verbal to test the voices of patients with coronary artery disease, the most common type of heart disease. They reason that chest pain caused by hardening of the arteries may affect voice production.

In an initial study, the Mayo Clinic enrolled 150 patients and asked them to produce three short voice recordings using an app developed by Beyond Verbal. Researchers analyzed the voices using machine learning and identified 13 different vocal features associated with patients at risk of coronary artery disease.

One characteristic, related to the frequency of the voice, was associated with a 19-fold increase in the likelihood of coronary artery disease. Amir Lerman, a cardiologist and professor of medicine at the Mayo Clinic, says this vocal trait isn’t discernable to the human ear and can only be picked up using the app’s software.

“What we found out is that specific segments of the voice can be predictive of the amount or degree of the blockages found by the angiography,” Lerman says.

Lerman says a vocal test app on a smartphone could be used as a low-cost, predictive screening tool to identify patients most at risk of heart disease, as well as to remotely monitor patients after cardiac surgery. For example, changes in the voice could indicate whether patients have stopped taking their medication.

Next Mayo plans to conduct a similar study in China to determine if the voice biomarkers identified in the initial study are the same in a different language.

Jim Harper, CEO of Sonde Health in Boston, sees value in using voice tests to monitor new mothers for postpartum depression, which is widely believed to be underdiagnosed, and older people with dementia, Parkinson’s, and other diseases of aging. His company is working with hospitals and insurance companies to set up pilot studies of its AI platform, which detects acoustic changes in the voice to screen for mental health conditions.

“We’re trying to make this ubiquitous and universal by engineering a technology that allows our software to operate on mobile phones and a range of other voice-enabled devices,” Harper says.

One major problem researchers are working on is whether these different vocal characteristics can be faked by patients. If so, the tests might not be very reliable.

The technology also raises privacy and security concerns. Not all patients will want to give voice samples that contain personal information or let apps have access to their phone calls. Researchers insist that their algorithms are capturing patterns in the voice, not logging what you say.


PET, MRI find link between TBI and Alzheimer’s

An easy-to-use, automated computer algorithm based on diffusion-tensor MRI (DTI-MRI) scanning is helping to evaluate people with mild traumatic brain injury (TBI). Researchers hope the algorithm will spur more widespread adoption of DTI-MRI in the clinical setting, according to a study published February 1 in Radiology.

The researchers used Shannon entropy, an information and mathematical model designed to look at areas of disorder in complex biological systems, such as the brain. In this case, Shannon entropy works in parallel with DTI-MRI to measure the amount of damage done to white-matter tracts in concussed patients (Radiology, February 1, 2016).

As the amount of information or complexity contained in the data is accumulated by Shannon entropy, the algorithm can determine the degree of injury and its aftereffects. In other words, a healthy brain has high entropy, while a brain with white-matter damage from a mild traumatic trauma may lose some of its complexity and have less entropy.

“The more injury indicated by Shannon entropy, the more likely there could be a longer recovery time,” said study co-author Dr. Lea Alhilali, a neuroradiologist with the Barrow Neurological Institute in Phoenix. “It also can better detect in a patient whether he or she is at future risk of neurocognitive issues.”

Severe aftereffects

Headaches and migraines are common among people with mild TBI. Post-traumatic migraines have especially high morbidity, are associated with lower neurocognitive test scores, and can aggravate other post-traumatic symptoms that delay recovery, the authors noted.

In fact, previous research by Alhilali and colleagues used DTI-MRI to uncover distinct injury patterns in the brains of people with concussion-related depression or anxiety.

Alhilali explained that many changes occur in the brain after a concussion. The long, thin parts of the nerve cell that send impulses from cell to cell — known as axons — may swell, which causes an increase in fractional anisotropy values. If the axons are damaged, fractional anisotropy values will decrease.

“If all you look at is the average of these two different [fractional anisotropy] directions, you don’t see a change,” she said. “Because Shannon entropy measures how complex the dataset is, if one type of injury moves the fractional anisotropy up and one moves it down, there are two different states, and the Shannon entropy detects the complexity [of the changes].”

That deficiency in DTI-MRI and fractional anisotropy measurements led to the current endeavor.

“We felt that the way radiologists were using diffusion-tensor imaging to analyze water tracts was not sufficient to accurately detect white-matter injuries across the spectrum of concussion patients,” Alhilali said. “So, we decided to utilize Shannon entropy to analyze the diffusion-tensor images to see how complex the dataset is.”

Targeting mild TBI

The researchers reviewed radiology reports from the University of Pittsburgh Medical Center between January 2006 and January 2014. They found 74 patients with mild TBI, who had a mean age of 18 years (range, 10-47 years). Within this group, 30 patients had experienced a prior concussion and 57 had post-traumatic migraines.

The study also included 22 healthy control subjects and 20 control subjects with migraine headaches. The median time from injury to clinical presentation was 20 days (range, 0-506 days). The most common types of trauma were sports injuries (43 patients, 57%) and motor vehicle accidents (nine patients, 12%).

Diffusion-tensor imaging was performed with a 1.5-tesla MRI scanner (Signa, GE Healthcare) with a standard head coil to acquire fractional anisotropy maps.

The researchers calculated mean fractional anisotropy values and Shannon entropy scores from DTI total brain fractional anisotropy maps and compared the results between the subject groups. They also analyzed the outcomes of participants with and without post-traumatic migraines.

Mild TBI values

Patients with mild TBI tended to have lower mean fractional anisotropy values (0.379), compared with the healthy control subjects (0.383) and control subjects who experienced migraines (0.382), Alhilali and colleagues found. The mild TBI patients also had significantly lower Shannon entropy scores (0.737) than both the healthy control subjects (0.808) and control subjects with migraines (0.795).

There was no significant difference between healthy control subjects and control subjects with migraines for either fractional anisotropy or Shannon entropy values.

Based on area under the curve (AUC) analysis, Shannon entropy (0.85) outperformed mean fractional anisotropy (0.52) in determining which patients with mild TBI developed post-traumatic migraines (p < 0.001). In addition, patients with Shannon entropy of less than 0.750 were “approximately 16 times more likely to have experienced mild TBI and were three times more likely to develop post-traumatic migraine,” the authors wrote.

Post-traumatic migraine was also a factor in determining recovery time. It took patients with migraines a median 51.9 days to recover, compared with a median 39.4 days for those without migraines.

Shannon entropy’s future

While Shannon entropy has been used in electrocardiographic (ECG) analysis, it is not well-known or widely used in radiology.

“That is what is very novel about this topic,” Alhilali said. “Not only has it never been applied to the imaging of brain white matter, but it also was successful in detecting white-matter injuries.”

The authors speculated that Shannon entropy analysis of DTI might help clinicians more accurately diagnose concussion, anticipate patients’ symptoms, and predict prognosis in mild TBI.

Alhilali said a benefit of Shannon entropy is that it is easy to use.

“When you do the analysis, which is an easy automated computer algorithm, you get a number, which is very easy for a clinician, radiologist, or researcher to understand,” she explained. “A lower number means less complexity in the white matter and a higher number means greater complexity and recovery from mild TBI.”

The Barrow Neurological Institute currently has an ongoing study using athletes from Arizona State University to explore factors including accelerometer data, molecular markers, and blood samples, correlating that information with imaging markers of injury.

“We hope that Shannon entropy can be one imaging marker we can use to correlate with mechanical and molecular markers of injury that we detected in other portions of the study,” Alhilali said.

She does not think that Shannon entropy will change “the way we analyze diffusion-tensor imaging, because it is a very powerful tool that has yet to find a strong clinical use,” she added. “Because there is a great deal of variability in diffusion-tensor imaging measurements, it requires group statistics and comparable analysis that will not be performed by anyone in the clinical setting.”

Therefore, she hopes Shannon entropy will help move DTI to the forefront, to be used on individual patients where the results would be more automated and more easily interpreted.

“I think it will help to change the way we analyze diffusion-tensor imaging beyond analyzing injury patterns and mild traumatic brain injury and many other fields in which we use [DTI] for research purposes,” she said. “Perhaps Shannon entropy can bring DTI more into the clinical field.”

Pentagon’s giant blood serum bank may provide PTSD clues.

The massive repository of genetic material is poised to advance research—just don’t bother asking for your samples back.

Nestled inside a generic-looking office building here in suburban Maryland, down the hall from cable-provider Comcast, sits the largest blood serum repository in the world.


Seven freezers, each roughly the size of a high school basketball court, are stacked high with row upon row of small cardboard boxes containing tubes of yellow or pinkish blood serum, a liquid rich in antibodies and proteins, but devoid of cells. The freezers hover at –30 degrees Celsius—cold enough to make my pen dry up and to require that workers wear protective jumpsuits, hats, gloves and face masks. Four more empty freezers, which are now kept at room temperature, await future samples.

The bank of massive freezers—and its contents—is maintained by the Department of Defense (DoD). The cache of government-owned serum may provide unique insights into the workings of various maladies when linked with detailed information on service members’ demographics, deployment locations and health survey data. New research projects tapping the precious serum could lead to breakthroughs in some of the hottest topics in military research—including the hunt for biomarkers for post-traumatic stress disorder and suicide risk. But DoD’s policy of keeping its samples in perpetuity—even after troops leave the force—could raise a few eyebrows.

From humble beginnings

The military started collecting serum samples 28 years ago as a by-product of its HIV surveillance. Since then serum has been routinely collected from leftover blood from HIV tests or standard post-deployment health check-ups and then frozen for future reference. Now the Department of Defense Serum Repository (DoDSR) has swelled to include 55.5 million samples of serum from 10 million individuals—mostly service members, veterans or military applicants. The armed forces use DoDSR for general health surveillance to track infectious diseases and to shape health policies. But the repository is also ripe for targeted research programs.

Annually the facility may field as many as 100 requests to use some of the serum from that icy reserve. Sixty-two requests received the green light to sample from DoDSR last year, half of them for research and half for clinical testing of an individual patient’s samples. In the past five years DoDSR has filled 278 such requests. But not all DoDSR uses are medical: they have also played a role in criminal proceedings, serving as a reference point for female victims in two rape cases, says Mark Rubertone, who oversees the DoDSR. “The value of the specimens does not go away, even after [service members] leave the military,” he says.

Even with the promise of ongoing health surveillance and potential research that would benefit the force, not all contributors to the repository are enthusiastic about—or even necessarily aware of—their participation. DoDSR does not discard serum samples, even if individual service members or military applicants request that their samples be removed. Fewer than 10 individuals have asked for the removal of their samples, according to Rubertone. But the requests are likely rare because service members and their families are not actively aware of the serum, even though they may know that their blood—in one form or another—is on file, Rubertone acknowledges. Thus far, no one has successfully retrieved his or her biological materials from the facility.

A RAND Corp. report on the facility, published in 2010 (after an earlier draft was revealed via Wikileaks), pointed out that nearly 900,000 samples in the repository were not from active duty or reservist personnel—they were from so-called “dependent beneficiaries” in service members’ families. Those numbers have since grown, to a “couple million” samples, according to the DoDSR count. The biological material from military family members often ends up in the repository after beneficiaries receive pregnancy care or visit a sexually transmitted infection clinic. The data accompanying those samples are more sparse and so the serum specimens are not as useful for studies, although they are still kept in the repository. Another 4 percent of the samples come from civilians who applied for military service but did not join.

Research payoffs

Researchers who draw on the serum bank note that the wealth of longitudinal data from DoDSR enables cutting-edge research. Take, for example, several projects that are searching for biomarkers of post-traumatic stress disorder. By matching up pre- and post-deployment DNA from individuals who developed PTSD and also comparing the genetic material with DNA from a control population, researchers are hoping to discern clues about when and how PTSD becomes apparent at a genetic level, impacting the DNA building blocks via DNA methylation and perhaps the silencing of certain genes. Related work is also focusing on microRNA—a small, noncoding RNA molecule—that helps regulate numerous biological processes and serves as a fingerprint for disease development.

Meanwhile, other researchers are studying serum to garner clues about links between traumatic brain injury (TBI) and DNA methylation among individuals who served in Iraq and Afghanistan, gleaning information from samples on 150 service members with mild to severe TBI, along with 50 control subjects. Because individuals—both on and off the battlefield—can suffer from mild TBI and not know it, identifying a biomarker could help speed up clinical care, says study investigator Jennifer Rusiecki, an epidemiologist at Uniformed Services University of the Health Sciences in Bethesda, Md.

Without the serum available through DoDSR and its accompanying information, some of this work would likely be impossible. “I’m not aware of other banks that have this data,” Rusiecki says. All told, almost 75 publications have depended on data gleaned from the samples in these freezers. Still more projects have drawn on them but did not make it into print. And because the repository’s stated purpose is health surveillance, the samples would not be chucked even if all the studies were halted, DoDSR’s Rubertone says.



The military has instituted safeguards to prevent misuse of the serum reserve. All studies conducted with DoDSR serums are required to have a military co-investigator, a policy DoD put in place to help ensure that the serum is being used for military-relevant purposes. Researchers must also receive approval from their home institutions’ institutional review boards, groups that ensure investigators will guard patients’ confidentiality and adhere to ethical research principles.

Unfortunately, despite the scale of the military repository, blood serum has its limits as a medical resource. For research and health surveillance, the serum can only tell you so much, says Capt. Kevin Russell, the director of the Armed Forces Health Surveillance Center that oversees DoDSR. Because the serum samples are not linked to very specific exposure information—such as exactly where a service member was stationed or what he or she encountered while deployed—they only stand in as a surrogate for exposure. At the moment DoD is exploring whether other materials—urine, throat cultures, blood clots—or perhaps new technologies could enhance their repository. Nevertheless, it would be “unlikely” that Defense would get rid of its serum reserve or stop adding new samples, Russell says. And so four freezers remain empty, waiting.

Source: Nature





Time to Rethink Our Assumptions About ICP Monitoring for TBI.

A randomized trial finds no benefit from therapy guided by intracranial pressure monitoring rather than clinical and radiographic signs.

Guidelines recommend intracranial pressure (ICP) monitoring in the acute management of severe traumatic brain injury (TBI). However, only observational data support this recommendation, and not all clinicians follow it. Investigators have now performed the first randomized trial of ICP monitoring in patients with severe TBI.

Taking advantage of widespread equipoise in South America regarding the benefits of ICP monitoring, the trial involved six Bolivian and Ecuadorian hospitals with intensivist-staffed ICUs, 24-hour computed tomography availability, and neurosurgical coverage. Investigators enrolled patients older than 12 years with a Glasgow Coma Scale (GCS) score of 3–8, excluding those with unsurvivable injuries or a GCS score of 3 and bilateral fixed and dilated pupils. Those randomized to ICP monitoring received an intraparenchymal monitor and treatment to keep ICP <20 mm Hg. The other half of patients received treatment triggered by signs of increased ICP on clinical examination or imaging.

The 324 enrolled patients had characteristics of severe TBI, with a median GCS score of 4 and midline shift in about one third. Six months after their injury, patients in both groups had similar scores on a composite measure of functional status and cognition, and similar cumulative mortality (39% in the ICP-monitoring group vs. 41% in the imaging-examination group, a nonsignificant difference). Patients who underwent ICP monitoring received fewer specific treatments for cerebral edema.

Comment: This impressive study requires us to rethink how we define and measure intracranial hypertension. In the meantime, it should be noted that this trial did not test whether we should treat intracranial hypertension, which was treated aggressively in both groups. Instead, the authors found no benefit to ICP monitoring in guiding this treatment. These results indicate that the treatment of intracranial hypertension after TBI can be guided appropriately by either ICP monitoring or the clinical approach outlined in the trial protocol.

Source: Journal Watch Neurology



Amantadine Accelerates Recovery from Post-Traumatic Disorders of Consciousness.

The benefit rapidly disappeared after amantadine was stopped, leaving questions about its long-term effects.

Traumatic brain injury (TBI) often causes disorders of consciousness such as minimally conscious or vegetative states. Psychotropic medications are frequently used to promote alertness in these patients, but none has been evaluated in rigorous, randomized, clinical trials. Investigators have now performed a multicenter, placebo-controlled clinical trial of amantadine hydrochloride, an N-methyl-D-aspartate (NMDA) antagonist and indirect dopamine agonist, for this indication. The 184 patients enrolled were aged 16 to 65, receiving inpatient rehabilitation, and in a minimally conscious or vegetative state 4 to 16 weeks after sustaining a nonpenetrating TBI. The patients were randomized to 4 weeks of treatment with placebo or amantadine, titrated to as much as 200 mg twice daily at week 4. The primary outcome was the rate of change on the Disability Rating Scale (DRS), a validated 29-point scale commonly used in this population.

The average DRS score at baseline was 22 (the lowest score that still indicates a vegetative state). During treatment, patients receiving amantadine had significantly faster improvement in arousal and function, with scores declining by 0.24 points more per week on the DRS than the placebo group. However, the groups had similar DRS scores (approximately 18) when assessed 2 weeks after the end of treatment. There was no evidence of significant adverse effects from amantadine.

Comment: Besides dispelling the notion that TBI is too complex to be properly studied in randomized clinical trials, this study provides good evidence that amantadine accelerates recovery from severe TBI. The converging trajectories of the two groups’ DRS scores after treatment cessation suggest that, rather than promoting neuroregeneration, amantadine simply stimulates patients to regain consciousness faster. Still, that difference is no small benefit given the morbidity associated with immobility after brain injury. Although the short-term benefits may be modest and the long-term benefits remain unknown, this benign and inexpensive drug appears worthwhile for patients with post-traumatic disorders of consciousness.

Source: Journal Watch Neurology








Effect of slosh mitigation on histologic markers of traumatic brain injury.

Helmets successfully prevent most cranial fractures and skull traumas, but traumatic brain injury (TBI) and concussions continue to occur with frightening frequency despite the widespread use of helmets on the athletic field and battlefield. Protection against such injury is needed. The object of this study was to determine if slosh mitigation reduces neural degeneration, gliosis, and neuroinflammation.


Two groups of 10 adult male Sprague-Dawley rats were subjected to impact-acceleration TBI. One group of animals was fitted with a collar inducing internal jugular vein (IJV) compression prior to injury, whereas the second group received no such collar prior to injury. All rats were killed 7 days postinjury, and the brains were fixed and embedded in paraffin. Tissue sections were processed and stained for markers of neural degeneration (Fluoro-Jade B), gliosis (glial fibrillary acidic protein), and neuroinflammation (ionized calcium binding adapter molecule 1).


Compared with the controls, animals that had undergone IJV compression had a 48.7%–59.1% reduction in degenerative neurons, a 36.8%–45.7% decrease in reactive astrocytes, and a 44.1%–65.3% reduction in microglial activation.


The authors concluded that IJV compression, a form of slosh mitigation, markedly reduces markers of neurological injury in a common model of TBI. Based on findings in this and other studies, slosh mitigation may have potential for preventing TBI in the clinical population.

Source: Journal of neurosurgery.




Increased mortality in patients with severe traumatic brain injury treated without intracranial pressure monitoring.

Evidence-based guidelines recommend intracranial pressure (ICP) monitoring for patients with severe traumatic brain injury (TBI), but there is limited evidence that monitoring and treating intracranial hypertension reduces mortality. This study uses a large, prospectively collected database to examine the effect on 2-week mortality of ICP reduction therapies administered to patients with severe TBI treated either with or without an ICP monitor.


From a population of 2134 patients with severe TBI (Glasgow Coma Scale [GCS] Score <9), 1446 patients were treated with ICP-lowering therapies. Of those, 1202 had an ICP monitor inserted and 244 were treated without monitoring. Patients were admitted to one of 20 Level I and two Level II trauma centers, part of a New York State quality improvement program administered by the Brain Trauma Foundation between 2000 and 2009. This database also contains information on known independent early prognostic indicators of mortality, including age, admission GCS score, pupillary status, CT scanning findings, and hypotension.


Age, initial GCS score, hypotension, and CT scan findings were associated with 2-week mortality. In addition, patients of all ages treated with an ICP monitor in place had lower mortality at 2 weeks (p = 0.02) than those treated without an ICP monitor, after adjusting for parameters that independently affect mortality.


In patients with severe TBI treated for intracranial hypertension, the use of an ICP monitor is associated with significantly lower mortality when compared with patients treated without an ICP monitor. Based on these findings, the authors conclude that ICP-directed therapy in patients with severe TBI should be guided by ICP monitoring.

Source: Journal of Neurosurgery.





Late mortality after severe traumatic brain injury.

Traumatic brain injury (TBI) continues to be a significant public health issue in Australia. Despite advances in acute medical care and decreases in mortality, those affected experience long-term morbidity and have an increased late mortality rate. TBI is the leading cause of death and disability among young people, and the incidence of severe TBI is higher in men than women at a ratio of 3.5 : 1.The leading causes of TBI include: motor vehicle accidents (50%); falls (21%); violence (12%); and sports and recreation (10%). In Australia in 2008, there were 2493 new cases of TBI (about 1000 of these were severe), and the estimated total cost of care was $8.6 billion. Across Australia, lifetime cost per incident case of severe TBI was estimated at $4.8 million. In 2007, more than 16 000 patients were admitted to hospitals with TBI, with an average length of stay of 6.1 days in acute care, 64.2 days in rehabilitation and 84.1 days in other care. These patients characteristically have multiple disabilities and, in addition to health care services, they frequently receive other disability support services (eg, case management, individual therapy support, life skills development).

Many factors affecting outcomes after TBI are modifiable, and influenced by medical management. Multidisciplinary assessments early in the course of the disease guide medical care and provide predictive information about the potential for recovery. Rehabilitation interventions have documented benefit in patients with TBI. Research into rehabilitation in severe TBI is challenging because of: the heterogenous manifestations of sequelae of severe TBI; the unpredictable course of the disease; the range and variety of rehabilitation services; and inconsistent use of appropriate outcome measures. Few studies tackle long-term outcomes in this population, so evidence is insufficient for establishing optimum integrated care, agreement on a minimum clinical dataset for effective communication between clinicians, and incorporation of patient and caregiver perspectives.

The multicentre study by Baguley and colleagues in this issue of the Journal adds clarity by describing the long-term mortality pattern in adults with severe TBI, and identifies the risk factors associated with mortality. Among their 2545 patients with severe TBI discharged from tertiary rehabilitation units of the New South Wales Brain Injury Rehabilitation Program, with a mean follow-up period of 10 years, there were 258 recorded deaths. The authors report an increased risk of death up to 8 years after discharge from rehabilitation services that was 3.2 times greater than that for the general population, and higher than rates in previous reports (range of long-term mortality estimates, 1.1–3.1). The mortality rates remained higher than for the general population for up to 5 years after discharge from rehabilitation. True mortality rates may be underestimated; similar data for late mortality after TBI in children and Indigenous people are needed. The findings of Baguley and colleagues have implications for health service use and health modelling.

The study by Baguley et al is the first long-term mortality report of Australian data, and shows an increased risk of death among patients with more severe TBI, greater functional dependence, previous drug and alcohol misuse, epilepsy before their TBI and older age at injury; these findings are consistent with those of other studies. Compared with the general population, those with severe TBI had a particularly high risk of death from respiratory disorders, and a high risk of death from nervous system, mental and behavioural, and digestive disorders. Discharge to an aged care facility was identified as a risk factor independent of functional dependency at discharge from rehabilitation, and needs further investigation. Older patients are considered at risk because of an altered pathophysiological response in the ageing central nervous system. Further, health, lifestyle and social deprivation have been linked with survival. Other reports suggest that TBI itself provokes lifestyle and behavioural changes, or defines a subgroup in the population at higher risk of death for other reasons. Future research should target interventions for general preventive measures to maintain health, and social and lifestyle changes in people discharged to the community after a TBI.

The important elements of service provision for patients with TBI are similar to those in other conditions requiring neurorehabilitation:

  • involvement and support of primary health practitioners;
  • education of doctors, patients and caregivers about mortality, declining health and high-risk behaviours for targeted intervention;
  • clinical guidelines to include routine postdischarge follow-up over a longer time, and a flexible health care delivery system that prioritises the rehabilitation needs of patients with TBI; and
  • a clear plan of action and compliance, including indications for referral to specialised multidisciplinary services.

Policy recommendations to establish services for continuity of care (acute to subacute and community care) for patients with TBI include:

  • develop rehabilitation services (including infrastructure and personnel) for patients with severe TBI;
  • provide services to meet the complex needs of those with severe TBI, to identify unmet needs for assistance and reduce reliance on informal assistance;
  • link TBI rehabilitation programs with the existing Australian Rehabilitation Outcomes Centre dataset for long-term collection of clinical data, using standardised common data elements;
  • computerise national monitoring systems in real-time to document mortality and morbidity in TBI, and monitor patterns of recovery;
  • review policy and implement rigorous assessment of the impact of quality care to decrease mortality rates and harm from ineffective or insufficient treatment;
  • expand national insurance schemes to fund non-compensatable TBI rehabilitation; and
  • maintain a sustained public health information campaign to publicise issues and promote strategies for implementation in patients with TBI.





GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study

Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of 1.5 mug/L for GFAP and 1.13 mug/L for S100B from a previous study.
METHODS: In 79 patients with TBI (Glasgow Coma Scale score [GCS] </=12), serum, taken at hospital admission, was analyzed for GFAP and S100B. Data collected included injury mechanism, age, gender, mass lesion on CT, GCS, pupillary reactions, Injury Severity Score (ISS), presence of hypoxia, and hypotension. Outcome was assessed, using the Glasgow Outcome Scale Extended (dichotomized in death vs alive and unfavorable vs favorable), 6 months post injury.
RESULTS: In patients who died compared to alive patients, median serum levels were increased: GFAP 33.4-fold and S100B 2.1-fold. In unfavorable compared to favorable outcome, GFAP was increased 19.8-fold and S100B 2.1-fold. Univariate logistic regression analysis revealed that mass lesion, GFAP, absent pupils, age, and ISS, but not GCS, hypotension, or hypoxia, predicted death and unfavorable outcome. Multivariable analysis showed that models containing mass lesion, pupils, GFAP, and S100B were the strongest in predicting death and unfavorable outcome. S100B was the strongest single predictor of unfavorable outcome with 100% discrimination.
CONCLUSION: This study confirms that GFAP and S100B levels in serum are adjuncts to the assessment of brain damage after TBI and may enhance prognostication when combined with clinical variables.

source: neurology