Tag Archives: TBI

Head

A Blood Test For TBI? Part 2

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Yesterday, I wrote about one blood biomarker, GFAP, and its possible application in detecting traumatic brain injury (TBI). Today, I’ll discuss a complementary marker called UCH-L1.

Fewer studies have been done looking at the utility of UCH-L1 in detecting TBI than of GFAP.  A review article published last month pooled existing literature to get a sense of how good this biomarker really is. It also examined the risk of bias due to the small numbers of studies involved.

Here are the factoids:

  • Only 38 abstracts were eligible, but full text was available for analysis in only 13 (meaning it was only an abstract and never passed muster for publication). The authors of the published studies were contacted for additional information, which is an interesting (and helpful) practice.
  • Of all of those, only 4 were selected for meta-analysis! This significantly limited the value of the analysis.
  • Serum UCH-L1 has a high accuracy in predicting CT findings in mild to moderate TBI, but there is a high risk of bias affecting this result
  • Plasma UCH-L1 has a moderate accuracy predicting CT findings across all GCS levels, with a low risk of bias
  • Pooling all studies, this is high accuracy in predicting CT findings in patients with TBI across all GCS levels, but there is a high risk of bias affecting the results

Bottom line: UCH-L1 show promise as a predictor of CT findings in patients with TBI. However, the research papers were few and far between, and the possibility of bias was high. What does this mean? That using this test alone is better than a coin toss, but not good enough to change our practice in ordering CT scans in head injured patients. More well-designed studies are needed tell us whether this new (and undoubtedly expensive) test is worth the trouble.

Tomorrow, I’ll discuss a blood test incorporating both UCH-L1 and GFAP that was recently approved by the FDA.

Reference: The diagnostic values of UCH-L1 in traumatic brain injury: A meta-analysis. Brain Inj 32(1):1-17, 2018.

Head

A Blood Test For TBI? Part 1

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Traumatic brain injury (TBI) is an extremely common problem encountered by trauma professionals. Diagnostic and management pathways are fairly well-defined, and rely mainly on physical examination, as well as CT imaging in select cases.

In recent years, work has been done to identify markers of brain injury in the blood. The theory is that the injured brain may release substances that can be assayed with a simple blood test. The presence of these blood markers could then influence our use of CT for diagnosis, decision to admit or send home, and possibly help identify patients likely to develop post-concussive symptoms.

Two particular biomarkers are being evaluated: UCH-L1 and GFAP. A recently published review examined the current status of GFAP in diagnosis of head injury.

Here are the factoids:

  • A total of 27 pertinent research papers were identified for review, and 24 of 27 demonstrated a positive association between GFAP levels and TBI
  • GFAP prediction of intracranial pathology by CT scan was good to excellent
  • GFAP appeared to be able to discriminate between mass lesions and diffuse injury
  • There was considerable variability in the average GFAP values. This means that the cutoff value that predicts significant injury is not yet clear.
  • The number of pediatric studies reviewed was low, so the results may not be generalizable to children
  • GFAP may be elevated in patients with orthopedic injuries, and this was not well controlled for in the studies reviewed. It is unclear whether GFAP can be used in patients with fractures.

Bottom line: GFAP looks promising as a marker for detecting significant TBI in some trauma patients. 

Tomorrow, I’ll take a look at the other biomarker, UCH-L1, and the following day I’ll discuss the recent FDA approval of an assay for both of these by a US company, Banyan Biomarkers.

Reference: A systematic review of the usefulness of glial fibrillary acidic protein for predicting intracranial lesions following head trauma. Frontiers in Neurology 8(652):1-16.

I have no financial interest in Banyan Biomarkers.

Head

A Quick and Dirty Test for Traumatic Brain Injury

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Traumatic brain injury (TBI) is an extremely common diagnosis in trauma patients. The majority are minor concussions that show no evidence of injury on head CT. Despite normal findings, however, a short conversation with the patient frequently demonstrates that they really do have a TBI.

Scoring systems can help quantify how significant the head injury is. The Glasgow Coma Scale (GCS) score is frequently used. This scoring system is not sensitive enough for minor head injuries, since a patient may be perseverating even with a GCS of 15.

The Short Blessed Test (SBT) is a 25 year old scoring system for minor TBI that has been well-validated. It takes only a few minutes to administer, and is very easy to score.

The most important part of the administration process is choosing a threshold for further evaluation and testing. We administer this test to all trauma patients with a suspected TBI (defined as known or suspected loss of consciousness, or amnesia for the traumatic event). If the final score is >7, we refer the patient for more extensive evaluation by physical and occupational therapy. If the score is 7 or less but not zero, consideration should be given to offering routine followup in a minor neurotrauma clinic as an outpatient. In all cases, patients should be advised to avoid situations that would lead to a repeat concussion in the next month.

Reference: Validation of a short Orientation-Memory-Concentration Test of cognitive impairment. Am J Psychiatry. 1983 Jun;140(6):734-9.

Head

Cognitive Rest? What Is It?

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One of the more commonplace recommendations for recovery from mild traumatic brain injury (TBI) is “cognitive rest.” Sports medicine professionals recommend it, physiatrists recommend it, and trauma professionals talk about it.

First, what is it, exactly? I’ve seen a number of descriptions, and they vary quite a bit. The main concept is to avoid all activities that involve mental exertion. This includes using a computer, watching TV, talking on a cell phone, reading, playing video games, and listening to loud music. Huh?

What good does this allegedly do? Most articles that I’ve read theorize that cognitive activity somehow increases the metabolic activity of the brain and that this is bad. One of the more interesting papers I read (from 2010!) says it best: “It is now well-accepted that excessive neurometabolic activity can interfere with recovery from a concussion and that physical rest is needed.”

Read carefully. Well-accepted. The paper cites unpublished data on children by one of the authors, 2 meta-analyses and 2 consensus opinions. In other words, no data at all. Yet somehow the concept has caught on.

First of all, I don’t think it’s possible for most people to realistically practice cognitive rest. Who knows if there is really any difference in metabolism and energy use by the brain if you are engaging in any of the banned activities above? And let’s go to the other extreme: if one lies quietly in bed meditating, shouldn’t this be the ultimate cognitive rest? Yet fMRI and PET studies suggest (also limited data) that cerebral flow in specific areas of the brain increases during this state.

Maybe a modest increase in activity is good. Physical activity (within limits) has been shown to be very beneficial to physical and psychological well being time and time again. And the only paper I could find on the topic with respect to TBI showed that randomization to bedrest vs normal physical activity had no difference in post-concussive syndrome incidence or severity. However, the active group recovered with significantly less dizziness.

Bottom line: There is no data to support the concept of cognitive rest. Any type of activity, either mental or physical, can cause fatigue in a variable amount of time in people with mild TBI. It is probably best to interpret this as a signal to take it easy and recover for a while before exerting oneself again. But so far there is no objective data to show that cognitive activity either helps or hinders recovery.

References:

  • Cognitive rest: the often neglected aspect of concussion management. Athletic Therapy Today, March 2010, pg 1-3.
  • Effectiveness of bed rest after mild traumatic brain injury: a randomised trial of no versus six days of bed rest. J Neurol Neurosurg Psychiatry 73:167-172, 2002.
Abstracts

EAST 2018 #1: Plasma Over-Resuscitation And Mortality In Pediatric TBI

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The first EAST abstract I will discuss is the very first to be presented at the annual meeting. This is a prospective, observational studied that was carried out at the University of Pittsburgh. It looked at the association between repeated rapid thromboelastography (rTEG) results in pediatric patients and their death and disability after plasma administration. They specifically looked at the degree of fibrinolysis 30 minutes after maximum clot amplitude and tried to correlate this to mortality.

For those of you who need a refresher on TEG, the funny sunfish shape above shows the clot amplitude as it increases from nothing at the end of R, hits its maximum at TMA, then begins to lyse. The percent that has lysed at 30 mins (LY30%) gives an indication if the clot is dissolving too quickly (LY30% > 3%) or too slowly (LY30% < 0.8%).

The authors selected pediatric patients with TBI and performed an initial rTEG, then one every day afterward. They looked at correlations with transfusion of blood, plasma, and platelets.

Here are the factoids:

  • A total of 101 patients under age 18 were studied, with a median age of 8, median ISS of 25, and 47% with severe TBI (head AIS > 3)
  • Overall mortality was 16%, with 45% having discharge disability
  • On initial analysis, it appeared that transfusion of any product impeded fibrinolysis, but when controlling for the head injury, only plasma infusion correlated with this
  • Increasing plasma infusion was associated with increasing shutdown of fibrinolysis
  • The combination of severe TBI and plasma transfusion showed sustained fibrinolysis shutdown, and was associated with 75% mortality and 100% disability in the remaining survivors
  • The authors conclude that transfusing plasma in pediatric patients with severe TBI may lead to poor outcomes, and that TEG should be used for guidance rather than INR values.

Bottom line: There is a lot that is not explained well in this abstract. It looks like an attempt at justification for using TEG in place of chasing INR in pediatric TBI patients. This may be a legitimate thing, but I can’t really come to any conclusions based on what has been printed in this abstract so far.

Here are some questions for the authors to consider before their presentation:

  • There seem to be a lot of typos, especially with < and > signs in the methods.
  • Disability is a vague term. What was it exactly? Was it related to TBI or the other injuries as well?
  • These children also appear to have had other injuries, otherwise why would they need what looks like massive transfusion activation? Why did they need so much blood? Could that be the reason for their fibrinolysis changes and poor outcomes?
  • I can see the value of the initial rTEG, and maybe one the next day. But why daily? What did you learn from the extra days of measurements? Would a pre- and post-resuscitation pair have been sufficient?
  • Plasma is the focus of this abstract, but it does not describe how much plasma was given, or whether there was any departure from the usual acceptable ratios of PRBC to plasma administration.
  • Big picture questions: Most importantly, why would you think that poor outcomes, which are the focus of this paper, are related to plasma administration? Why haven’t we noticed this correlation before? And how does daily TEG testing help you identify and/or avoid this? What questions raised here are you going to pursue?

Reference: EAST 2018 Podium paper #1.