Wednesday 30 March 2016

Can concussion be tested for with a 'simple' blood test?

Can concussion be tested for with a 'simple' blood test?

"A new blood test can detect a concussion up to a week after a head injury," the Daily Mail reports. The test involved checking for biomarkers, which are substances created by a specific biological condition or state.

In this case researchers looked at two biomarkers – proteins called glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1).

These proteins are known to be associated with mild to moderate traumatic brain injury. These types of injury can result in concussion, which is short-lived loss of mental function.

The study included more than 500 people with suspected brain injury. Researchers found both proteins were sometimes present in the blood.

There were higher levels of UCH-L1 in the early stages after injury, while GFAP was found to be a relatively good indicator for up to a week after injury.

However, the two biomarkers were not always detectable in people with a brain injury. One in five people assessed by researchers did not have GFAP and 1 in 10 did not have UCH-L1.

As the tests were not able to correctly identify all people with and without a brain injury, these two biomarkers would not meet the requirements for a stand-alone diagnostic test.

Concussion ideally needs to be diagnosed by a health professional trained in assessing patients with head injury. You should visit your nearest accident and emergency (A&E) department if you or someone in your care has a head injury.

Where did the story come from?

The study was carried out by researchers from a number of institutions in the US, such as Orlando Medical Center, Virginia Commonwealth University, and Wayne State University School of Medicine.

It was funded by the US National Institute of Neurological Disorders and Stroke.

The study was published in the peer-reviewed journal, JAMA Neurology.

This study has been widely covered in the UK media, but a great deal of the reporting is misleading and inaccurate.

The Daily Telegraph stated that, "Scientists' finding means children who bang their heads many not need to undergo radiation-exposing scans" – but the study did not include anyone under the age of 18, so we can't be sure that this finding would be the same in children.

The Daily Express also mentioned an analysis of 152 children, but this was not part of the same study. None of the stories alerted readers to the fact that these tests were not able to correctly identify all people with a brain injury.
What kind of research was this?

This prospective cohort study aimed to investigate the time course and diagnostic accuracy of two protein markers in the blood – glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) – for detecting mild to moderate traumatic brain injury.

This type of study is good for comparing the levels of such markers in those with mild to moderate traumatic brain injury with those who have not had a head injury, and drawing links. However, it is not able to prove the injury itself is the cause of the rise in serum levels.
What did the research involve?

This study enrolled participants from the Orlando Regional Medical Center between March 2010 and March 2014. All were adult trauma patients who were screened to see if they had experienced mild to moderate traumatic brain injury.

This was considered blunt head trauma with loss of consciousness, amnesia, or disorientation within four hours of injury and a Glasgow Coma Scale score of between 9 and 15.

Blood samples were taken from participants within four hours of injury and repeat samples at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury (if the participant was still at the medical facility and had not been discharged). All blood samples were then analysed in duplicate for GFAF and UCH-L1.

Most participants had a CT scan as part of their usual care (412 people out of 584). The scans were interpreted by radiologists, who recorded the location, extent and type of brain injury.
What were the basic results?

The researchers included 584 trauma patients with an average age of 40 years. The majority of cases were the result of road traffic accidents. Overall, 325 people (55.7%) had trauma with mild to moderate traumatic brain injury, and 259 (44.3%) had trauma without brain injury.

In total, 1,831 blood samples were drawn from the 584 patients (1,243 with mild to moderate traumatic brain injury and 588 trauma without).

GFAP was not detected in 21.6% of samples from people with a brain injury and 56.6% of the samples from trauma controls. UCH-L1 was not detected in 11.7% of samples from people with a brain injury and 15.8% of the samples from trauma controls.

When the markers were detected, they were present in the blood within one hour of injury. Both were higher in people with brain injury. GFAP levels reached their highest at 20 hours after injury and slowly declined over 72 hours, but UCH-L1 peaked at eight hours and had a more rapid decline over 48 hours.
How did the researchers interpret the results?

The researchers concluded that, "GFAP performed consistently in detecting mild to moderate traumatic brain injury, CT lesions, and neurosurgical intervention across seven days. UCH-L1 performed best in the early post-injury period."
Conclusion

This study is a prospective cohort study that aimed to investigate the use of two proteins in the blood – GFAP and UCH-L1 – as markers for detecting mild to moderate traumatic brain injury.

The study found both proteins could be present in the blood after a head injury, with higher levels of UCH-L1 in the early stages after injury, while GFAP seemed to be a good marker for up to a week after injury.

But both biomarkers were not found in all cases. One in five people with a brain injury did not have detectable levels of GFAP, and 1 in 10 did not have UCH-L1. This substantially reduces their ability to be used as a diagnostic test.

The study has both strengths and limitations. Strengths are that the researchers included a reasonable number of participants and a control group to draw comparisons between trauma patients with and without brain injury.

Laboratory personnel analysing the samples were also masked to clinical data and radiologists were masked to study protocol when assessing the scans, which reduced the risk of bias.

The study's limitations include that the participants were all from a single centre in the US – this may not be representative of other populations.

Also, as the authors state, the number of samples available for analysis decreased substantially over the study period, with only 51 people providing samples after the first 24 hours and just four patients after 180 hours.

As the tests were not able to correctly identify all people with and without brain injury, these two biomarkers would not meet the requirements for a stand-alone diagnostic test for brain injury.

You should go to the nearest accident and emergency (A&E) department if you or someone in your care has symptoms of concussion after experiencing a head injury, such as loss of memory, blurred vision or mental confusion.

While concussion is not usually serious, as the symptoms typically pass quickly it is better to err on the side of caution.

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