AANS Neurosurgeon | Volume 26, Number 3, 2017

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Impact on Injury: Five Trends to Watch

Are the Days of the ICP Monitor Numbered? 
To date, three prospective randomized clinical trials have failed to demonstrate improved outcomes with either monitoring or reduction of intracranial pressure (ICP). The Decompressive Craniectomy in Patients with Severe Traumatic Brain Injury (DECRA) trial  reduced ICP with decompressive hemicraniectomy but did not impact survival or quality of life (1). The BEST-TRIP study showed that ICP monitoring was not superior to observational medical management (2). And now, Eurotherm shows that temperature reduction drops ICP but actually worsens outcome (3).

ICP has long been considered a vital sign as close to our hearts as its own rate and blood pressure, but the question of its continued significance for management of acute brain injury are not clear. Will the “it’s not the number, it’s the shape of the waveform” posse stage a rescue, successfully convincing doubters that when the non-compliant brain’s waveform has a higher second peak the patient is in trouble no matter what the number? Or is it the “area under the curve” that counts? Will the Camino tread the sad footsteps of the Swan-Ganz Catheter into oblivion?

Writers of the AANS/CNS Joint Section on Neurotrauma and Critical Care Guidelines are standing by, twist drills holstered, waiting for the RESCUEicp clinical trial results. Even if RESCUEicp comes out in favor of monitoring, there may still be non-invasive proxies guided by transcranial Doppler, ultrasound, quantitative electroencephalogram (EEG) and other technologies that ultimately supplant an invasive technology (4) – particularly given the trend of non-neurosurgeons and ancillary providers managing acute care in the brain-injured patient.

Follow my Finger Goes Digital  
Eye tracking, long a bastion of marketing and advertising geeks, is increasingly part of the video game and assistive devices market and will very shortly change the way we diagnose and classify brain injury. While previous FDA-cleared eye tracking algorithms were spatially calibrated, and thus assessed what people choose to look at (visual attention/ability to follow instructions), a newer algorithm follows eye movements by looking at the Cartesian coordinates (x,y) of the pupils over time as the patient views natural stimuli, such as television or videos (5). Thus, even subtly and sub-clinically decreased horizontal (cranial nerve VI palsy) and vertical (cranial nerve III palsy) movement resulting from infra and supratentorial mass effect respectively can be detected (5).

Disrupted coordination of eye movements is noted in structurally brain injured and concussed subjects relative to uninjured controls, while trauma subjects without brain injury did not have disrupted coordination relative to uninjured controls. The severity of eye movement disruption correlates with the severity of concussion symptoms and both improve over time (6). In a pediatric concussion center population assessed at one to 109 weeks post injury, eye tracking metrics correlate with convergence and accommodation dysfunction assessed clinically, as well as concussion symptom presence (7,8). Elevated ICP also disrupts eye tracking – resulting in cranial VI palsy as well as other measurable deficits. FDA clearance for non-spatially calibrated tracking is currently being pursued and will enable objective, non-invasive assessment of ICP and oculomotor dysfunction related to brain injury and concussion in the awake patient – changing the way neurosurgeons diagnose and define brain injury.

The End of the Road for the MVC
Afflicting approximately 2.5 million patients per year, the motor vehicle collision (MVC) has long been a leading cause of brain injury at all ages. In 2014, 21,022 passenger vehicle occupants died in motor vehicle traffic crashes, which is more than double the number of deaths from homicide (9). Car accidents lead to $80 billion per year in medical costs. Thus, factors impacting MVC rates will directly impact neurosurgical volume and workforce, as well as global hospital, insurance and societal costs. Such factors include autonomous vehicles, autonomous braking, blind spot detection, lane departure warning, drowsiness detection and reverse cameras. 

McKinsey Consulting estimates that 81 percent of car crashes in the U.S. are caused by human error (11). Tesla, Google, Audi, BMW and Mercedes are among the car companies developing autonomous vehicle prototypes to eliminate these mistakes.  Google’s prototype, which will market in 2020, has driven over 1.5 million miles on the streets of Mountain View, Calif., Austin, Texas, Kirkland, Wash., and Phoenix (12). 

Autonomous emergency braking detects when the vehicle is too close to one in front or back of it and brakes spontaneously, reducing rear end striking crash rates by 39 percent compared to the same model car with no autonomous emergency braking in a 27-state study conducted from 2010-2014. Blind spot detection systems may reduce some of the 450,000 blind spot crashes per year per the Insurance Institute for Highway Safety research (13). By 2018, rear camera systems will be mandatory in all new car models. Rear cameras aid in reverse parking and backing out, which prevent hitting pedestrians – particularly children – behind cars.  

While current automation of cars continues to have many limitations, such that they continue to rely on human backup, semi-automatic driving conditions are closer to becoming a reality (10,14). Without driving as a deterrent to excess drinking, alcohol consumption may increase, resulting in more accidents on the walk to the car and increased risk of dementia. At least the traumas will occur at lower velocity and impact fewer innocent bystanders!   

Where Pokemon Goes, Will Neurosurgery Follow?
Pokemon GO launched on July 7, 2016, and by July 11, had more than 21 million users and at least 20 reported accidents linked to people chasing down virtual creatures hiding in real places (15). While virtual reality (VR) games have been popular on laptops in the past, mobile device integration is clearly changing the nature of use.  Does this portend a reversal in sedentary trends? Increased mobility increases longevity. Will there be less dementia (reversal of both sedentary lifestyle and lack of social interaction risk factors)? Will there be fewer suicide attempts due to less social isolation depression (16), or will there be simply more distracted walking accidents and muggings from players not minding their surroundings?

The real impact of virtual reality; however, will likely be felt in the operating room as augmented reality. The startup Surgical Theater uses Oculus Rift VR technology to enhance pre-operative imaging. They are merging this technology with conventional image guidance to superimpose virtual guides on a real world through the microscope. Ultimately, Google Glass could become surgical glasses – impacting everything from placing a difficult ventriculostomy catheter, to aneurysm clipping, to driving C1-2 screws transarticularly for a spine fracture – a la Stealth or Brainlab without the wand and viewing monitor.

The Doctor Will Zap You Now 
As electroceuticals slowly start to cross the pond from their testing grounds in Europe (17), they are finding increased application in the neurosurgical community for conditions ranging from headache to memory loss and depression (18-22). As narcotic prescribing has been more closely scrutinized due to increased concern for addiction and overdose, electroceuticals present themselves as a less dangerous alternative. Our laboratory is investigating non-invasive vagus nerve stimulation for moderate traumatic brain injury (TBI) using a device called gammaCore from the company electroCore, in which Merck Ventures is invested. 

The global electroceuticals/bioelectric medicine market is expected to reach $25.2 billion by 2021 (23), which has prompted massive investment from federal agencies, pharma companies and startups. The Defense Advanced Research Projects Agency (DARPA) began a $79.8 million research project on electroceuticals in 2015 (24). Project manager David Weber has a vision of these devices being able to detect biomarkers present in the body at the development of disease. GlaxoSmithKline (GSK) is investing roughly $50 million into start-up companies that are developing electroceuticals, as well as supporting 20 different research groups.

The impact of electroceuticals on neurosurgery is currently not yet known. Will the tech supplant current invasive procedures for neuromodulation or serve as a “gateway drug” increasing the total number of neurosurgical procedures? Already, the American Medical Association (AMA) has issued a warning recommending that people avoid deliberate shocking at home in response to attempts to replicate the impact of electroceuticals.


References
1. Cooper  D.J., Rosenfeld  J.V., Murray  L., Polin, R.S., Shaffrey, M.E., Bogaev, C.A., … & Ward, J.D. (2011). Decompressive craniectomy in diffuse traumatic brain injury. New England Journal of Medicine, 364(16), 1493-1502.

2. Chesnut R.M., Temkin N., Carney N., Dikmen, S., Rondina, C., Videtta, W., … & Machamer, J. (2012). A trial of intracranial-pressure monitoring in traumatic brain injury. The New England Journal of Medicine, 367(26), 2471-2481.

3. Andrews, P.J., Sinclair, H.L., Rodriguez A., Harris, B.A., Battison, C.G., Rhodes, J.K., & Murray, G.D. (2015) Hypothermia for intracranial hypertension after traumatic brain injury. New England Journal of Medicine, 373(25), 2403-2412.

4. Kristiansson, H., Nissborg, E., Bartek Jr, J., Andresen, M., Reinstrup, P., & Romner, B. (2013). Measuring elevated intracranial pressure through noninvasive methods: a review of the literature. Journal of neurosurgical anesthesiology, 25(4), 372-385.

5. Samadani, U., Farooq, S., Ritlop, R., Warren, F., Reyes, M., Lamm, E., … & Schneider, J. (2015). Detection of third and sixth cranial nerve palsies with a novel method for eye tracking while watching a short film clip. Journal of neurosurgery, 122(3), 1-14.

6. Samadani, U., Ritlop, R., Reyes, M., Nehrbass, E., Li, M., Lamm, E., … & Burris, P. (2015). Eye tracking detects disconjugate eye movements associated with structural traumatic brain injury and concussion. Journal of neurotrauma, 32(8) 548-556.

7. Bin Zahid, A., Lockyer, J., Podolak O, et al. (2016). Eye tracking as a biomarker for concussion in the pediatric population.

8. (2013). Scat3. British Journal of Sports Medicine, 47(5), 259.

9. Statistics Query and Reporting System. US Department of Health and Human Services 2010, 2016.

10. Nees, M.A., Helbein, B., & Porter, A. (2016). Speech auditory alerts promote memory for alerted events in a video-simulated self-driving car ride. Human Factors: The Journal of the Human Factors and Ergonomics Society, 58(3), 416-426.

11. Bertoncello M., & Wee, D. (2015). Ten ways autonomous driving could redefine the automotive world. Market evaluation on development of autonomous vehicles.

12. Tabassi, A., Salmasi, A.H., & Jalali, M. (2005). Serum and CSF vitamin A concentrations in idiopathic intracranial hypertension. Neurology, 64(11), 1893-1896.

13. Cicchino, J. (2016). Effectiveness of forward collision warning systems with and without autonomous emergency braking in reducing police-reported crash rates. Online Insurance Institute for Highway Safety.

14. Shladover, S.E. (2016). The truth about “self-driving” cars. Scientific American, 314(6), 52-57.

15. Press, A. Playing Pokemon Go is becoming dangerous. New York Post. http://nypost.com/2016/07/09/pokemon-go-is-afflicting-players-with-real-world-injuries/2016.

16. Goodman B. (2016). The pokemon go pick-me-up. Inside health news. Vol 2016. Online: WebMD.

17. Sinha, G. (2013). Charged by GSK investment, battery of electroceuticals advance. Nature medicine, 19(6), 654-654.

18. Ghacibeh, G.A., Shenker, J.I., Shenal, B., Uthman, B.M., & Heilman, K.M. (2006). The influence of vagus nerve stimulation on memory. Cognitive behavioral neurology, 19(3), 119-122.

19. Smith, D.C., Tan, A.A., Duke, A., Neese, S.L., Clough, R.W., Browning, R.A., & Jensen, R.A. (2006). Recovery of function after vagus nerve stimulation initiated 24 hours after fluid percussion brain injury. Journal of neurotrauma, 23(10), 1549-1560.

20. Kumaria, A., & Tolias, C.M. (2012). Is there a role for vagus nerve stimulation therapy as a treatment of traumatic brain injury? British journal of neurosurgery, 26(3), 316-320.

21. Goadsby, P.J., Grosberg, B.M., Mauskop, A., Cady, R., & Simmons, K.A. (2014). Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study. Cephalalgia, 34(12), 986-993.

22. Malow, B.A., Edwards, J., Marzec, M., Sagher, O., Ross, D., &  Fromes, G. (2001). Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients. Neurology, 57(5), 879-884.

23. marketsandmarkets.com. Electroceuticals/Bioelectric Medicine Market by Product (Pacemakers, Cochlear Implants, Spinal Cord Stimulators), Type of Device (Implantable, Non-Invasive), Application (Arrhythmia, Depression, Migraine), End User (Hospitals) – Global Forecast to 2021. http://www.marketsandmarkets.com/Market-Reports/electroceutical-market-222053956.html2016.

24. Hodsden, S. (2015). DARPA begins funding “electroceutical” research.

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