Neurotrauma and Critical Care of the Future

Jam Ghajar

Looking forward to what neurotrauma care could potentially deliver in 2065 brings to mind what is new in 2015 and what could be imagined in the future, given sufficient time and funding. The following topics explore neurotrauma care from concussion to coma and from prevention to rehabilitation. They by no means cover all the very exciting developments that are currently on the horizon, but rather focus on areas I believe will significantly impact morbidity and mortality.

The recent public interest in concussion and its long-term sequelae have fueled tremendous federal and commercial funding for clinical research that promises solutions not only for traumatic brain injury (TBI) but also for cognitive neuroscience in general.

Concussion selectively disrupts attention, which is the main cognitive impairment following a concussion. What is attention, and how do we pay attention? These are questions that will be answered once we understand the biology of concussion—hopefully much sooner than 2065.

Prevention and Trauma Systems

Cars: Motor vehicle deaths have dropped dramatically since the wide implementation of airbags and seatbelts; however, survivors still have significant TBI. Side airbags and decreasing rotational motion of cars on impact are now appearing in cars.

For 2065 expect driverless cars and an increase in mass transit leading to minimal transportation-related TBI.

Helmets: Helmets prevent scalp and skull fractures but do not prevent concussions, which are caused by rotational forces exaggerated by the flexibility of the neck.

For 2065 expect much smaller profile helmets (to prevent scalp and skull injuries) with integrated neck-sensor-restraint devices to reduce angular acceleration/deceleration.

Trauma systems: Early resuscitation of blood pressure and oxygenation in severe TBI patients is key to improving survival and long-term outcome. Pre-hospital services and regional trauma system organization have contributed significantly to improved outcomes from severe TBI.

For 2065 expect globalization of prehospital and integrated trauma systems in a cost-efficient model that is financed by innovative taxation.

Figure 1: 2015

Brain Resuscitation

In the past, resuscitation of the brain and torso were contrary; “dry the brain” was the mantra, achieved by vigorous hyperventilation, mannitol, and restriction of fluids. Now we know that the brain and body need full resuscitation to reduce ischemia reperfusion syndrome.

For 2065 expect brain-specific resuscitation fluids/pharmaceuticals that ensure oxygenated perfusion, reduce the inflammatory process, and recharge mitochondria.

Biomarkers of Injury

Currently, CT imaging is our only biomarker of acute injury, with MRI used rarely. Research on white matter integrity using MRI diffusion tensor imaging is promising, but involves comparing groups of subjects rather than individual analysis. Unfortunately, the variance in normal anatomy makes determination of “minor” injury problematic without a normative database.

Blood biomarkers derived from glial and neuronal elements are very promising, analogous to cardiac ischemia markers, and can potentially represent the degree, timing, and functional impact of TBI.

For 2065 expect extensive knowledge about “normal” imaging specific to age, gender, and socio-educational status. MRI will be the standard of imaging with auto-standardized comparison to detect abnormalities in anatomy, metabolism, as well as functional networks.

Blood biomarkers will detect minor trauma and give focal-antigen information that combine with other functional markers to determine management and prognosis.

Functional Metrics

GCS is our current metric for functional assessment. It is an excellent and easy-to-use metric for determining arousal status (awake, lethargy, stupor, and coma), but it fails in determining higher cognitive function (it was not designed to do so). Assessing higher cognitive function in concussion is usually focused on attention and those functions dependent on it—working memory, orientation, processing etc. Current cognitive tests have learning effects, are effort-dependent, and are unreliable when used multiple times. In addition, these tests mix the selective attention function with cognitive processing—one has to select 2 and 3 (selective attention) to process the addition of 2+3.

To solely assess selective attention one needs a test that can measure spatial and temporal prediction—the selection of information in dynamic space and time that needs to be processed. Neuromotor analytics can assess this predictive brain state that is operant in selective attention with variance as the key metric. Measurement of eye tracking a predictable moving target or gait analytics on a treadmill are examples of neuromotor analytics that can be used, have little to no learning or effort effects, and are highly reliable.

For 2065 expect head mounted, gogglebased, eye-tracking analytics that can be done in 10 seconds to assess attention, and bodysensor technology to assess other neuromotor variance. Baseline values of neuromotor analytics for individuals will be available for immediate comparison and to evaluate patients for return to work/athletics/school.

ICP and Beyond

The leading cause of death in severe TBI is from intracranial hypertension and systemic hypotension. Controlling early rises in ICP with ventriculostomy and osmotic diuretics while maintaining cerebral perfusion pressure works for 85 percent of patients, but the 15 percent that exhibit severe, uncontrollable ICP are difficult to manage. Lumbar CSF drainage in concert with ventricular CSF drainage has proven very effective in mixed pathology studies (TBI and stroke), dramatically reducing high ICP and maintaining the reduction. Early prophylactic lumbar CSF drainage has not been studied. The reluctance to use lumbar CSF drainage comes from an expectation of cerebral herniation, which is infrequent in published studies and may represent frontal lobe edema pressure on the third nerve rather than herniation.

Figure 2: 2065

Blood flow, metabolism, and function are normally linked but can be disrupted in TBI. Direct measurement of these three parameters would be useful in directing therapy. One candidate locus for measurement of these multiple parameters is the ventriculostomy catheter sitting in gray and white matter as well as in the ventricular system, but the ventricular catheter is currently largely used to measure ICP and drain CSF (oxygen, temperature, and parenchymal ICP are available currently). EEG measurement off a ventricular catheter in gray and white matter would be extremely useful to assess seizures, depth of sedation/anesthesia (propofol), and wakening/extubation indications.

For 2065 expect prophylactic lumbar and ventricular CSF drainage and monitoring/ management TBI algorithms that use multiparametric ventricular catheter technology containing sensors for cerebral blood flow, oxygen and glucose consumption, and EEG.

Rehabilitation

Early management of concussion involves rest and removal from activities that could produce another injury. This “natural course of recovery” approach is also seen in cognitive rehabilitation for severe TBI survivors. This approach comes from a lack of understanding of the true cognitive deficits in concussion and coma survivors. Motor disorders or sensory disorders are targeted for specific rehabilitation based on measureable deficits, yet cognition has escaped precise measurement and rehabilitation.

The brain has delays in sensorimotor processing yet manages to interact in real time. A major problem for cognition is to anticipate incoming sensory input to process/ interact just in time. This predictive brain state is the pre-processing state usually labeled as “selective attention.” The predictive brain state is sub-served by cerebellar, basal ganglia (both involved in timing), and parietal (spatial) areas, which synchronize the individual with the outside world. Both cognition and motor synchronization share these subcortical timers.

Impairments in prediction create an “out of sync” individual, who cannot maintain the normal cadence of interactions— conversations, work, school, sports, driving, etc. The utility of identifying this brain function is that it can be measured and rehabilitated.

For 2065 expect active, early rehabilitation of cognitive and motor synchronization in concussion and coma recovered subjects using neuromotor analytics with auditory, visual, and tactile online feedback techniques. Also direct neuromodulation techniques with transcranial and cranial nerve stimulation will be used to treat TBI-associated depression, anxiety, and attention disorders.

>WHAT IS ATTENTION, AND HOW DO WE PAY ATTENTION? THESE ARE QUESTIONS THAT WILL BE ANSWERED ONCE WE UNDERSTAND THE BIOLOGY OF CONCUSSION—HOPEFULLY MUCH SOONER THAN 2065.< >FOR 2065 EXPECT ACTIVE, EARLY REHABILITATION OF COGNITIVE AND MOTOR SYNCHRONIZATION IN CONCUSSION AND COMA RECOVERED SUBJECTS USING NEUROMOTOR ANALYTICS WITH AUDITORY, VISUAL, AND TACTILE ONLINE FEEDBACK TECHNIQUES.<