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To cite this article: David J. Barton, Patrick J. Coppler, Nadine N. Talia, Alexi Charalambides,
Brian Stancil, Ava M. Puccio, David O. Okonkwo, Clifton W. Callaway, Francis X. Guyette &
Jonathan Elmer (2023): Prehospital Electroencephalography to Detect Traumatic Brain Injury
during Helicopter Transport: A Pilot Observational Cohort Study, Prehospital Emergency Care,
DOI: 10.1080/10903127.2023.2185333
determined Rotterdam CT scores on all patients with available in the delta (0–4 Hz), theta (4–8 Hz), and alpha (8–13 Hz)
data. Injury Severity Scores (ISS) and Abbreviated Injury Scale ranges, as well as the ratio of alpha/delta power.
(AIS) scores were later obtained from the UPMC Trauma We performed statistical analyses with Stata SE 17.0,
Registry. including descriptive statistics and bivariate analyses. We
tested categorical variables for between-group differences
using Pearson exact tests due to low expected cell counts.
Blood Collection and Biomarker Assays
We assessed continuous variables for normal distribution
Study personnel collected venous blood samples from patients using Shapiro-Wilk tests; variables with significant test val-
in the emergency department immediately upon arrival using ues were reported as medians (interquartile range [IQR])
tri-potassium ethylenediaminetetraacetic acid coated tubes. and analyzed using non-parametric tests (e.g., Mann-
We obtained second blood samples at approximately 72 hours Whitney tests and Spearman correlation coefficients). All p-
post-injury in patients who were still hospitalized. Blood sam- values were considered significant at <0.05.
ples were obtained at the time of clinical blood draws or
from existing intravenous catheters to avoid excessive veni-
Results
punctures. We kept samples at room temperature for 30–
60 minutes (five samples were placed on ice for up to several Cohort Information
hours when logistically required due to investigator availabil-
ity), then centrifuged samples for 10 minutes at 1500x relative A flow diagram of patients eligible during the study period is
centrifugal force. Plasma supernatants were aliquoted and in Figure 2. Four of six missed enrollments came within the
immediately frozen at 80 C for batch analysis. first 2 months of study initiation, and the rate of missed
Samples were sent for commercial measurement to Abbott enrollments decreased over time. One missed enrollment was
Laboratories on dry ice. Plasma levels of glial fibrillary acidic due to crewmembers not having time to do so because the
protein (GFAP) and ubiquitin C-terminal hydrolase L1 patient required continuous resuscitation. Otherwise, no spe-
(UCHL1) were measured using the Abbot Alinity immuno- cific injuries precluded placement or use of the device. All
assay platform. Both assays have <10% coefficients of vari- patients tolerated the device, and there were no observed
ation. The laboratory was blinded to clinical data, and cases of patients removing the leads, requiring additional sed-
biomarker data were analyzed by the authors. ation, or harm. Device battery failure occurred in five cases;
this was addressed by providing EMS flight crews with in-
helicopter charging cords to keep the EEG device constantly
Data Analysis charged. After this intervention, no battery failures occurred.
All data, including EEG, were analyzed post-hoc and not Overall, we included 34 subjects in whom EEG and/or
during patient care. An investigator experienced at EEG blood was collected. Clinical characteristics of the cohort are
interpretation visually inspected EEG waveform recordings summarized in Table 1. Subjects were mostly male (79%),
to determine if interpretable EEG was recorded. For each had a mean age of 48 y (range 17–79 y), and were most fre-
interpretable recording, we visually selected one 90-second quently injured due to falls (38%). Median (IQR) ISS was 9
period of the most artifact-free data for quantitative analysis. (2–17). Twelve subjects had AIS head region scores > 0,
In this pilot study, we focused on frequency decompositions and the median (IQR) of these 12 subjects was 2 (1–3).
of the EEG signal, since this has been used successfully in Eight subjects (24%) had initial CT imaging with evidence
past research to identify brain hypoperfusion (1), preclinical of TBI; six of these individuals had presenting Glasgow
signs of concussion (2), and risk of traumatic encephalop- Coma Scale (GCS) scores of 15 (Table 2). One individual
athy (2), and can be used to grade TBI severity in both the with CT-positive TBI developed delayed low-pressure hydro-
acute and chronic phases (3). We used the eegkit package cephalus and coma requiring placement of an external ven-
(12) and R version 4.0.4 (13) to conduct Fast Fourier trans- tricular drain and ventriculoperitoneal shunt.
form for frequency decomposition. A Fourier transform
decomposes a complex waveform into its component fre- EEG Measures
quencies (i.e., the original waveform is treated as a sum of
multiple sinusoidal functions). Each of these functions has Mean (standard deviation) electrographic recording time was
an amplitude and frequency. The signal decomposition we 9.5 (7.4) minutes. Twenty-six of 31 individuals (84%) had
performed uses this approach to approximate the sum of the 90 second periods of interpretable EEG for quantitative ana-
total power with specific clinically relevant frequency bands. lysis. Five subjects (16%) had uninterpretable recordings, all
We applied a bandpass filter from 0.1 to 30 Hz, and then of whom were enrolled in the first half of the study. The five
used a notch-filter (using the signal package (14)) to exclude subjects with uninterpretable EEG recordings were older than
non-physiological electromechanical interference attributable those with interpretable EEG (median age 64 vs 44 years;
to harmonics of the helicopter rotor blades or other invariant, p ¼ 0.02 by Mann-Whitney test), but there was no difference
high-amplitude, non-physiological spikes occurring at fixed in subjects’ sex, race, mechanisms of injury, endotracheal
frequencies. We summarized results of the frequency decom- intubation, presence of intoxication, or presence of TBI on
position by considering total band-pass filtered spectral power CT (p > 0.05 for all comparisons via Fisher exact tests).
4 D. J. BARTON ET AL.
Table 1. Patient characteristics. Comparisons between subjects with and without CT-posi-
Patient characteristic Total N ¼ 34 tive TBI (Figure 3) demonstrated no significant differences
Age – y, mean (SD) 48 (16) between median values of alpha-power (63.0 vs. 72.1 mV;
Male sex, n (%) 27 (79)
Race, n (%)
p ¼ 0.74), theta-power (97.5 vs. 88.8 mV; p ¼ 0.41), delta-
White 30 (88) power (458.4 vs. 353.6 mV; p ¼ 0.79), or alpha-delta ratios
African-American/Black 4 (12) (0.19 vs. 0.20; p ¼ 0.41).
Mechanism of Injury, n (%)
Fall 13 (38)
Motor vehicle crash 9 (26)
Motorcycle crash 6 (18) Blood Biomarker Analysis
Pedestrian struck by vehicle 2 (6)
Gunshot wound 2 (6) We collected blood upon ED arrival (day 1; n ¼ 19) and
Amputation 1 (3) 72 hours after admission (day 3; n ¼ 17) and analyzed plasma
Hanging 1 (3)
Systolic blood pressure – mmHg, mean (SD) 138 (29)
levels of UCH-L1 and GFAP (Figure 4). Median (IQR) level of
Diastolic blood pressure – mmHg, mean (SD) 92 (25) UCH-L1 was 2242 (353.3-4624.1) pg/mL on day 1 and 123.7
Heart rate – min-1, mean (SD) 92 (20) (87.4-209.6) pg/mL on day 3 among all individuals. Median
Respiratory rate – min-1, mean (SD) 19 (4)
Prehospital intubation, n (%) 5 (15) (IQR) level of GFAP was 29.4 (19.2-77.6) pg/mL on day 1 and
Traumatic brain injury on CT scan 8 (24) 96.7 (28.4-330.8) pg/mL on day 3 among all individuals. Two
Clinical seizures within 3 days 1 (3) individuals with CT-positive TBI had blood available on day 1,
Clinical seizures within 30 days 4 (17)a
Length of hospital stay – days, median (IQR) 5 (2–10) and four had blood available on day 3. No significant differen-
Mortality at 30 days 0 (0)a ces in UCH-L1 or GFAP levels were noted between CT-posi-
a
29 patients had follow-up information available via medical record review. tive TBI vs. CT-negative groups at either time point (p > 0.05
PREHOSPITAL EMERGENCY CARE 5
Table 2. Characteristics of patients with CT-positive TBI. be as low as 26 of 40 (65%) if considering the entire enrolled
TBI, n ¼ 8 population as the denominator (Figure 2). Trauma victims
Glasgow coma scale score, median (IQR) 15 (12.5-15) comprise a sizable proportion of patients treated by helicopter
CT injury types
Subarachnoid hemorrhage 7 (88)
EMS. Identifying TBI can facilitate triage, trigger time-sensi-
Subdural hemorrhage 2 (25) tive interventions, and reduce secondary injury. Recent guid-
Intraventricular hemorrhage 2 (25) ance from the Excellence in Prehospital Injury Care-TBI
Contusion 1 (12.5)
Diffuse axonal injury 1 (12.5)
study reinforces the importance of evidence-based prehospital
Epidural hemorrhage 0 (0) medical care for improving TBI-related outcomes (15).
Intraparenchymal hemorrhage 0 (0) Limited prior work has assessed EEG in prehospital set-
Rotterdam CT score, median (IQR) 2 (1-2)
Neurosurgical intervention within 3 days 0 (0) tings. Jakab et al. first reported on design and testing of a
Neurosurgical intervention within 30 days 1 (12.5) six-channel EEG system intended for rapid deployment;
they tested two healthy volunteers in an ambulance and
reported sufficient diagnostic recordings (16). In a small
military study of soldiers with closed head injury, authors
demonstrated the BrainScope One device (which uses EEG
as one component) may be a useful tool for identifying and
ruling out structural brain lesions in the battlefield; however
this study included only 13 subjects, and only three subjects
received CT scans (17). Most recently, a dry electrode EEG
system has been reported to have modest utility in prehospi-
tal detection of stroke with large vessel occlusion (18). There
remains interest in applying simplified, point-of-care EEG in
emergency and prehospital settings to screen for stroke
(19, 20) and non-convulsive status epilepticus (21–23),
which is frequently missed in prehospital settings (24). Such
applications could be helpful in guiding prehospital treat-
ments and determination of transport destination. However,
further work is needed to demonstrate feasibility and trans-
lation to the prehospital setting with its associated challenges
to implementation such as patient movement, electrode
placement, external bleeding, cranial trauma, intoxication,
combativeness, and helicopter motion. Our work adds to the
literature by demonstrating satisfactory EEG is possible des-
pite these operational barriers.
Prior literature demonstrates acute quantitative EEG
changes in mild TBI include reduction in alpha power and
increase in theta and delta power (25). In our exploratory
analyses, we did not detect significant differences in quanti-
Figure 3. Quantitative EEG measures in non-TBI vs. TBI groups based on CT
imaging. tative EEG measures, with the significant limitation of our
small sample size, although our median values agree with
for all comparisons), although we had a low sample size for this relationship directionality in TBI vs. non-TBI. Thus, it
this exploratory comparison (Supplemental Figure 1). remains our hypothesis that these quantitative EEG meas-
We calculated correlation coefficients between quantita- ures are associated with presence of TBI. Alternatively, it is
tive EEG measures and day 1 biomarker levels (generally possible that effect sizes are too small to show clinical effect
in the early post-trauma time course of prehospital care.
collected < 1 hour after EEG recordings). Delta power was
Larger studies are needed to better answer this question.
inversely correlated with UCH-L1 levels upon ED arrival
We provide novel data of UCH-L1 and GFAP relation-
(Spearman’s r ¼ 0.60; p ¼ 0.03), but other measures did not
ships with quantitative EEG measures, independent of radio-
have significant relationships (Figure 4).
graphic TBI. Delta power was inversely correlated with
UCH-L1 levels. While this analysis is unadjusted and
Discussion remains small in sample size, this exploratory finding is
interesting because of the proximate time between the EEG
In this prospective observational cohort, we report on our recording and blood collection and the role of UCH-L1 in
experience with single-channel EEG in trauma patients in the maintaining neuron axonal integrity (26) and synaptic struc-
prehospital helicopter ambulance setting. We find that EMS ture (27). Blood biomarkers of TBI remain an active area of
clinicians can successfully acquire limited frontal EEG in the investigation. Currently, the FDA-approved assay for these
prehospital (air medical) setting. Alternative calculations biomarkers is only available for plasma, not whole blood,
could yield the success rate of obtaining interpretable EEG to which would be necessary for prehospital use.
6 D. J. BARTON ET AL.
Figure 4. Scatter plots of quantitative EEG measures and plasma UCH-L1 and GFAP levels.
Our work has associated limitations. First, we used a sin- improve spatial coverage would affect either signal quality
gle channel, two-electrode EEG device to simplify the moni- or feasibility. Second, we used CT-positive findings to desig-
toring as much as possible for EMS clinicians who used it as nate TBI comparison groups for logistical practicality. TBI is
a new tool. It is unknown if adding additional channels to not solely defined by CT findings, and symptom-based
PREHOSPITAL EMERGENCY CARE 7
measures may help better stratify groups. Nonetheless, CT- 3. Figueira Rodrigues Vieira G, Guedes Correa JF. Early computed
positive findings of TBI are an important marker for potential tomography for acute post-traumatic diffuse axonal injury: a sys-
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need for neurosurgical intervention and triage to a neurosur-
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group delineator. This study has a small sample size given Salim A, Bukur M. Prehospital hypertension is predictive of
the pilot nature of the work, which limits our ability to test traumatic brain injury and is associated with higher mortality. J
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measures, and relationships with TBI. As a single-center 5. Yumoto T, Mitsuhashi T, Yamakawa Y, Iida A, Nosaka N,
study, confirmatory evaluation should precede larger-scale Tsukahara K, Naito H, Nakao A. Impact of Cushing’s sign in the
implementation. prehospital setting on predicting the need for immediate neuro-
Given the current work is a pilot study, EEG analysis was surgical intervention in trauma patients: a nationwide retrospect-
performed by investigators. Translation to clinical use would ive observational study. Scand J Trauma Resusc Emerg Med.
2016;24(1):147. doi:10.1186/s13049-016-0341-1.
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ically perform such processing in real time to provide clini- neuroimaging reveal a severe intracranial injury in this adult
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7. Hanley D, Prichep LS, Badjatia N, Bazarian J, Chiacchierini R,
Conclusions Curley KC, Garrett J, Jones E, Naunheim R, O’Neil B, et al. A
brain electrical activity electroencephalographic-based biomarker
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a feasible monitoring modality in acute trauma for air med- validation trial. J Neurotrauma. 2018;35(1):41–47. doi:10.1089/
neu.2017.5004.
ical transport. Further study is needed to identify the most 8. Hanley D, Prichep LS, Bazarian J, Huff JS, Naunheim R, Garrett
useful multimodal biomarkers for identifying and monitor- J, Jones EB, Wright DW, O’Neill J, Badjatia N, et al. Emergency
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Acknowledgments 1111/acem.13175.
9. Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P,
This work was presented at the Society of Academic Emergency Bogner-Flatz V, Gunnar Brolinson P, B€ uki A, Chen JY,
Medicine Annual Meeting on May 13, 2022 in New Orleans, LA. Christenson RH, et al. Serum GFAP and UCH-L1 for prediction
of absence of intracranial injuries on head CT (ALERT-TBI): a
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Disclosure Statement 789. doi:10.1016/S1474-4422(18)30231-X.
10. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG.
AC and BS are co-founders of Lifeware Labs, LLC which produced the
Research electronic data capture (REDCap)–a metadata-driven
EEG devices used in this study.
methodology and workflow process for providing translational
research informatics support. J Biomed Inform. 2009;42(2):377–
381. doi:10.1016/j.jbi.2008.08.010.
Funding 11. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal
This study was supported by the National Institutes of Health under L, McLeod L, Delacqua G, Delacqua F, Kirby J, REDCap
grant numbers T32HL134615, K23NS091629, and UL1TR001857 Consortium, et al. The REDCap consortium: building an inter-
through the Clinical and Translational Sciences Institute at the national community of software platform partners. J Biomed
University of Pittsburgh. Biomarker measurements were provided as Inform. 2019;95:103208. doi:10.1016/j.jbi.2019.103208.
gift-in-kind by Abbott Laboratories (Chicago, IL, USA). 12. Helwig NE. eegkit: toolkit for electroencephalography data
[Internet]; 2018. https://CRAN.R-project.org/package=eegkit.
13. R Core Team. R: a language and environment for statistical com-
puting [Internet]. Vienna, Austria: R Foundation for Statistical
ORCID
Computing; 2021. https://www.R-project.org
David J. Barton http://orcid.org/0000-0003-0976-0383 14. fsignalg: Signal processing [Internet]. 2014. http://r-forge.r-pro-
Patrick J. Coppler http://orcid.org/0000-0002-0731-7989 ject.org/projects/signal/.
Clifton W. Callaway http://orcid.org/0000-0002-3309-1573 15. Spaite DW, Bobrow BJ, Keim SM, Barnhart B, Chikani V,
Francis X. Guyette http://orcid.org/0000-0002-9151-4896 Gaither JB, Sherrill D, Denninghoff KR, Mullins T, Adelson PD,
et al. Association of statewide implementation of the prehospital
traumatic brain injury treatment guidelines with patient survival
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