Brain Injury Forces of Moderate Magnitude Elicit the Fencing Response

Abstract

Introduction:

Traumatic brain injury is heterogeneous, both in its induction and ensuing neurological sequelae. In this way, medical care depends on accurately identifying the severity of injury-related forces. Clinically, injury severity is determined by a combination of the Glasgow Coma Scale, length of unconsciousness, posttraumatic amnesia, and persistence of neurological sequelae. In the laboratory, injury severity is gauged by the biomechanical forces and the acute suppression of neurological reflexes. The present communication describes and validates the “fencing response” as an overt indicator of injury force magnitude and midbrain localization to aid in injury identification and classification.

Methods:

Using YouTube^™, the Internet video database, videos were screened for head injury resulting in unconsciousness and documented for the fencing response. Adult male rats were subjected to midline fluid percussion brain injury at two severities, observed for acute neurological reflexes and the midbrain evaluated histopathologically.

Results:

Tonic posturing (fencing response) has been observed to precede convulsions in sports injuries at the moment of impact, where extension and flexion of opposite arms occurs despite body position or gravity. Of the 35 videos identified by an impact to the head and period of unconsciousness, 66% showed a fencing response at the moment of impact, regardless of the side of impact, without ensuing convulsion. Similarly, diffuse brain-injured rats demonstrate a fencing response upon injury at moderate (1.9 atm, 39/44 animals) but not mild severity (1.1 atm, 0/19 animals). The proximity of the lateral vestibular nucleus to the cerebellar peduncles makes it vulnerable to mechanical forces that initiate a neurochemical storm to elicit the neuromotor response, disrupt the blood–brain barrier, and alter the nuclear volume.

Conclusions:

Therefore, the fencing response likely indicates neurological disturbance unique from convulsion associated with mechanical forces of moderate magnitude imparted on the midbrain and can assist in guiding medical care after injury.

In the United States, a traumatic brain injury (TBI) occurs every 15 s, which amounts to 2.1 million incidents annually, not including those that go untreated or related to military engagement. Even mild TBI, which accounts for 80% of all cases, can be devastating in persistent neurological dysfunction (21,34,40,41). The majority of these TBI are sports-related and routinely classified as a concussion (6,7,26). The purpose of this communication was to provide an additional screening criterion for identifying the magnitude of the injury forces at the moment of impact because medical care depends on accurately identifying injury severity.

A concussion is defined as a mild TBI that is brought about by a direct or indirect force to the head (2), which results in loss of consciousness, disorientation, slurred or incoherent speech, gross observable incoordination, or a variety of other chronic problems associated with emotional instability, memory deficits, and confusion (2,8). Many of the acute symptoms would implicate the midbrain and cerebellum as potential sites of damage. Unfortunately, these manifestations are often ephemeral and difficult to diagnose or pinpoint, specifically about decisions that have to be made about the return of athletes into game play after a suspected injury. As a result, a greater emphasis has regularly been placed on the management of the concussion in athletes than on the immediate identification and treatment of such an injury (2,19). On-field predictors of injury severity can define return-to-play guidelines and urgency of care. For example, vomiting or convulsion that accompanies an impact to the head overtly indicates a TBI, but the low incidence would detract from their utility (9,36). Other on-field assessments include loss of consciousness, disorientation, and amnesia, which do not directly address the severity of the injury (8). Additional criteria, one of which is described here, can contribute to the diagnostic and treatment rubric for TBI patients.

The Glasgow Coma Scale (GCS) is one of the most widely used evaluations of consciousness after head injury, originally designed to gauge changes in the depth of coma in vegetative patients (51). Since its inception, the GCS has been extended beyond its initial intent, being applied too soon after injury and representing injury severity rather than coma. The scale’s utility in less severely injured individuals may be compromised by the skew toward motor responses and the fact that they typically do not have “an inability to obey commands, utter recognizable words or open their eyes” (13,22,49). Typically, injury severity is determined by a combination of the GCS, length of unconsciousness, and posttraumatic amnesia. Over time, additional scales have been developed that build upon, incorporate, extend, or even simplify the GCS (49). However, these tools become cumbersome and fraught with interrater reliability issues (16), often becoming distanced from the injury itself. Moreover, the working range of these scales for TBI of mild to moderate severity is limited.

The most challenging aspect to managing sport-related concussion (mild TBI) is recognizing the injury (19). Consensus conferences have worked toward objective criterion to identify mild TBI in the context of severe TBI (2,3,5,19,35). However, few tools are available for distinguishing mild TBI from moderate TBI. Concussive convulsions are nonepileptic phenomena that are potential immediate sequelae of concussive brain injury. They include an initial tonic posturing phase, followed by a clonic or myoclonic phase that may last several minutes. Because of the acute onset and transient presentation, concussive convulsions are distinct from posttraumatic epilepsy (36,38), which likely requires time-dependent structural alterations to form the epileptogenic circuits within the injured brain (44). The present communication refines the tonic posturing phase as an immediate forearm motor response to indicate the magnitude and location of the applied forces.

In experimental models of head injury, the injury-induced suppression of several neurological reflexes (e.g., corneal, pinna, toe pinch) is routinely evaluated to gauge injury severity (10,12). These acute neurological reflexes are modeled from the ones evaluated clinically. In the laboratory, however, injury severity can be directly correlated to the biomechanical forces applied to the head or the brain.

Tonic posturing preceding convulsion has been observed in sports injuries at the moment of impact (37,38), where extension and flexion of opposite arms occur despite body position or gravity. The fencing response emerges from the separation of tonic posturing from convulsion to provide an indicator of injury force magnitude. The fencing response designation arises from the similarity to the asymmetric tonic neck reflex in infants (commonly called the fencing reflex). Standardization of on-field criteria for TBI using straightforward objective metrics would improve the diagnosis and ultimately the treatment of such injuries. The diagnostic value of the fencing response depends on the incidence in human TBI. To address the incidence, an online video database was screened for the fencing response induced by head injury. To address the diagnosis, rats had diffuse brain injuries at varying severities, observed for a fencing response, and histologically examined. To date, the pathophysiological mechanism of the tonic posturing and acute convulsive motor responses after TBI remains speculative (36). The present communication presents a combination of transdisciplinary studies to address the localized pathophysiological mechanism that elicits the acute injury-induced forearm neuromotor response. A fencing response was evident in two thirds of the videos involving an individual knocked unconscious. Similarly, diffuse brain injury of moderate severity in the rat resulted in a fencing response that correlated with blood–brain barrier disruption and nuclear shrinkage within the midbrain lateral vestibular nucleus (LVN). The observations in the current communication address the hypothesis that the fencing response can discern moderate brain injury forces from milder forces.

MATERIALS AND METHODS

Incidence of fencing in human head injury: YouTube^™ epidemiology.

To determine the prevalence of the fencing response in human subjects, the popular online video site, YouTube^™ (Google Inc, Mountain View, CA; http://www.youtube.com), was used as a source of data between July 2007 and June 2008. Using various search terms, such as “knocked out” and “concussed, ” the first 500 results were sorted by relativity and examined for the following criteria: 1) a clear, visible impact to the head or face; 2) the vantage point of the camera is unobstructed and clear at the moment of impact; 3) the video is long enough so that a fencing response or lack thereof may be established; and 4) the injured individual does not immediately get up after the blow. Any duplicates and videos under different titles exhibiting the same footage were disregarded. Approximately 2000 videos were screened; 35 met the inclusion criteria (Table 1).

TABLE 1.

Videos containing knockouts compiled during YouTube^™ survey.

Description	Means of Injury	Fencing Response	URL
Collegiate wrestler knocked out from an elbow to the head	Left elbow to right side of head	N/A	http://www.youtube.com/watch?v=KJZD9JRRSdk
Compilation of knockouts: Boxing knockout number 9	Left hook to right side of head	N/A	http://www.youtube.com/watch?v=4R5Mhvf9mkc
Child is knocked out by a swinging kick from Turkish dancer	Left kick to front side of head	N/A	http://youtube.com/watch?v=mUi6eLB_4OA
Compilation of knockouts: Boxing knockout number 5	Right hook to left side of head	N/A	http://www.youtube.com/watch?v=4R5Mhvf9mkc *
MMA fighter knocks out opponent	Right hook to left side of head	N/A	http://www.youtube.com/watch?v=HLqfE4l9PPQ
Male teenager allows another teenager to punch him in the face	Right hook to left side of head	N/A	http://youtube.com/watch?v=uyCsuPwd0tU
Boxer knocked unconscious by opponent	Right hook to left side of head	N/A	http://www.youtube.com/watch?v=7yDS1tic0dc
MMA double knockout	Right hook to left side of head	N/A	http://www.youtube.com/watch?v=xBawJUq8BGI
Kickboxing knockout	Right hook to left side of head	N/A	http://www.youtube.com/watch?v=lvQalkt_cOA
MMA knockout from kick	Right kick to left side of head	N/A	http://www.youtube.com/watch?v=mgyVMyLoIgI
Vale tudo championship knockout kick	Right kick to left side of the head	N/A	http://www.youtube.com/watch?v=uzg7Z7CzrIE
Hockey player checked on open ice and knocked out by opponent	Right shoulder to left side of head	N/A	http://www.youtube.com/watch?v=i3Gvfr9GUC0
Boxing knockout	Left hook to right side of head	Left arm extension during attempt to sit up	http://www.youtube.com/watch?v=nkMZ2bl_-n4
Boxing knockout	Left hook to right side of head	Left elbow twitching, arms at side on ground	http://www.youtube.com/watch?v=i27PrfnowRM
UFC knockout with a kick	Left kick to right side of head	Left arm extension with right arm flexion	http://youtube.com/watch?v=_AJIxopqgGk *
Rapper gets knocked out from behind	Right hook to right side of head	Left arm extension to slow flexion with right arm flexion	http://www.youtube.com/watch?v=RXmMVqxKc7U
Boxing knockout	Left straight to front side of face	Left arm extension bent upward	http://www.youtube.com/watch?v=JLYXXUlCM58
Female boxer knockout	Right hook to front side of head	Left arm extension with right arm flexed while falling	http://www.youtube.com/watch?v=FT4G8F4s9zU
Boxer loses by TKO, threatens winner and gets knocked out	Right hook to left side of head	Left arm extension with right arm flexion	http://www.youtube.com/watch?v=_C9_jJhqAKA
Guy kisses opponent before fight and gets knocked out	Right hook to left side of head	Left arm extension with right arm flexion	http://www.youtube.com/watch?v=3Wg2UMj6YFk
After school fight	Right hook to left side of head	Left arm extension with right arm flexion	http://www.youtube.com/watch?v=_ZChyjGzTY8
Compilation of knockouts	Right hook to left side of head	Left arm extension with right arm flexion while attempting to sit up	http://www.youtube.com/watch?v=4R5Mhvf9mkc †
Boxing knockout	Right hook to left side of head	Left arm extension with right arm flexion while falling	http://www.youtube.com/watch?v=z5eGSwogoBM
Boxing knockout	Right hook to left side of head	Left arm repeated extension and flexion	http://www.youtube.com/watch?v=mda40d-41rs
Boxing knockout	Left hook to right side of head	Both arms extended and rigid, right higher than the left	http://www.youtube.com/watch?v=0pM9lnlqThY
Hockey fight knockout	Left hook to front side of head	Both arms extended while falling	http://www.youtube.com/watch?v=qVAONp08ep0
Football player unconscious after hard tackle	Shoulder and helmet to front side of head	Both arms extended while falling, right arm extension for longer period	http://youtube.com/watch?v=Qd3V4Fvmk7E
MMA double knockout (bald fighter)	Right hook and head butt to left side of head	Both arms extended during fall	http://www.youtube.com/watch?v=2zhRz6zV9wU
MMA double knockout (man on right)	Right hook to left side of head	Both arms extended to left arm extension and right arm flexion, left leg extension with right leg flexion	http://www.youtube.com/watch?v=xBawJUq8BGI
Hockey fight ends with knockout	Right hook to left side of head	Both arms extended while falling, hands perpendicular to ground	http://www.youtube.com/watch?v=U9_c4FquJAI
MMA knockout	Right elbow to right side of head	Right arm extension in air during barrage	http://www.youtube.com/watch?v=NK7Cq9RsT28
Soccer player knocked out after getting kicked in the head during a dive	Right kick to front side of head	Right arm slight extension upward	http://www.youtube.com/watch?v=8GEB-TYLMmQ
MMA knockout	Right hook to left side of head	Right arm extension and rigidity	http://www.youtube.com/watch?v=hjgcVbnPYaU
Charity boxing match knockout	Right hook to left side of head	Right arm extension with left arm flexion	http://www.youtube.com/watch?v=No_z9NyIf8s
Boxing knockout	Right hook to left side of head	Right arm extension with left arm flexion	http://www.youtube.com/watch?v=bL86dJEXkLI

Each video is listed by description of event, how the knockout-causing injury occurred, the type of fencing response observed, and the Internet address by which it can be found.

^*This video is no longer available because of a copyright claim by Pride FC Worldwide Holdings, LLC.

^†This video has been removed because of the terms of use violation.

MMA, mixed martial arts; N/A, not applicable (no fencing); TKO, technical knockout; UFC, Ultimate Fighting Championship^®; URL, uniform resource locator (Web address).

Videos were then replayed to establish the location of the impact to the head (left side, right side, front), the presence of a fencing response, the laterality of the fencing response (left arm extended, right arm extended, or both), and the duration of the response.

Midline fluid percussion brain injury.

Adult male Sprague-Dawley rats (375–400 g) were subjected to midline fluid percussion injury (FPI) consistent with methods described previously (29,30). Fluid percussion brain injury has the ability to quantify and control the forces that directly injure the brain. Briefly, rats were anesthetized with 5% isoflurane in 100% O₂ and maintained at 2% via nose cone. During surgery, body temperature was maintained with a Deltaphase^® isothermal heating pad (Braintree Scientific Inc., Braintree, MA). In a head holder assembly (Kopf Instrument, Tujunga, CA), a midline scalp incision exposed the skull. A 4.8-mm circular craniotomy was performed (centered laterally on the sagittal suture midway between bregma and lambda) without disrupting the underlying dura or superior sagittal sinus. An injury cap was fabricated from the female portion of a Luer-Loc needle hub, which was cut, beveled, and scored to fit within the craniotomy. A skull screw was secured in a 1-mm hand-drilled hole into the right frontal bone. The injury hub was affixed over the craniotomy using cyanoacrylate gel, and methyl-methacrylate (Hygenic Corp. Akron, OH) was applied around the injury hub and screw. The incision was sutured at the anterior and posterior edges, and topical lidocaine ointment was applied. Animals were returned to a warmed holding cage and monitored until ambulatory (approximately 60–90 min).

For injury induction, animals were reanesthetized with 5% isoflurane 60–90 min after surgery. The incision was opened, and the dura was inspected. The injury hub assembly was filled with normal saline and attached to the male end of the fluid percussion device (Custom Design and Fabrication, Virginia Commonwealth University, Richmond, VA). An injury of moderate severity (1.9–2.0 atm), mild severity (1.1–1.2 atm), or sham injury was administered by releasing the pendulum onto the fluid-filled cylinder (10), as reflexive responses returned. Animals were monitored for the presence of a forearm fencing response and the return of the righting reflex. After injury, the injury hub assembly was removed en bloc, the integrity of the dura was observed, the bleeding was controlled with Gelfoam (Pharmacia, Kalamazoo, MI), and the incision was sutured. After recovery of the righting reflex, animals were placed in a warmed holding cage before being returned to the vivarium. For sham-injured animals, the identical surgical procedures were followed, without the induction of the injury. Animal experiments were conducted in accordance with National Institutes of Health (NIH) and institutional guidelines concerning the care and use of laboratory animals, which meet or exceed the American College of Sports Medicine standards. Adequate measures were taken to minimize pain or discomfort.

Tissue preparation and histology.

At 5–10 min after injury, animals were euthanized by an overdose of sodium pentobarbital (150 mg·kg⁻¹, intraperitoneally) and transcardially perfused within 10–15 min after injury with 4% paraformaldehyde in phosphate-buffered saline. Brains were removed, cryopreserved in 30% sucrose, and sectioned in the coronal plane at 30 μm on a cryostat. For histopathology, every sixth section through the hindbrain was stained with 10% Giemsa (no. 26156-01; EM Sciences, Hatfield, PA) at 60°C, differentiated with 1% acetic acid, dehydrated, and coverslipped, as previously reported (29). To detect blood–brain barrier disruption, an alternate set of tissue was immunostained with antirat IgG. Briefly, endogenous peroxidase activity was quenched with 0.9% H₂O₂ in EtOH and Tris buffered saline (TBS) for 20 min. After antigen retrieval (5% citric acid, 30 min, 45°C), sections were preincubated in 10% normal horse serum (NHS) with 0.2% Triton X-100 in TBS (60 min). Sections were incubated overnight with IgG (4°C, 1:5000, biotinylated goat antirat IgG; Vector Labs, Burlingame, CA) antibody in 1% NHS in TBS. The following day, immunostaining was visualized using avidin–biotin enzyme complex (Vectastain ABC Standard Elite Kit; Vector Labs) for 1 h followed by 0.04% diaminobenzidine and 0.006% H₂O₂ in 0.1 M TBS for 10–20 min. Sections were dehydrated and coverslipped. Additional sections processed without primary antibody served as a negative control. Images were captured using an Olympus AX80 microscope (Olympus, Center Valley, PA) equipped with an integrated digital camera and image capture software. Final publication micrographs were adjusted to use the maximum range of levels in the red, green, and blue channels (Adobe Photoshop CS2, Adobe Systems Incorporated, San Jose, CA).

Neuronal nuclear volume estimation.

Design-based stereological estimates of neuronal nuclear volume were obtained bilaterally in the LVN of brain-injured and uninjured rats, approximately −10.7 mm through −11.2 mm from bregma, according to the Paxinos and Watson rat brain atlas (42). Briefly, for a neuron which is systematically sampled using the fractionator, a unique point, the nucleolus, is indicated by the user. Three parallel lines are randomly placed through the neuron for the user to indicate the intersections between the lines and the nuclear boundary. The software estimates and records nuclear volumes for each sampled neuron.

The LVN was identified on the basis of morphology and identifiable anatomical landmarks: the inferior cerebellar peduncle on the lateral edge and the vestibulocochlear nerve (VIII) on the inferior–lateral edge. All Giemsa-stained tissue sections from one set of slides containing the LVN were selected, yielding one to four sections per brain. A counting frame (80 μm × 120 μm) was used for sampling the LVN at predetermined regular x, y intervals (80 μm × 120-μm step size) (18). All neurons within the counting frame were subjected to nuclear volume estimation using the rotator probe (see below). Healthy neurons were distinguished from other objects such as astrocytes and microglia on the basis of the presence of a readily distinguishable nucleus and nucleolus within the cell in question, in accordance with criteria previously used in stereological studies to identify neurons (29,30). Unhealthy neurons (dystrophic or multiple nuclei and/or inconsistent nuclear membranes) were not quantified. All sampling was conducted using an Olympus BX-51 microscope (Olympus), with a 60×, 1.42 numerical aperture oil immersion objective, in conjunction with VisioPharm newCAST software (VisioPharm, Hørsholm, Denmark).

The nuclear volume of each sampled LVN neuron was measured with a semiautomated procedure using the new-CAST computer program. The rotator method estimates the volume of an arbitrary object by rotating it about an arbitrary axis through a unique point in the object, the nucleolus (23,50). The arbitrary vertical axis is aligned parallel to the y axis on the screen. When the neuronal nucleolus was in focus, the rotator was applied. The boundary points of the major axis of each nucleus are indicated by the user, and the program systematically creates uniformly random test lines perpendicular to the vertical axis. Intersections between the lines and the nuclear boundaries are marked by the user, and the volume is given in cubic micrometers. The mean nuclear volumes were compared using a Kruskal-Wallis (KW) ANOVA followed by Dunn multiple comparisons test. For each group, the entire sampled population was subjected to a histogram analysis across twenty 250-μm³ bins to determine the population shift in neuronal nucleus volume as a result of brain injury.

RESULTS

Fencing response in YouTube^™ knockout videos.

During an 11-month period, the online video database YouTube^™ was queried for videos associated with an impact to the head and a period of unconsciousness. Of the 35 videos that met the inclusion criteria (Materials and Methods), 66% (n = 23) showed a fencing response at the moment of impact (Fig. 1), regardless of the side of impact (Table 2). Moreover, the side of impact does not determine handedness of the fencing response, either ipsilateral or contralateral. However, the limited sample size may have diminished the ability to detect a significant interaction between the side of impact and the fencing response. Of those videos with a positive fencing response, the response duration ranged from 2 to 16 s with a mean duration of 6.3 ± 4.0 s. The fencing duration was based on the uploaded videos and likely subject to Internet speed and video compression software that could shift the time stamp or frame rate. None of the impacts in the videos resulted in immediate vomiting or convulsion.

FIGURE 1—

Incidence of the fencing response versus nonfencing responses in the compilation of YouTube^™ knockout videos.

TABLE 2.

Incidence of fencing by side of impact and response laterality.

	Left Arm Fencing	Both Arms Fencing	Right Arm Fencing	No Fencing	Total
Right side impact	4	1	1	2	8
Frontal impact	2	2	1	1	6
Left side impact	6	3	3	9	21
Total	12	6	5	12	35

Schematic line drawings were constructed on the basis of the posturing observed in the video clips to illustrate the fencing response (Fig. 2). The injured party receives a blow to the head (Fig. 2A). Unconscious, the person falls to the ground and one arm begins to extend as the other flexes (Fig. 2B). On the ground unconscious, the fencing response is sustained, despite gravity (Fig. 2C). A positive fencing response resembles the “en garde” position that initiates a fencing bout, with the extension of one arm and flexion of the other.

FIGURE 2—

Schematic illustrations of the fencing response during a knockout. A, The individual receives a punch to the head. B, After the traumatic blow to the head, the unconscious individual immediately exhibits extension in one arm and contralateral flexion while falling to the ground. C, During prostration, the rigidity of the extended and flexed arms is retained for several seconds as flaccidity gradually returns.

Severity-dependent fencing response in fluid percussion brain-injured rats.

FPI is scalable over mild and moderate severity on the basis of peak atmospheres (atm) of fluid pressure at the moment of injury (Fig. 3A). The duration of the suppression of the righting reflex increases with injury severity (Fig. 3B). Mild brain injury is empirically defined by an injury level of 1.13 ± 0.01 atm, which results in a righting reflex time of 3 min 16 s ± 29 s. Moderate brain injury is empirically defined by an injury level of 1.88 ± 0.02 atm, which results in a righting reflex time of 6 min 25 s ± 31 s. Mild brain-injured animals did not demonstrate a fencing response (0/19), whereas a fencing response predominated in moderate brain-injured animals (39/44; Fig. 3C). Uninjured sham animals have no injury level, righting reflex times of approximately 10 s, and no fencing response.

FIGURE 3—

In the rodent, the incidence of the fencing response is injury severity dependent. A, FPI is scalable between mild and moderate severity on the basis of injury atmospheres (atm). B, The duration of righting reflex suppression increases with injury severity. Uninjured sham animals have ~10-s righting reflex times. C, Mild brain-injured animals do not demonstrate a fencing response. In moderate brain-injured animals, the fencing response predominates.

Time-lapse images after moderate midline fluid percussion brain injury (Fig. 4) demonstrate that before the injury, the anesthetized animal’s forearms are flaccid and fall toward the ground (Fig. 4A). Animals were administered the brain injury (Fig. 4B) at a level of anesthesia when a positive withdrawal response to toe pinch was elicited. At the moment of impact, bilateral extension of both forelimbs gives way to a fencing response (Fig. 4C–F). Over the next second, the extension of the left limb and flexion of the right limb, coupled with the formation of “fists” in both paws, becomes visible (Fig. 4G–K). The rigidity of the response is sustained, and flaccidity gradually returns (Fig. 4L). Laterality of the fencing response in the rat was not recorded.

FIGURE 4—

Time-lapse images of the fencing response in the rat after fluid percussion brain injury. Anesthetized animals are hand-held in a right lateral recumbent position and attached to the injury device, at right (not shown). A, Before the injury, the animal’s forearms are flaccid and fall toward the ground. B, At 0.0 s, the brain injury is induced. C–K, The extension of the left limb and flexion of the right limb, coupled with the formation of “fists” in both paws, can be seen over the 0.2-s intervals. L, The rigidity of the response is sustained as flaccidity gradually returns.

Histopathology in the LVN.

The fencing response closely resembles the asymmetrical tonic neck reflex in human infants, suggesting that similar anatomical circuitry is involved, namely, the LVN (52). The LVN is adjacent medially to the inferior cerebellar peduncle at the terminus of the vestibulocochlear (VIII) nerve (Fig. 5A and B). Without gross histopathology in the brainstem (Fig. 5A, E, and I), the neurons of the LVN appear more heterogeneous in size and shape after moderate (Fig. 5B) and mild (Fig. 5F) brain injuries compared with uninjured sham (Fig. 5J). The mechanical forces of injury disrupt blood–brain barrier integrity at these anatomical foci as evidenced by an injury severity-dependent extravasation of IgG. Perivascular IgG in this region is evident after moderate brain injury (Fig. 5C and D) to less of an extent after mild brain injury (Fig. 5G and H) and absent in uninjured sham brain (Fig. 5K and L). Blood–brain barrier permeability was not restricted to the LVN, such that perivascular IgG extravasation could be found at multifoci sites throughout the brainstem.

FIGURE 5—

Brainstem histopathology after midline fluid percussion brain injury in the rat. A, E, and I, The proximity of the LVN to the inferior cerebellar peduncles (icp) and vestibulocochlear nerve (8vn) predicts axonal pathology from injury-related forces. In moderate brain-injured rats 15 min after injury, lateral vestibular neurons appear shrunken (B) and proximal to blood–brain barrier (BBB) disruption as indicated by IgG extravasation (C, D). In mild brain-injured rats, neurons display altered morphology (F) and BBB disruption (G, H). The lateral vestibular nuclei in sham animals have large motor neurons (J) and patent BBB (K, L). Scale bars, 50 μm.

The histological observations in the LVN after brain injury were quantified using the rotator procedure to estimate neuronal nucleus volumes (23). Measurements were pooled between animals and hemispheres to increase the size of the sampled population. By 10–15 min after injury, the mean nuclear volume for neurons in the LVN of moderate brain-injured animals (1274 ± 1465 μm³; n = 345) is significantly reduced in comparison to mild brain injury (1801 ± 1550 μm³; n = 271) and sham control (1506 ± 920 μm³; n = 123; Kruskal-Wallis ANOVA; KW [2,736] = 64.39). When the individual measurements form a population distribution histogram (Fig. 6), the redistribution toward smaller and larger neuronal nuclear volumes as a result of brain injury becomes evident. The larger proportions of smaller and larger volumes are more pronounced in the moderate brain injury group.

FIGURE 6—

Using the rotator, the volume of a three-dimensional object can be estimated in two-dimensional tissue sections. For each neuron identified within the sampling frame, the neuronal nuclear volume was estimated. Measurements were pooled within a group and binned into 20 size ranges. The percentage of nuclear volume measurements within each bin size is plotted for each group at 10–15 min after sham or brain injury. After mild and moderate brain injury, the nuclear size distribution shows a shift toward smaller volumes compared with the sham group. To provide a reference point, the mean nuclear volume for the sham group is indicated by the black vertical line in each graph.

DISCUSSION

The goal of this communication was to describe and validate an additional criterion that could improve the ability to rapidly and accurately indicate the forces associated with brain injury. The sustained rigid extension of one forearm and flexion of the opposite arm does occur immediately after brain injury and has been termed the “fencing response” because it mimics the “en garde” position that initiates a fencing bout. This response has historically been grouped with concussive convulsions (36) but likely represents a separate phenomenon. Using selective inclusion criteria, we observed a two-to-one bias in positive fencing responses in individuals knocked unconscious without convulsion. In our hands, experimental diffuse brain injury of moderate severity induces an immediate neuromuscular response that resembles the fencing response. Further investigation suggests that blood–brain barrier disruption, and neuronal shrinkage in the lateral vestibular nucleus (LVN) of the brainstem may mediate the fencing response. By implementing the fencing response as an acute sign of TBI, diagnosis and treatment can be improved.

The incidence of the fencing response was evaluated by identifying videos within the public domain that met the inclusion criteria of unconsciousness and adequate video content for observation. The small sample size is primarily because of the voluntary sharing of videos and the capricious nature of applying keywords. Regardless, a positive fencing response was evident in two thirds of the identified videos. Because of the grouping of tonic posturing with concussive convulsion, the incidence has been reported in the range of 25%–75% of concussions (36–38), with tonic posturing of 2–30 s observed in 25 of 75 concussion cases with a loss of consciousness (37). The sustained fencing response (2–16 s) would permit an on-field or bystander observation, providing information beneficial to directing patient care. The predominance of sports-related videos (31/35) biases the results toward a left-sided impact from a right-handed or right-footed athlete. However, no direct correlation could be drawn about the laterality of the response, obscuring whether the fencing response is an ipsilateral or contralateral phenomenon resulting from the coup or contracoup injury. The prevalence of the fencing response among all TBI remains obscured within the biased pool of videos yet may include at least half of all TBI resulting in unconsciousness. Even still, the presence of the fencing response is overt and sustained, such that its utility in assessing the magnitude of force associated with the injury remains valid. The fencing response may help stratify brain injuries that result in unconsciousness between mild and moderate severity.

Concussive convulsions, including both tonic posturing and myoclonic jerking, were initially explored as a risk factor for late-onset epilepsy (38). In the original retrospective studies, brain injuries comorbid with a concussive convulsion did not present structural, electroencephalographic, or neuropsychological signs or symptoms that were significantly different from patients without convulsion (36,38). The review of case reports was limited to contemporary standards of care, for which details were not provided, and precludes a reevaluation of the results. On the basis of these descriptions (37,38), concussion consensus statements have come to indicate that, although dramatic, concussive convulsions are benign and require no special treatment (2,3,5,19,35). However, the loss of consciousness reported as 10–300 s indicates a potentially moderate to severe concussion using standard injury scales, this but cannot be verified without the duration of posttraumatic amnesia. The historical interpretation of concussive convulsion has neglected its use in determining injury severity (5,36–38). The present data indicate that the fencing response (tonic posturing alone) is elicited by mechanical forces of moderate magnitude imparted on the midbrain. Convulsive phenomena were absent in the 35 videos that met the inclusion criteria and the brain-injured animals. In our preclinical experience, myoclonic jerking is only associated with a dural tear at the cortical injury site, which results in herniation likely due to rising intracranial pressure (data not shown). Therefore, we contend that the tonic posturing associated with concussive convulsions warrants a distinct terminology, the fencing response, to serve as a visible indicator of injury force magnitude.

Posttraumatic unconsciousness depends on the plane of rotational acceleration, with respect to the orientation of the brainstem (15,48). By the very nature of the videos available online, a determination of the direction or magnitude of forces was not possible, but all are likely associated with sufficient rotational forces to induce unconsciousness. In the laboratory, injury severity was directly manipulated to demonstrate that the fencing response is injury severity-dependent. The longer durations of righting reflex suppression in moderate brain-injured animals is supported by the strong correlation between loss of consciousness and concussive convulsions in athletes (37). Milder injuries result in shorter periods of righting reflex suppression, without a fencing response. More severe injuries were not attempted as they typically result in death from pulmonary edema. Undoubtedly, a loss of consciousness signifies underlying pathology in neurons, glia, and/or the vasculature (14,45). However, the fencing response, or any single parameter including loss of consciousness, does not necessarily imply severity of injury (5). The signs and symptoms observed at the moment of injury contribute to the overall determination of injury severity and course of treatment. Yet, the presence of a fencing response likely indicates a complex concussion, with or without convulsion (3).

The acute clinical symptoms of concussive convulsion have been attributed to a complex pathway of transient functional decerebration that releases brainstem activity (36), reflecting a functional disturbance rather than gross structural injury (5,19,37). Speculation on the mechanism has included a mismatch in metabolic supply and demand resulting in cell dysfunction, which would establish vulnerability to subsequent insults (2,17). However, the altered neurophysiology likely arises from microscopic injury to neurons, glia, and blood vessels in brain regions susceptible to mechanical injury. The mechanical forces would impart compressive, tensile, and/or shearing stresses on vulnerable brain regions, such as gray–white matter interfaces and nerves exiting the CNS (27). The mechanical forces likely permeabilize plasma membranes (11,43), disrupt the blood–brain barrier, redistribute ions across the neurovascular unit that transiently activate neuronal circuits, and result in osmotic shrinkage of neurons. This midbrain neurochemical storm would activate motor neurons to elicit the fencing response, without a cortical contribution. Neurovascular compromise may exacerbate the injury and establish susceptibility to secondary insults or subsequent traumatic events. In this way, the fencing response can provide an indication of the magnitude and localization of mechanical forces from the trauma.

The neuromotor manifestation of the fencing response resembles reflexes initiated by vestibular stimuli. Vestibular stimuli activate primitive reflexes in human infants, which are likely mediated by vestibular nuclei in the brainstem, such as asymmetrical tonic neck reflex, Moro reflex, and parachute reflexes (31). In adults, stumbling can activate vestibulospinal reflexes that provoke arm movement toward the direction of the fall. To maintain postural control, the cerebellum and dorsal raphe control LVN (Deiters nucleus) activity with tonic GABAergic inhibition and serotoninergic modulation, respectively (28,32). The LVN itself has descending efferent fibers in the vestibulocochlear nerve distributed to the motor nuclei of the anterior column and exerts an excitatory influence on ipsilateral limb extensor motoneurons and suppresses flexor motoneurons. The anatomical location of the LVN, adjacent to the cerebellar peduncles, suggests that mechanical forces to the head may stretch the cerebellar peduncles and activate the LVN. LVN activity would manifest as limb extensor activation and flexor inhibition, defined as a fencing response. Flexion of the opposite limb is likely mediated by crossed inhibition, necessary for pattern generation (33). In addition, the fencing response may resemble posturing responses associated with other conditions, such as forebrain or cerebellar seizure activity (1,39).

Brain injury severity may reflect directly the extent of axonal injury within the brainstem (47). In the rodent, moderate diffuse brain injury that elicits a fencing response tears blood vessels as demonstrated by IgG extravasation in the LVN and across the brainstem (45). Moreover, the ionic redistribution, likely resulting from plasma membrane permeability (11), could initiate action potentials and shift neuronal nuclear volumes through osmotic swelling and shrinkage. Similar chronic changes in diffuse vascular injury and neuronal atrophy have been observed in the cerebrum (24,29).

Presently, no neuroanatomical or physiological measurements can be used to determine the severity of a concussion or when complete recovery has occurred (5). Advanced imaging techniques, such as computed tomography or magnetic resonance imaging, are necessary to detect or rule out macroscopic lesions such as intracranial bleeding, cerebral edema, or diffuse axonal injury (5,35). However, these techniques may lack the sensitivity to detect the functional disturbance and microscopic damage associated with the diffuse brain injury (40). The present communication provides pathophysiological mechanisms, including blood–brain barrier disruption and acute neuronal atrophy in the brainstem, which likely mediate the transient dysfunction necessary to elicit the fencing response. Future studies may be able to identify specific midbrain regions and mechanisms of injury that underlie both the fencing response and convulsions.

The fencing response can be incorporated into the battery of on-field indicators of TBI as an acute sign of injury force magnitude (8). Incorporating the fencing response as a diagnostic criterion would not preclude sideline neurologic assessment or mental status testing after a long series of continued refinement of the grading scales for TBI and concussion (5). Coupled with loss of consciousness (the period unresponsive to external stimuli), the fencing response may advance the triage and treatment of the brain-injured population. Together, these signs may become predictive of symptomatic, neurocognitive, or neurologic sequelae of TBI. The compilation and duration of the post-concussion symptoms weigh heavily in defining injury severity (2). These indicators are born out of others’ work and ours with experimental models of traumatic brain injury that focus on acute neurological reflexes to indicate brain injury severity (46). It is recommended that concussion severity should only be determined after signs and symptoms have cleared and the results of neurological, neuropsychological, or cognitive examination return to normal (2,3,5,19,35).

Earlier, more sensitive methods of identifying and categorizing degrees of brain injury have the potential to better predict outcome, and thus guide clinical management (20). The fencing response provides a simple observation, rather than invasive or specialist techniques, to rapidly and definitively grade head injury severity. The predictive values of serum markers, such as S-100B or calpain activation, are less reliable in mild brain injury and require extensive collection and processing time before contributing meaningfully to patient diagnosis or treatment (4,25). Similarly, neuropsychological testing to discriminate mild from moderate TBI may exceed the time frame for rapid return-to-play decisions or treatment options. Mechanical forces of sufficient magnitude on the midbrain to elicit a fencing response warrant significant caution in guiding return to play. This approach may be conservative but is likely to minimize any long-term neuropsychological effects of the initial or subsequent concussions.

Traumatic brain injury (TBI) is heterogeneous, both in its induction and ensuing neurological sequelae. A visible sign or symptom, such as vomiting, convulsion, or the fencing response, can provide objective criteria for an athletic trainer to justify decisions regarding return to play (2,3,5,19,35). The fencing response provides an objective measure of the magnitude of injury-related forces to be used in the identification and classification of concussion. We provide a scientific foundation for the injury severity dependence and anatomical origin of the fencing response. By no means is a TBI without a fencing response too trivial to neglect; the mild TBI must be treated with the same gravity as more severe brain injuries. Regardless of the anatomical nature or the specific forces involved, the fencing response can be immediately implemented as a diagnostic tool in the management of TBI.