Review Article

https://doi.org/10.12965/jer.2244146.073 Journal of Exercise Rehabilitation 2022;18(3):142-154

A brief descriptive outline of the rules of mixed martial

arts and concussion in mixed martial arts
Jessica L. Hamdan, Meghan Rath, Jacqueline Sayoc, Joon-Young Park*
Department of Kinesiology, College of Public Health; Cardiovascular Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

Mixed martial arts (MMA), a combat sport consisting of wrestling, box- were to outline (a) the rules of MMA; (b) the postconcussion protocol
ing, and martial arts, is a popular activity associated with danger and vi- for UFC athletes; (c) current behavioral and biochemical diagnostic
olence. Of concern are the repetitive head impacts, both subconcussive measures; (d) epidemiology and prevalence of concussion in MMA; (e)
and concussive, sustained by MMA athletes. The rules of MMA en- long-term effects of subconcussive repetitive head impacts; (f) biome-
courage head strikes, but there was no formal concussion protocol in chanics of head impacts; and (g) considerations and research topics
the Ultimate Fighting Championship (UFC) until 2021. Because the UFC that warrant future research.
was established less than 30 years, the long-term consequences of
these repetitive concussive head blows are lacking. In this review, we Keywords: Mixed martial arts, Concussion, Mild traumatic brain injury,
focus on current literature sought to summarize the current knowledge Chronic traumatic encephalopathy, Repetitive subconcussive head im-
of repetitive head impacts and concussions in MMA. The objectives pacts

INTRODUCTION concussions sustained by the athletes.

In the U.S., the UFC and MMA came under fire in the early
Mixed martial arts (MMA) can be traced back to 648 B.C.E. in years for being so dangerous. Because of this, the Unified Rules of
ancient Greece where it was called pankration, a combat sport MMA were established in 2001. Even though rules are in place,
consisting of wrestling, boxing, and street fighting. After pankra- one of the main objectives of MMA is to give the opponent a con-
tion was banned in 393 C.E., this sport did not resurface until the cussion via knockout. Head injuries are encouraged in MMA, but
20th century in Brazil where it was called “vale tudo” or “anything the UFC did not release its first concussion protocol until 2021.
goes” (https://www.britannica.com/sports/mixed-martial-arts). This raises the question of whether the true prevalence of concus-
MMA made its mark in 1993 during a competition called the sions is known within MMA. Many studies have attempted to de-
Ultimate Fighting Championship (UFC) in the United States termine the prevalence of concussions in MMA, with variable
(U.S.). MMA then became known as a no-holds-barred combat ranges of 8.3% to 62.3% (Curran-Sills and Abedin, 2018; Fares
sport, meaning that anything other than biting or eye-gouging et al., 2021; Ji, 2016; Karpman et al., 2016). Regardless of the
was fair game. As the top promoter for MMA, the UFC has turned large variation, concussion rates are still much higher than those
MMA into the fastest-growing sport in the world. Since its incep- cited in the National Football League (NFL). The average concus-
tion, the UFC has grown exponentially with an estimated net sion rate among NFL players over a 5-year period from 2015 to
worth of approximately $10 billion. Because of the popularity and 2019 was 7.4% (Mack et al., 2021).
growth of the UFC and MMA, it is more crucial than ever to bet- There has yet to be written a comprehensive review of the liter-
ter understand the effects of repetitive head impacts (RHIs) and ature, to our best knowledge, relating to RHIs and concussions in

*Corresponding author: Joon-Young Park https://orcid.org/0000-0002-7705-7086 This is an Open Access article distributed under the terms of the Creative Commons At-
Department of Kinesiology, College of Public Health; Cardiovascular Research tribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/)
Center, Lewis Katz School of Medicine, Temple University, 3500 N. Broad Street, which permits unrestricted non-commercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Philadelphia, PA 19140, USA
Email: parkjy@temple.edu
Received: March 19, 2022 / Accepted: April 8, 2022
Copyright © 2022 Korean Society of Exercise Rehabilitation 142 https://www.e-jer.org pISSN 2288-176X
eISSN 2288-1778
Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

Table 1. Sport-related concussion (SRC) described in the Unified Rules of MMA. The scenarios in which
According to McCrory et al. (2017), a sport-related concussion is a mild traumatic an athlete wins a fight include the following: technical submission
brain injury that can be characterized by the following features: (when a submission results in unconsciousness), technical knock-
• Caused by biomechanical forces transferred to the head following a blow to out (TKO) by referee stoppage (when an athlete is not intelligent-
the body, which may or may not result in loss of consciousness.
• Signs and symptoms typically occur quickly or may develop minutes to hours
ly defending themselves, e.g., physical exhaustion), TKO by med-
following SRC. ical stoppage (includes when an athlete loses control of bodily
• Signs and symptoms vary and typically resolve progressively, but they may be function), and knockout (KO; when the referee stops a game be-
prolonged. cause an athlete cannot intelligently defend themselves because
• May result in neurological dysfunction that shows up as normal on structural

neuroimaging.
they are unconscious). These decisions encourage strikes to the
head, which can result in repetitive, subconcussive, or concussive
head impacts, and eventually cause chronic traumatic encephalop-
MMA athletes. Therefore, the objectives of this literature review athy (CTE).
were to outline (a) the rules of MMA; (b) the postconcussion pro- A brief overview of the postconcussion protocol can be found in
tocol for UFC athletes; (c) diagnostic measures; (d) epidemiology Table 3, and the full concussion protocol can be found in the UFC
and prevalence of concussion in MMA; (e) long-term effects of Performance Institute’s 2021 volume of research (https://ufc-pi.
subconcussive RHIs; (f) biomechanics of head impacts; and (g) fu- webflow.io/). Following a fight, MMA athletes with suspected
ture considerations and research topics needed moving forward. concussions should be assessed by a medical professional (McCrory
Although mild traumatic brain injury (mTBI) and concussion are et al., 2017). Concussion evaluation should include a detailed con-
often used interchangeably, operational definitions vary across the cussion history, presence of clinical symptoms and physical signs,
literature (Greenwald et al., 2012; McCrory et al., 2017). For the and neurocognitive testing such as the Sport Concussion Assess-
sake of consistency, we will be using the term ‘concussion’ through- ment Tool-5 (SCAT5) (McCrory et al., 2017). The UFC concus-
out this paper. The definition of ‘sport-related concussion’ is sum- sion protocol states that athletes should be managed by a health-
marized in Table 1. care provider to ensure proper completion of each progression
stage, and if at any point in the protocol athletes experience symp-
SUMMARY toms, they must rest and be symptom-free for at least 24 hr before
returning to the stage prior to when symptoms arose.
Rules of MMA As described above, the postconcussion protocol is fairly com-
After a public outcry over the danger of the sport, the UFC ad- prehensive, sequential, and detailed; however, it is only the first
opted new rules for the safety of the athletes in 2001. The Associ- official concussion protocol of the UFC, and there is room for im-
ation of Boxing Commissions and Combative Sports created the provement. During stage one, the protocol requires athletes to go
Unified Rules of Mixed Martial Arts in 2001. Since then, the rules to the hospital if they experience ‘red-flag’ symptoms, but the red-
have been amended several times, most recently in 2019 (https:// flag symptoms are not listed on the protocol itself. It is recom-
www.abcboxing.com/wp-content/uploads/2020/02/unified-rules- mended that the red-flag symptoms are detailed, so athletes can
mma-2019.pdf). The Unified Rules of MMA state that a fight accurately identify them.
must consist of 5-minute rounds and a 1-minute rest between
rounds with no more than five rounds total. All athletes are re- Current status of diagnostic measures of concussions
quired to wear a mouthguard during the game, thus the referee Elucidating the underlying mechanisms of head impacts that
will call ‘time’ if the mouthguard becomes dislodged and needs to occur during MMA fights may be helpful to diagnose concussions
be replaced. Originally, MMA only prohibited biting and eye- (Karton and Hoshizaki, 2018). Concussions are difficult to diag-
gouging; however, the Association of Boxing Commissions and nose because diagnoses are subjective in nature and rely on infor-
Combative Sports added additional fouls to the Unified Rules of mation obtained regarding signs and symptom severity, concus-
MMA, which are delineated in Table 2. sion history, and neurocognitive and behavioral testing (Jackson
Despite the rules in place, one of the main objectives of a fight and Starling, 2019; McCrory et al., 2017); however, researchers
is to knock the opponent unconscious. This is demonstrated by are exploring new ways to potentially diagnose concussions. The
the types of decisions that determine the outcome of a fight, as objective of this section is to evaluate current neurocognitive and

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

Table 2. Fouls as outlined in the unified rules of mixed martial arts

Fouls Description
Head-butting The head may not be used to strike the opponent.
Eye-gouging Eye-gouging using fingers, chin, or elbow is illegal. Legal strikes or punches to the eye socket are not considered eye-gouging.
Biting or spitting at an opponent Biting or spitting in any form is illegal.
Fish-hooking An athlete may not use their fingers to stretch the skin of their opponent’s mouth, nose, or ears. Fish-hooking usually involves an
athlete placing their fingers into the mouth of the opponent and pulling their hands in opposite directions.
Hair-pulling Hair-pulling in any fashion is illegal. An athlete may not grab a hold of their opponent's hair. If an athlete has long hair, they may
not use their hair as a tool for holding or choking their opponent.
Spiking the opponent to the floor onto the A pile-driver occurs when an athlete holds the opponent with their feet in the air and head straight down and then forcibly drives
head or neck (pile-driving) the opponent’s head into the floor.
Strikes to the spine or back of the head The back of the head starts at the crown of the head with a one-inch variance to either side, running down the back of the head
to the occipital junction. This area stretches out at the occipital junction (nape of the neck) to cover the entire width of the
neck. It then travels down the spine with a one-inch variance from the spine's centerline, including the tailbone.
Throat strikes of any kind and/or grabbing No directed throat strikes are allowed, including an athlete pulling his opponent's head in a way to open the neck area for a
the trachea striking attack. An athlete may not gouge their fingers or thumb into their opponent's neck or trachea in an attempt to submit
their opponent.
Fingers outstretched toward an opponent’s An athlete may not move their arm(s) toward their opponent with an open hand, fingers pointing at the opponent's face/eyes.
face/eyes
Downward pointing elbow strike (12 to 6) The use of a linear ‘straight up, straight down’ elbow strike is prohibited.
Groin attacks of any kind Any attack to the groin area including striking, grabbing, pinching, or twisting is illegal for both men and women.
Kneeling and/or kicking the head of a A grounded athlete is defined as any part of the body, other than a single hand and soles of the feet, touching the floor. At this
grounded opponent time, kicks or knees to the head will not be allowed.
Stomping of a grounded opponent Stomping is when the athlete lifts their leg by bending at the knee and initiates a striking action with the bottom of their foot or
heel.
Small joint manipulation Fingers and toes are considered small joints. Grabbing the majority of fingers or toes at once is allowed.
Throwing an opponent out of the ring or An athlete shall not throw their opponent out of the ring or cage.
cage area
Intentionally placing a finger into any An athlete may not place their fingers into an open laceration in an attempt to enlarge the cut. An athlete may not place their
orifice or laceration of your opponent fingers into an opponent's nose, ears, mouth, or body cavity.
Clawing, pinching, and twisting the flesh Any attack that targets the athlete's skin by clawing at the skin or attempting to pull or twist the skin to apply pain is illegal.
Unsportsmanlike conduct that causes an Any athlete that disrespects the rules of the sport or attempts to inflict unnecessary harm on an opponent who has been either
injury to the opponent taken out of the competition by the referee or has tapped out of the competition shall be viewed as being unsportsmanlike.
Attacking an opponent after the bell has The end of a round is signified by the sound of the bell and the call of time by the referee. Once the referee has made the call of
sounded time, any offensive actions initiated by the athlete shall be considered after the bell and illegal.
Attacking an opponent during the break An athlete shall not engage their opponent in any fashion during a time-out or break of action in competition.
Attacking an opponent who is under the Once the referee has called for a stop of the action to protect an athlete who has been incapacitated or is unable to continue to
care of the referee compete in the fight, an athlete must cease all offensive actions against their opponent.

behavioral assessments that assist in concussion diagnosis, as well multiple components, including the background of the athlete,
as explore novel diagnostic techniques such as imaging and bio- symptom checklist, the Standardized Assessment of Concussion
marker analysis. (SAC), neurological screen, and delayed recall (McCrory et al.,
2017; Putukian and Schepart, 2018; Sport concussion assessment tool,
Neurocognitive and behavioral testing 2017).
Following a head impact, athletes with a suspected concussion The symptom checklist is useful in tracking symptoms over
must be properly assessed using neurocognitive and behavioral time, especially with recovery, as symptom resolution is necessary
testing (McCrory et al., 2017). The SCAT5 is a commonly used for athletes when completing the UFC concussion protocol and
standardized assessment tool, which can help with concussion rec- prior to returning to play (McCrory et al., 2017; Putukian and
ognition; however, it should not be solely used to diagnose or rule Schepart, 2018). The SAC is useful in testing orientation, imme-
out a concussion (McCrory et al., 2017; Putukian and Schepart, diate memory, concentration, and delayed memory in order to as-
2018; Sport concussion assessment tool, 2017). The SCAT5 consists of sess neurocognitive function following injury (Putukian and Schep-

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

Table 3. Postconcussion protocol for Ultimate Fighting Championship athletes trauma during the fight saw a significantly worse change in score
Stage 1: Initial recovery from pre- to postfight (Galetta et al., 2011). Among those who
• 24 to 48 hr of physical and mental rest suffered from head trauma, athletes who lost consciousness had
• Monitor symptoms
higher postfight scores than those who did not lose consciousness
• Allowed to sleep and take Acetaminophen
(Galetta et al., 2011). Athletes who did not sustain head trauma
For each following stage:
during their fight showed high test-retest reliability between the
• Check symptom score daily with concussion assessment tool

• Physical therapy (if needed)

pre- and postfight scores, with an intraclass correlation coefficient
• Post-exercise symptom check and progress to next stage if symptom-free
of 0.95 (95% confidence interval [CI], 0.87–1.0) (Galetta et al.,
Stage 2: No contact I 2011). These results suggest that the King-Devick test is an accu-
Stage 2.1: Low intensity aerobic training rate and reliable measure of head trauma and concussions among
Stage 2.2: Moderate intensity aerobic training MMA athletes and boxers (Galetta et al., 2011).
Stage 2.3: Low intensity technical training
Stage 3: No contact II Neuroimaging
Stage 3.1: Low intensity strength training
Concussions are functional impairments of the brain, not struc-
Stage 3.2: Moderate intensity strength training
tural injuries, meaning that brains suffering from these conditions
Stage 3.3: Low to moderate intensity technical training
Stage 4: Moderate contact
show up normally on neuroimaging (McCrory et al., 2017; Suri
Stage 4.1: Moderate to high intensity interval training and Lipton, 2018). However, there have been great strides to uti-
Stage 4.2: High intensity strength training lize advanced imaging techniques to view the microstructural and
Stage 5: Return to Full Contact functional impairments of the brain following mTBI (McCrory et
• Medical clearance from physician needed before being cleared to return al., 2017; Suri and Lipton, 2018). Computed tomography (CT)
to contact
and magnetic resonance imaging (MRI) are conventional imaging
• Strength and conditioning program to resume as normal
techniques that can be used to rule out moderate to severe TBI,
Stage 5.1: Moderate intensity technical training and low intensity live work
Stage 5.2: High intensity technical training and moderate intensity live work
which may be characterized by intracranial bleeding, contusion,
Stage 5.3: Return to sparring edema, and fracture (Suri and Lipton, 2018).
Barring the presence of any characteristics of moderate to severe
TBI, neuroimaging results will be normal for those suffering from
art, 2018; Sport concussion assessment tool, 2017). The neurological a concussion (McCrory et al., 2017; Suri and Lipton, 2018). This
screen assesses an athlete’s ability to read and follow instructions, may prompt the use of advanced imaging to determine the pres-
passively move their cervical spine without pain, look up-and- ence of concussion. One such technique is diffusion tensor imag-
down and side-to-side without double vision, touch their finger ing (DTI), a specific type of MRI (Suri and Lipton, 2018). DTI
to their nose, walk with a tandem gait, and perform the modified has been found to distinguish between individuals with concus-
Balance Error Scoring System (BESS) test (Putukian and Schepart, sion from healthy controls, making this a viable imaging tech-
2018; Sport concussion assessment tool, 2017). nique in the diagnosis of concussion (Hulkower et al., 2013; Suri
The King-Devick test is another neurocognitive test useful in and Lipton, 2018). A study found that the number of knockouts
concussion diagnosis, and it assesses eye movement, attention, and in MMA athletes correlated with decreased fractional anisotropy
language (Putukian and Schepart, 2018). Boxers and MMA ath- in the posterior corpus callosum and increased transversal diffusiv-
letes were assessed using the King-Devick test pre- and postfight ity in the posterior cingulate using DTI, both of which have been
(Galetta et al., 2011). Statistical analyses were performed to com- found in individuals with concussion compared to healthy con-
pare participants who sustained head trauma during the fight to trols (Shin et al., 2014).
those who did not sustain head trauma on differences in postfight Resting-state functional MRI (rs-fMRI) has also shown promise
scores and to compare changes in scores from pre- to postfight as an imaging technique that can be used to diagnose concussions
(Galetta et al., 2011). Results showed that athletes who suffered (Suri and Lipton, 2018; Zhu et al., 2015). Because conventional
head trauma during the fight performed significantly worse on imaging techniques do not find structural damage to the brain
the postfight King-Devick test compared to those without head following concussion, the rs-fMRI can be used to detect the dis-
trauma (Galetta et al., 2011). Athletes who suffered from head ruption of functional connectivity of the default-mode network

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

(DMN), which is a potential sign of concussion (Zhu et al., 2015). fight (Neselius et al., 2012). NfL is the most abundant neurofila-
Concussed collegiate football players were sign and symptom-free ment and key structural component of axons, while tau is a mi-
6.0 ± 2.4 days following injury; however, within 24 hr of injury, crotubule stabilizing protein. Both are believed to increase in the
rs-fMRI showed high functional connectivity of the DMN, but CSF and blood following concussion (Zetterberg et al., 2006).
was significantly impaired 7 days postinjury and was not fully re- Previous findings suggest plasma NfL concentrations significantly
covered 30 days later (Suri and Lipton, 2018; Zhu et al., 2015). increase from baseline to 24–48 hr postinjury among contact
Compared to the healthy control subjects, functional connectivity sport athletes diagnosed with concussion (Asken et al., 2020).
of the DMN in the concussed athletes was 14.5% higher on day 1, Among athletes with more severe concussions, as determined by
41.4% lower on day 7, and 15% lower on day 30. Because of the loss of consciousness (LOC) or postinjury amnesia, plasma NfL
comparison to healthy control subjects who showed no significant concentrations followed an upward trajectory and remained ele-
difference across the 3 time points, this study showed evidence vated even after medical clearance to return-to-play compared to
that rs-fMRI has utility as a diagnostic imaging technique (Zhu athletes with less severe concussions (without LOC or postinjury
et al., 2015). Additional imaging techniques that show promise amnesia) and athlete controls (McCrea et al., 2020).
in the diagnosis of concussions include magnetic resonance spec- Recently, NfL and tau were detected in the blood of profession-
troscopy (MRS), arterial spin labeling, magnetoencephalography, al and retired athletes (Bernick et al., 2018). Professional, active
single-photon emission CT, and positron emission tomography athletes included boxers and MMA athletes, while retired athletes
(PET) (Suri and Lipton, 2018). included only boxers. Among all MMA athletes and control group,
MMA athletes experienced a significant increase in plasma tau
Biomarkers concentrations between measurements approximately 1 to 2 years
Candidate biomarkers for use as diagnostic tools to assess con- apart, which was not observed with the active boxers. Baseline
cussion have emerged in recent years. Although many potential concentrations of NfL among athletes were elevated in active box-
biomarkers have been investigated, the main proteins that are ers compared to MMA athletes and retired boxers. This evidence
currently identifiable in the peripheral circulation and have re- is the first to compare blood-based biomarkers between different
mained highly regarded as top candidates include amyloid beta style athletes and the effect of repetitive impacts on plasma con-
42 peptide (Aβ42) (Asken et al., 2018), neuron-specific enolase centrations over time. These findings suggest that MMA athletes
(Thelin et al., 2019), neurogranin (Çevik et al., 2019), and phos- experience a different physiological response, as shown by differ-
phorylated tau at threonine 181 (Sjögren et al., 2001). Although ing tau and NfL longitudinal changes in plasma concentrations,
well studied, S100 calcium-binding protein B (Thelin et al., 2019) from boxers. Additionally, MMA athletes may experience differ-
is influenced by exercise and consequently has become less desir- ences in baseline concentrations of tau compared to contact sport
able as a potential biomarker for concussion. athletes. The largest study to date, with over 200 athletes diag-
Other candidate biomarkers include inflammatory cytokines nosed with concussion, found plasma tau concentration rapidly
(Peltz et al., 2020) such as interleukin 6 or interleukin 10, and decreases and is significantly lower than healthy athletes 24–48 hr
damage-associated molecular patterns (Corps et al., 2015). With after injury, despite an initial increase within the first 4–16 hr fol-
advancements in scientific technology, tau, glial fibrillary acidic lowing concussion (McCrea et al., 2020).
protein (GFAP), ubiquitin carboxyl hydrolase L1 (UCH-L1), neu- As recently as 2018, two known brain-specific proteins were
rofilament light chain peptides (NfL), and other brain-specific approved by the U.S. Food and Drug Administration for use in
markers can be quantified in the blood through single-molecule Emergency Department (ED) settings to determine if patients ad-
array technologies, which have also been termed digital enzyme- mitted to the ED needed a CT scan to examine cerebral lesions or
linked immunosorbent assay (ELISA) due to the greater sensitivi- not (Gill et al., 2018; Welch et al., 2016). GFAP and UCH-L1
ty and automation compared to traditional ELISA methods. were shown to discriminate patients with normal and abnormal
Many studies investigating the effect of concussion on candi- CT scans postconcussion. Although approved in this context, evi-
date biomarkers have included contact sport athletes, rather than dence regarding the use of GFAP and UCH-L1 for diagnostic
professional athletes. Early biomarker research investigated tau tools in the identification of athletes suffering from concussion has
and NfL as potential biomarkers for axonal injury or disease using been equivocal. GFAP is a cytoskeletal protein found predomi-
the cerebrospinal fluid (CSF) collected from boxers following a nantly in glial cells, most notably astrocytes. Concentrations of

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

GFAP detected in the blood have been significantly elevated hours cussion and returns to near baseline levels after 24–48 hr (Asken
and days after concussion among contact sport athletes. Addition- et al., 2020; McCrea et al., 2020). As promising as these biomark-
ally, circulating levels of GFAP were significantly high among ers may be, GFAP and UCH-L1 have not yet been studied in
athletes with an acute concussion than at baseline (Asken et al., MMA athletes.
2020; McCrea et al., 2020).
First investigated in patients with severe TBI, UCH-L1 signifi- LITERATURE REVIEW
cantly increases in the CSF and serum within the first 24 hr of in-
jury, followed by a rapid decline over the following 7 days. UCH-L1 Epidemiology/prevalence of sport-related concussion in
is predominantly expressed in the neuronal soma and has been MMA
shown to be released into the CSF after TBI (Mondello et al., 2012). Many studies have examined the incidence of head strikes and
More recent studies have found that UCH-L1 is significantly concussion relationships in MMA; however, the literature reports
higher within the first 24 hr of injury among athletes with con- significantly varying rates of concussions (Table 4). One study

Table 4. Prevalence of injuries and concussions in mixed martial arts athletes

Study Subjects Methods Outcomes
Ngai et al. (2008) 635 MMA matches in Nevada Retrospective cohort study analyzing 1,270 Fight exposures occurred across all matches. 23.6% (n= 300) of fight
with no data on sex of athletes. data from MMA fights between exposures resulted in injury. Out of 635 matches, 3.3% ended by KO,
2002 and 2007. resulting in a severe concussion.
Rainey (2009) 55 MMA athletes (n= 3 women) Data was collected retrospectively 38.2% of injuries occurred in the head, face, and neck region; however,
in Missouri, Kansas, and Illinois. from questionnaires. concussions accounted for only 1.8% of injuries.
Hutchison et al. 844 MMA matches involving Descriptive epidemiology study. 12.8% (n= 108) of matches ended by a KO, with an incidence rate of 6.4
(2014) 508 athletes (n= 0 women). Competition data and video records per 100 AEs. 21.2% (n= 179) of matches ended by TKO, with 89.9%
of UFC MMA matches between ending after repetitive strikes to the head. The incidence rate of TKOs
2006 and 2012 were analyzed. due to repetitive head strikes was 9.5 per 100 AEs.
Ji (2016) 455 MMA athletes in South Convenience sampling method used. 14.2% (118/831) injuries were to the head. 20.8% (179/860) of diagnosed
Korea (n= 17 women). Data was collected via injuries were concussions.
questionnaires between June 3,
2015, and November 6, 2015.
Karpman et al. 1,181 MMA athletes (n= 12 Data collected from postfight medical 8.3% (n= 98) of MMA athletes were diagnosed with a concussion. Only
(2016) women) and 550 boxers (n= 57 examinations between 2000 and 4.2% (n= 50) lost consciousness.
women) in Canada. 2013.
Curran-Sills and 343 Bouts with 686 MMA Retrospective cohort study analyzing The total injury rate per 100 AE was 23.6, and the concussion injury rate
Abedin (2018) athletes (n= 24 women) in official records of MMA matches per 100 AE was 14.7. Concussions were the most common injury,
Calgary, Canada. between 2010 and 2015. representing 62.3% (n= 101) of all injuries.
Fares et al. (2019) 285 UFC MMA matches with Descriptive epidemiological study 291 Injuries occurred across all matches. Head injuries (including
36 female athletes. analyzing match scorecards and concussions, fractures, and lacerations) consisted of 66% (193) of
medical records in Nevada between injuries, with a head injury rate of 34 per 100 AE. Concussions
2016 and 2018. represented 32.3% (94/291) of all injuries.
Fares et al. (2021) 816 MMA athletes Descriptive epidemiological study of Head injury rate was 35 injuries per 100 AE, with 65% of injuries
(n= 106 women) in the U.S. 408 matches. Data was collected via (288/445 injuries) occurring to the head. 45% (130/288) of head injuries
medical records from fights starting were concussions, resulting in 29.2% (130/445) of injuries being
in 2016 and ending in December concussions.
2019.
Bernick et al. 60 MMA athletes (n= 0 women) Retrospective video analysis by four The mean number of concussions per minute of fight time for MMA was
(2021) and 60 boxers (n= 0 women) in physicians and four nonphysicians. 0.085, with the winner sustaining a mean number of concussions of
the U.S. 30 MMA fights in the UFC and 30 0.011/minute and the loser sustaining 0.159 concussions/minute.
boxing fights in the Premier Boxing
Champions.
Ross et al. (2021) 503 MMA matches in Arizona Descriptive epidemiology study 38% (n= 189) of matches ended in TKO or KO. 15.7% of injuries among
and Wisconsin with no data on analyzing postfight injury reports amateur athletes were concussions, while 8.6% of injuries among
sex of athletes. from MMA matches between 2018 professional athletes were concussions. 1.5% of winners sustained a
and 2019. concussion compared to 17.4% of losers.
MMA, mixed martial arts; AEs, athletic exposures; KO, knockou; TKO, technical knockout; UFC, Ultimate Fighting Championship.

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

found the prevalence of concussions in MMA to be as low as 1.8% rates of 28 and 29 injuries per 100 AEs, respectively. Note that
of injuries (Rainey, 2009), while another found it to be as high as these head injuries included fractures, lacerations, and choking,
62.3% of injuries (Curran-Sills and Abedin, 2018). The study by not just concussions. In the same Fares et al. (2019) study, it was
Rainey (2009) should be interpreted carefully because injuries were found that 36% and 14% of matches ended with TKO/KO for
self-reported and only 20.1% of MMA athletes received medical males and females, respectively, while 33% of matches overall
attention, thus injury rates may be underestimated. Likewise, ended with TKO/KO.
Curran-Sills and Abedin (2018) may overestimate the rate of con-
cussions in MMA by counting all TKOs as concussions even though Long-term effects of subconcussive RHIs
a TKO does not necessarily occur due to head trauma (e.g., physi- Research on the long-term effects of RHIs on MMA athletes is
cal exhaustion). It was also reported that 8.3% of injuries sustained sparse, with most of the existing research focusing on boxers. The
by MMA athletes were concussions, but only 4.2% of athletes lost objective of this section is to evaluate CTE and examine long-term
consciousness (Karpman et al., 2016); this reinforced the knowl- effects of RHIs, including changes in brain volume, brain struc-
edge that not all concussions result in LOC, so a postfight medical ture, and cognition.
examination is of the utmost importance. CTE is described as a progressive tauopathy of the brain found
Not surprisingly, when analyzing concussion rates based on the in individuals who have suffered repetitive subconcussive and/or
winner and loser of a match, it was observed that the loser of both concussive head impacts (McKee et al., 2013). CTE was first dis-
boxing and MMA matches sustains more suspected concussions covered in boxers who were described as “punch drunk” (Martland,
compared to the winner, and the loser sustains the first concussion 1928). Since then, the neuropathology, signs and symptoms, risk
98% of the time (Bernick et al., 2021). Another study reported factors, and diagnostic criteria of CTE have been explored, but are
differing results with only 83% of MMA athletes sustaining head not well-defined (D’Ascanio et al., 2018; McKee et al., 2018;
injuries eventually losing the match; however, this takes into con- McKee et al., 2013). CTE is characterized by hyperphosphorylat-
sideration all types of head injuries, not just concussions (Fares et ed tau (p-tau) accumulation within neurons and astroglia at the
al., 2021). Similarly, Curran-Sills and Abedin (2018) observed depths of the cortical sulci (D’Ascanio et al., 2018). There are four
that 86.1% of injured MMA athletes lost their match. Addition- stages of CTE, each with their own neuropathology (tauopathy)
ally, it was found that 17.4% of losers sustained a concussion com- and signs and symptoms (D’Ascanio et al., 2018; McKee et al.,
pared to 1.5% of winners in MMA (Ross et al., 2021). 2018; McKee et al., 2013).
On average, MMA athletes with a head injury sustained 32 sig- Stage I CTE is characterized by focal epicenters of p-tau at the
nificant head impacts during a single match (Fares et al., 2021). depths of the cortical sulci. Subjects with stage I CTE suffer from
It was reported that the average time to stop a match following a varying symptoms including headaches, issues with attention and
KO was 3.5 ± 2.8 sec, and during this time, knocked out athletes concentration, short-term memory loss, aggression, depression,
sustained an additional average of 2.6 ± 3.0 strikes to the head executive dysfunction, and explosivity. In stage II CTE, p-tau
(Hutchison et al., 2014). It is just as concerning that athletes who spreads to adjacent superficial cortical layers. In addition to the
lost by TKO sustained 18.5 ± 8.8 strikes in the 30 sec before match symptoms seen in stage I CTE, those with stage II CTE experi-
stoppage, and 92.3% of those strikes were to the head (Hutchison ence mood swings, symptoms of motor neuron disease, impulsivi-
et al., 2014). Additionally, physicians analyzing videos of MMA ty, suicidality, and language difficulties. Stage III CTE is charac-
matches reported that 43% should have been stopped an average terized by p-tau widespread throughout the cortices. Symptoms
of 44.5 sec sooner than they were (Bernick et al., 2021). Letting a of stage III CTE, in addition to those previously listed, include
match go longer than necessary can lead to additional head im- memory loss, visuospatial difficulties, apathy, and cognitive im-
pacts and concussive injuries, with a potential for brain damage pairment. Finally, stage IV CTE is distinguished by widespread
(Bernick et al., 2021). p-tau in the cerebrum, diencephalon, basal ganglia, brainstem,
When considering sex, Fares et al. (2021) discovered that males and spinal cord, as well as neuronal loss. Symptoms of stage IV
in MMA suffer from concussions at a rate of 17 injuries per 100 CTE are more severe and include extreme memory loss in the
athletic exposures (AEs), while women suffer from concussions at form of dementia, executive dysfunction, paranoia, gait difficul-
a rate of 11 injuries per 100 AEs. In another Fares et al. (2019) ties, dysarthria, Parkinson disease, and suicidality (D’Ascanio et
study, males and females in MMA sustained similar head injury al., 2018; McKee et al., 2018; McKee et al., 2013).

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

Unfortunately, risk factors for CTE are not well known; howev- al., 2017; Lee et al., 2020). Cavum septum pellucidum and cavum
er, there are potential factors that have been explored. The most vergae are two types of anterior midline intracranial cysts, which
likely risk factor for CTE is RHIs, but not all individuals who ex- can be congenital and benign or form due to head trauma (Tubbs
perience RHIs are affected by CTE (D’Ascanio et al., 2018). This et al., 2011). The PFBHS found that boxers and MMA athletes
suggests that additional risk factors must be present for an indi- had a higher prevalence of cavum septum pellucidum and cavum
vidual to develop CTE. Advanced age may also play a role in CTE vergae compared to healthy controls. The presence of cavum ver-
development, as seen in the study by McKee et al. (2013), where gae was associated with smaller brain volumes in the supratentori-
those exposed to RHIs but negative for CTE were on average um, thalamus, corpus callosum, caudate, putamen, hippocampus,
32.6 ± 22.4 years old, while those exposed to RHIs and positive and amygdala compared to athletes without cavum vergae (Lee et
for CTE were on average 59.5 ± 20.4 years old. Additional risk al., 2020).
factors may include genetics, medical history, lifestyle, and other Compared to healthy controls, boxers and MMA athletes scored
head impact variables like age of first exposure (AFE) to head im- lower on processing speed and psychomotor speed (Lee et al.,
pacts, frequency of impacts, and severity of impacts. These risk 2020). Lower processing speed scores were associated with in-
factors all warrant further research to best determine those that are creased number of professional fights, increased fight exposure
modifiable in order to decrease the risk of CTE in individuals. scores, earlier AFE, and smaller volumes of the thalamus, amyg-
In addition to CTE, RHIs have been shown to affect brain vol- dala, and left hippocampus for both MMA athletes and boxers
ume, brain structure, and cognition. Much of the research on the combined (Bernick et al., 2015; Bryant et al., 2020). Interesting-
long-term effects of RHIs in MMA athletes has been conducted ly, sex was found to moderate the effects of number of professional
through the Professional Athletes Brain Health Study (PFBHS), fights on brain structure volumes and cognition, with male ath-
an observational and longitudinal study of the brain health of ac- letes having significantly smaller brain regions than female ath-
tive and retired MMA athletes and boxers (Bernick et al., 2013). letes when associated with number of professional fights (Bennett
MMA athletes did not have a significant difference in brain struc- et al., 2020). Additionally, as number of professional fights in-
ture volumes compared to healthy controls in the PFBHS; howev- creased, male athletes had lower verbal memory scores, while fe-
er, boxers had significantly lower left and right thalamus, caudate, male athletes had better verbal memory scores (Bennett et al.,
putamen, hippocampus, and amygdala volumes compared to 2020). In retired boxers, earlier AFE was correlated with higher
MMA athletes (Bernick et al., 2015). When combined, both BESS test scores, meaning that earlier AFE is correlated with
MMA athletes and boxers had an estimated 0.3% decrease in cau- worse balance (Bryant et al., 2020). When measuring neuropsy-
date volume per professional fight (Bernick et al., 2015). MMA chiatric symptoms, there was a correlation between earlier AFE
athletes had an estimated 0.2% and 0.3% decrease in thalamus and depression, impulsivity, attention issues, and motor impair-
volume for both the left and right sides, respectively, per profes- ments in retired boxers (Bryant et al., 2020).
sional fight (Bernick et al., 2015). Seemingly in opposition to
those findings, when looking at a larger cohort from the PFBHS, Biomechanical insights on head impacts
AFE did not correlate with changes in the volume of the thalamus The biomechanics of head impacts have been studied more ex-
or caudate (Bryant et al., 2020). However, the same study found tensively compared to the epidemiology and long-term effects of
that AFE for active and retired athletes correlated with smaller concussions within MMA. Through different mechanisms of head
left hippocampal, right hippocampal, and posterior corpus callo- impacts, linear and rotational accelerations/decelerations contrib-
sum volumes (Bryant et al., 2020). Interestingly, active athletes ute to head injuries (Karton and Hoshizaki, 2018). Within MMA
had smaller left amygdala volume in correlation with AFE, while specifically, head impact biomechanics are not as well known.
retired athletes had smaller right amygdala volume (Bryant et al., However, strain and shear stress in the brain have been document-
2020). Lee et al. (2020) found that boxers and MMA athletes have ed in MMA athletes, with variation between weight classes, as
smaller thalamus (-650 mm3 mean difference) and corpus callo- well as within specific regions of the brain (Khatib et al., 2021;
sum (-402 mm3 mean difference) volumes when compared to Tiernan et al., 2021).
healthy controls. The study of head impact biomechanics has largely focused on
Two additional alterations in the brain, cavum septum pellu- contact sports such as American football, ice hockey, soccer, and
cidum and cavum vergae, have been seen in MMA athletes (Lee et boxing. Head impacts in sports are each unique and depend on a

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

set of characteristics, including magnitude, frequency, interval, The rules of MMA encourage head strikes, particularly ones
and duration of head impact(s) (Karton and Hoshizaki, 2018). that will knock out an opponent and result in a concussion. The
When these characteristics were compared between light weight best way to reduce head trauma sustained by MMA athletes is to
(LW) and heavy weight (HW) MMA athletes, it was found that change the rules. One method is to discourage head strikes by de-
the frequency and interval of head impacts were similar between ducting points any time the head is hit. However, rules are un-
the weight classes; however, the magnitude of maximum princi- likely to change this drastically. To mitigate the effects of head
pal strain (MPS) differed between the weight classes with the LW strikes, MMA athletes should always wear a mouthguard and
athletes sustaining a greater frequency of very low and high mag- headgear, but there is conflicting evidence on whether protective
nitude MPS head impacts (Khatib et al., 2021). Interestingly, LW gear can reduce concussion risk. The UFC took a step in the right
athletes sustained high magnitude MPS impacts from punches to direction by implementing its first concussion protocol in 2021;
the head, while HW athletes sustained high magnitude MPS im- however, one of the biggest issues with the concussion protocol is
pacts from elbows to the head, implying that fighting-style differs that athletes return home following a fight, so it is up to the ath-
between weight classes (Khatib et al., 2021). As seen in the study lete and the coach to turn to a healthcare provider for guidance in
by Khatib et al. (2021), the magnitude, frequency, interval, and following the return-to-play protocol. Enforcing the concussion
duration of head impact(s) are influenced by the type of head im- protocol will not be easy, so the UFC must better educate athletes
pact observed in sports, which include but are not limited to, col- and coaches on the symptoms and dangers of concussion.
lisions between athletes, falls, projectile impacts, and punches Diagnosis of CTE is another area that merits further research
(Karton and Hoshizaki, 2018). because CTE can only be diagnosed postmortem (D’Ascanio et al.,
Linear and rotational accelerations contribute to the resulting 2018; Lin et al., 2018; Zetterberg and Blennow, 2018). Through
head injury through different mechanisms (Karton and Hoshiza- a literature review on CTE, McKee et al. (2013) defined neuro-
ki, 2018). High linear acceleration/deceleration results in pressure pathologic diagnosis of CTE as the presence of the following: “(a)
changes in the head, which leads to brain injury (Gurdjian et al., perivascular foci of p-tau immunoreactive astrocytic tangles and
1958). Ommaya and Gennarelli (1974) argued that rotational ac- neurofibrillary tangles; (b) irregular cortical distribution of p-tau
celeration causes shear stress between the skull and brain, thus re- immunoreactive neurofibrillary tangles and astrocytic tangles
sulting in brain injury, including concussions. Similar results were with a predilection for the depth of cerebral sulci; (c) clusters of
found in MMA athletes where knockouts resulting in transient subpial and periventricular astrocytic tangles in the cerebral cor-
LOC were overwhelmingly due to rotation of the head (Fogarty et tex, diencephalon, basal ganglia and brainstem; and (d) neuro-
al., 2019). Tiernan et al. (2021) found that the best strain indica- fibrillary tangles in the cerebral cortex located preferentially in the
tor for concussion is the corpus callosum where concussed MMA superficial layers.” However, this diagnostic criterion can only be
athletes had 87.9% higher strain values than uninjured athletes. used when examining a brain postmortem. Clinical diagnosis is
Furthermore, it was discovered that shear stress measured in the not currently possible, but researchers have proposed clinical diag-
corpus callosum is the best predictor for concussion. This was evi- nostic criteria that have not yet been accepted. There is a need for
denced by a 111.4% higher shear stress in the corpus callosum neuroimaging biomarkers or fluid biomarkers that can be used to
among concussed MMA athletes compared to uninjured athletes diagnose CTE antemortem (Lin et al., 2018; Zetterberg and Blen-
(Tiernan et al., 2021). now, 2018). Neuroimaging technology that may potentially be
adapted in the future to diagnose CTE includes PET, MRS, MRI,
Future considerations and research topics DTI, and fMRI (Lin et al., 2018). Fluid biomarkers found in CSF,
While there have been efforts to better define mTBI and con- blood, saliva, urine, and tears still need to be explored, especially
cussion, consensus is required on the definitions of these condi- because p-tau is associated with other tauopathies, like Alzheimer
tions such that they can be used consistently across the literature. disease, and may not be distinguishable from p-tau associated
Currently, mTBI and concussion are used interchangeably (Green- with CTE (Zetterberg and Blennow, 2018).
wald et al., 2012; McCrory et al., 2017), while the literature de- It is also important to accurately determine the prevalence of
fines them differently depending on the focus of the research, concussions in MMA because studies show conflicting results. To
making it difficult to truly know the prevalence of concussions aid in this, concussions must be defined consistently across the
across all sports and within MMA. literature. One study counted all TKOs as concussions (Curran-

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

Sills and Abedin, 2018), but this is not necessarily true. Another markers show the most promise, and future studies should focus
study only counted KOs as concussions (Ngai et al., 2008), but on finding novel biomarkers to be used moving forward. This also
not all concussions result in LOC. Finally, an additional study re- applies to the diagnosis of CTE, which is currently only possible
lied on self-reported injury, with only 20.1% of athletes receiving postmortem. Focusing on the prevention of head injuries and mit-
medical attention, likely underestimating the concussion rate igation of risk factors will hopefully decrease the prevalence of
(Rainey, 2009). All MMA athletes must be examined by a medi- concussions and reduce the long-term effects of RHIs.
cal professional after a fight, and notes from the examination
should be documented properly. CONCLUSION
To aid in the diagnosis of concussions, the biomechanics of head
impacts sustained by MMA athletes must be observed and ana- To the knowledge of the authors, this is the first overview of the
lyzed. Few studies have reported on the head impact biomechan- literature on RHIs and concussions sustained by MMA athletes to
ics of MMA athletes (Bartsch et al., 2012; Fogarty et al., 2019; outline (a) the rules of MMA; (b) the postconcussion protocol for
Khatib et al., 2021; Tiernan et al., 2021), but knowing the mech- UFC athletes; (c) diagnostic measures; (d) epidemiology and prev-
anism of injury could provide additional information to assist in alence of concussion in MMA; (e) long-term effects of subconcus-
diagnosing concussions. Of the utmost importance is developing sive RHIs; (f) biomechanics of head impacts; and (g) future con-
novel, reliable diagnostic measures that can objectively determine siderations and research topics needed moving forward (for sum-
the presence or absence of a concussion. Imaging and fluid bio- mary, refer to Fig. 1). There are significant knowledge gaps in the

Current knowns and unknowns of Research topics for preventing, mitigating,

mTBI in MMA and diagnosing mTBl in MMA

Rules encourage head

Fighters should follow the first
impacts to knock
official concussion protocol
opponent unconscious
released by UFC in 2021.
and cause a concussion.

Concussions in MMA should

True epidemiology of
be defined consistently to
concussions in MMA is
determine true epidemiology
unknown.
of concussions in MMA.

Biomechanics of head
Lack of literature on head impacts sustained by MMA
impact biomechanics of Fighters should be studied to
MMA fighters. determine mechanism of the
injury.

Novel, reliable diagnostic

Concussion diagnoses are
measures must be developed
subjective in nature and
to objectively diagnose
difficult to diagnose.
concussions.

Long-term effects of
Identify novel biomarker for
repetitive subconcussive
CTE diagnosis, and focus on
head impacts in MMA
prevention of head impacts
include CTE and
and mitigation of risk factors
microstructural and
to reduce long-term effects.
cognitive impairments.

Fig. 1. Current knowledge of head impacts sustained by MMA fighters and suggestions for future prevention, mitigation, diagnosis, and care of head impacts. MMA,
mixed martial arts; mTBI, mild traumatic brain injury; CTE, chronic traumatic encephalopathy; UFC, Ultimate Fighting Championship.

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Hamdan JL, et al. • Mild traumatic brain injury in MMA athletes

literature related to RHIs and head trauma sustained by MMA sports. Phys Sportsmed 2021;49:469-475.
athletes that need to be addressed in order to prevent future head Bernick C, Zetterberg H, Shan G, Banks S, Blennow K. Longitudinal per-
trauma, mitigate the risk of head trauma and long-term effects, formance of plasma neurofilament light and tau in professional ath-
and diagnose head trauma properly. letes: the professional athletes brain health study. J Neurotrauma
2018;35:2351-2356.
CONFLICT OF INTEREST Bryant BR, Narapareddy BR, Bray MJC, Richey LN, Krieg A, Shan G, Pe-
ters ME, Bernick CB. The effect of age of first exposure to competitive
No potential conflict of interest relevant to this article was re- fighting on cognitive and other neuropsychiatric symptoms and brain
ported. volume. Int Rev Psychiatry 2020;32:89-95.
Çevik S, Özgenç MM, Güneyk A, Evran Ş, Akkaya E, Çalış F, Katar S,
ACKNOWLEDGMENTS Soyalp C, Hanımoğlu H, Kaynar MY. NRGN, S100B and GFAP levels
are significantly increased in patients with structural lesions resulting
This work was supported by funding from the National Insti- from mild traumatic brain injuries. Clin Neurol Neurosurg 2019;183:
tute of Neurological Disorders and Stroke at the National Insti- 105380.
tutes of Health (NIH R01NS102157 to J.Y.P.). Corps KN, Roth TL, McGavern DB. Inflammation and neuroprotection in
traumatic brain injury. JAMA Neurol 2015;72:355-362.
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