Widespread White Matter Abnormalities in Concussed Athletes Detected by 7T Diffusion Magnetic Resonance Imaging.

Sports-related concussions may cause white matter injuries and persistent post-concussive symptoms (PPCS). We hypothesized that athletes with PPCS would have neurocognitive impairments and white matter abnormalities that could be revealed by advanced neuroimaging using ultra-high field strength diffusion tensor (DTI) and diffusion kurtosis (DKI) imaging metrics and cerebrospinal fluid (CSF) biomarkers. A cohort of athletes with PPCS severity limiting the ability to work/study and participate in sport school and/or social activities for ≥6 months completed 7T magnetic resonance imaging (MRI) (morphological T1-weighed volumetry, DTI and DKI), extensive neuropsychological testing, symptom rating, and CSF biomarker sampling. Twenty-two athletes with PPCS and 22 controls were included. Concussed athletes performed below norms and significantly lower than controls on all but one of the psychometric neuropsychology tests. Supratentorial white and gray matter, as well as hippocampal volumes did not differ between concussed athletes and controls. However, of the 72 examined white matter tracts, 16% of DTI and 35% of DKI metrics (in total 28%) were significantly different between concussed athletes and controls. DKI fractional anisotropy and axial kurtosis were increased, and DKI radial diffusivity and radial kurtosis decreased in concussed athletes when compared with controls. CSF neurofilament light (NfL; an axonal injury marker), although not glial fibrillary acidic protein, correlated with several diffusion metrics. In this first 7T DTI and DKI study investigating PPCS, widespread microstructural alterations were observed in the white matter, correlating with CSF markers of axonal injury. More white matter changes were observed using DKI than using DTI. These white matter alterations may indicate persistent pathophysiological processes following concussion in sport.

Cerebrospinal fluid levels of neuroinflammatory biomarkers are increased in athletes with persistent post-concussive symptoms following sports-related concussion.

A sports-related concussion (SRC) is often caused by rapid head rotation at impact, leading to shearing and stretching of axons in the white matter and initiation of secondary inflammatory processes that may exacerbate the initial injury. We hypothesized that athletes with persistent post-concussive symptoms (PPCS) display signs of ongoing neuroinflammation, as reflected by altered profiles of cerebrospinal fluid (CSF) biomarkers, in turn relating to symptom severity. We recruited athletes with PPCS preventing sports participation as well as limiting work, school and/or social activities for ≥ 6 months for symptom rating using the Sport Concussion Assessment Tool, version 5 (SCAT-5) and for cognitive assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Following a spinal tap, we analysed 27 CSF inflammatory biomarkers (pro-inflammatory chemokines and cytokine panels) by a multiplex immunoassay using antibodies as electrochemiluminescent labels to quantify concentrations in PPCS athletes, and in healthy age- and sex-matched controls exercising ≤ 2 times/week at low-to-moderate intensity. Thirty-six subjects were included, 24 athletes with PPCS and 12 controls. The SRC athletes had sustained a median of five concussions, the most recent at a median of 17 months prior to the investigation. CSF cytokines and chemokines levels were significantly increased in eight (IL-2, TNF-α, IL-15, TNF-ß, VEGF, Eotaxin, IP-10, and TARC), significantly decreased in one (Eotaxin-3), and unaltered in 16 in SRC athletes when compared to controls, and two were un-detectable. The SRC athletes reported many and severe post-concussive symptoms on SCAT5, and 10 out of 24 athletes performed in the impaired range (Z < - 1.5) on cognitive testing. Individual biomarker concentrations did not strongly correlate with symptom rating or cognitive function. Limitations include evaluation at a single post-injury time point in relatively small cohorts, and no control group of concussed athletes without persisting symptoms was included. Based on CSF inflammatory marker profiling we find signs of ongoing neuroinflammation persisting months to years after the last SRC in athletes with persistent post-concussive symptoms. Since an ongoing inflammatory response may exacerbate the brain injury these results encourage studies of treatments targeting the post-injury inflammatory response in sports-related concussion.

Shorter Recovery Time in Concussed Elite Ice Hockey Players by Early Head-and-Neck Cooling: A Clinical Trial.

A sports-related concussion (SRC) is most commonly sustained in contact sports, and is defined as a mild traumatic brain injury. An exercise-induced elevation of core body temperature is associated with increased brain temperature that may accelerate secondary injury processes following SRC, and exacerbate the brain injury. In a recent pilot study, acute head-neck cooling of 29 concussed ice hockey players resulted in shorter time to return-to-play. Here, we extended the clinical trial to include players of 19 male elite Swedish ice hockey teams over five seasons (2016-2021). In the intervention teams, acute head-neck cooling was implemented using a head cap for ≥45 min in addition to the standard SRC management used in controls. The primary endpoint was time from SRC until return-to-play (RTP). Sixty-one SRCs were included in the intervention group and 71 SRCs in the control group. The number of previous SRCs was 2 (median and interquartile range [IQR]: 1.0-2.0) and 1 (IQR 1.0-2.0) in the intervention and control groups, respectively; p = 0.293. Median time to initiate head-neck cooling was 10 min (IQR 7-15; range 5-30 min) and median duration of cooling was 45 min (IQR 45-50; range 45-70 min). The median time to RTP was 9 days in the intervention group (IQR 7.0-13.5 days) and 13 days in the control group (IQR 9-30; p < 0.001). The proportion of players out from play for more than the expected recovery time of 14 days was 24.7% in the intervention group, and 43.7% in controls (p < 0.05). Study limitations include that: 1) allocation to cooling or control management was at the discretion of the medical staff of each team, decided prior to each season, and not by strict randomization; 2) no sham cap was used and evaluations could not be performed by blinded assessors; and 3) it could not be established with certainty that injury severity was similar between groups. While the results should thus be interpreted with caution, early head-neck cooling, with the aim of attenuating cerebral hyperthermia, may reduce post-SRC symptoms and lead to earlier return-to-play in elite ice hockey players.

Long-term postural control in elite athletes following mild traumatic brain injury.

Background: Traumas to the head and neck are common in sports and often affects otherwise healthy young individuals. Sports-related concussions (SRC), defined as a mild traumatic brain injury (mTBI), may inflict persistent neck and shoulder pain, and headache, but also more complex symptoms, such as imbalance, dizziness, and visual disturbances. These more complex symptoms are difficult to identify with standard health care diagnostic procedures. Objective: To investigate postural control in a group of former elite athletes with persistent post-concussive symptoms (PPCS) at least 6 months after the incident. Method: Postural control was examined using posturography during quiet stance and randomized balance perturbations with eyes open and eyes closed. Randomized balance perturbations were used to examine motor learning through sensorimotor adaptation. Force platform recordings were converted to reflect the energy used to maintain balance and spectrally categorized into total energy used, energy used for smooth corrective changes of posture (i.e., <0.1 Hz), and energy used for fast corrective movements to maintain balance (i.e., >0.1 Hz). Results: The mTBI group included 20 (13 males, mean age 26.6 years) elite athletes with PPCS and the control group included 12 athletes (9 males, mean age 26.4 years) with no history of SRC. The mTBI group used significantly more energy during balance perturbations than controls: +143% total energy, p = 0.004; +122% low frequency energy, p = 0.007; and +162% high frequency energy, p = 0.004. The mTBI subjects also adapted less to the balance perturbations than controls in total (18% mTBI vs. 37% controls, p = 0.042), low frequency (24% mTBI vs. 42% controls, p = 0.046), and high frequency (6% mTBI vs. 28% controls, p = 0.040). The mTBI subjects used significantly more energy during quiet stance than controls: +128% total energy, p = 0.034; +136% low-frequency energy, p = 0.048; and +109% high-frequency energy, p = 0.015. Conclusion: Athletes with previous mTBI and PPCS used more energy to stand compared to controls during balance perturbations and quiet stance and had diminished sensorimotor adaptation. Sports-related concussions are able to affect postural control and motor learning.

Post-Concussive Vestibular Dysfunction Is Related to Injury to the Inferior Vestibular Nerve.

Symptoms of vestibular dysfunction such as dizziness and vertigo are common after sports-related concussions (SRC) and associated with a worse outcome and a prolonged recovery. Vestibular dysfunction after SRC can be because of an impairment of the peripheral or central neural parts of the vestibular system. The aim of the present study was to establish the cause of vestibular impairment in athletes with SRC who have persisting post-concussive symptoms (PPCS). We recruited 42 participants-21 athletes with previous SRCs and PPCS ≥6 months and 21 healthy athletic age- and sex-matched controls-who underwent symptom rating, a detailed test battery of vestibular function and 7T magnetic resonance imaging with diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) of cerebellar white matter tracts, and T1-weighted imaging for cerebellar volumetrics. Vestibular dysfunction was observed in 13 SRC athletes and three controls (p = 0.001). Athletes with vestibular dysfunction reported more pronounced symptoms on the Dizziness Handicap Inventory (DHI; p < 0.001) and the Hospital Anxiety and Depression Scale (HADS; p < 0.001). No significant differences in DTI metrics were found, while in DKI two metrics were observed in the superior and/or inferior cerebellar tracts. Cerebellar gray and white matter volumes were similar in athletes with SRC and controls. Compared with controls, pathological video head impulse test results (vHIT; p < 0.001) and cervical vestibular evoked myogenic potentials (cVEMP; p = 0.002) were observed in athletes with SRC, indicating peripheral vestibular dysfunction and specifically suggesting injury to the inferior vestibular nerve. In athletes with persisting symptoms after SRC, vestibular dysfunction is associated with injury to the inferior vestibular nerve.

Intracerebral Proinflammatory Cytokine Increase in Surgically Evacuated Intracerebral Hemorrhage: A Microdialysis Study.

BACKGROUND: Treatment options for spontaneous intracerebral hemorrhage (ICH) are limited. A possible inflammatory response in the brain tissue surrounding an ICH may exacerbate the initial injury and could be a target for treatment of subsequent secondary brain injury. The study objective was to compare levels of inflammatory mediators in the interstitial fluid of the perihemorrhagic zone (PHZ) and in seemingly normal cortex (SNX) in the acute phase after surgical evacuation of ICH, with the hypothesis being that a difference could be demonstrated between the PHZ and the SNX. METHODS: In this observational study, ten patients needing surgical evacuation of supratentorial ICH received two cerebral microdialysis catheters: one in the PHZ and one in the SNX that is remote from the ICH. The microdialysate was analyzed for energy metabolites (including lactate pyruvate ratio and glucose) and for inflammatory mediators by using a multiplex immunoassay of 27 cytokines and chemokines at 6-10 h, 20-26 h, and 44-50 h after surgery. RESULTS: A metabolic crisis, indicated by altered energy metabolic markers, that persisted throughout the observation period was observed in the PHZ when compared with the SNX. Proinflammatory cytokines interleukin (IL) 8, tumor necrosis factor α, IL-2, IL-1ß, IL-6 and interferon γ, anti-inflammatory cytokine IL-13, IL-4, and vascular endothelial growth factor A were significantly higher in PHZ compared with SNX and were most prominent at 20-26 h following ICH evacuation. CONCLUSIONS: Higher levels of both proinflammatory and anti-inflammatory cytokines in the perihemorrhagic brain tissue implies a complex role for inflammatory mediators in the secondary injury cascades following ICH surgery, suggesting a need for targeted pharmacological interventions.

Selective head-neck cooling after concussion shortens return-to-play in ice hockey players.

We aimed to investigate whether selective head-neck cooling could shorten recovery after sports-related concussions (SRCs). In a nonrandomized study of 15 Swedish professional ice hockey teams, 29 concussed players received immediate head and neck cooling for ≥30 min (initiated at 12.3 ± 9.2 min post-SRC by a portable cooling system), and 52 SRC controls received standard management. Players receiving head-neck cooling had shorter time to return-to-play than controls (7 vs 12.5 days, p < 0.0001), and 7% in the intervention group versus 25% in the control group were out of play for ≥3 weeks (p = 0.07). Immediate selective head-neck cooling is a promising option in the acute management of SRC that should be addressed in larger cohorts.

Quality of life of ice hockey players after retirement due to concussions.

BACKGROUND: Sports-related concussion (SRC) is increasingly recognized as a potential health problem in ice hockey. Quality of life (QoL) in players retiring due to SRC has not been thoroughly addressed. MATERIALS & METHODS: QoL using the Sports Concussion Assessment Tool 5th Edition, Impact of Event Scale-Revised and Short Form Health Survey was measured in Swedish ice hockey players who retired due to persistence of postconcussion symptoms or fear of attaining additional SRC. RESULTS: A total of 76 players were assessed, on average of 5 years after their most recent SRC. Overall, retired players had a high burden of postconcussion symptoms and reduced QoL. CONCLUSION: Retired concussed ice hockey players have a reduced QoL, particularly those retiring due to postconcussion symptoms. Symptom burden should be continuously evaluated and guide the decision to retire.