Somatic Mosaicism in the Pathogenesis of de novo Cerebral Arteriovenous Malformations: A Paradigm Shift Implicating the RAS-MAPK Signaling Cascade.

Cerebral arteriovenous malformations (AVMs) are leading causes of lesional hemorrhagic stroke in both the pediatric and young adult population, with sporadic AVMs accounting for the majority of cases. Recent evidence has identified somatic mosaicism in key proximal components of the RAS-MAPK signaling cascade within endothelial cells collected from human sporadic cerebral AVMs, with early preclinical models supporting a potential causal role for these mutations in the pathogenesis of these malformations. Germline mutations that predispose to deregulation of the RAS-MAPK signaling axis have also been identified in hereditary vascular malformation syndromes, highlighting the key role of this signaling axis in global AVM development. Herein, we review the most recent genomic and preclinical evidence implicating somatic mosaicism in the RAS-MAPK signaling pathway in the pathogenesis of sporadic cerebral AVMs. Also, we review evidence for RAS-MAPK dysregulation in hereditary vascular malformation syndromes and present a hypothesis suggesting that this pathway is central for the development of both sporadic and syndrome-associated AVMs. Finally, we examine the clinical implications of these recent discoveries and highlight potential therapeutic targets within this signaling pathway.

Blood Biomarkers of Sports-Related Concussion in Pediatric Athletes.

OBJECTIVE: To examine changes in blood biomarkers, serum neurofilament light (Nf-L), and plasma tau, as well as the relationship between blood biomarkers and symptom reports, in athletes with a sports-related concussion. DESIGN: Prospective cohort study. SETTING: Private community-based concussion clinic. PARTICIPANTS: Athletes aged 13 to 18 years old with a diagnosed sports-related concussion presenting to a concussion clinic within 7 days of injury and noninjured athletes with no history of concussion aged 13 to 23 years old. ASSESSMENT AND MAIN OUTCOME MEASURES: Injured athletes provided a blood sample at the initial clinical evaluation and again at least 6 months after injury. Noninjured athletes provided a single blood sample. All participants completed symptom reports during each visit. Statistical comparisons of biomarker concentrations and symptom reports were conducted. RESULTS: The mean rank for tau was significantly lower for concussed athletes compared with nonconcussed athletes. In contrast, the mean rank of Nf-L was higher for concussed athletes than for nonconcussed athletes, although the difference was nonsignificant. Plasma tau was significantly lower postinjury compared with 6 months after injury, whereas serum Nf-L was significantly higher postinjury. There was a weak but significant inverse relationship observed between tau and the number of symptoms reported, but no relationship was observed between Nf-L and the number of symptoms reported. CONCLUSIONS: These data indicate that in the days following a sports-related concussion, the blood biomarkers tau and Nf-L display contrasting patterns of change but may not be related to self-reported symptom scores.

Compressive myelopathy from diffuse spinal dural calcifications in a patient with end-stage renal disease: illustrative case.

BACKGROUND: Diffuse spinal dural calcification is a rare disorder associated with hyperparathyroidism, including the secondary forms associated with renal failure, osteodystrophy, and chronic hypocalcemia. Here, the authors report a rare case of diffuse dural calcification causing spinal cord compression with myelopathy, requiring decompressive surgery with duraplasty to achieve adequate decompression. OBSERVATIONS: A 46-year-old male with a history of renal failure on dialysis presented with 2 months of progressive neuropathic pain, lower-extremity weakness, and nonsustained clonus. Spine imaging showed severe renal osteodystrophy with multilevel compression fractures and diffuse dural calcifications with areas of invagination causing severe spinal cord compression. Decompressive surgery was recommended. In surgery, a thickened and calcified dura was encountered with areas of buckling causing spinal cord compression. The invaginated area of the dura was resected and reconstructed with patch duraplasty. The patient's neurological status remained unchanged postoperatively, and at the 6-month follow-up, the patient reported significant improvement in pain and muscle spasms. LESSONS: Diffuse dural calcifications are a rare complication of prolonged dialysis and secondary hyperparathyroidism. When there is resultant spinal cord compression, this condition requires an intradural approach that addresses the thickened, calcified dura directly to obtain adequate spinal cord decompression.

Laser interstitial thermal therapy for first-line treatment of insular glioma.

OBJECTIVE: Insular gliomas pose a significant surgical challenge due to the complex surrounding functional and vascular anatomy. The authors report their experience using a novel framework for the treatment of insular gliomas with laser interstitial thermal therapy (LITT) and provide representative case examples emphasizing indications, rationale, and technical pearls. METHODS: A prospectively gathered institutional database was used to identify patients with newly diagnosed insular gliomas who underwent LITT between 2015 and 2023. The proposed framework of insular glioma management is guided by tumor size and extent of extra-insular tumor involvement. Patients with tumors localized to the insula (insula-only) were treated with single-session or staged LITT. Patients with insular tumors with frontotemporal involvement (insular+) were treated with insular LITT and standard frontotemporal resection of extra-insular tumor. Clinical and volumetric lesional characteristics were analyzed, with particular emphasis on extent of cytoreductive treatment and safety. RESULTS: Of the 261 patients treated at the authors' institution with LITT between 2015 and 2023, 33 LITT procedures were identified involving 22 unique patients with treatment-naive insular gliomas. Of the 22 patients, 12 had insular-only tumors and were treated with LITT alone, while 10 patients had insular+ lesions and were treated with LITT and resection. The median tumor volume for insular-only tumors was 13.4 cm3 (IQR 10.6, 26.3 cm3), with a median extent of treatment of 100% (IQR 92.1%, 100%). Insular+ lesions were significantly larger, with a median volume of 81.2 cm3 (IQR 51.9, 97 cm3) and median extent of treatment of 96.6% (IQR 93.7%, 100%). All patients with insular-only tumors were discharged the day after ablation, while insular+ patients had significantly longer hospital stays, with 50% staying more than 3 days. Overall, 8% of insular-only patients had permanent neurological deficits compared with 33% of insular+ patients. Two patients' tumors progressed during follow-up: one patient with WHO grade 4 astrocytoma and the other with diffuse glioma not otherwise specified. Patients with grade 4 tumors had the highest rate of permanent neurological deficit (43%) and a larger decline in postoperative Karnofsky Performance Status score (p = 0.046). CONCLUSIONS: The authors present their experience using a novel insular glioma treatment paradigm that incorporates LITT into the broader framework of insular glioma surgery. Their findings suggest that insular LITT is feasible and may allow for high rates of cytoreduction while potentially ameliorating the risks of conventional insular glioma surgery.

Use of magnetic source imaging to assess recovery after severe traumatic brain injury-an MEG pilot study.

Rationale: Severe TBI (sTBI) is a devastating neurological injury that comprises a significant global trauma burden. Early comprehensive neurocritical care and rehabilitation improve outcomes for such patients, although better diagnostic and prognostic tools are necessary to guide personalized treatment plans. Methods: In this study, we explored the feasibility of conducting resting state magnetoencephalography (MEG) in a case series of sTBI patients acutely after injury (~7 days), and then about 1.5 and 8 months after injury. Synthetic aperture magnetometry (SAM) was utilized to localize source power in the canonical frequency bands of delta, theta, alpha, beta, and gamma, as well as DC-80 Hz. Results: At the first scan, SAM source maps revealed zones of hypofunction, islands of preserved activity, and hemispheric asymmetry across bandwidths, with markedly reduced power on the side of injury for each patient. GCS scores improved at scan 2 and by scan 3 the patients were ambulatory. The SAM maps for scans 2 and 3 varied, with most patients showing increasing power over time, especially in gamma, but a continued reduction in power in damaged areas and hemispheric asymmetry and/or relative diminishment in power at the site of injury. At the group level for scan 1, there was a large excess of neural generators operating within the delta band relative to control participants, while the number of neural generators for beta and gamma were significantly reduced. At scan 2 there was increased beta power relative to controls. At scan 3 there was increased group-wise delta power in comparison to controls. Conclusion: In summary, this pilot study shows that MEG can be safely used to monitor and track the recovery of brain function in patients with severe TBI as well as to identify patient-specific regions of decreased or altered brain function. Such MEG maps of brain function may be used in the future to tailor patient-specific rehabilitation plans to target regions of altered spectral power with neurostimulation and other treatments.

Transcranial ultrasonography to detect intracranial pathology: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Transcranial ultrasonography (TCU) can be a useful diagnostic tool in evaluating intracranial pathology in patients with limited or delayed access to routine neuroimaging in critical care or austere settings. We reviewed available literature investigating the diagnostic utility of TCU for detecting pediatric and adult patient's intracranial pathology in patients with intact skulls and reported diagnostic accuracy measures. METHODS: We performed a systematic review of PubMed® , Cochrane Library, Embase® , Scopus® , Web of Science™, and Cumulative Index to Nursing and Allied Health Literature databases to identify articles evaluating ultrasound-based detection of intracranial pathology in comparison to routine imaging using broad Medical Subject Heading sets. Two independent reviewers reviewed the retrieved articles for bias using the Quality Assessment of Diagnostic Accuracy Studies tools and extracted measures of diagnostic accuracy and ultrasound parameters. Data were pooled using meta-analysis implementing a random-effects approach to examine the sensitivity, specificity, and accuracy of ultrasound-based diagnosis. RESULTS: A total of 44 studies out of the 3432 articles screened met the eligibility criteria, totaling 2426 patients (Mean age: 60.1 ± 14.52 years). We found tumors, intracranial hemorrhage (ICH), and neurodegenerative diseases in the eligible studies. Sensitivity, specificity, and accuracy of TCU and their 95% confidence intervals were 0.80 (0.72, 0.89), 0.71 (0.59, 0.82), and 0.76 (0.71, 0.82) for neurodegenerative diseases; 0.88 (0.74, 1.02), 0.81 (0.50, 1.12), and 0.94 (0.92, 0.96) for ICH; and 0.97 (0.92, 1.03), 0.99 (0.96, 1.01), and 0.99 (0.97, 1.01) for intracranial masses. No studies reported ultrasound presets. CONCLUSIONS: TCU has a reasonable sensitivity and specificity for detecting intracranial pathology involving ICH and tumors with clinical applications in remote locations or where standard imaging is unavailable. Future studies should investigate ultrasound parameters to enhance diagnostic accuracy in diagnosing intracranial pathology.

An Evaluation of Omega-3 Status and Intake in Canadian Elite Rugby 7s Players.

BACKGROUND: EPA and DHA n-3 FA play crucial roles in both neurological and cardiovascular health and high dietary intakes along with supplementation suggest potential neuroprotection and concussion recovery support. Rugby athletes have a high risk of repetitive sub-concussive head impacts which may lead to long-term neurological deficits, but there is a lack of research looking into n-3 FA status in rugby players. We examined the dietary n-3 FA intake through a FFQ and n-3 FA status by measuring the percentage of n-3 FA and O3I in elite Canadian Rugby 7s players to show distribution across O3I risk zones; high risk, <4%; intermediate risk, 4 to 8%; and low risk, >8%. METHODS: n-3 FA profile and dietary intake as per FFQ were collected at the beginning of the 2017-2018 Rugby 7s season in male (n = 19; 24.84 ± 2.32 years; 95.23 ± 6.93 kg) and female (n = 15; 23.45 ± 3.10 years; 71.21 ± 5.79 kg) athletes. RESULTS: O3I averaged 4.54% ± 1.77, with female athlete scores slightly higher, and higher O3I scores in supplemented athletes (4.82% vs. 3.94%, p = 0.183), with a greater proportion of non-supplemented athletes in the high-risk category (45.5% vs. 39.1%). Dietary intake in non-supplemented athletes did not meet daily dietary recommendations for ALA or EPA + DHA compared to supplemented athletes. CONCLUSIONS: Overall, despite supplementation, O3I score remained in the high-risk category in a proportion of athletes who met recommended n-3 FA dietary intakes, and non-supplemented athletes had a higher proportion of O3I scores in the high-risk category, suggesting that dietary intake alone may not be enough and athletes may require additional dietary and n-3 FA supplementation to reduce neurological and cardiovascular risk.

The effect of omega-3 fatty acids on a biomarker of head trauma in NCAA football athletes: a multi-site, non-randomized study.

BACKGROUND: American-style football (ASF) athletes are at risk for cardiovascular disease (CVD) and exhibit elevated levels of serum neurofilament light (Nf-L), a biomarker of axonal injury that is associated with repetitive head impact exposure over the course of a season of competition. Supplementation with the w-3 fatty acid (FA) docosahexaenoic acid (DHA) attenuates serum Nf-L elevations and improves aspects of CVD, such as the omega-3 index (O3I). However, the effect of combining the w-3 FA eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) with DHA on, specifically, serum Nf-L in ASF athletes is unknown. Therefore, this study assessed the effect of supplemental w-3 FA (EPA+DPA+DHA) on serum Nf-L, plasma w-3 FAs, the O3I, and surrogate markers of inflammation over the course of a season. METHODS: A multi-site, non-randomized design, utilizing two American football teams was employed. One team (n = 3 1) received supplementation with a highly bioavailablew-3 FA formulation (2000mg DHA, 560mg EPA, 320mg DPA, Mindset®, Struct Nutrition, Missoula, MT) during pre-season and throughout the regular season, while the second team served as the control (n = 35) and did not undergo supplementation. Blood was sampled at specific times throughout pre- and regular season coincident w ith changes in intensity, physical contact, and changes in the incidence and severity of head impacts. Group differences were determined via a mixed-model between-within subjects ANOVA. Effect sizes were calculated using Cohen's dfor all between-group differences. Significance was set a priori at p< .05. RESULTS: Compared to the control group, ASF athletes in the treatment group experienced large increases in plasma EPA (p < .001, d = 1.71) and DHA (p < .001, d = 2.10) which contributed to increases in the O3I (p < .001, d = 2.16) and the EPA:AA ratio (p = .001, d = 0.83) and a reduction in the w-6: w-3 ratio (p < .001, d = 1.80). w-3 FA supplementation attenuated elevations in Nf-L (p = .024). The control group experienced a significant increase in Nf-L compared to baseline at several measurement time points (T2, T3, and T4 [p range < .001 - .005, drange = 0.59-0.85]). CONCLUSIONS: These findings suggest a cardio- and neuroprotective effect of combined EPA+DPA+DHA w-3 FA supplementation in American-style football athletes. TRIAL REGISTRATION: This trial was registered with the ISRCTN registry ( ISRCTN90306741 ).

Probiotic Administration Increases Amino Acid Absorption from Plant Protein: a Placebo-Controlled, Randomized, Double-Blind, Multicenter, Crossover Study.

The fate of dietary protein in the gut is determined by microbial and host digestion and utilization. Fermentation of proteins generates bioactive molecules that have wide-ranging health effects on the host. The type of protein can affect amino acid absorption, with animal proteins generally being more efficiently absorbed compared with plant proteins. In contrast to animal proteins, most plant proteins, such as pea protein, are incomplete proteins. Pea protein is low in methionine and contains lower amounts of branched-chain amino acids (BCAAs), which play a crucial role in muscle health. We hypothesized that probiotic supplementation results in favorable changes in the gut microbiota, aiding the absorption of amino acids from plant proteins by the host. Fifteen physically active men (24.2 ± 5.0 years; 85.3 ± 12.9 kg; 178.0 ± 7.6 cm; 16.7 ± 5.8% body fat) co-ingested 20 g of pea protein with either AminoAlta™, a multi-strain probiotic (5 billion CFU L. paracasei LP-DG® (CNCM I-1572) plus 5 billion CFU L. paracasei LPC-S01 (DSM 26760), SOFAR S.p.A., Italy) or a placebo for 2 weeks in a randomized, double-blind, crossover design, separated by a 4-week washout period. Blood samples were taken at baseline and at 30-, 60-, 120-, and 180-min post-ingestion and analyzed for amino acid content. Probiotic administration significantly increased methionine, histidine, valine, leucine, isoleucine, tyrosine, total BCAA, and total EAA maximum concentrations (Cmax) and AUC without significantly changing the time to reach maximum concentrations. Probiotic supplementation can be an important nutritional strategy to improve post-prandial changes in blood amino acids and to overcome compositional shortcomings of plant proteins. ClinicalTrials.gov Identifier: ISRCTN38903788.

The Omega-3 Index in National Collegiate Athletic Association Division I Collegiate Football Athletes.

CONTEXT: The essential omega-3 fatty acids (ω-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibit vital biological roles and are critical for cardiovascular and neurologic health. Compared with the general population, football athletes may be at an increased risk of cardiovascular disease. Further, those same athletes are also exposed to repetitive head impacts, which may lead to long-term neurologic deficits. Both diets high in ω-3 FAs and supplementation with ω-3 FAs have been reported to reduce the risk of cardiovascular disease, and early evidence suggests a potential neuroprotective effect of supplementation. OBJECTIVE: To determine the (1) erythrocyte content of DHA and EPA, as measured by the Omega-3 Index, expressed as a percentage of total fatty acids, in National Collegiate Athletic Association Division I football athletes and (2) distribution across the Omega-3 Index risk zones established for cardiovascular disease: high risk, <4%; intermediate risk, 4% to 8%; and low risk, >8%. DESIGN: Cross-sectional descriptive study. SETTING: Multicenter trial. PATIENTS OR OTHER PARTICIPANTS: Deidentified data including complete erythrocyte fatty acid profile from the 2017-2018 season, age at time of testing, height, weight, and ethnicity were collected from 404 athletes. MAIN OUTCOME MEASURE(S): Omega-3 Index. RESULTS: About 34% of athletes (n = 138) had an Omega-3 Index considered high risk (<4%), and 66% (n = 266) had a risk considered intermediate (4%-8%). None had a low-risk Omega-3 Index. CONCLUSIONS: The Omega-3 Index is a simple, minimally invasive test of ω-3 FA status. Our data indicate that football athletes may be deficient in the ω-3 FAs DHA and EPA. The fact that no athlete had an Omega-3 Index associated with low risk suggests football athletes may be at increased risk for cardiovascular disease in later life.

Protection Before Impact: the Potential Neuroprotective Role of Nutritional Supplementation in Sports-Related Head Trauma.

Even in the presence of underreporting, sports-related concussions/mild traumatic brain injuries (mTBI) are on the rise. In the absence of proper diagnosis, an athlete may return to play prior to full recovery, increasing the risk of second-impact syndrome or protracted symptoms. Recent evidence has demonstrated that sub-concussive impacts, those sustained routinely in practice and competition, result in a quantifiable pathophysiological response and the accumulation of both concussive and sub-concussive impacts sustained over a lifetime of sports participation may lead to long-term neurological impairments and an increased risk of developing neurodegenerative diseases. The pathophysiological, neurometabolic, and neurochemical cascade that initiates subsequent to the injury is complex and involves multiple mechanisms. While pharmaceutical treatments may target one mechanism, specific nutrients and nutraceuticals have been discovered to impact several pathways, presenting a broader approach. Several studies have demonstrated the neuroprotective effect of nutritional supplementation in the treatment of mTBI. However, given that many concussions go unreported and sub-concussive impacts result in a pathophysiological response that, too, may contribute to long-term brain health, protection prior to impact is warranted. This review discusses the current literature regarding the role of nutritional supplements that, when provided before mTBI and traumatic brain injury, may provide neurological protection.

Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season.

OBJECTIVERepetitive subconcussive head trauma is a consequence of participation in contact sports and may be linked to neurodegenerative diseases. The degree of neurological injury caused by subconcussive head trauma is not easily detectible, and this injury does not induce readily identifiable clinical signs or symptoms. Recent advancements in immunoassays make possible the detection and quantification of blood biomarkers linked to head trauma. Identification of a blood biomarker that can identify the extent of neurological injury associated with subconcussive head trauma may provide an objective measure for informed decisions concerning cumulative exposure to subconcussive head trauma. The purpose of the current study was to examine changes in the blood biomarkers of subconcussive head trauma over the course of an American football season.METHODSThirty-five National Collegiate Athletic Association (NCAA) American football athletes underwent blood sampling throughout the course of a football season. Serial samples were obtained throughout the 2016 season, during which the number and magnitude of head impacts changed. Blood samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light polypeptide (NF-L). Athletes were grouped based on their starter status, because athletes identified as starters are known to sustain a greater number of impacts. Between-group differences and time-course differences were assessed.RESULTSIn nonstarters, plasma concentrations of tau decreased over the course of the season, with lower values observed in starters; this resulted in a lower area under the curve (AUC) (starters: 416.78 ± 129.17 pg/ml/day; nonstarters: 520.84 ± 163.19 pg/ml/day; p = 0.050). Plasma concentrations of tau could not be used to discern between starters and nonstarters. In contrast, serum concentrations of NF-L increased throughout the season as head impacts accumulated, specifically in those athletes categorized as starters. The higher serum concentrations of NF-L observed in starters resulted in a larger AUC (starters: 1605.03 ± 655.09 pg/ml/day; nonstarters: 1067.29 ± 272.33 pg/ml/day; p = 0.007). The AUC of the receiver operating characteristic curve analyses displayed fair to modest accuracy to identify athletes who were starters with the use of serum NF-L following periods of repetitive impacts.CONCLUSIONSThe different patterns observed in serum NF-L and plasma tau concentrations provide preliminary evidence for the use of blood biomarkers to detect the neurological injury associated with repetitive subconcussive head trauma. Although further investigation is necessary, such findings might lay the foundation for the further development of an objective measure for the detection of neurological injury caused by subconcussive head trauma.

A Season of American Football Is Not Associated with Changes in Plasma Tau.

American football athletes are routinely exposed to sub-concussive impacts over the course of the season. This study sought to examine the effect of a season of American football on plasma tau, a potential marker of axonal damage. Nineteen National Collegiate Athletic Association (NCAA) football athletes underwent serial blood sampling over the course of the 2014-2015 season at those times in which the number and magnitude of head impacts likely changed. Non-contact sport controls (NCAA men's swim athletes; n = 19) provided a single plasma sample for comparison. No significant differences were observed between control swim athletes and football athletes following a period of non-contact (p = 0.569) or a period of contact (p = 0.076). Football athletes categorized as starters (n = 11) had higher tau concentrations than non-starters (n = 8) following a period of non-contact (p = 0.039) and contact (p = 0.036), but not higher than swimmers (p = 1.000 and p = 1.000, respectively). No difference was noted over the course of the season in football athletes, irrespective of starter status. Despite routine head impacts common to the sport of American football, no changes were observed over the course of the season in football athletes, irrespective of starter status. Further, no difference was observed between football athletes and non-contact control swim athletes following a period of non-contact or contact. These data suggest that plasma tau is not sensitive enough to detect damage associated with repetitive sub-concussive impacts sustained by collegiate-level football athletes.

A Positive Vestibular/Ocular Motor Screening (VOMS) Is Associated With Increased Recovery Time After Sports-Related Concussion in Youth and Adolescent Athletes.

BACKGROUND: Vestibular and ocular motor impairments are routinely reported in patients with sports-related concussion (SRC) and may result in delayed return to play (RTP). The Vestibular/Ocular Motor Screening (VOMS) assessment has been shown to be consistent and sensitive in identifying concussion when used as part of a comprehensive examination. To what extent these impairments or symptoms are associated with length of recovery is unknown. PURPOSE: To examine whether symptom provocation or clinical abnormality in specific domains of the VOMS results in protracted recovery (time from SRC to commencement of RTP protocol). STUDY DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: A retrospective chart review was conducted of 167 patients (69 girls, 98 boys; mean ± SD age, 15 ± 2 years [range, 11-19 years]) presenting with SRC in 2014. During the initial visit, VOMS was performed in which symptom provocation or clinical abnormality (eg, unsmooth eye movements) was documented by use of a dichotomous scale (0 = not present, 1 = present). The VOMS used in this clinic consisted of smooth pursuits (SMO_PUR), horizontal and vertical saccades (HOR_SAC and VER_SAC), horizontal and vertical vestibular ocular reflex (HOR_VOR and VER_VOR), near point of convergence (NPC), and accommodation (ACCOM). Domains were also categorized into ocular motor (SMO_PUR, HOR_SAC, VER_SAC, NPC, ACCOM) and vestibular (HOR_VOR, VER_VOR). Cox proportional hazard models were used to explore the relationship between the domains and recovery. Alpha was set at P ≤ .05. RESULTS: Symptom provocation and/or clinical abnormality in all domains except NPC ( P = .107) and ACCOM ( P = .234) delayed recovery (domain, hazard ratio [95% CI]: SMO_PUR, 0.65 [0.47-0.90], P = .009; HOR_SAC, 0.68 [0.50-0.94], P = .018; VER_SAC, 0.55 [0.40-0.75], P < .001; HOR_VOR, 0.68 [0.49-0.94], P = .018; VER_VOR, 0.60 [0.44-0.83], P = .002). The lowest crude hazard ratio was for ocular motor category (0.45 [0.32-0.63], P < .001). CONCLUSION: These data suggest that symptom provocation/clinical abnormality associated with all domains except NPC and ACCOM can delay recovery after SRC in youth and adolescents. Thus, the VOMS not only may augment current diagnostic tools but also may serve as a predictor of recovery time in patients with SRC. The findings of this study may lead to more effective prognosis of concussion in youth and adolescents.

Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise.

Probiotics have immunomodulatory effects. However, little is known about the potential benefit of probiotics on the inflammation subsequent to strenuous exercise. In a double-blind, randomized, placebo controlled, crossover design separated by a 21-day washout, 15 healthy resistance-trained men ingested an encapsulated probiotic Streptococcus (S.) thermophilus FP4 and Bifidobacterium (B.) breve BR03 at 5 bn live cells (AFU) concentration each, or a placebo, daily for 3 weeks prior to muscle-damaging exercise (ClinicalTrials.gov NCT02520583). Isometric strength, muscle soreness, range of motion and girth, and blood interleukin-6 (IL-6) and creatine kinase (CK) concentrations were measured from pre- to 72 h post-exercise. Statistical analysis was via mixed models and magnitude-based inference to the standardized difference. Probiotic supplementation resulted in an overall decrease in circulating IL-6, which was sustained to 48 h post-exercise. In addition, probiotic supplementation likely enhanced isometric average peak torque production at 24 to 72 h into the recovery period following exercise (probiotic-placebo point effect ±90% CI: 24 h, 11% ± 7%; 48 h, 12% ± 18%; 72 h, 8% ± 8%). Probiotics also likely moderately increased resting arm angle at 24 h (2.4% ± 2.0%) and 48 h (1.9% ± 1.9%) following exercise, but effects on soreness and flexed arm angle and CK were unclear. These data suggest that dietary supplementation with probiotic strains S. thermophilus FP4 and B. breve BR03 attenuates performance decrements and muscle tension in the days following muscle-damaging exercise.