The purpose of this study was to determine whether the effects of cumulative head impacts during a season of high school football produce changes in diffusional kurtosis imaging (DKI) metrics in the absence of clinically diagnosed concussion. Subjects were recruited from a high school football team and were outfitted with the Head Impact Telemetry System (HITS) during all practices and games. Biomechanical head impact exposure metrics were calculated, including: total impacts, summed acceleration, and Risk Weighted Cumulative Exposure (RWE). Twenty-four players completed pre-and post-season magnetic resonance imaging, including DKI; players who experienced clinical concussion were excluded. Fourteen subjects completed pre-and post-season Immediate Post-Concussion Assessment and Cognitive Testing (Im-PACT). DKI-derived metrics included mean kurtosis (MK), axial kurtosis (K axial), and radial kurtosis (K radial), and white matter modeling (WMM) parameters included axonal water fraction, tortuosity of the extra-axonal space, extraaxonal diffusivity (D e axial and radial), and intra-axonal diffusivity (D a ). These metrics were used to determine the total number of abnormal voxels, defined as 2 standard deviations above or below the group mean. Linear regression analysis revealed a statistically significant relationship between RWE combined probability (RWE CP ) and MK. Secondary analysis of other DKI-derived and WMM metrics demonstrated statistically significant linear relationships with RWE CP after covariate adjustment. These results were compared with the results of DTI-derived metrics from the same imaging sessions in this exact same cohort. Several of the DKI-derived scalars (D a , MK, K axial, and K radial) explained more variance, compared with RWE CP , suggesting that DKI may be more sensitive to subconcussive head impacts. No significant relationships between DKI-derived metrics and ImPACT measures were found. It is important to note that the pathological implications of these metrics are not well understood. In summary, we demonstrate a single season of high school football can produce DKI measurable changes in the absence of clinically diagnosed concussion.Keywords: concussion; diffusion kurtosis imaging; football; Head Impact Telemetry System; Risk Weighted Cumulative Exposure Introduction F ootball has the highest concussion rate of any competitive contact sport.1 Parents, coaches, and physicians of youth athletes are becoming increasingly concerned about the effects of head impacts. These concerns are reflected in the recent 9.5% decrease in participation in the Pop Warner youth football program.2 While concussion can represent a serious and immediate clinical manifestation of any head impact, the effects of repeated subconcussive impacts on youth and high school populations are largely unknown.Previous research has focused primarily on collegiate football players. [3][4][5][6][7] Recent biomechanical studies of head impacts have shown impact distributions for youth and high school players to ...

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Acute onset of encephalopathy is often due to infections or intoxications, but a high index of suspicion should exist for metabolic or autoimmune causes particularly in recurrent cases. A 6-year-old previously healthy Caucasian male presented with confusion and somnolence. He had several days of fever, myalgia, headaches, and rhinorrhea and was influenza-A positive. He was noted to have new urinary incontinence, inability to follow commands, and was responsive only to noxious stimuli. His neurological examination revealed bilateral ankle clonus. Laboratory results were significant for hypoglycemia and high anion gap metabolic acidosis. Cerebrospinal fluid was unremarkable and cultures remained negative. A magnetic resonance imaging (MRI) of the brain showed diffuse gray matter restricted diffusion. His presentation was attributed to acute influenza-A encephalitis. Four months later, he presented with emesis, abdominal pain, dehydration, and hypoglycemia. He subsequently developed dysarthria and confusion. A brain MRI was similar to his previous presentation. A repeat lumbar puncture was normal. A urine organic acid profile showed elevations of ketones and branched chain ketoacids, with mild elevations of N-acetylleucine and N-acetyl isoleucine. This pattern is consistent with maple syrup urine disease (MSUD). Genetic testing revealed that he is a heterozygote for 2 pathogenic variants in the BCKDHB gene (P200X and G278S), confirming MSUD. This case highlights the importance of broadening workup to include inborn errors of metabolism in cases of unexplained encephalopathy. Providers should be aware that diseases such as MSUD can occur in intermittent forms that may not be detected until early childhood.