Clinical Characteristics and Outcomes of Children with Acute Catastrophic Brain Injury: A 13-Year Retrospective Cohort Study.

BACKGROUND: The purpose of this study was to describe and analyze clinical characteristics and outcomes in children with acute catastrophic brain injury (CBI). METHODS: This was a single-center, 13-year (2008-2020) retrospective cohort study of children in the pediatric and cardiac intensive care units with CBI, defined as (1) acute neurologic injury based on clinical and/or imaging findings, (2) the need for life-sustaining intensive care unit therapies, and (3) death or survival with a Glasgow Coma Scale score < 13 at discharge. Patients were excluded if they were discharged directly to home < 14 days from admission or had a chronic neurologic condition with a baseline Glasgow Coma Scale score < 13. The association between the primary outcome of death and clinical variables was analyzed by using Kaplan-Meier estimates and multivariable Cox proportional hazard models. Outcomes assessed after discharge were technology dependence, neurologic deficits, and Functional Status Score. Improved functional status was defined as a change in total Functional Status Score [Formula: see text] 2. RESULTS: Of 106 patients (58% boys, median age 3.9 years) with CBI, 86 (81%) died. Withdrawal of life-sustaining therapies was the most common cause of death (60 of 86, 70%). In our multivariable analysis, each unit increase in admission pediatric sequential organ failure assessment score was associated with 10% greater hazard of death (hazard ratio 1.10, 95% confidence interval 1.04-1.17, p < .01). After controlling for admission pediatric sequential organ failure assessment scores, compared with those of patients with traumatic brain injury, all other etiologies of CBI were associated with a greater hazard of death (p = .02; hazard ratio 3.76-10). The median survival time for the cohort was 22 days (95% confidence interval 14-37 days). Of 23 survivors to hospital discharge, 20 were still alive after a median of 2 years (interquartile range 1-3 years), 6 of 20 (30%) did not have any technology dependence, 12 of 20 (60%) regained normal levels of alertness and responsiveness, and 15 of 20 (75%) had improved functional status. CONCLUSIONS: Most children with acute CBI died within 1 month of hospitalization. Having traumatic brain injury as the etiology of CBI was associated with greater survival, whereas increased organ dysfunction score on admission was associated with a higher hazard of mortality. Of the survivors, some recovered consciousness and functional status and did not require permanent technology dependence. Larger prospective studies are needed to improve prediction of CBI among critically ill children, understand factors guiding clinician and family decisions on the continuation or withdrawal of life-sustaining treatments, and characterize the natural history and long-term outcomes among CBI survivors.

Recurrent Encephalopathy During Febrile Illnesses in a 6-Year-Old Boy.

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.

Head drop after botox: Electrodiagnostic evaluation of iatrogenic botulinum toxicity.

BACKGROUND: Botulinum is a potent neurotoxin with increasing indications for neurologic disorders. While clinical benefit manifests primarily due to local actions at the neuromuscular junction, regional and systemic effects do occur. Rarely, systemic symptoms including weakness, dysarthria, dysphagia and other side effects occur as a result of iatrogenic botulinum neurotoxicity. CASE: A 72 year-old female with right leg dystonia developed head drop, bulbar and systemic weakness following right lower extremity botulinum toxin injection. Routine nerve conduction studies were normal. Repetitive stimulation of the spinal accessory nerve showed decrement; electromyography (EMG) demonstrated slightly small units with subtle signs of denervation, and single fiber EMG revealed increased jitter with blocking, all of which are consistent with systemic botulism. CONCLUSION: This case highlights and reviews the important electrodiagnostic features of iatrogenic systemic botulinum neurotoxicity.

Abnormalities in Diffusional Kurtosis Metrics Related to Head Impact Exposure in a Season of High School Varsity Football.

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 (ImPACT). 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, extra-axonal diffusivity (De axial and radial), and intra-axonal diffusivity (Da). 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 (RWECP) and MK. Secondary analysis of other DKI-derived and WMM metrics demonstrated statistically significant linear relationships with RWECP 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 (Da, MK, K axial, and K radial) explained more variance, compared with RWECP, 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.