Temporal response profiles of serum ubiquitin C-terminal hydrolase-L1 and the 145-kDa alpha II-spectrin breakdown product after severe traumatic brain injury in children.

OBJECTIVE: Traumatic brain injury (TBI) is the leading cause of acquired disability among children. Brain injury biomarkers may serve as useful diagnostic and prognostic indicators for TBI. Levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and the 145-kDa alpha II-spectrin breakdown product (SBDP-145) correlate with outcome in adults after severe TBI. The authors conducted a pilot study of these biomarkers in children after severe TBI to inform future research exploring their utility in this population. METHODS: The levels of UCH-L1 and SBDP-145 were measured in serum, and UCH-L1 in CSF from pediatric patients after severe TBI over 5 days after injury. Both biomarkers were also measured in age-matched control serum and CSF. RESULTS: Adequate numbers of samples were obtained in serum, but not CSF, to assess biomarker temporal response profiles. Using patients with samples from all time points, UCH-L1 levels increased rapidly and transiently, peaking at 12 hours after injury. SBDP-145 levels showed a more gradual and sustained response, peaking at 48 hours. The median serum UCH-L1 concentration was greater in patients with TBI than in controls (median [IQR] = 361 [187, 1330] vs 147 [50, 241] pg/ml, respectively; p < 0.001). Receiver operating characteristic (ROC) analysis revealed an AUC of 0.77. Similarly, serum SBDP-145 was greater in children with TBI than in controls (median [IQR] = 172 [124, 257] vs 69 [40, 99] pg/ml, respectively; p < 0.001), with an ROC AUC of 0.85. When only time points of peak levels were used for ROC analysis, the discriminability of each serum biomarker increased (AUC for UCH-L1 at 12 hours = 1.0 and for SBDP-145 at 48 hours = 0.91). Serum and CSF UCH-L1 levels correlated well in patients with TBI (r = 0.70, p < 0.001). CONCLUSIONS: Findings from this exploratory study reveal robust increases of UCH-L1 and SBDP-145 in serum and UCH-L1 in CSF obtained from children after severe TBI. In addition, important temporal profile differences were found between these biomarkers that can help guide optimal time point selection for future investigations of their potential to characterize injury or predict outcomes after pediatric TBI.

Clinical reasoning: a 12-year-old boy with ascending weakness.

A 12-year-old boy presented with 3 weeks of calf pain, tripping, and progressive inability to walk. The onset was preceded by a sore throat 4 weeks prior, but no recent immunizations and no sick contacts. He began having problems "catching his toes" for 2 weeks. He had no visual complaints and no bowel or bladder incontinence. He had no recent travel and there were no heavy metal or solvent exposures. He had no prior medical history and he was on no prescription medications. Developmentally, he was on track and had just successfully completed fifth grade. However, he was reported to be behaviorally oppositional, especially regarding his diet which was restricted to beef jerky, yogurt from a squeeze tube, and fruit drinks. Family history included diabetic peripheral neuropathy in his mother, idiopathic peripheral neuropathy in his maternal grandfather, and left lower extremity neuropathy from trauma in his father. There was no known family history of recurrent pressure palsies or cardiac problems.

Drugs in pediatric ischemic stroke.

Traditionally, drug therapy for pediatric ischemic stroke has been extrapolated from adult guidelines and studies. This approach is not optimal due to important differences between adult and pediatric stroke (e.g. etiologies, maturation changes in hemostasis). Research in pediatric stroke is increasing, and pediatric specific management guidelines have recently become available. This manuscript summarizes available drug therapy recommendations for pediatric ischemic stroke. Both acute management and secondary stroke prevention are discussed, including antiplatelet, anticoagulant, and thrombolytic drugs. When relevant, recommendations from adult ischemic stroke guidelines and data from pediatric stroke studies are incorporated.

Methylenetetrahydrofolate reductase gene polymorphism and childhood stroke.

Genotyping for the methylenetetrahydrofolate reductase gene (MTHFR) has been recommended for part of the evaluation for underlying prothrombotic state in childhood stroke; however, studies are inconclusive regarding the role of this gene and also the role of hyperhomocysteinemia, which is the putative mechanism by which MTHFR polymorphism is related to stroke. The prevalence of MTHFR polymorphism in childhood arterial ischemic stroke and cerebral sinovenous thrombosis was compared with that of a reference population, and prevalence of hyperhomocysteinemia was reviewed. In arterial ischemic stroke, the prevalence of at-risk methylenetetrahydrofolate reductase genotypes was 27%, and in cerebral sinovenous thrombosis it was 13%; the population prevalence was 26%. The odds ratio for at-risk genotype in childhood arterial ischemic stroke was 1.06 (95% confidence interval, 0.22-4.0); in cerebral sinovenous thrombosis, it was 0.42 (95% confidence interval, 0.01-3.6). No tested cases had hyperhomocysteinemia. MTHFR polymorphism and hyperhomocysteinemia were not risk factors in childhood arterial ischemic stroke or cerebral sinovenous thrombosis in the Intermountain West region.

Do nonspecific focal EEG slowing and epileptiform abnormalities favor one hemisphere?

PURPOSE: Several EEG-based studies suggest that epileptiform activity originates from the left more than the right hemisphere. In contrast, other pathophysiologies such as stroke lateralize relatively symmetrically. Study of focal slowing and other EEG abnormalities allows assessment of favoring as well as referral and interpretation bias. METHODS: The 1,331 consecutive adult EEG reports were reviewed for epileptiform discharges (EDs) and nonepileptiform focal slowing. Side of slowing or EDs, interpreting electoencephalographer, and whether the patient was undergoing long-term monitoring or routine EEG were tallied. Results were statistically analyzed. RESULTS: Focal slowing occurred symmetrically; EDs favored the left hemisphere (p < 0.01). CONCLUSIONS: The left hemisphere may be more prone to epileptiform abnormalities in adults, but not to the nonspecific pathophysiologic processes that cause slowing. These findings suggest that potential interpretation bias does not influence left hemispheric favoring of EDs and instead may implicate a biologic etiology.