Serum Biochemical Markers for Brain Damage in Children with Emphasis on Mild Head Injury

Menascu, Shay; Brezner, Amichai; Tshechmer, Shany M; Rumeny, Peter G

doi:10.1159/000319004

Cited by 10 publications

(6 citation statements)

References 77 publications

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“…Based on these prior studies and the fact that neurologic injury commonly occurs in infants and children with CHD, we hypothesized that SBDPs would be readily detectable in the serum of neonates with CHD in the perioperative period. Because accessing CSF is impractical following heart surgery, the ability to detect SBDPs in circulating blood carries importance because candidate biomarkers should be able to cross the blood-brain barrier following injury to enable ease of measurability (21). Furthermore, because alpha II-spectrin is not found in RBCs, breakdown of the protein and generation of SBDPs are not confounded by hemolysis commonly encountered during heart surgery (3).…”

Section: Discussionmentioning

confidence: 99%

Detection of Alpha II-Spectrin Breakdown Products in the Serum of Neonates With Congenital Heart Disease*

Jain¹,

Spaeder²,

Donofrio³

et al. 2014

Pediatric Critical Care Medicine

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Objectives To determine if alpha II-spectrin breakdown products can be detected in the serum of neonates with congenital heart disease in the perioperative period. Design Prospective observational cohort study. Setting Pediatric cardiac ICU in an urban tertiary care academic center. Patients Neonates with congenital heart disease undergoing surgical repair or palliation. Interventions Serial blood sampling for measurement of 120 and 150 kDa spectrin breakdown products. Measurements and Main Results Fourteen neonates with congenital heart disease undergoing cardiac surgery were evaluated. Nine infants underwent open-heart surgery and five underwent closed-heart surgery. Serum spectrin breakdown products were measured with sandwich enzyme-linked immunosorbent assay preoperatively and then 6, 24, 48, 72, and 96 hours following surgery. Brain imaging was obtained as part of routine clinical care in 12 patients pre-operatively and six patients postoperatively. Six patients had normal preoperative imaging (three closed-heart surgery and three open-heart surgery), whereas six had evidence of neurologic injury prior to surgery (one closed-heart surgery and five open-heart surgery). Only one patient had a postoperative imaging study that lacked injury. All others demonstrated infarction or hemorrhage. Spectrin breakdown product 120 kDa significantly increased 24 hours after open-heart surgery compared to preoperative values and time-matched closed-heart surgery levels. Spectrin breakdown product 150 kDa significantly increased 6 hours after open-heart surgery compared to preoperative values. There was no significant change in spectrin breakdown products following closed-heart surgery. Peak spectrin breakdown products significantly increased following open-heart surgery compared to closed-heart surgery. Conclusions Spectrin breakdown products can be detected in the serum of neonates with congenital heart disease in the perioperative period and levels increased to a greater degree in infants following open-heart surgery. These findings suggest that, in future work, serum spectrin breakdown products may potentially be developed as biomarkers for brain necrosis and apoptosis in infants with congenital heart disease.

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Section: Discussionmentioning

confidence: 99%

Detection of Alpha II-Spectrin Breakdown Products in the Serum of Neonates With Congenital Heart Disease*

Jain¹,

Spaeder²,

Donofrio³

et al. 2014

Pediatric Critical Care Medicine

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“…Because of the non-specificity of subjective postconcussive complaints, any lack of a residual biomarker objectively identifying the presence or absence of brain injury limits characterization of injured participants from a neuropsychological standpoint. The 25 reference studies were conducted prior to current objective biomarkers of injury such as those found with diffusion tenor imaging (DTI) and other neuroimaging techniques (Kou et al, 2010;Niogi & Mukherjee, 2010), eye tracking or ocular convergence as a reflection of brainstem integrity (Contreras, Ghajar, Bahar, & Suh, 2011;Heitger et al, 2009), blood biomarkers (Dash, Zhao, Hergenroeder, & Moore, 2010;Kovesdi et al, 2010;Menascu, Brezner, Tshechmer, & Rumeny, 2010), or postural stability (Sheedy, Harvey, Faux, Geffen, & Shores, 2009;Slobounov, Cao, Sebastianelli, Slobounov, & Newell, 2008)-to list the most promising current biomarkers. As previously discussed, the recent studies by Messe et al (2011) andHeitger et al (2009) unmistakably show the importance of using a biomarker when investigating the effects of mTBI.…”

Section: Data Transparency: the Meta-analysis Spread Sheetmentioning

confidence: 99%

Reaffirmed Limitations of Meta-Analytic Methods in the Study of Mild Traumatic Brain Injury: A Response to Rohling et al.

Bigler

Farrer

Pertab

et al. 2013

The Clinical Neuropsychologist

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In 2009 Pertab, James, and Bigler published a critique of two prior meta-analyses by Binder, Rohling, and Larrabee (1997) and Frencham, Fox, and Maybery (2005) that showed small effect size difference at least 3 months post-injury in individuals who had sustained a mild traumatic brain injury (mTBI). The Binder et al. and Frencham et al. meta-analyses have been widely cited as showing no lasting effect of mTBI. In their critique Pertab et al. (2009) point out many limitations of these two prior meta-analyses, demonstrating that depending on how inclusion/exclusion criteria were defined different meta-analytic findings occur, some supporting the persistence of neuropsychological impairments beyond 3 months. Rohling et al. (2011) have now critiqued Pertab et al. (2009). Herein we respond to the Rolling et al. (2011) critique reaffirming the original findings of Pertab et al. (2009), providing additional details concerning the flaws in prior meta-analytic mTBI studies and the effects on neuropsychological performance.

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“…TBI often involves a combination of mechanical trauma and local hypoxemia, on which serum biomarker concentrations may provide critical therapeutic data to evaluate the brain injury. Serum biomarker after TBI could be used as a source for the identification of the brain injury, the extent of the injury, and the time of its occurrence and even for identifying its most likely outcome [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Determination of Serum Lost Goodwill Target Proteome in Patients with Severe Traumatic Brain Injury

Zhang

et al. 2015

BioMed Research International

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Serum Biochemical Markers for Brain Damage in Children with Emphasis on Mild Head Injury

Cited by 10 publications

References 77 publications

Detection of Alpha II-Spectrin Breakdown Products in the Serum of Neonates With Congenital Heart Disease*

Detection of Alpha II-Spectrin Breakdown Products in the Serum of Neonates With Congenital Heart Disease*

Reaffirmed Limitations of Meta-Analytic Methods in the Study of Mild Traumatic Brain Injury: A Response to Rohling et al.

Determination of Serum Lost Goodwill Target Proteome in Patients with Severe Traumatic Brain Injury

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