Tag: Biomarkers

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Circulating Brain Injury Biomarkers: A Novel Method for Quantification of the Impact on the Brain After Tumor Surgery

Neurosurgery 93:847–856, 2023

Clinical methods to quantify brain injury related to neurosurgery are scarce. Circulating brain injury biomarkers have recently gained increased interest as new ultrasensitive measurement techniques have enabled quantification of brain injury through blood sampling.

OBJECTIVE: To establish the time profile of the increase in the circulating brain injury biomarkers glial fibrillary acidic protein (GFAP), tau, and neurofilament light (NfL) after glioma surgery and to explore possible relationships between these biomarkers and outcome regarding volume of ischemic injury identified with postoperative MRI and new neurological deficits.

METHODS: In this prospective study, 34 adult patients scheduled for glioma surgery were included. Plasma concentrations of brain injury biomarkers were measured the day before surgery, immediately after surgery, and on postoperative days 1, 3, 5, and 10.

RESULTS: Circulating brain injury biomarkers displayed a postoperative increase in the levels of GFAP (P < .001), tau (P < .001), and NfL (P < .001) on Day 1 and a later, even higher, peak of NFL at Day 10 (P = .028). We found a correlation between the increased levels of GFAP, tau, and NfL on Day 1 after surgery and the volume of ischemic brain tissue on postoperative MRI. Patients with new neurological deficits after surgery had higher levels of GFAP and NfL on Day 1 compared with those without new neurological deficits.

CONCLUSION: Measuring circulating brain injury biomarkers could be a useful method for quantification of the impact on the brain after tumor surgery or neurosurgery in general.

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Blood Biomarkers and Structural Imaging Correlations Post-Traumatic Brain Injury: A Systematic Review

Neurosurgery 90:170–179, 2022

Blood biomarkers are of increasing importance in the diagnosis and assessment of traumatic brain injury (TBI). However, the relationship between them and lesions seen on imaging remains unclear.

OBJECTIVE: To perform a systematic review of the relationship between blood biomarkers and intracranial lesion types, intracranial lesion injury patterns, volume/number of intracranial lesions, and imaging classification systems.

METHODS: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica dataBASE, and Cumulative Index to Nursing and Allied Health Literature from inception to May 2021, and the references of included studies were also screened. Heterogeneity in study design, biomarker types, imaging modalities, and analyses inhibited quantitative analysis, with a qualitative synthesis presented.

RESULTS: Fifty-nine papers were included assessing one or more biomarker to imaging comparisons per paper: 30 assessed imaging classifications or injury patterns, 28 assessed lesion type, and 11 assessed lesion volume or number. Biomarker concentrations were associated with the burden of brain injury, as assessed by increasing intracranial lesion volume, increasing numbers of traumatic intracranial lesions, and positive correlations with imaging classification scores. There were inconsistent findings associating different biomarkers with specific imaging phenotypes including diffuse axonal injury, cerebral edema, and intracranial hemorrhage.

CONCLUSION: Blood-based biomarker concentrations after TBI are consistently demonstrated to correlate burden of intracranial disease. The relation with specific injury types is unclear suggesting a lack of diagnostic specificity and/or is the result of the complex and heterogeneous nature of TBI.

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Role of Biomarkers in Adaptive Modulation of Clinical Brain Stimulation

Neurosurgery, Volume 85, Issue 3, September 2019:  E430–E439

Therapeutic brain stimulation has proven efficacious for treatment of nervous system diseases, exerting widespread influence via disease-specific neural networks. Activation or suppression of neural networks could theoretically be assessed by either clinical symptom modification (ie, tremor, rigidity, seizures) or development of specific biomarkers linked to treatment of symptomatic disease states.

For example, biomarkers indicative of disease state could aid improved intraoperative localization of electrode position, optimize device efficacy or efficiency through dynamic control, and eventually serve to guide automatic adjustment of stimulation settings.

Biomarkers to control either extracranial or intracranial stimulation span from continuous physiological brain activity, intermittent pathological activity, and triggered local phenomena or potentials, to wearable devices, blood flow, biochemical or cardiac signals, temperature perturbations, optical or magnetic resonance imaging changes, or optogenetic signals.

The goal of this review is to update new approaches to implement control of stimulation through relevant biomarkers. Critical questions include whether adaptive systems adjusted through biomarkers can optimize efficiency and eventually efficacy, serve as inputs for stimulation adjustment, and consequently broaden our fundamental understanding of abnormal neural networks in pathologic states.

Neurosurgeons are at the forefront of translating and developing biomarkers embedded within improved brain stimulation systems. Thus, criteria for developing and validating biomarkers for clinical use are important for the adaptation of device approaches into clinical practice.

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Molecular stereotactic biopsy technique improves diagnostic accuracy and enables personalized treatment strategies in glioma patients

Molecular stereotactic biopsy technique

Acta Neurochir (2014) 156:1427–1440

In gliomas molecular biomarkers are increasingly gaining diagnostic, prognostic and predictive significance. Determination of biomarker status after biopsy is important as not all patients are eligible for open tumor resection.We developed and validated prospectively (6/10–12/11) a protocol allowing for both reliable determination of multiple biomarkers and representative histological diagnoses from small-sized biopsies.

Methods All molecular stereotactic biopsies were performed according to a detailed workflow. The selection of specimens best suited for molecular analyses was intra-operatively guided by the attending neuropathologist. Postoperative screening was done by methylation specific PCR using two distinct cryopreserved specimens to test for reproducibility of the findings and to rule out contamination. The DNA of a single best-suited specimen (1 mm3) was subjected to detailed molecular analysis (MGMT promoter methylation, IDH1/2 mutational status, LOH 1p and/or 19q).

Results 159 consecutively enrolled untreated gliomas were analyzed (94 glioblastomas, 2 gliosarcomas, 24 anaplastic astrocytomas, 10 oligo-tumors grade II/III, 20 grade II astrocytomas and 9 pilocytic astrocytomas). Transient morbidity was 2 %. Overall, the drop-out rate due to tissue contamination was 0.4 %. Median time from biopsy to histological and molecular genetic analyses was 3 and 5 days, respectively. Distributions of the respective biomarker status for tumor subgroups were consistent with the literature. The final histological diagnosis was changed/modified in 5/159 patients according to molecular findings. Treatment after molecular biopsy was highly personalized.

Conclusions Molecular stereotactic biopsy is feasible and safe, can be implemented in daily clinical practice, improves diagnostic precision and enables personalized treatment. Keywords

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Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics

Purpose  This review summarizes protein biomarkers in mild and severe traumatic brain injury in adults and children and presents a strategy for conducting rationally designed clinical studies on biomarkers in head trauma.
Methods  We performed an electronic search of the National Library of Medicine’s MEDLINE and Biomedical Library of University of Pennsylvania database in March 2008 using a search heading of traumatic head injury and protein biomarkers. The search was focused especially on protein degradation products (spectrin breakdown product, c-tau, amyloid-β1–42) in the last 10 years, but recent data on “classical” markers (S-100B, neuron-specific enolase, etc.) were also examined.
Results  We identified 85 articles focusing on clinical use of biomarkers; 58 articles were prospective cohort studies with injury and/or outcome assessment.
Conclusions  We conclude that only S-100B in severe traumatic brain injury has consistently demonstrated the ability to predict injury and outcome in adults. The number of studies with protein degradation products is insufficient especially in the pediatric care. Cohort studies with well-defined end points and further neuroproteomic search for biomarkers in mild injury should be triggered. After critically reviewing the study designs, we found that large homogenous patient populations, consistent injury, and outcome measures prospectively determined cutoff values, and a combined use of different predictors should be considered in future studies.
Doi: 10.1007/s00701-009-0463-6
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