Biomarkers of Drug Resistance in Temporal Lobe Epilepsy in Adults

Panina, Yulia S.; Timechko, Elena E.; Usoltseva, A. А.; Yakovleva, Kristina D.; Кантимирова, Е. А.; Дмитренко, Д. В.

doi:10.3390/metabo13010083

Cited by 14 publications

(8 citation statements)

References 49 publications

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“…82 Interestingly, in a cohort of adults with drug-resistant temporal lobe epilepsy, plasma HMGB1 levels were lower than controls and were not affected by seizure severity. 83 In our setting, LFPI or early seizures did not alter plasma HMGB1 levels. Similarly, LEV treatment was associated with elevated plasma 7d-IL-1β levels, but there was no significant effect of early seizures or LFPI on plasma IL-1β levels.…”

Section: Discussionmentioning

confidence: 42%

“…Seizures may result in increased HMGB1 plasma levels during the first postictal hours in humans, 80,81 and in rats 4d after status epilepticus 82 . Interestingly, in a cohort of adults with drug‐resistant temporal lobe epilepsy, plasma HMGB1 levels were lower than controls and were not affected by seizure severity 83 . In our setting, LFPI or early seizures did not alter plasma HMGB1 levels.…”

Section: Discussionmentioning

confidence: 44%

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Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

et al. 2023

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Objective We used the lateral fluid percussion injury (LFPI) model of moderate‐to‐severe traumatic brain injury (TBI) to identify early plasma biomarkers predicting injury, early post‐traumatic seizures or neuromotor functional recovery (neuroscores), considering the effect of levetiracetam, which is commonly given after severe TBI. Methods Adult male Sprague–Dawley rats underwent left parietal LFPI, received levetiracetam (200 mg/kg bolus, 200 mg/kg/day subcutaneously for 7 days [7d]) or vehicle post‐LFPI, and were continuously video‐EEG recorded (n = 14/group). Sham (craniotomy only, n = 6), and naïve controls (n = 10) were also used. Neuroscores and plasma collection were done at 2d or 7d post‐LFPI or equivalent timepoints in sham/naïve. Plasma protein biomarker levels were determined by reverse phase protein microarray and classified according to injury severity (LFPI vs. sham/control), levetiracetam treatment, early seizures, and 2d‐to‐7d neuroscore recovery, using machine learning. Results Low 2d plasma levels of Thr231‐phosphorylated tau protein (pTAU‐Thr231) and S100B combined (ROC AUC = 0.7790) predicted prior craniotomy surgery (diagnostic biomarker). Levetiracetam‐treated LFPI rats were differentiated from vehicle treated by the 2d‐HMGB1, 2d‐pTAU‐Thr231, and 2d‐UCHL1 plasma levels combined (ROC AUC = 0.9394) (pharmacodynamic biomarker). Levetiracetam prevented the seizure effects on two biomarkers that predicted early seizures only among vehicle‐treated LFPI rats: pTAU‐Thr231 (ROC AUC = 1) and UCHL1 (ROC AUC = 0.8333) (prognostic biomarker of early seizures among vehicle‐treated LFPI rats). Levetiracetam‐resistant early seizures were predicted by high 2d‐IFNγ plasma levels (ROC AUC = 0.8750) (response biomarker). 2d‐to‐7d neuroscore recovery was best predicted by higher 2d‐S100B, lower 2d‐HMGB1, and 2d‐to‐7d increase in HMGB1 or decrease in TNF (P < 0.05) (prognostic biomarkers). Significance Antiseizure medications and early seizures need to be considered in the interpretation of early post‐traumatic biomarkers.

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Section: Discussionmentioning

confidence: 42%

Section: Discussionmentioning

confidence: 44%

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

et al. 2023

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“…In experimental models, a dependence was found between the expression of a number of proteins and the stage of the course of the disease [ 19 , 20 ], in particular: different stages of pathogenesis can demonstrate not only quantitatively, but also qualitatively, different expression patterns. Additionally, in our earlier study [ 21 ], a significant decrease in TNFa expression in the plasma of patients with TLE with a disease experience of more than 10 years was found, compared with patients with a shorter disease experience. Additionally, most studies do not indicate the age of patients and the duration of the disease.…”

Section: Resultsmentioning

confidence: 80%

Mass Spectrometry as a Quantitative Proteomic Analysis Tool for the Search for Temporal Lobe Epilepsy Biomarkers: A Systematic Review

Timechko,

Yakimov,

Paramonova

et al. 2023

IJMS

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Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the expression patterns of protein molecules. The study of mRNA and its corresponding proteins is crucial for understanding the pathogenesis of the disease. Protein expression profiles do not always directly correlate with the levels of their transcripts; therefore, it is protein profiling that is no less important for understanding the molecular mechanisms and biological processes of TLE. The study and annotation of proteins that are statistically significantly different in patients with TLE is an approach to search for biomarkers of this disease, various stages of its development, as well as a method for searching for specific targets for the development of a further therapeutic strategy. When writing a systematic review, the following aggregators of scientific journals were used: MDPI, PubMed, ScienceDirect, Springer, and Web of Science. Scientific articles were searched using the following keywords: “proteomic”, “mass-spectrometry”, “protein expression”, “temporal lobe epilepsy”, and “biomarkers”. Publications from 2003 to the present have been analyzed. Studies of brain tissues, experimental models of epilepsy, as well as biological fluids, were analyzed. For each of the groups, aberrantly expressed proteins found in various studies were isolated. Most of the studies omitted important characteristics of the studied patients, such as: duration of illness, type and response to therapy, gender, etc. Proteins that overlap across different tissue types and different studies have been highlighted: DPYSL, SYT1, STMN1, APOE, NME1, and others. The most common biological processes for them were the positive regulation of neurofibrillary tangle assembly, the regulation of amyloid fibril formation, lipoprotein catabolic process, the positive regulation of vesicle fusion, the positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, removal of superoxide radicals, axon extension, and the regulation of actin filament depolymerization. MS-based proteomic profiling for a relevant study must accept a number of limitations, the most important of which is the need to compare different types of neurological and, in particular, epileptic disorders. Such a criterion could increase the specificity of the search work and, in the future, lead to the discovery of biomarkers for a particular disease.

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“…Conflicting results were observed in only one study that was part of our review. Panina et al [51]. discovered that, in contrast to a control group, patients with both controlled and refractory temporal lobe epilepsy had decreased serum HMGB1 levels.…”

Section: Hmgb1mentioning

confidence: 99%

Biomarkers of Neuroinflammation and Epileptogenesis: A Systematic Review

Aguilar-Castillo,

Cabezudo-García,

Garcia-Martin

et al. 2024

Preprint

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Introduction: A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). Material and Methods: The study analysed articles published in JCR journals from 2019 to 2024, including retrospective, prospective, case-control, or cross-sectional studies. It combined MESH and free terms for "Epileptogenesis" and "Neuroinflammation" and included searches for biomarkers previously reported in narrative reviews. Results: The study analysed 243 articles related to epileptogenesis and neuroinflammation, with 356 from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 52 evaluated by authors. 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. This systematic review provides acceptable support for five biomarkers: TNF-a and some of its soluble receptors (sTNFr2), HMGB1 and TLR-4, CCL2 and IL-33. Discussions: Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control levels of epileptic patients. Their value will be better defined by future studies.

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Biomarkers of Drug Resistance in Temporal Lobe Epilepsy in Adults

Cited by 14 publications

References 49 publications

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

Mass Spectrometry as a Quantitative Proteomic Analysis Tool for the Search for Temporal Lobe Epilepsy Biomarkers: A Systematic Review

Biomarkers of Neuroinflammation and Epileptogenesis: A Systematic Review

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