Elevated blood purine levels as a biomarker of seizures and epilepsy

Beamer, Edward; Lacey, Austin; Alves, Mariana; Conte, Giorgia; Tian, Faming; Diego-García, Laura de; Khalil, M. I.; Rosenow, Felix; Delanty, Norman; Dale, Nicholas; El‐Naggar, Hany; Henshall, David C.; Engel, Tobías

doi:10.1111/epi.16839

Cited by 23 publications

(22 citation statements)

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“…Our results suggest that analyzing blood purine levels may not only support the detection of NE, but may also help in the identification of infants at risk of neonatal seizures. This would be in good agreement with a previous study showing increased blood purine concentrations following provoked seizures in mice ( Beamer et al, 2021 ). It is tempting to speculate, therefore, that the elevated blood purine levels in infants with NE and seizures are a combination of both hypoxia- and seizure-driven increases in purine release.…”

Section: Discussionsupporting

confidence: 93%

“…Importantly, purine concentrations measured in this study (low μM concentration range) are similar to previous studies using the electrochemical detection approach (i.e., SMARTChip) ( Dale et al, 2019 ; Beamer et al, 2021 ) or studies using other detection techniques (e.g., HPLC) ( Harkness and Lund, 1983 ; Zielinski et al, 2019 ). Moreover, blood purine concentrations at baseline and blood purine increases under pathological conditions (i.e., hypoxia in mice and NE in neonates) are similar between species, demonstrating its translatability from animal models to patients.…”

Section: Discussionsupporting

confidence: 85%

“…Blood purines were measured via SMARTChip in whole blood in P7 mouse pups subjected to hypoxia or normoxia (Control) conditions for 15 min at the time of re-oxygenation ( Figure 1A ). This analysis provides a quantitative and summative analysis of adenosine and the adenosine downstream purines inosine, hypoxanthine and xanthine ( Dale et al, 2019 ; Beamer et al, 2021 ). Hypoxia-induced seizures were confirmed via cranial EEG recordings ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

“…The function of the SMARTChip (Sarissa Biomedical, Coventry, United Kingdom) has previously been described in detail ( Tian D.S. et al, 2017 ; Dale et al, 2019 ; Beamer et al, 2021 ). Briefly, a gel matrix is anchored to a gold-plated electrode and contains a layer of three enzymes allowing for the detection of adenosine, inosine, hypoxanthine and xanthine ( Figure 1A ).…”

Section: Methodsmentioning

confidence: 99%

“…Recently a novel enzyme-based amperometric biosensor (SMARTChip) was demonstrated to detect a summed concentration of the purine nucleoside adenosine and its metabolites, xanthine, hypoxanthine and inosine ( Dale and Frenguelli, 2009 ). Increases in purine nucleoside concentration measured using this tool from whole blood can offer a fast and reliable diagnostic tool for ischemic stroke in adults ( Dale et al, 2019 ), and can distinguish epileptic patients from healthy individuals ( Beamer et al, 2021 ). Here, we investigated whether this approach was also useful in the detection of NE.…”

Section: Introductionmentioning

confidence: 99%

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Novel Point-of-Care Diagnostic Method for Neonatal Encephalopathy Using Purine Nucleosides

Beamer

O’Dea

Garvey

et al. 2021

Front. Mol. Neurosci.

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Background: Evidence suggests that earlier diagnosis and initiation of treatment immediately after birth is critical for improved neurodevelopmental outcomes following neonatal encephalopathy (NE). Current diagnostic tests are, however, mainly restricted to clinical diagnosis with no molecular tests available. Purines including adenosine are released during brain injury such as hypoxia and are also present in biofluids. Whether blood purine changes can be used to diagnose NE has not been investigated to date.Methods: Blood purines were measured in a mouse model of neonatal hypoxia and infants with NE using a novel point-of-care diagnostic technology (SMARTChip) based on the summated electrochemical detection of adenosine and adenosine metabolites in the blood.Results: Blood purine concentrations were ∼2–3-fold elevated following hypoxia in mice [2.77 ± 0.48 μM (Control) vs. 7.57 ± 1.41 μM (post-hypoxia), p = 0.029]. Data in infants with NE had a 2–3-fold elevation when compared to healthy controls [1.63 ± 0.47 μM (Control, N = 5) vs. 4.87 ± 0.92 μM (NE, N = 21), p = 0.0155]. ROC curve analysis demonstrates a high sensitivity (81%) and specificity (80%) for our approach to identify infants with NE. Moreover, blood purine concentrations were higher in infants with NE and seizures [8.13 ± 3.23 μM (with seizures, N = 5) vs. 3.86 ± 0.56 μM (without seizures, N = 16), p = 0.044].Conclusion: Our data provides the proof-of-concept that measurement of blood purine concentrations via SMARTChip technology may offer a low-volume bedside test to support a rapid diagnosis of NE.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel Point-of-Care Diagnostic Method for Neonatal Encephalopathy Using Purine Nucleosides

Beamer

O’Dea

Garvey

et al. 2021

Front. Mol. Neurosci.

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Recent Progress on Biosensors for the Early Detection of Neurological Disorders.

Chougale

Vedante

Kulkarni³

et al. 2022

ChemistrySelect

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Neurological disorders are a point of attraction these days due to their physical, mental, and genetic threat to human beings. The researchers are refining the therapeutics and striving to eradicate the life-threatening burden of chronic diseases by upsurging and proposing advanced instrumentation. There are a number of neurological diseases that cause alterations in the genetic sequences due to pathogenic or self-negligence. According to the WHO, stroke, septicemia, PD, epilepsy, and MS are found to be the deadliest and most invading among millions of people. Various diagnostic methods are employed for monitoring these disorders in the human body at an early stage, in process of cure. The current review highlights the strengths of several advanced detection devices, such as biosensors to identify and quantify biomarkers, some sensing gadgets, and other genetic tactics or innovations to ameliorate traditional protocols. Furthermore, the meticulous description of ongoing experiments with the help of relevant case studies of neurodegenerative disorders supports the impact and vitality of advanced equipment. Further, the necessity of biosensors in distinct disorders to aid in an early diagnosis, and the influence of nano-based materials in preparation is emphasized. Finally, several issues that should be addressed in upcoming decades with the steep rise in analytical technology have been discussed.

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Multiomics and blood-based biomarkers of electroconvulsive therapy in severe and treatment-resistant depression: study protocol of the DetECT study

von Mücke-Heim,

Pape,

Grandi

et al. 2023

Eur Arch Psychiatry Clin Neurosci

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Electroconvulsive therapy (ECT) is commonly used to treat treatment-resistant depression (TRD). However, our knowledge of the ECT-induced molecular mechanisms causing clinical improvement is limited. To address this issue, we developed the single-center, prospective observational DetECT study (“Multimodal Biomarkers of ECT in TRD”; registered 18/07/2022, www.clinicalTrials.gov, NCT05463562). Its objective is to identify molecular, psychological, socioeconomic, and clinical biomarkers of ECT response in TRD. We aim to recruit n = 134 patients in 3 years. Over the course of 12 biweekly ECT sessions (± 7 weeks), participant blood is collected before and 1 h after the first and seventh ECT and within 1 week after the twelfth session. In pilot subjects (first n = 10), additional blood draws are performed 3 and 6 h after the first ECT session to determine the optimal post-ECT blood draw interval. In blood samples, multiomic analyses are performed focusing on genotyping, epigenetics, RNA sequencing, neuron-derived exosomes, purines, and immunometabolics. To determine clinical response and side effects, participants are asked weekly to complete four standardized self-rating questionnaires on depressive and somatic symptoms. Additionally, clinician ratings are obtained three times (weeks 1, 4, and 7) within structured clinical interviews. Medical and sociodemographic data are extracted from patient records. The multimodal data collected are used to perform the conventional statistics as well as mixed linear modeling to identify clusters that link biobehavioural measures to ECT response. The DetECT study can provide important insight into the complex mechanisms of ECT in TRD and a step toward biologically informed and data-driven-based ECT biomarkers.

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Elevated blood purine levels as a biomarker of seizures and epilepsy

Cited by 23 publications

References 50 publications

Novel Point-of-Care Diagnostic Method for Neonatal Encephalopathy Using Purine Nucleosides

Novel Point-of-Care Diagnostic Method for Neonatal Encephalopathy Using Purine Nucleosides

Recent Progress on Biosensors for the Early Detection of Neurological Disorders.

Multiomics and blood-based biomarkers of electroconvulsive therapy in severe and treatment-resistant depression: study protocol of the DetECT study

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