Liquid biopsies in epilepsy: biomarkers for etiology, diagnosis, prognosis, and therapeutics

Whitlock, Jordan; Soelter, Tabea M.; Williams, Avery S.; Hardigan, Andrew A.; Lasseigne, Brittany N.

doi:10.1007/s13577-021-00624-x

“…In our study, the proportion of patients with epilepsy with a poor prognosis was 35.42%. Previous research results showed that the proportion of patients with epilepsy with a poor prognosis was about 10% [ 15 – 17 ]. There is such a difference, which may be because we only target refractory epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Screening of Risk Factors for Poor Prognosis in Patients with Refractory Epilepsy Secondary to Encephalomalacia

Zhong

¹

2022

Computational and Mathematical Methods in Medicine

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Objective. The study was aimed at screening the independent prognostic risk factors for refractory epilepsy associated with encephalomalacia (REAE). Methods. Patients with REAE treated in the First People’s Hospital of Linping District from January 2018 to December 2019 were selected. The prognosis was represented by Engel grading. Clinical data of the patients were collected, including age, sex, BMI, lesion sites, number of lesion sites, lesion size, seizure frequency, epilepsy type, and treatment methods. Independent risk factors for poor prognosis were screened by logistic regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the prognostic efficacy of independent risk factors. Results. A total of 48 patients were included in this study, including 31 patients (64.58%) in the good prognosis group and 17 patients (35.42%) in the poor prognosis group. The mean age of the poor prognosis group was higher than that of the good prognosis group ( P = 0.002 ). The proportion of patients with multisite lesions in the poor prognosis group was higher than that in the good prognosis group ( P = 0.016 ). The proportion of patients with cerebral malacia lesion diameter ≥ 3 cm in the poor prognosis group was higher than that in the good prognosis group ( P = 0.002 ). The proportion of patients with attack frequency ≥ 2 times / month in the poor prognosis group was higher than in the good prognosis group ( P = 0.002 ). The proportion of patients receiving surgical treatment in the poor prognosis group was lower than that in the good prognosis group ( P < 0.001 ). Age, number of lesion sites, size of encephalomalacia, and seizure frequency were independent risk factors for the prognosis of patients with REAE ( OR > 1 , P < 0.05 ). Surgical treatment was an independent protective factor associated with the prognosis of patients with REAE ( OR < 1 , P < 0.05 ). The area under the ROC curve of surgical treatment was 0.83 ( P = 0.004 ). The area under the ROC curve of the size of encephalomalacia was 0.72 ( P = 0.008 ). There was a positive correlation between age and size of encephalomalacia and Engel grade ( r > 0 , P < 0.05 ). Surgical treatment was negatively correlated with Engel grade ( r < 0 , P < 0.05 ). The number of lesion sites and seizure frequency had no significant correlation with Engel ( P > 0.05 ). The proportion of Engel I patients treated with surgery was higher than that treated with drugs ( P = 0.001 ). The ratio of Engel III and IV patients treated with surgery was lower than that treated with medications ( P < 0.05 ). Conclusion. Age, number of lesion sites, size of encephalomalacia, and seizure frequency are independent risk factors for the prognosis of patients with REAE. Surgical treatment is an independent prognostic factor for patients with REAE. Surgical treatment can significantly improve patient outcomes.

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“…Missing are reports of increasing concentrations of an inflammation indicator preceding a seizure 121 . Without this type of information everything presented here is rather indirect support for the putative benefits of a closed‐loop system.…”

Section: Timingmentioning

confidence: 88%

“…Among the more interesting candidates are microRNA (miRNA) 120 , 121 , 122 , 123 and circular RNA (circRNA), 124 , 125 which can play a prominent role in regulating the immune system. 121 , 126 , 127 In vivo measurement capabilities are not yet available.…”

Section: Measurement Of Inflammation—what To Measure?mentioning

confidence: 99%

Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity

Coral

¹

,

Rotenberg

²

,

Leviton

³

et al. 2023

Epilepsia Open

2

0

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People with diabetes can wear a device that measures blood glucose and delivers just the amount of insulin needed to return the glucose level to within bounds.Currently, people with epilepsy do not have access to an equivalent wearable device that measures a systemic indicator of an impending seizure and delivers a rapidly acting medication or other intervention (e.g., an electrical stimulus) to terminate or prevent a seizure. Given that seizure susceptibility is reliably increased in systemic inflammatory states, we propose a novel closed-loop device where release of a fast-acting therapy is governed by sensors that quantify the magnitude of systemic inflammation. Here, we review the evidence that patients with epilepsy have raised levels of systemic indicators of inflammation than controls, and that some anti-inflammatory drugs have reduced seizure occurrence in animals and humans. We then consider the options of what might be incorporated into a responsive anti-seizure system.

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“…Similarly, once a treatment is initiated, it is hard to follow up certain patients who cannot report their seizure frequency due to intellectual disability, the presence of solely nocturnal seizures, or focal seizures with impaired consciousness and amnesia. 1,[5][6][7] All of these arguments demonstrate the value that a good (fluid) biomarker could offer.…”

Section: Introductionmentioning

confidence: 97%

“…However, the main aim of these tests is the exclusion of other pathologies, lacking a representative fluid biomarker for epileptogenesis, seizures, or status epilepticus (SE). Similarly, once a treatment is initiated, it is hard to follow up certain patients who cannot report their seizure frequency due to intellectual disability, the presence of solely nocturnal seizures, or focal seizures with impaired consciousness and amnesia 1,5–7 . All of these arguments demonstrate the value that a good (fluid) biomarker could offer.…”

Section: Introductionmentioning

confidence: 99%

Neurofilament light chain: A possible fluid biomarker in the intrahippocampal kainic acid mouse model for chronic epilepsy?

Custers,

Vande Vyver,

Kaltenböck

et al. 2023

Epilepsia

1

0

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ObjectiveIn the management of epilepsy, there is an ongoing quest to discover new biomarkers to improve the diagnostic process, the monitoring of disease progression, and the evaluation of treatment responsiveness. In this regard, biochemical traceability in biofluids is notably absent in contrast to other diseases. In the present preclinical study, we investigated the potential of neurofilament light chain (NfL) as a possible diagnostic and response fluid biomarker for epilepsy.MethodsWe gained insights into NfL levels during the various phases of the intrahippocampal kainic acid mouse model of temporal lobe epilepsy—namely, the status epilepticus (SE) and the chronic phase with spontaneous seizures. To this end, NfL levels were determined directly in the cerebral interstitial fluid (ISF) with cerebral open flow microperfusion as sampling technique, as well as in cerebrospinal fluid (CSF) and plasma. Lastly, we assessed whether NfL levels diminished upon curtailing SE with diazepam and ketamine.ResultsNfL levels are higher during SE in both cerebral ISF and plasma in kainic acid‐treated mice compared to sham‐injected mice. Additionally, ISF and plasma NfL levels are lower in mice treated with diazepam and ketamine to stop SE compared with the vehicle‐treated mice. In the chronic phase with spontaneous seizures, higher NfL levels could only be detected in ISF and CSF samples, and not in plasma. No correlations could be found between NfL levels and seizure burden, nor with immunohistological markers for neurodegeneration/inflammation.SignificanceOur findings demonstrate the translational potential of NfL as a blood‐based fluid biomarker for SE. This is less evident for chronic epilepsy, as in this case higher NfL levels could only be detected in ISF and CSF, and not in plasma, acknowledging the invasive nature of CSF sampling in chronic epilepsy follow‐up.

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Liquid biopsies in epilepsy: biomarkers for etiology, diagnosis, prognosis, and therapeutics

Cited by 10 publications

References 83 publications

Screening of Risk Factors for Poor Prognosis in Patients with Refractory Epilepsy Secondary to Encephalomalacia

Screening of Risk Factors for Poor Prognosis in Patients with Refractory Epilepsy Secondary to Encephalomalacia

Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity

Neurofilament light chain: A possible fluid biomarker in the intrahippocampal kainic acid mouse model for chronic epilepsy?

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