Personalized translational epilepsy research — Novel approaches and future perspectives

Rosenow, Felix; Alphen, Natascha van; Becker, Albert; Chiocchetti, Andreas G.; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas M.; Freitag, Christine M.; Gehrig, Johannes; Hermsen, A.; Jedlicka, Paul; Kell, Christian A.; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M.; Liebner, Stefan; Norwood, Braxton A.; Omigie, Diana; Plate, Karl-Heinz; Reif, Andreas; Reif, Philipp S.; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W.; Steinbach, Joachim P.; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C.; Wegner, Frederic von; Bauer, Sebastian

doi:10.1016/j.yebeh.2017.06.041

Cited by 27 publications

(24 citation statements)

References 43 publications

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“…The importance of individual prediction and personalized medicine is increasingly stressed in modern clinical practice . Since memory decline is one of the most common negative side effects after TLR, it is essential to provide patients with as personalized information as possible, giving them the best opportunities to foresee what life will be like past surgery.…”

Section: Discussionmentioning

confidence: 99%

Predicting verbal memory decline following temporal lobe resection for epilepsy

et al. 2019

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Objectives:The aim of the study was to develop a prediction model for verbal memory decline after temporal lobe resection (TLR) for epilepsy. The model will be used in the preoperative counselling of patients to give individualized information about risk for verbal memory decline. Materials and Methods:A sample of 110 consecutive patients who underwent TLR for epilepsy at Sahlgrenska University Hospital between 1987 and 2011 constituted the basis for the prediction model. They had all gone through a formal neuropsychological assessment before surgery and 2 years after. Penalized regression and 20 × 10-fold cross-validation were used in order to build a reliable model for predicting individual risks. Results: The final model included four predictors: side of surgery; inclusion or not of the hippocampus in the resection; preoperative verbal memory function; and presence/absence of focal to bilateral tonic-clonic seizures (TCS) the last year prior to the presurgical investigation. The impact of a history of TCS is a new finding which we interpret as a sign of a more widespread network disease which influences neuropsychological function and the cognitive reserve. The model correctly identified 82% of patients with post-operative decline in verbal memory, and the overall accuracy was 70%-85% depending on choice of risk thresholds. Conclusions:The model makes it possible to provide patients with individualized prediction regarding the risk of verbal memory decline following TLR. This will help them make more informed decisions regarding treatment, and it will also enable the epilepsy surgery team to prepare them better for the rehabilitation process. K E Y W O R D Sepilepsy surgery, penalized regression, temporal lobe resection, verbal memory decline

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Section: Discussionmentioning

confidence: 99%

Predicting verbal memory decline following temporal lobe resection for epilepsy

et al. 2019

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“…According to a report by the World Health Organization, it affects about 50 million people worldwide [1]. Despite the availability of a wide range of antiepileptic drugs, these cannot prevent seizures in 20–30% of patients [2,3,4]. Because of the lack of therapeutic efficacy, it is crucial to develop new pharmacological strategies to control seizures.…”

Section: Introductionmentioning

confidence: 99%

Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats

Zaitsev

Malkin

Postnikova

et al. 2019

IJMS

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Epilepsy is a common neurological disorder. Despite the availability of a wide range of antiepileptic drugs, these are unsuccessful in preventing seizures in 20–30% of patients. Therefore, new pharmacological strategies are urgently required to control seizures. Modulation of glutamate uptake may have potential in the treatment of pharmacoresistant forms of epilepsy. Previous research showed that the antibiotic ceftriaxone (CTX) increased the expression and functional activity of excitatory amino acid transporter 2 (EAAT2) and exerted considerable anticonvulsant effects. However, other studies did not confirm a significant anticonvulsant effect of CTX administration. We investigated the impacts of CTX treatment on EAAT expression and glutamatergic neurotransmission, as well its anticonvulsant action, in young male Wistar rats. As shown by a quantitative real-time polymerase chain reaction (qPCR) assay and a Western blot analysis, the mRNA but not the protein level of EAAT2 increased in the hippocampus following CTX treatment. Repetitive CTX administration had only a mild anticonvulsant effect on pentylenetetrazol (PTZ)-induced convulsions in a maximal electroshock threshold test (MEST). CTX treatment did not affect the glutamatergic neurotransmission, including synaptic efficacy, short-term facilitation, or the summation of excitatory postsynaptic potentials (EPSPs) in the hippocampus and temporal cortex. However, it decreased the field EPSP (fEPSP) amplitudes evoked by intense electrical stimulation. In conclusion, in young rats, CTX treatment did not induce overexpression of EAAT2, therefore exerting only a weak antiseizure effect. Our data provide new insight into the effects of modulation of EAAT2 expression on brain functioning.

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“…The findings described above may contribute to the development of personalized approaches to the treatment of epilepsy, whose motto is to treat a particular patient and not a disease in general [97]. Due to the poly-etiological nature of epilepsy, most epileptologists agree that such approaches will pave the way to highefficacy antiepileptic therapy [98,99].…”

Section: Resultsmentioning

confidence: 99%

Individual Approaches to Diagnosis and Treatment of Epilepsia (Review)

Zemlyanaya¹,

Федотчев²

2018

Sovrem Tehnol Med

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Epilepsy is one of the most common and treatment-resistant neurological diseases; it has heterogenic manifestations and requires individual approaches to its diagnosis and treatment. The ground for such approaches has been laid by modern science-based technologies, currently available in clinical practice. The aim of this review is to analyze publications on personalized approaches to the diagnosis and treatment of epilepsy over the past 10 years. In this review, we discuss the issue of individual markers of epilepsy and their predictive power, new approaches to localizing the epileptic foci, the relationship between the left-sided, right-sided and interhemispheric asymmetry and epileptogenesis, the role of comorbid disorders in epilepsy, as well as the available options for identifying the predictors of treatment efficacy.

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Personalized translational epilepsy research — Novel approaches and future perspectives

Cited by 27 publications

References 43 publications

Predicting verbal memory decline following temporal lobe resection for epilepsy

Predicting verbal memory decline following temporal lobe resection for epilepsy

Ceftriaxone Treatment Affects EAAT2 Expression and Glutamatergic Neurotransmission and Exerts a Weak Anticonvulsant Effect in Young Rats

Individual Approaches to Diagnosis and Treatment of Epilepsia (Review)

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