WONOEP appraisal: Biomarkers of epilepsy‐associated comorbidities

Abstract

Neurologic and psychiatric comorbidities are common in patients with epilepsy. Diagnostic, predictive, and pharmacodynamic biomarkers of such comorbidities do not exist. They may share pathogenetic mechanisms with epileptogenesis/ictogenesis, and as such are an unmet clinical need. The objectives of the subgroup on biomarkers of comorbidities at the XIII Workshop on the Neurobiology of Epilepsy (WONOEP) were to present the state-of-the-art recent research findings in the field that highlighting potential biomarkers for comorbidities in epilepsy. We review recent progress in the field, including molecular, imaging, and genetic biomarkers of comorbidities as discussed during the WONOEP meeting on August 31-September 4, 2015, in Heybeliada Island (Istanbul, Turkey). We further highlight new directions and concepts from studies on comorbidities and potential new biomarkers for the prediction, diagnosis, and treatment of epilepsy-associated comorbidities. The activation of various molecular signaling pathways such as the "Janus Kinase/Signal Transducer and Activator of Transcription," "mammalian Target of Rapamycin," and oxidative stress have been shown to correlate with the presence and severity of subsequent cognitive abnormalities. Furthermore, dysfunction in serotonergic transmission, hyperactivity of the hypothalamic-pituitary-adrenocortical axis, the role of the inflammatory cytokines, and the contributions of genetic factors have all recently been regarded as relevant for understanding epilepsy-associated depression and cognitive deficits. Recent evidence supports the utility of imaging studies as potential biomarkers. The role of such biomarker may be far beyond the diagnosis of comorbidities, as accumulating clinical data indicate that comorbidities can predict epilepsy outcomes. Future research is required to reveal whether molecular changes in specific signaling pathways or advanced imaging techniques could be detected in the clinical settings and correlate with epilepsy-associated comorbidities. A reliable biomarker will allow a more accurate diagnosis and improved treatment of epilepsy-associated comorbidities.

A knock‐in mouse model for KCNQ2‐related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment

“…Breathing pattern was investigated at P100 using plethysmography and revealed no difference between heterozygous knock‐in and WT animals for all measured parameters (mean frequency, hyperventilation, apnea, tidal volume, and respiratory rate; n = 10 Kcnq2 +/+ mice and n = 11 K cnq2 Thr274Met/+ mice; Figure ). We also investigated the presence of stereotypies in the two groups using the marble‐burying test because of the unusual rate of stereotypy in patients with epilepsies 12,13. The test quantifies repetitive and perseverating behavior.…”

Adenosine Kinase, a Common Pathologic Biomarker for Human Pharmacoresistant Epilepsy

“…In addition, endothelial cells displayed marked ADK immunoreactivity ( Figure 1H) within the damaged hemosphere. associated with epilepsy are crucial to improve the quality of life in patients with epilepsy [7].…”

“…Therefore, treatment of comorbidity associated with epilepsy could contribute to the therapeutic effect of epilepsy and improve the quality of life. More than one third of patients with epilepsy are pharmacoresistant [2][3][4], and apart from those who are candidates for resective surgery, most patients will continue to suffer recurrent seizures and comorbidities comprising of neurologic, cognitive and psychiatric symptoms [5][6][7][8]. Therefore, novel solid biomarkers for the prediction, diagnosis, and treatment of epilepsy and comorbidities Review Tianfu Li pathological hallmark in patients with pharmacoresistant epilepsy caused by a wide range of neurodegenerative conditions [14].…”

Toward evidence‐based severity assessment in rat models with repeated seizures: III. Electrical post‐status epilepticus model

“…Besides severity assessment, the data generated in the different epilepsy animal models can be used to gain further insight into psychiatric comorbidities of epilepsy and the respective face validity of different animal models. Studies have demonstrated the existence of psychiatric comorbidities in patients, with matching behavioral alterations seen in rodent epilepsy models . However, previous findings were not always consistent and robust, so that a comprehensive analysis of behavioral alterations in different epilepsy models under identical conditions is of particular interest.…”

“…Studies have demonstrated the existence of psychiatric comorbidities in patients, with matching behavioral alterations seen in rodent epilepsy models. [13][14][15] However, previous findings were not always consistent and robust, [16][17][18] so that a comprehensive analysis of behavioral alterations in different epilepsy models under identical conditions is of particular interest.…”