Epilepsy and Comorbidities: Towards unraveling the common underlying mechanisms

  • Yam Nath Paudel Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor, Malaysia.
  • Christos Panagiotis Lisgaras Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Kheng Seang Lim Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • Mohd. Farooq Shaikh Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor, Malaysia.
Keywords: depression, anxiety, cognitive decline, epilepsy, comorbidities

Abstract

Epilepsy is a chronic neurological disorder characterized by the rapid occurrence of epileptic seizures affecting approximately 70 million people worldwide. The quality of life of people with epilepsy (PWE) is challenged by a series of comorbidities that might include neurologic and neuropsychiatric disorders (cognitive decline, depression, anxiety, schizophrenia, and autism) as well as metabolic, cardiovascular and respiratory diseases. Neurobehavioral and other comorbidities might share a reciprocal and complex relationship with epileptogenesis and ictogenesis thus biomarkers of the former might be useful for the prediction of the latter and vice versa. This bidirectional relationship between epilepsy and associated comorbidities has attracted significant attention in recent years as supported by data showing that one half of PWE demonstrate cognitive impairments, 30-50% depressive behavior, 10-25% anxiety disorders and 5-40% autism or autism spectrum disorder (ASD). In the past decades, epilepsy-related neurobehavioral comorbidities have been critically discussed, but the current need in unraveling the precise mechanism associated with epilepsy and these neurobehavioral comorbidities is unmet. The precise understanding of the mechanistic pathway underlying these epilepsy-associated comorbid conditions could be instrumental in developing therapeutic interventions that might modify seizure burden and accompanying comorbid conditions.

References

Allendorfer JB, Arida RM. Role of Physical Activity and Exercise in Alleviating Cognitive Impairment in People With Epilepsy. Clinical Therapeutics. 2018;40(1):26-34. https://doi.org/10.1016/j.clinthera.2017.12.004

Depaulis A, Helfer V, Deransart C, Marescaux C. Anxiogenic-like consequences in animal models of complex partial seizures. Neurosci Biobehav Rev. 1998;21(6):767-774. https://doi.org/10.1016/S0149-7634(96)00060-7

Frye RE, Casanova MF, Fatemi SH, Folsom TD, Reutiman TJ, Brown GL, et al. Neuropathological Mechanisms of Seizures in Autism Spectrum Disorder. Frontiers in Neuroscience. 2016;10:192. https://doi.org/10.3389/fnins.2016.00192

Gaitatzis A, Sisodiya SM, Sander JW. The somatic comorbidity of epilepsy: A weighty but often unrecognized burden. Epilepsia. 2012;53(8):1282-1293. https://doi.org/10.1111/j.1528-1167.2012.03528.x

Josephson CB, Jetté N. Psychiatric comorbidities in epilepsy. Int Rev Psychiatry. 2017;29(5):409-424. https://doi.org/10.1080/09540261.2017.1302412

Keezer MR, Sander JW. Epilepsy is a neurological and a systemic disorder. Epilepsy & Behavior. 2018;78:57-61. https://doi.org/10.1016/j.yebeh.2017.10.010

Keezer MR, Sisodiya SM, Sander JW. Comorbidities of epilepsy: current concepts and future perspectives. The Lancet Neurology. 2016;15(1):106-115. https://doi.org/10.1016/s1474-4422(15)00225-2

Kohane IS, McMurry A, Weber G, MacFadden D, Rappaport L, Kunkel L, et al. The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS ONE. 2012;7(4):e33224. https://doi.org/10.1371/journal.pone.0033224

Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry. 2012;83(5):495-502. https://doi.org/10.1136/jnnp-2011-301779

Lopez-Gomez M, Espinola M, Ramirez-Bermudez J, Sosa AL. Clinical presentation of anxiety among patients with epilepsy. Neuropsychiatric Disease and Treatment. 2008;4(6):1235-1239. https://doi.org/10.2147/ndt.s3990

Marsland AL, Gianaros PJ, Sheu LK, Krajina K, Manuck SB. Brain morphology links systemic inflammation to cognitive function in midlife adults. Brain, Behavior, and Immunity. 2015;48:195-204. https://doi.org/10.1016/j.bbi.2015.03.015

Mazarati AM, Lewis ML, Pittman QJ. Neurobehavioral comorbidities of epilepsy: Role of inflammation. Epilepsia. 2017;58(Suppl 3):48-56. https://doi.org/10.1111/epi.13786

McAfoose J, Baune BT. Evidence for a cytokine model of cognitive function. Neurosci Biobehav Rev. 2008;33(3):355-366. https://doi.org/10.1016/j.neubiorev.2008.10.005

Müller N, Weidinger E, Leitner B, Schwarz MJ. The role of inflammation in schizophrenia. Frontiers in Neuroscience. 2015;9:372. https://doi.org/10.3389/fnins.2015.00372

Paudel YN, Shaikh MF, Chakraborti A, Kumari Y, Aledo-Serrano Á, Aleksovska K, et al. HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction. Frontiers in Neuroscience. 2018;12:628. https://doi.org/10.3389/fnins.2018.00628

Paudel YN, Shaikh MF, Shah S, Kumari Y, Othman I. Role of inflammation in epilepsy and neurobehavioral comorbidities: Implication for therapy. Eur J Pharmacol. 2018;837:145-155. https://doi.org/10.1016/j.ejphar.2018.08.020

Ravizza T, Onat FY, Brooks-Kayal AR, Depaulis A, Galanopoulou AS, Mazarati A, et al. WONOEP appraisal: Biomarkers of epilepsy-associated comorbidities. Epilepsia. 2016;58(3):331-342. https://doi.org/10.1111/epi.13652

Richard AE, Scheffer IE, Wilson SJ. Features of the broader autism phenotype in people with epilepsy support shared mechanisms between epilepsy and autism spectrum disorder. Neurosci Biobehav Rev. 2017;75:203-233. https://doi.org/10.1016/j.neubiorev.2016.12.036

Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. Psychological Bulletin. 2014;140(3):774-815. https://doi.org/10.1037/a0035302

Vazquez B, Devinsky O. Epilepsy and anxiety. Epilepsy Behav. 2003;4 Suppl 4:S20-25. https://doi.org/10.1016/j.yebeh.2003.10.005

Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nature Reviews Neurology. 2010;7(1):31-40. https://doi.org/10.1038/nrneurol.2010.178

Vezzani A. Inflammation and Epilepsy. Epilepsy Currents. 2005;5(1):1-6. https://doi.org/10.1111/j.1535-7597.2005.05101.x

Vogelzangs N, Beekman ATF, de Jonge P, Penninx BWJH. Anxiety disorders and inflammation in a large adult cohort. Translational Psychiatry. 2013;3(4):e249. https://doi.org/10.1038/tp.2013.27

Xie W, Cai L, Yu Y, Gao L, Xiao L, He Q, et al. Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy. J Neuroinflammation. 2014;11(1):41. https://doi.org/10.1186/1742-2094-11-41

Published
2018-10-14
How to Cite
Paudel, Y., Lisgaras, C., Lim, K. S. and Shaikh, M. F. (2018) “Epilepsy and Comorbidities: Towards unraveling the common underlying mechanisms”, Neuroscience Research Notes, 1(3), pp. 1-4. doi: 10.31117/neuroscirn.v1i3.20.