Pharmacological Effects on Brain Morphology and Cognitive Functions in Idiopathic Generalized Epilepsy
-
Zhamak Akhlaghi
,
Jafar Zamani
,
Hassan Ashayeri
,
Seyed Amir Hossein Batouli
,
Hamed Cheraghmakani
,
Roohollah Abdi
,
Mohammad-Reza Nazem-Zadeh
Abstract
Purpose: Sodium Valproate (VPA) is one of the first-generation Antiepileptic Drugs (AEDs) which mediates epileptic activities by releasing stimulators of Gamma-Aminobutyric Acid (GABA) and is greatly used to treat partial and generalized seizures. Lamotrigine )LTG( is commonly used as AEDs that are widely utilized in first-line monotherapy or in combination with other AEDs. Our specific goal was to compare these two AEDs with different molecular mechanisms on both cortical and subcortical brain structures, along with cognitive performance and dysfunctions.
Materials and Methods: We conducted a retrospective study comparing LTG with sodium VPA, both administrated as monotherapy. Twenty patients with a confirmed generalized-epilepsy tonic-clonic seizure who had been treated at least 6 months with LTG (n=8) and Sodium VPA (n=12) were retrospectively recruited. We also included 12 age, gender, and education-matched Healthy Controls (HC). We evaluated cognitive performances. All participants underwent a Magnetic Resonance Imaging (MRI) scanner and T1-weighted MR images were acquired. Voxel-based morphometric alterations in the brain cortex, as well as subcortical structures, were inspected using Statistical Parametric Mapping (SPM) software.
Results: The cognitive performance was revealed inferior in patients on Sodium VPA. Poor performance was associated with significant volume reduction in insula bilaterally, and subcortical structures of thalamus, cerebellum, and hippocampus compared to the HC. Comparing patients on LTG to HC revealed significant volume reduction in the anterior cingulate cortex in concordance with slight cognitive dysfunctions.
Conclusion: These findings suggested that different molecular mechanisms of Antiepileptic Drugs (AEDs) may affect brain structures and cognition with different severity levels, presumably with more adverse effects induced by GABA mediations from sodium VPA.
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16- Lori Reisner and Craig A Pettengill, "The use of anticonvulsants in orofacial pain." Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, Vol. 91, No. 1, pp. 2-7, (2001).
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18- Helena Janssen and Paul Boon, "Anticonvulsant Agents: Lamotrigine." NeuroPsychopharmacotherapy, pp. 1-16, (2020).
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21- Laura Scévola, Mercedes Sarudiansky, Alejandra Lanzillotti, Silvia Oddo, Silvia Kochen, and Luciana D'Alessio, "To what extent does depression influence quality of life of people with pharmacoresistant epilepsy in Argentina?" Epilepsy & Behavior, Vol. 69pp. 133-38, (2017).
22- Anny Reyes et al., "Cognitive phenotypes in temporal lobe epilepsy are associated with distinct patterns of white matter network abnormalities." Neurology, Vol. 92, No. 17, pp. e1957-e68, (2019).
23- Imane A Yassine, Waleed M Eldeeb, Khaled A Gad, Yossri A Ashour, Inas A Yassine, and Ahmed O Hosny, "Cognitive functions, electroencephalographic and diffusion tensor imaging changes in children with active idiopathic epilepsy." Epilepsy & Behavior, Vol. 84pp. 135-41, (2018).
24- John S Duncan, "Imaging in the surgical treatment of epilepsy." Nature Reviews Neurology, Vol. 6 (No. 10), p. 537, (2010).
25- Hossein Sanjari Moghaddam et al., "Distinct patterns of hippocampal subfield volume loss in left and right mesial temporal lobe epilepsy." Neurological Sciences, pp. 1-11, (2020).
26- Simon Sean Keller and Neil Roberts, "Voxel‐based morphometry of temporal lobe epilepsy: an introduction and review of the literature." Epilepsia, Vol. 49, No. 5, pp. 741-57, (2008).
27- Aimen Kasasbeh et al., "Association of magnetic resonance imaging identification of mesial temporal sclerosis with pathological diagnosis and surgical outcomes in children following epilepsy surgery." Journal of Neurosurgery: Pediatrics, Vol. 9, No. 5, pp. 552-61, (2012).
28- Ahmadreza Keihani et al., "Lower Gray Matter Density in the Anterior Cingulate Cortex and Putamen Can Be Traceable in Chronic Heroin Dependents After Over Three Months of Successful Abstinence." Iranian Journal of Radiology, Vol. 14, No. 3, (2017).
29- Manuela Tondelli, Anna Elisabetta Vaudano, Andrea Ruggieri, and Stefano Meletti, "Cortical and subcortical brain alterations in juvenile absence epilepsy." NeuroImage: Clinical, Vol. 12pp. 306-11, (2016).
30- Y Tang et al., "Single-dose intravenous administration of antiepileptic drugs induces rapid and reversible remodeling in the brain: evidence from a voxel-based morphometry evaluation of valproate and levetiracetam in rhesus monkeys." Neuroscience, Vol. 303pp. 595-603, (2015).
31- Pasquale Striano and Vincenzo Belcastro, "Treating myoclonic epilepsy in children: state-of-the-art." Expert opinion on pharmacotherapy, Vol. 14, No. 10, pp. 1355-61, (2013).
32- Ganna Balagura, Giulia Iapadre, Alberto Verrotti, and Pasquale Striano, "Moving beyond sodium valproate: choosing the right anti-epileptic drug in children." Expert opinion on pharmacotherapy, Vol. 20, No. 12, pp. 1449-56, (2019).
33- John R Hughes, "Absence seizures: a review of recent reports with new concepts." Epilepsy & behavior, Vol. 15 No. 4, pp. 404-12, (2009).
34- Tamar M van Veenendaal et al., "Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study." World journal of radiology, Vol. 9, No. 6, p. 287, (2017).
35- Qirui Zhang et al., "Resting-state fMRI revealed different brain activities responding to valproic acid and levetiracetam in benign epilepsy with central-temporal spikes." European radiology, Vol. 27, No. 5, pp. 2137-45, (2017).
36- Manuela Tondelli, Anna Elisabetta Vaudano, Sanjay M Sisodiya, and Stefano Meletti, "Valproate Use Is Associated With Posterior Cortical Thinning and Ventricular Enlargement in Epilepsy Patients." Frontiers in neurology, Vol. 11p. 622, (2020).
37- Yfke Huber-Mollema, Loretta van Iterson, Frans J Oort, Dick Lindhout, and Roos Rodenburg, "Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure." Journal of Neurology, pp. 1-13, (2020).
38- Seyed Amir Hossein Batouli, Perminder S Sachdev, Wei Wen, Margaret J Wright, David Ames, and Julian N Trollor, "Heritability of brain volumes in older adults: the Older Australian Twins Study." Neurobiology of aging, Vol. 35, No. 4, pp. 937. e5-37. e18, (2014).
39- Vitalie Chiosa et al., "Large-scale network architecture and associated structural cortico-subcortical abnormalities in patients with sleep/awake-related seizures." Sleep, Vol. 42, No. 4, p. zsz006, (2019).
40- E Perucca, "Valproate: a summary of the pharmacological and therapeutic properties of a mainstay antiepileptic drug after 35 years of clinical experience." CNS Drugs, Vol. 16, No. 10, pp. 695-714, (2002).
41- Michele Romoli et al., "Valproic acid and epilepsy: from molecular mechanisms to clinical evidences." Current neuropharmacology, Vol. 17, No. 10, pp. 926-46, (2019).
42- Kayode Ogungbenro and Leon Aarons, "A physiologically based pharmacokinetic model for Valproic acid in adults and children." European Journal of Pharmaceutical Sciences, Vol. 63, pp. 45-52, (2014).
43- Piero Perucca, Ingrid E Scheffer, and Michelle Kiley, "The management of epilepsy in children and adults." Medical Journal of Australia, Vol. 208, No. 5, pp. 226-33, (2018).
44- AS Fleisher et al., "Chronic divalproex sodium use and brain atrophy in Alzheimer disease." Neurology, Vol. 77, No. 13, pp. 1263-71, (2011).
45- Pierre N Tariot et al., "Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease." Archives of General Psychiatry, Vol. 68, No. 8, pp. 853-61, (2011).
46- JA Armijo, EM Valdizan, I Las Cuevas De, and A Cuadrado, "Advances in the physiopathology of epileptogenesis: molecular aspects." Revista de neurologia, Vol. 34, No. 5, pp. 409-29, (2002).
47- Shailesh N Khatri, Wan-Chen Wu, Ying Yang, and Jason R Pugh, "Mechanisms of GABA B receptor enhancement of extrasynaptic GABA A receptor currents in cerebellar granule cells." Scientific reports, Vol. 9, No. 1, pp. 1-16, (2019).
48- NG Bowery, AL Hudson, and GW Price, "GABAA and GABAB receptor site distribution in the rat central nervous system." Neuroscience, Vol. 20, No. 2, pp. 365-83, (1987).
49- Jacky YT Yeung, Kevin J Canning, Guoyun Zhu, Peter Pennefather, John F MacDonald, and Beverley A Orser, "Tonically activated GABAA receptors in hippocampal neurons are high-affinity, low-conductance sensors for extracellular GABA." Molecular pharmacology, Vol. 63, No. 1, pp. 2-8, (2003).
50- Martina Manns and Onur Güntürkün, "Light experience induces differential asymmetry pattern of GABA-and parvalbumin-positive cells in the pigeon's visual midbrain." Journal of Chemical Neuroanatomy, Vol. 25, No. 4, pp. 249-59, (2003).
51- Jae-Won Jang et al., "Hypermetabolism in the left thalamus and right inferior temporal area on positron emission tomography–statistical parametric mapping (PET–SPM) in a patient with Charles Bonnet syndrome resolving after treatment with valproic acid." Journal of Clinical Neuroscience, Vol. 18, No. 8, pp. 1130-32, (2011).
52- Heath R Pardoe, Anne T Berg, and Graeme D Jackson, "Sodium valproate use is associated with reduced parietal lobe thickness and brain volume." Neurology, Vol. 80, No. 20, pp. 1895-900, (2013).
53- Isabelle E Bauer et al., "Changes in amygdala, cerebellum, and nucleus accumbens volumes in bipolar patients treated with lamotrigine." Psychiatry Research: Neuroimaging, Vol. 278pp. 13-20, (2018).
54- Amy L Buller, Heidi C Larson, Benjamin E Schneider, Jean A Beaton, Richard A Morrisett, and Daniel T Monaghan, "The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition." Journal of Neuroscience, Vol. 14, No. 9, pp. 5471-84, (1994).
55- Andrew N Iwaniuk, Peter L Hurd, and Douglas RW Wylie, "Comparative morphology of the avian cerebellum: I. Degree of foliation." Brain, behavior and evolution, Vol. 68, No. 1, pp. 45-62, (2006).
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| Files | ||
| Issue | Vol 9 No 2 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/fbt.v9i2.8846 | |
| Keywords | ||
| Sodium Valproate lamotrigine Antiepileptic Drugs Idiopathic Generalized-Epilepsy Cognitive Performance Voxel-Based Morphometry | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Akhlaghi Z, Zamani J, Ashayeri H, Batouli SAH, Cheraghmakani H, Abdi R, Nazem-Zadeh M-R. Pharmacological Effects on Brain Morphology and Cognitive Functions in Idiopathic Generalized Epilepsy. Frontiers Biomed Technol. 2022;9(2):76-89.
