Glutamate concentrations vary with antiepileptic drug use and mental slowing

Tamar M van Veenendaal; Dominique M IJff; Albert P Aldenkamp; Richard H C Lazeron; Nicolaas A J Puts; Richard A E Edden; Paul A M Hofman; Anton J A de Louw; Walter H Backes; Jacobus F A Jansen

doi:10.1016/j.yebeh.2016.08.027

Glutamate concentrations vary with antiepileptic drug use and mental slowing

Epilepsy Behav. 2016 Nov;64(Pt A):200-205. doi: 10.1016/j.yebeh.2016.08.027. Epub 2016 Oct 13.

Affiliations

¹ Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; School for Mental Health and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: tamar.van.veenendaal@mumc.nl.
² School for Mental Health and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; Departments of Neurology and Neuropsychology, Epilepsy Center Kempenhaeghe, P.O. Box 61, 5590 AB Heeze, The Netherlands and Academic Center for Epileptology, Kempenhaeghe/Maastricht University Medical Center, Heeze/Maastricht, The Netherlands. Electronic address: IJffD@kempenhaeghe.nl.
³ School for Mental Health and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; Departments of Neurology and Neuropsychology, Epilepsy Center Kempenhaeghe, P.O. Box 61, 5590 AB Heeze, The Netherlands and Academic Center for Epileptology, Kempenhaeghe/Maastricht University Medical Center, Heeze/Maastricht, The Netherlands; Department of Neurology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; Department of Neurology, Gent University Hospital, De Pintelaan 185, 9000 Gent, Belgium; Faculty of Electrical Engineering, University of Technology Eindhoven, P.O. Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address: AldenkampB@kempenhaeghe.nl.
⁴ Departments of Neurology and Neuropsychology, Epilepsy Center Kempenhaeghe, P.O. Box 61, 5590 AB Heeze, The Netherlands and Academic Center for Epileptology, Kempenhaeghe/Maastricht University Medical Center, Heeze/Maastricht, The Netherlands. Electronic address: LazeronR@kempenhaeghe.nl.
⁵ Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, 601 N Caroline St., Baltimore 21287, MD, USA; F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 North Broadway, Baltimore 21205, MD, USA. Electronic address: nickputs@gmail.com.
⁶ Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, 601 N Caroline St., Baltimore 21287, MD, USA; F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 North Broadway, Baltimore 21205, MD, USA. Electronic address: richardedden@gmail.com.
⁷ Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; School for Mental Health and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands; Departments of Neurology and Neuropsychology, Epilepsy Center Kempenhaeghe, P.O. Box 61, 5590 AB Heeze, The Netherlands and Academic Center for Epileptology, Kempenhaeghe/Maastricht University Medical Center, Heeze/Maastricht, The Netherlands. Electronic address: paul.hofman@mumc.nl.
⁸ Departments of Neurology and Neuropsychology, Epilepsy Center Kempenhaeghe, P.O. Box 61, 5590 AB Heeze, The Netherlands and Academic Center for Epileptology, Kempenhaeghe/Maastricht University Medical Center, Heeze/Maastricht, The Netherlands; Department of Neurology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; Faculty of Electrical Engineering, University of Technology Eindhoven, P.O. Box 513, 5600 MB Eindhoven, The Netherlands. Electronic address: LouwA@kempenhaeghe.nl.
⁹ Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; School for Mental Health and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: w.backes@mumc.nl.
¹⁰ Departments of Radiology and Nuclear Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; School for Mental Health and Neuroscience, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: jacobus.jansen@mumc.nl.

PMID: 27744245
DOI: 10.1016/j.yebeh.2016.08.027

Abstract

Objective: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs.

Methods: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories.

Results: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed.

Conclusions: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects.

Keywords: Anticonvulsant; Cognitive side effects; GABA; Glutamate; MR spectroscopy.

MeSH terms

Adult
Anticonvulsants / therapeutic use*
Cognition / physiology*
Cross-Sectional Studies
Epilepsy / diagnostic imaging
Epilepsy / drug therapy
Epilepsy / metabolism*
Epilepsy / psychology
Female
Glutamic Acid / metabolism*
Humans
Magnetic Resonance Spectroscopy
Male
Middle Aged
Neuropsychological Tests
Occipital Lobe / diagnostic imaging
Occipital Lobe / metabolism*
gamma-Aminobutyric Acid / metabolism

Substances

Anticonvulsants
Glutamic Acid
gamma-Aminobutyric Acid