title: Glutamate concentrations vary with antiepileptic drug use and mental slowing.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Tamar M
authors.initials: TM
authors.lastname: van Veenendaal
authors.affiliation: 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.
authors.forename: Dominique M
authors.initials: DM
authors.lastname: IJff
authors.affiliation: 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.
authors.forename: Albert P
authors.initials: AP
authors.lastname: Aldenkamp
authors.affiliation: 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.
authors.forename: Richard H C
authors.initials: RHC
authors.lastname: Lazeron
authors.affiliation: 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.
authors.forename: Nicolaas A J
authors.initials: NAJ
authors.lastname: Puts
authors.affiliation: 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.
authors.forename: Richard A E
authors.initials: RAE
authors.lastname: Edden
authors.affiliation: 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.
authors.forename: Paul A M
authors.initials: PAM
authors.lastname: Hofman
authors.affiliation: 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.
authors.forename: Anton J A
authors.initials: AJA
authors.lastname: de Louw
authors.affiliation: 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.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Backes
authors.affiliation: 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.
authors.forename: Jacobus F A
authors.initials: JFA
authors.lastname: Jansen
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D003071:Cognition / Q000502:physiology*; D003430:Cross-Sectional Studies; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009778:Occipital Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Anticonvulsant; Cognitive side effects; GABA; Glutamate; MR spectroscopy