The Cognitive Profile of Ethosuximide in Children

Introduction: Although ethosuximide is one of the oldest antiepileptic drugs (AEDs), little information is available about the cognitive side effects of ethosuximide. Objective: The aim of this study was to investigate the cognitive profile of ethosuximide. Methods: In this cross-sectional study, we used an extensive neuropsychological test battery in patients with epilepsy aged 6–16 years who were treated with monotherapy ethosuximide. We evaluated the efficacy of the drug by seizure frequency (seizure free or not). Results: We included 61 patients with a mean age of 9.4 years [standard deviation (SD) 2.7] who used on average 686 mg/day (SD 245) ESM as monotherapy. ESM was effective in the majority of the patients (70 % were seizure free for at least 6 months at moment of inclusion). The total study population showed impairments of intelligence, visuomotor, and attentional function including activation/alertness. Comparisons between the well-controlled patients and patients who were not in remission showed significantly lower intelligence values and lower performance on the visual-perceptual and attentional tasks for the group with ongoing seizures. Our results suggested that the higher order cognitive dysfunctions (such as intelligence and visual-perceptual functions) may be regarded as seizure or aetiology effects and that the impaired fluid cognitive functions, such as activation/alertness, sustained auditory attention and attentional control or switching, were due to ESM. Conclusion: This study suggests the attentional dysfunction resulting in psychomotor slowing and alertness deficits may be regarded as effects of ethosuximide. Although no untreated baseline assessment was available, these effects are comparable to those of other AEDs, and ethosuximide may therefore be considered an AED with only mild effects on cognition. As ethosuximide is a first-line therapy for absence seizures in childhood, and drug-induced cognitive impairment may interfere with development, learning, and academic achievement, these findings are of interest to clinicians who prescribe this drug, especially when informing parents

Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy:Initial Findings in a 7T MRI Study

BACKGROUND AND PURPOSE In 30% of the patients with focal epilepsy, an epileptogenic lesion cannot be visually detected with structural MRI. Ultra-high field MRI may be able to identify subtle pathology related to the epileptic focus. We set out to assess 7T MRI-derived volumetric and functional activity lateralization of the hippocampus, hippocampal subfields, temporal and frontal lobe in healthy subjects and MRI-negative patients with focal epilepsy. METHODS Twenty controls and 10 patients with MRI-negative temporal or frontal lobe epilepsy (TLE and FLE, respectively) underwent a 7T MRI exam. T-1-weigthed imaging and resting-state fMRI was performed. T-1-weighted images were segmented to yield volumes, while from fMRI data, the fractional amplitude of low frequency fluctuations was calculated. Subsequently, volumetric and functional lateralization was calculated from left-right asymmetry. RESULTS In controls, volumetric lateralization was symmetric, with a slight asymmetry of the hippocampus and subiculum, while functional lateralization consistently showed symmetry. Contrarily, in epilepsy patients, regions were less symmetric. In TLE patients with known focus, volumetric lateralization in the hippocampus and hippocampal subfields was indicative of smaller ipsilateral volumes. These patients also showed clear functional lateralization, though not consistently ipsilateral or contralateral to the epileptic focus. TLE patients with unknown focus showed an obvious volumetric lateralization, facilitating the localization of the epileptic focus. Lateralization results in the FLE patients were less consistent with the epileptic focus. CONCLUSION MRI-derived volume and fluctuation amplitude are highly symmetric in controls, whereas in TLE, volumetric and functional lateralization effects were observed. This highlights the potential of the technique

Metabolic and functional MR biomarkers of antiepileptic drug effectiveness:A review

\u3cp\u3eAs a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects.\u3c/p\u3

Functional brain networks are altered in type 2 diabetes and pre-diabetes signs for compensation of cognitive decrements? - The Maastricht Study: signs for compensation of cognitive decrements? - The Maastricht Study

Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Participants with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of (pre-)diabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study was designed to investigate whether functional brain networks are affected in type 2 diabetes and pre-diabetes. Forty-seven participants with diabetes, 47 pre-diabetic participants, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency compared with controls. The network measures of the pre-diabetic participants fell between those of the diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. To conclude, participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the pre-diabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as compensatory mechanism for cognitive decrements

Glutamate concentrations vary with antiepileptic drug use and mental slowing

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

High field imaging of large-scale neurotransmitter networks : Proof of concept and initial application to epilepsy

The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0 T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the 'neurotransmitter networks' concept might also provide new insights for other neurological diseases

High field imaging of large-scale neurotransmitter networks: Proof of concept and initial application to epilepsy

The brain can be considered a network, existing of multiple interconnected areas with various functions. MRI provides opportunities to map the large-scale network organization of the brain. We tap into the neurobiochemical dimension of these networks, as neuronal functioning and signal trafficking across distributed brain regions relies on the release and presence of neurotransmitters. Using high-field MR spectroscopic imaging at 7.0 T, we obtained a non-invasive snapshot of the spatial distribution of the neurotransmitters GABA and glutamate, and investigated interregional associations of these neurotransmitters. We demonstrate that interregional correlations of glutamate and GABA concentrations can be conceptualized as networks. Furthermore, patients with epilepsy display an increased number of glutamate and GABA connections and increased average strength of the GABA network. The increased glutamate and GABA connectivity in epilepsy might indicate a disrupted neurotransmitter balance. In addition to epilepsy, the ‘neurotransmitter networks’ concept might also provide new insights for other neurological diseases