Bilateral reductions of hippocampal volume, glucose metabolism, and Wada hemispheric memory performance are related to the duration of mesial temporal lobe epilepsy

Jokeit, Hennric; Ebner, Alois; Arnold, Stefan; Schüller, Michael; Antke, Christine; Huang, Yanxiong; Steinmetz, H.; Seitz, Rüdiger J.; Witte, Otto W.

doi:10.1007/s004150050484

Cited by 77 publications

(58 citation statements)

References 55 publications

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“…Our findings confirm and extend earlier FDG-PET studies on the distribution of hypometabolism and seizure spread in mTLE, as shown by pixel-to-pixel comparison (6), ROI-based analysis (7,33), and EEG (34). It has been argued that remote depressions of metabolism do not simply reflect regional atrophy (35).…”

Section: Discussionsupporting

confidence: 90%

Gender‐specific Differences of Hypometabolism in mTLE: Implication for Cognitive Impairments

Nickel¹,

Jokeit²,

Wunderlich³

et al. 2003

Epilepsia

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Summary:Purpose: To determine gender differences of hypometabolism and their implications for cognitive impairment in patients with medically refractory mesial temporal lobe epilepsy (mTLE).Methods: Regional cerebral glucose metabolism (rCMRGlu) was studied in 42 patients (21 male, 21 female) with either leftor right-sided mTLE (22 left, 20 right) and in 12 gender-and age-matched healthy controls during resting wakefulness and in 12 sex-and age-matched healthy controls. Clinical characteristics were balanced across the patient subgroups. All patients were subjected to neuropsychological assessment: 41 patients had histologic changes of definite or probable hippocampal sclerosis.Results: Data analysis based on pixel-by-pixel comparisons and on a laterality index of regions of interest (ROIs) showed significant depressions of the mean rCMRGlu extending beyond the mesiotemporal region and temporolateral cortex to extratemporal regions including the frontoorbital and insular cortex in mTLE patients. Extramesiotemporal hypometabolism prevailed in the male patients. Metabolic asymmetry in temporal and frontal regions was related to performance in the Trail-Making Test and WAIS-R subitems.Conclusions: Our data showed a gender-specific predominance of extramesiotemporal hypometabolism in male patients with mTLE related to abnormalities of temporal and frontal lobe functions. Key Words: FDG-PET-mTLEGender differences-Hypometabolism-Neuropsychology.Mesial temporal lobe epilepsy (mTLE) is the most common and best-defined syndrome of symptomatic localization-related epilepsy (1). Positron emission tomography (PET) using 18-fluoro-deoxyglucose (FDG-PET) was the first functional neuroimaging method allowing location of regions generating epileptiform EEG changes noninvasively (2) and has been established as a sensitive and reliable method for presurgical evaluation of TLE patients (3-5). FDG-PET has been used for lateralization of the seizure-onset zone, especially in those cases in which surface EEG and magnetic resonance imaging (MRI) provided discordant findings. However, FDG-PET revealed not only hypometabolism in the epileptogenic zone in mTLE, but also extratemporal metabolic disturbances (6-8).Accepted July 2, 2003. Address correspondence and reprint requests to Dr. R.J. Seitz at University-Hospital Düsseldorf, Department of Neurology, Moorenstrasse 5, D-40225 Düsseldorf, Germany. E-mail: seitz@neurologie.uniduesseldorf.de These "remote depressions" can affect the ipsi-and contralateral neocortical part of the temporal lobe, the frontoorbital cortex, and the thalamus. These areas are supposed to be affected secondarily by ongoing subclinical seizure activity, inhibition, and deafferentation rather than by morphologic tissue damage (8,9). The degree of hypometabolism in these regions was shown to correlate well with neuropsychological impairments such as verbal memory function or cognitive abilities (6,7).Apart from its use in the assessment of neuropsychiatric abnormalities, FDG-PET also has the capacity to provide phy...

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Section: Discussionsupporting

confidence: 90%

Gender‐specific Differences of Hypometabolism in mTLE: Implication for Cognitive Impairments

Nickel¹,

Jokeit²,

Wunderlich³

et al. 2003

Epilepsia

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“…In 18 of the latter (47.4%), 14,16,[20][21][22]24,30,[33][34][35][36][37][38]40,42,[50][51][52] no statistical approaches were implemented to correct for the effects of age. Although the remaining studies addressed aging, no consistent method was chosen: 3 reported no significant effects of age on morphometric measures in controls, 15,32,48 3 found no effect of age or no effect of age at epilepsy onset in patients, 19,29,53 2 corrected for age at onset, 18,28 5 corrected for age in patients, 17,26,47,49,54 4 utilized MRI measures adjusted for age 13,31,39,46 (based on regression models derived from controls), 1 calculated epilepsy duration/age ratios, 23 2 statistically compared chronological age effects between patients and controls. 41,45 Among the longitudinal studies, 3 were singlecohort studies of patients without controls (interscan interval ranging from 2.3 to 3.4 years 27,41,44 ).…”

Section: Resultsmentioning

confidence: 99%

A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy

et al. 2017

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Objective: It remains unclear whether drug-resistant temporal lobe epilepsy (TLE) is associated with cumulative brain damage, with no expert consensus and no quantitative syntheses of the available evidence.Methods: We conducted a systematic review and meta-analysis of MRI studies on progressive atrophy, searching PubMed and Ovid MEDLINE databases for cross-sectional and longitudinal quantitative MRI studies on drug-resistant TLE.Results: We screened 2,976 records and assessed eligibility of 248 full-text articles. Forty-two articles met the inclusion criteria for quantitative evaluation. We observed a predominance of cross-sectional studies, use of different clinical indices of progression, and high heterogeneity in age-control procedures. Meta-analysis of 18/1 cross-sectional/longitudinal studies on hippocampal atrophy (n 5 979 patients) yielded a pooled effect size of r 5 20.42 for ipsilateral atrophy related to epilepsy duration (95% confidence interval [CI] 20.51 to 20.32; p , 0.0001; I 2 5 65.22%) and r 5 20.35 related to seizure frequency (95% CI 20.47 to 20.22; p , 0.0001; I 2 5 61.97%). Sensitivity analyses did not change the results. Narrative synthesis of 25/3 crosssectional/longitudinal studies on whole brain atrophy (n 5 1,504 patients) indicated that .80% of articles reported duration-related progression in extratemporal cortical and subcortical regions. Detailed analysis of study design features yielded low to moderate levels of evidence for progressive atrophy across studies, mainly due to dominance of cross-sectional over longitudinal investigations, use of diverse measures of seizure estimates, and absence of consistent age control procedures.

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“…Hippocampal damage is often bilateral in patients with unilateral temporal lobe epilepsy by clinical and neurophysiological criteria (Babb, 1991;Jokeit et al, 1999;Araú jo et al, 2006). Furthermore, SE can lead to bilateral CA3 damage in humans (Fujikawa et al, 2000) and in animal models, transforming the contralateral hippocampus into an independent epileptogenic focus, capable of generating spontaneous and evoked seizures (Araki et al, 2002;Khalilov et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Differential DNA Methylation Patterns Define Status Epilepticus and Epileptic Tolerance

Miller-Delaney¹,

Das²,

Sano³

et al. 2012

J. Neurosci.

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Prolonged seizures (status epilepticus) produce pathophysiological changes in the hippocampus that are associated with large-scale, wide-ranging changes in gene expression. Epileptic tolerance is an endogenous program of cell protection that can be activated in the brain by previous exposure to a non-harmful seizure episode before status epilepticus. A major transcriptional feature of tolerance is gene downregulation. Here, through methylation analysis of 34,143 discrete loci representing all annotated CpG islands and promoter regions in the mouse genome, we report the genome-wide DNA methylation changes in the hippocampus after status epilepticus and epileptic tolerance in adult mice. A total of 321 genes showed altered DNA methylation after status epilepticus alone or status epilepticus that followed seizure preconditioning, with Ͼ90% of the promoters of these genes undergoing hypomethylation. These profiles included genes not previously associated with epilepsy, such as the polycomb gene Phc2. Differential methylation events generally occurred throughout the genome without bias for a particular chromosomal region, with the exception of a small region of chromosome 4, which was significantly overrepresented with genes hypomethylated after status epilepticus. Surprisingly, only few genes displayed differential hypermethylation in epileptic tolerance. Nevertheless, gene ontology analysis emphasized the majority of differential methylation events between the groups occurred in genes associated with nuclear functions, such as DNA binding and transcriptional regulation. The present study reports select, genome-wide DNA methylation changes after status epilepticus and in epileptic tolerance, which may contribute to regulating the gene expression environment of the seizure-damaged hippocampus.

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Bilateral reductions of hippocampal volume, glucose metabolism, and Wada hemispheric memory performance are related to the duration of mesial temporal lobe epilepsy

Cited by 77 publications

References 55 publications

Gender‐specific Differences of Hypometabolism in mTLE: Implication for Cognitive Impairments

Gender‐specific Differences of Hypometabolism in mTLE: Implication for Cognitive Impairments

A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy

Differential DNA Methylation Patterns Define Status Epilepticus and Epileptic Tolerance

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