Short- and long-term limbic abnormalities after experimental febrile seizures

Jansen, Jacobus F. A.; Lemmens, Evi; Strijkers, Gustav J.; Prompers, Jeanine J.; Schijns, Olaf; Kooi, M. Eline; Beuls, E. A. M.; Nicolay, Klaas; Backes, Walter H.; Hoogland, Govert

doi:10.1016/j.nbd.2008.07.010

Cited by 23 publications

(26 citation statements)

References 43 publications

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“…Chronic neuronal damage due to seizures is often associated with increased water content, leading to increased pericortical CSF fractions, and T2 and ADC values (Hugg et al, 1999;Jansen et al, 2008a). In this study, however, we very consistently observed the opposite effect: a high number of SGTCS was associated with decreased T2, ADC, and fractional CSF values.…”

Section: Microstructural Mrsupporting

confidence: 47%

Multimodal MRI Reveals Secondarily Generalized Seizure Related Abnormalities at 1.5 T: Preliminary Findings

Jansen¹,

Vlooswijk²,

Reijs³

et al. 2015

JMED

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Patients with chronic epilepsy, who have suffered a high number of secondarily generalized tonicclonic seizures (SGTCS) frequently show cognitive comorbidity. It is yet unclear whether a higher number of SGTCS is associated with tissue changes in the brain. We have investigated in patients with chronic epilepsy whether a high number of SGTCS accumulated over life is associated with microstructural changes in brain tissue. Sixteen patients with localization-related epilepsy with SGTCS underwent a multimodal quantitative Magnetic Resonance (MR) examination at 1.5 T, comprising T2 relaxometry, and diffusion weighted imaging to study microstructural changes in the temporal and frontal lobes. Fourteen healthy volunteers were also included to assess the effect of age. Patients with more than 20 SGTCS (n=8) showed a significantly lower IQ (-20%, p<0.05) compared to those with less than 20 SGTCS (n=8). Furthermore, regional combined multimodal analysis revealed that significant quantitative MRI changes, related to the number of SGTCS, were present in the frontal lobe but not in the temporal lobe. Moreover, the left and right frontal lobe generally displayed lower T2 relaxation times, smaller pericortical cerebrospinal fluid fraction and lower apparent diffusion coefficients, in the patients with more than 20 SGTCS. These findings suggest that SGTCS are associated with substantial changes in microstructural brain tissue characteristics within the frontal lobes. These frontal changes possibly explain the cognitive problems which are often observed in patients with many SGTCS. This knowledge may help in the development of treatment aimed at preventing decline in cognitive abilities.

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Section: Microstructural Mrsupporting

confidence: 47%

Multimodal MRI Reveals Secondarily Generalized Seizure Related Abnormalities at 1.5 T: Preliminary Findings

Jansen¹,

Vlooswijk²,

Reijs³

et al. 2015

JMED

View full text Add to dashboard Cite

show abstract

“…Studies using the FPI model have also used MRS to identify acute abnormalities after injury [58,59], though whether these changes are associated with PTE has yet to be determined. Abnormalities in NAA and Cr have also been reported after FS in rats and may be related to the later development of spontaneous seizures [48]. Overall, these findings demonstrate that MRS is capable of identifying biomarkers associated with numerous pathophysiological changes occurring throughout the epileptogenic process, and support its use in future investigations.…”

Section: Magnetic Resonance Spectroscopysupporting

confidence: 55%

“…Of particular importance, acute and chronic hippocampal ADC changes in the FPI model were associated with electroencephalography (EEG) parameters (i.e., total number of interictal epileptiform spikes and epileptiform discharges), mossy fibre sprouting, and seizure susceptibility after a chemoconvulsant challenge [23,37]. It should also be noted that reductions in FA and associated tractography have been reported in animal models of genetic generalized epilepsy with absence seizures (i.e., WAG/Rij rats) [47], and decreased ADC and increased FA have been reported in rats after FS [48]. Taken together, DWI-based approaches are sensitive and promising in identifying potential epileptogenic-related changes throughout the disease process.…”

Section: Diffusion-weighted Mrimentioning

confidence: 99%

Neuroimaging the Epileptogenic Process

et al. 2014

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Epilepsy is one of the most common chronic neurological conditions worldwide. Anti-epileptic drugs (AEDs) can suppress seizures, but do not affect the underlying epileptic state, and many epilepsy patients are unable to attain seizure control with AEDs. To cure or prevent epilepsy, disease-modifying interventions that inhibit or reverse the disease process of epileptogenesis must be developed. A major limitation in the development and implementation of such an intervention is the current poor understanding, and the lack of reliable biomarkers, of the epileptogenic process. Neuroimaging represents a non-invasive medical and research tool with the ability to identify early pathophysiological changes involved in epileptogenesis, monitor disease progression, and assess the effectiveness of possible therapies. Here we will provide an overview of studies conducted in animal models and in patients with epilepsy that have utilized various neuroimaging modalities to investigate epileptogenesis.

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“…An increased T2-weighted MRI signal implies that the free water concentration of the tissue is increased, which might be caused by neuronal loss, brain edema, gliosis, increased fiber density, or anisotropy [39,40,41,42]. We have previously shown alterations in gross hippocampal morphology with MRI in prenatally stressed adult offspring [30].…”

Section: Discussionmentioning

confidence: 99%

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

et al. 2015

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Prenatal glucocorticoid exposure causes brain damage in adult offspring; however, the underlying mechanisms remain unclear. Melatonin has been shown to have beneficial effects in compromised pregnancies. Pregnant Sprague-Dawley rats were administered vehicle (VEH) or dexamethasone between gestation days 14 and 21. The programming effects of prenatal dexamethasone exposure on the brain were assessed at postnatal days (PND) 7, 42, and ∼120. Melatonin was administered from PND21 to the rats exposed to dexamethasone, and the outcome was assessed at ∼PND120. In total, there were four groups: VEH, vehicle plus melatonin (VEHM), prenatal dexamethasone-exposure (DEX), and prenatal dexamethasone exposure plus melatonin (DEXM). Spatial memory, gross hippocampal morphology, and hippocampal biochemistry were examined. Spatial memory assessed by the Morris water maze showed no significant differences among the four groups. Brain magnetic resonance imaging showed that all rats with prenatal dexamethasone exposure (DEX + DEXM) exhibited increased T2-weighted signals in the hippocampus. There were no significant differences in the levels of mRNA expression of hippocampal reln, which encodes reelin, and GAD1, which encodes glutamic acid decarboxylase 67, at PND7. At both PND42 and ∼PND120, reln and GAD1 mRNA expression levels were decreased. At ∼PND120, melatonin restored the reduced levels of hippocampal reln and GAD1 mRNA expression in the DEXM group. In addition, melatonin restored the reln mRNA expression levels by (1) reducing DNA methyltransferase 1 (DNMT1) mRNA expression and (2) reducing the binding of DNMT1 and the methyl-CpG binding protein 2 (MeCP2) to the reln promoter. The present study showed that prenatal dexamethasone exposure induced gross alterations in hippocampal morphology and reduced the levels of hippocampal mRNA expression of reln and GAD1. Spatial memory was unimpaired. Thus, melatonin had a beneficial effect in restoring hippocampal reln mRNA expression by reducing DNMT1 and MeCP2 binding to the reln promoter.

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Short- and long-term limbic abnormalities after experimental febrile seizures

Cited by 23 publications

References 43 publications

Multimodal MRI Reveals Secondarily Generalized Seizure Related Abnormalities at 1.5 T: Preliminary Findings

Multimodal MRI Reveals Secondarily Generalized Seizure Related Abnormalities at 1.5 T: Preliminary Findings

Neuroimaging the Epileptogenic Process

Effects of Melatonin on Prenatal Dexamethasone-Induced Epigenetic Alterations in Hippocampal Morphology and Reelin and Glutamic Acid Decarboxylase 67 Levels

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