Dataset Information

Olfactory function in focal epilepsies: Understanding mesial temporal lobe epilepsy beyond the hippocampus.

ABSTRACT: Several lines of research have linked olfactory regions with the pathophysiology of focal epilepsies. Among those regions, the piriform cortex represents the major part of the primary olfactory cortex. According to these data, we raised the hypothesis that in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis exists an interictal dysfunction of olfactory processing that could be more significant compared to patients with extra-hippocampal focal epilepsy and healthy controls. This could be the consequence of a dysfunctional epileptogenic network that extends beyond the hippocampus and affects other structures, including the piriform cortex. To test this hypothesis, we evaluated the olfactory function with the Sniffin' Sticks test in 32 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis, 30 patients with extra-hippocampal focal epilepsy, and 22 healthy controls. Compared to the other study groups, patients with temporal lobe epilepsy due to hippocampal sclerosis showed a basal olfactory dysfunction characterized by an impairment in odor discrimination and odor identification. We also found that high seizure frequency had a strong correlation with the evaluated olfactory tasks. Our results are consistent with neuroimaging and neuropathological data that establish a link between olfactory regions and the pathophysiology of temporal lobe epilepsy.

SUBMITTER: Espinosa-Jovel C

PROVIDER: S-EPMC6698687 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Olfactory function in focal epilepsies: Understanding mesial temporal lobe epilepsy beyond the hippocampus.

Espinosa-Jovel Camilo C Toledano Rafael R Jiménez-Huete Adolfo A Aledo-Serrano Ángel Á García-Morales Irene I Campo Pablo P Gil-Nagel Antonio A

Epilepsia open 20190606 3

Several lines of research have linked olfactory regions with the pathophysiology of focal epilepsies. Among those regions, the piriform cortex represents the major part of the primary olfactory cortex. According to these data, we raised the hypothesis that in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis exists an interictal dysfunction of olfactory processing that could be more significant compared to patients with extra-hippocampal focal epilepsy and healthy ...[more]

PMID: 31440730

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Project description:PurposeIdentifying relationships between clinical features and quantitative characteristics of the amygdala-hippocampal and thalamic subregions in mesial temporal lobe epilepsy (mTLE) may offer insights into pathophysiology and the basis for imaging prognostic markers of treatment outcome. Our aim was to ascertain different patterns of atrophy or hypertrophy in mesial temporal sclerosis (MTS) patients and their associations with post-surgical seizure outcomes. To assess this aim, this study is designed in 2 folds: (1) hemispheric changes within MTS group and (2) association with postsurgical seizure outcomes.Methods and materials27 mTLE subjects with mesial temporal sclerosis (MTS) were scanned for conventional 3D T1w MPRAGE images and T2w scans. With respect to 12 months post-surgical seizure outcomes, 15 subjects reported being seizure free (SF) and 12 reported continued seizures. Quantitative automated segmentation and cortical parcellation were performed using Freesurfer. Automatic labeling and volume estimation of hippocampal subfields, amygdala, and thalamic subnuclei were also performed. The volume ratio (VR) for each label was computed and compared between (1) between contralateral and ipsilateral MTS using Wilcoxon rank-sum test and (2) SF and not seizure free (NSF) groups using linear regression analysis. False Discovery rate (FDR) with significant level of 0.05 were used in both analyses to correct for multiple comparisons.ResultsAmygdala: The medial nucleus of the amygdala was the most significantly reduced in patients with continued seizures when compared to patients who remained seizure free. Hippocampus: Comparison of ipsilateral and contralateral volumes with seizure outcomes showed volume loss was most evident in the mesial hippocampal regions such as CA4 and hippocampal fissure. Volume loss was also most explicit in the presubiculum body in patients with continued seizures at the time of their follow-up. Ipsilateral MTS compared to contralateral MTS analysis showed the heads of the ipsilateral subiculum, presubiculum, parasubiculum, dentate gyrus, CA4, and CA3 were more significantly affected than their respective bodies. Volume loss was most noted in mesial hippocampal regions. Thalamus: VPL and PuL were the most significantly reduced thalamic nuclei in NSF patients. In all statistically significant areas, volume reduction was observed in the NSF group. No significant volume reductions were noted in the thalamus and amygdala when comparing ipsilateral to contralateral sides in mTLE subjects.ConclusionsVarying degrees of volume loss were demonstrated in the hippocampus, thalamus, and amygdala subregions of MTS, especially between patients who remained seizure-free and those who did not. The results obtained can be used to further understand mTLE pathophysiology.Clinical relevance/applicationIn the future, we hope these results can be used to deepen the understanding of mTLE pathophysiology, leading to improved patient outcomes and treatments.

Project description:The epilepsies represent one of the most common neurological disorders. Mesial temporal lobe epilepsies (MTLE) are the most frequent form of partial epilepsies and display frequent resistance to anti-epileptic drugs thus representing a major health care problem. In TLE, the origin of seizure activity typically involves the hippocampal formation, which displays major neuropathological features, described with the term hippocampal sclerosis (HS). HS is the most frequent pathological substrate of refractory mesial temporal lobe epilepsy. Complex partial seizures (CPS) are the predominant seizure type associated with medial temporal lobe epilepsy. MTLE is commonly due to mesial temporal sclerosis (MTS). The biology underlying the epilepstic seizures and the transcriptome associated to the seizure in intractable medial temporal lobe epilepsy is ill understood. The aim of the study was to identify potential biomarkers that could identify epileptic seizure. Thus we performed transcriptome profiling of ten medial temporal lobe epilepsy cases which are resistant to the drug and underwent temporal lobectomy. The cases constitutes of patients with intractable complex partial seizure, treated medically and have undergone detailed presurgical evaluation and subjected to surgery for standard temporal lobectomy and amygdalo-hippocampectomy. The spiking areas identified after the electrocorticography will form the test tissues, which compared with the nonspiking areas removed during the surgery, from the same patient. This could probably form one of the appropriate controls, as test and control are from same patient, which eliminates the genome variations that could incur due to the comparison with the tissues from the another patient. Also this could get rid of expression changes due to the treatments undergone by the patient. We performed two color microarray wherein we labled seizure focus (spiking area) with Cy5 and non-seizure region tissues (non-spiking) with Cy3. As a strategy to test the possibility of potential diagnostic biomarkers we are intended to test the differentially regulated molecules in an independent set of epilepsy samples. Two color experiment

Project description:OBJECTIVES:Brain functional topology was investigated in patients with mesial temporal lobe epilepsy (mTLE) by means of graph theory measures in two differentially defined graphs. Measures of segregation, integration, and centrality were compared between subjects with mTLE and healthy controls (HC). METHODS:Eleven subjects with mTLE (age 36.5±10.9years) and 15 age-matched HC (age 36.8±14.0years) participated in this study. Both anatomically and functionally defined adjacency matrices were used to investigate the measures. Binary undirected graphs were constructed to study network segregation by calculating global clustering and modularity, and network integration by calculating local and global efficiency. Node degree and participation coefficient were also computed in order to investigate network hubs and their classification into provincial or connector hubs. Measures were investigated in a range of low to medium graph density. RESULTS:The group of patients presented lower global segregation than HC while showing higher global but lower local integration. They also failed to engage regions that comprise the default-mode network (DMN) as hubs such as bilateral medial frontal regions, PCC/precuneus complex, and right inferior parietal lobule, which were present in controls. Furthermore, the cerebellum in subjects with mTLE seemed to be playing a major role in the integration of their functional networks, which was evident through the engagement of cerebellar regions as connector hubs. CONCLUSIONS:Functional networks in subjects with mTLE presented both global and local abnormalities compared to healthy subjects. Specifically, there was significant separation between groups, with lower global segregation and slightly higher global integration observed in patients. This could be indicative of a network that is working as a whole instead of in segregated or specialized communities, which could translate into a less robust network and more prone to disruption in the group with epilepsy. Furthermore, functional irregularities were also observed in the group of patients in terms of the engagement of cerebellar regions as hubs while failing to engage DMN-related areas as major hubs in the network. The use of two differentially defined graphs synergistically contributed to findings.

Dataset Information

Olfactory function in focal epilepsies: Understanding mesial temporal lobe epilepsy beyond the hippocampus.

Publications

Olfactory function in focal epilepsies: Understanding mesial temporal lobe epilepsy beyond the hippocampus.

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