Hippocampal Sclerosis Group Research Articles

Temporal Trends in Hippocampal Sclerosis Surgery: An Observational Study From a Tertiary Epilepsy Centre.

Temporal lobe epilepsy with hippocampal sclerosis (HS) is a surgically remediable syndrome. We determined temporal trends in the prevalence of hippocampal sclerosis surgeries and related factors. We analysed a prospective cohort of adults who underwent epilepsy surgery at the NHNN, London, between 1990 and 2019. HS group was compared with other pathologies. Demographics, surgical trends for HS and associations with sex, age, prior neurological insults and febrile seizures were analysed. Temporal trends were assessed by one-way or Welch ANOVA, with post hoc analysis. Surgery latency over three decades was evaluated with the Kruskal-Wallis H test, using Dunn's procedure for pairwise comparisons. Chi-squared analyses examined associations with sex, age at operation, febrile seizures, and between resection side and handedness. Of 1069 people operated, 586 had hippocampal sclerosis. After increasing, surgeries declined in the last decade (from 322 to 131), as did the number of people with hippocampal sclerosis and a history of childhood febrile seizures (from 87 to 23). The median interval from epilepsy onset to surgery increased from 22 to 24 and 27 years over each decade. Female sex and febrile seizures were associated with pathology (HS vs. non-HS) but not age at surgery, previous neurological insults, or the resection side and handedness. Our study confirms the decline in hippocampal surgeries. This trend may be due to changes in the syndrome's natural history, possibly from improved paediatric care, and an increase in complex cases. The impact of delayed referrals, surgical risk fears and newer anti-seizure medications remains unclear.

Exploring Cortical and Hippocampal Changes in Temporal Lobe Epilepsy Using Automated MRI Segmentation Techniques.

To investigate the applicability of MR-based automated segmentation techniques in evaluating cortical and hippocampal changes in adults with temporal lobe epilepsy (TLE), specifically emphasizing the affected hemisphere. A retrospective analysis involved 48 cases diagnosed with TLE based on clinical and EEG criteria. The cohort comprised 30 patients with hippocampal sclerosis (HS) and 18 with nonlesional temporal lobe epilepsy (TLE-NL) on MR. 30healthy volunteers constituted the control group. FreeSurfer software facilitated the segmentation of cortical regions and hippocampal subfields, generating numerical values for cortical thickness and hippocampal subfield volumes on the left hemisphere. Independent sample Wilcoxon rank-sum tests enabled pairwise comparisons of cortical thickness and hippocampal subfield volumes between the control, TLE-NL, and HS groups. Significant differences emerged in hippocampal total volume and volumes of the head, body, and tail regions between the control and HS groups and the TLE-NL and HS groups. Cortical thickness of 6 regions exhibited statistical differences between the control and TLE-NL groups, while 15 regions showed distinctions between the control and HS groups. 2 regions displayed variations in cortical thickness between the TLE-NL and HS groups. MRI-based automated segmentation techniques provide valuable insights into cortical and hippocampal structural variations in distinct TLE subtypes. This methodology effectively delineates changes in cortical regions and hippocampal subfields, augmenting clinical comprehension of TLE progression.

Surgical treatment may improve depressive and hysterical traits in temporal lobe epilepsy with hippocampal sclerosis: Study using the Minnesota Multiphasic Personality Inventory.

The influence of surgeries on psychiatric symptoms and personality traits is not well known in patients with intractable temporal lobe epilepsy (TLE). We investigated changes in personality traits with respect to postoperative seizure outcomes, etiology, side of surgery, and sex differences. Clinical information was retrospectively collected for 44 patients whose Minnesota Multiphasic Personality Inventory (MMPI) was examined before and 1 year after surgical treatment for drug-resistant TLE. Postoperative changes in MMPI T-scores were analyzed using a paired t-test. Participants were divided into two groups based on postoperative seizure outcome, the presence or absence of hippocampal sclerosis (HS) as the etiology, side of surgery, and sex differences. The effect of these clinical factors on postoperative changes in MMPI T-scores was evaluated using analysis of covariance (P-values < 0.05). The hypochondria (Hs) scale decreased significantly in all patients (p = 0.022). The postoperative seizure-free group had a significant decrease in the depression (D) scale (p = 0.037). The HS group had significant decreases in the D scale and the hysteria (Hy) scale (p = 0.016 and 0.004, respectively), and a significant increase in the masculinity-femininity (Mf) scale (p = 0.009). No significant differences existed between the sides of surgery or sex. Depressive traits were improved in patients with postoperative seizure freedom. Depressive and hysterical traits were improved in patients with HS, which may be attributed to a reduction in anxiety and fear associated with aura. Most personality traits are not significantly changed or exacerbated by surgical treatment of TLE.

TNF-α: A serological marker for evaluating the severity of hippocampal sclerosis in medial temporal lobe epilepsy?

ObjectiveBy analysing the difference in TNF-α levels in the peripheral blood of patients with medial temporal lobe epilepsy (mTLE) with or without hippocampal sclerosis and the correlation between TNF-α and N-acetylaspartate levels in the hippocampus, we explored the relationship between TNF-α and the degree of damage to hippocampal sclerosis neurons in medial temporal lobe epilepsy. MethodsThis is a prospective, population-based study. A total of 71 Patients with medial temporal lobe epilepsy diagnosed by clinical seizures, video-EEG, epileptic sequence MRI, and other imaging examinations were recruited from October 2020 to July 2022 in the Department of Neurology, Affiliated Hospital of Xuzhou Medical University. Twenty age-matched healthy subjects were selected as the control group. The patients were divided into two groups: the medial temporal epilepsy with hippocampal sclerosis group (positive group, mTLE-HS-P group) and the medial temporal epilepsy without hippocampal sclerosis group (negative group, mTLE-HS-N group). The levels of IL-1β, IL-5, IL-6, IL-8, IL-17, IFN-γ and TNF-α in the peripheral blood of the patients in the three groups were detected by multimicrosphere flow immunofluorescence assay. The level of N-acetylaspartate (NAA) in the hippocampus was measured by 1H-MRS. The differences in cytokine levels among the three groups were analysed, and the correlation between cytokine and NAA levels was analysed. ResultsThe level of TNF-α in the peripheral blood of the patients in the mTLE-HS-P group was significantly higher than that of the patients in the mTLE-HS-N and healthy control groups, and the level of TNF-α in the patients in the mTLE-HS-N group was significantly higher than that of the patients in the healthy control group. The NAA level in mTLE-HS-P group patients was significantly lower than that of mTLE-HS-N patients and healthy controls, but there was no significant difference between mTLE-HS-N patients and healthy controls (P > 0.05). Spearman correlation analysis showed that TNF-α level (rs = -0.437, P < 0.05) and the longest duration of a single seizure (rs = -0.398, P < 0.05) were negatively correlated with NAA level. Logistic regression analysis showed that there was no significant correlation between the longest duration of a single seizure and hippocampal sclerosis, but TNF-α level was closely related to hippocampal sclerosis in patients with mTLE (OR = 1.315, 95 % CI 1.084–1.595, P = 0.005). ConclusionThe level of TNF-α in the peripheral blood of patients with medial temporal lobe epilepsy with hippocampal sclerosis was higher, and it was correlated with NAA and hippocampal sclerosis. The high expression of TNF-α may be of important value in the evaluation of hippocampal sclerosis patients.

Metabolic connectivity as a predictor of surgical outcome in mesial temporal lobe epilepsy.

The study investigated metabolic connectivity (MC) differences between patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) and healthy controls (HCs), based on [18 F]-fluorodeoxyglucose (FDG)-PET data. We focused on the MC changes dependent on the lateralization of the epileptogenic lobe and on correlations with postoperative outcomes. FDG-PET scans of 47 patients with unilateral MTLE with histopathologically proven HS and 25 HC were included in the study. All the patients underwent a standard anterior temporal lobectomy and were more than 2 years after the surgery. MC changes were compared between the two HS groups (left HS, right HS) and HC. Differences between the metabolic network of seizure-free and non-seizure-free patients after surgery were depicted afterward. Network changes were correlated with clinical characteristics. The study showed widespread metabolic network changes in the HS patients as compared to HC. The changes were more extensive in the right HS than in the left HS. Unfavorable surgical outcomes were found in patients with decreased MC within the network including both the lesional and contralesional hippocampus, ipsilesional frontal operculum, and contralesional insula. Favorable outcomes correlated with decreased MC within the network involving both orbitofrontal cortices and the ipsilesional temporal lobe. There are major differences in the metabolic networks of left and right HS, with more extensive changes in right HS. The changes within the metabolic network could help predict surgical outcomes in patients with HS. MC may identify patients with potentially unfavorable outcomes and direct them to a more detailed presurgical evaluation. Metabolic connectivity is a promising method for metabolic network mapping. Metabolic networks in mesial temporal lobe epilepsy are dependent on lateralization of the epileptogenic lobe and could predict surgical outcomes.

Postoperative seizure and memory outcome of temporal lobe epilepsy with hippocampal sclerosis: A systematic review.

We conducted a systematic review and meta-analysis to evaluate postoperative seizure and memory outcomes of temporal lobe epilepsy with different hippocampal sclerosis (HS) subtypes classified by International League Against Epilepsy (ILAE) Consensus Guidelines in 2013. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and MOOSE (Meta-Analysis of Observational Studies in Epidemiology) guidelines, we searched PubMed, Embase, Web of Science, and Cochrane Library from January 1, 2013 to August 6, 2023. Observational studies reporting seizure and memory outcomes among different HS subtypes were included. We used the Newcastle-Ottawa scale to assess the risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to grade the quality of evidence. Seizure freedom and improved outcome (Engel 1 or ILAE class 1-2) ≥1 year after surgery were defined as the primary and secondary seizure outcome. A random-effects meta-analysis by DerSimonian and Laird method was performed to obtain pooled risk ratio (RRs) with 95% confidence interval (CIs). The memory impairment was narratively reviewed because of various evaluation tools. Fifteen cohort studies with 2485 patients were eligible for the meta-analysis of seizure outcome. Six cohorts with detailed information on postoperative memory outcome were included. The pooled RRs of seizure freedom, with moderate to substantial heterogeneity, were .98 (95% CI = .84-1.15) between HS type 2 and type 1, 1.11 (95% CI = .82-1.52) between type 3 and type 1, and .80 (95% CI = .62-1.03) between the no-HS and HS groups. No significant difference of improved outcome was found between different subtypes (p > .05). The quality of evidence was deemed to be low to very low according to GRADE. The long-term seizure outcome (≥5 years after surgery) and memory impairment remained controversial.

Performance of hippocampal radiomics models based on T2-FLAIR images in mesial temporal lobe epilepsy with hippocampal sclerosis

PurposePreoperative identification of hippocampal sclerosis (HS) is crucial to successful surgery for mesial temporal lobe epilepsy (MTLE). We aimed to investigate the diagnostic performance of hippocampal radiomics models based on T2 fluid-attenuated inversion recovery (FLAIR) images in MTLE with HS. MethodsWe analysed 210 cases, including 172 HS pathology-confirmed cases (100 magnetic resonance imaging [MRI]-positive cases [MRI + HS], 72 MRI-negative HS cases [MRI − HS]), and 38 healthy controls (HC). The hippocampus was delineated slice by slice on an oblique coronal plane by a T2-FLAIR sequence, perpendicular to the hippocampus’s long axis, to obtain a three-dimensional region of interest. Radiomics were processed using Artificial Intelligence Kit software; logistic regression radiomics models were constructed. The model evaluation indexes included the area under the curve (AUC), accuracy, sensitivity, and specificity. ResultsThe respective AUC, accuracy, sensitivity, and specificity were 0.863, 81.4%, 78.0%, and 84.6% between the MRI − HS and HC groups in the training set and 0.855, 75.0%, 68.2%, and 81.8% in the test set; 0.975, 95.0%, 92.9%, and 98.0% between the MRI + HS and HC groups in the training set and 0.954, 88.7%, 90.0%, and 87.0% in the test set; and 0.912, 84.3%, 83.3%, and 86.5% between the MTLE and HC groups in the training set and 0.854, 79.7%, 80.8%, and 77.3% in the test set. The AUC values of the comparative radiomics models were > 0.85, indicating good diagnostic efficiency. ConclusionThe hippocampal radiomics models based on T2-FLAIR images can help diagnose MTLE with HS. They can be used as biological markers for MTLE diagnosis.

More extensive structural damage in temporal lobe epilepsy with hippocampal sclerosis type 1

ObjectiveTo explore clinical and structural differences between mesial temporal lobe epilepsy (mTLE) patients with different hippocampal sclerosis (HS) subtypes. MethodsHigh-resolution T1-weighted MRI and diffusion tensor imaging data were obtained in 41 refractory mTLE patients and 52 age- and sex-matched healthy controls. Postoperative histopathological examination confirmed HS type 1 in 30 patients and HS type 2 in eleven patients. Clinical features, postoperative seizure outcomes, hippocampal subfields volumes, fractional anisotropy (FA) values of white matter regions and graph theory parameters were explored and compared between the HS type 1 and HS type 2 groups. ResultsNo significant differences in clinical features and postsurgical seizure outcomes were found between the HS type 1 and type 2 groups. However, the HS type 1 group showed extra atrophy in ipsilateral parasubiculum than healthy controls and more severe atrophy in contralateral hippocampal fissure than the HS type 2 group. More extensive FA decrease were also observed in the HS type 1 group, involving ipsilateral optic radiation, superior fronto-occipital fasciculus, contralateral uncinate fasciculus, tapetum, bilateral hippocampal cingulum, corona radiata, etc. Furthermore, in spite of similar impairments in characteristic path length, global efficiency and local efficiency in two HS groups, the HS type 1 group showed additional decrease of clustering coefficient than healthy controls. ConclusionsHS type 1 and 2 groups had similar clinical characteristics and postoperative seizure outcomes. More widespread neuronal cell loss in the HS type 1 group contributed to more extensive structural damage and connectivity abnormality. These results shed new light on the imaging correlates of different HS pathology.

Mesial temporal lobe epilepsy with amygdalar hamartoma-like lesion: Is it a distinct syndrome?

IntroductionWe examined the clinical, semiological, scalp electroencephalographic (EEG), and neuropsychological features of patients with amygdalar hamartoma-like lesion (AHL) without hippocampal sclerosis (HS). MethodsThis retrospective study included 9 patients with mesial temporal lobe epilepsy (MTLE) who had an amygdalar lesion on preoperative MRI; underwent mesial temporal resection; were diagnosed with amygdalar hamartoma-like lesion (AHL) without hippocampal sclerosis (HS); were followed up for at least 2 years after surgery; and had a favourable postoperative seizure outcome (Engel Class I). There were 5 women and 4 men, and age at surgery ranged from 19 to 54 (mean, 36.6) years. Clinical characteristics, auras, video-recorded seizure semiology, interictal and ictal EEG, and preoperative neuropsychological data were reviewed. Twenty patients with MTLE with HS who had favourable postoperative seizure outcomes (Engel Class I) were selected as controls. ResultsAge at seizure onset was significantly higher in patients with AHL without HS than in those with HS. Fear was more frequently seen in patients with AHL (44 %) than in those with HS (5 %) (P = 0.022). There were no significant differences in interictal epileptiform discharges or ictal EEG pattern. Preoperative full-scale IQ score was significantly higher in the AHL group than in the HS group (mean, 92.9 v. 74.8, P = 0.004), as was preoperative memory quotient score (mean 100.7 v. 85.1, P = 0.028). ConclusionWe clarified the clinical, semiological, and neuropsychological features of patients with MTLE-AHL. These findings may be useful for preoperative evaluation, especially of patients with suspected MTLE but without apparent HS on preoperative MRI.

Memory changes in patients with hippocampal sclerosis submitted to surgery to treat mesial temporal lobe epilepsy

PurposeThis study was performed with the purpose of analysing the relationship between epileptological and surgical variables and post-operative memory performance, following surgery for refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). MethodsLogical memory (LM) and visual memory (VM) scores for immediate and late follow-up of 201 patients operated for MTLE/HS were reviewed. Scores were standardized with a control group of 54 healthy individuals matched for age and education. The Reliable Change Index (RCI) was calculated to verify individual memory changes for late LM and VM scores. A multiple linear regression analysis was carried out with the RCI, using LM and VM scores as well as the clinical variables. ResultsA total of 112 (56%) patients had right HS. The RCI of the right HS group demonstrated that 6 (7%) patients showed improvement while 5 (6%) patients showed decreased scores in late LM; for late VM, 7 (8%) patients presented improvement, and 2 (3%) patients showed poorer scores. RCI of the left HS group showed that 3 (3%) individuals showed improved scores, while scores of 5 (4%) patients worsened for late LM; for late VM, 3 (3%) patients presented higher scores and 6 (5%) showed lower scores. Left HS and advanced age at onset of the first epileptic seizure were predictors of late LM loss (p<.05). ConclusionLeft MTLE/HS and seizure onset at advanced ages were predictive factors for the worsening of late LM. We observed poorer baseline LM function in the left HS group and improvement of LM in some patients who had resection of the right MTL. Patients in the right HS group showed a higher percentage of reliable post-operative improvement for both VM and LM scores.

Quantitative assessment of structural and functional changes in temporal lobe epilepsy with hippocampal sclerosis

Magnetic resonance imaging (MRI) changes in hippocampal sclerosis (HS) could be subtle in a significant proportion of mesial temporal lobe epilepsy (mTLE) patients. In this study, we aimed to document the structural and functional changes in the hippocampus and amygdala seen in HS patients. Quantitative features of the hippocampus and amygdala were extracted from structural MRI data in 66 mTLE patients and 28 controls. Structural covariance analysis was undertaken using volumetric data from the amygdala and hippocampus. Functional connectivity (FC) measured using resting intracranial electroencephalography (EEG) was analyzed in 22 HS patients and 16 non-HS disease controls. Hippocampal atrophy was present in both MRI-positive and MRI-negative HS groups (Mann-Whitney U: 7.61, P<0.01; Mann-Whitney U: 6.51, P<0.01). Amygdala volumes were decreased in the patient group (Mann-Whitney U: 2.92, P<0.05), especially in MRI-negative HS patients (Mann-Whitney U: 2.75, P<0.05). The structural covariance analysis showed the normalized volumes of the amygdala and hippocampus were tightly coupled in both controls and HS patients (ρSpearman =0.72, P<0.01). FC analysis indicated that HS patients had significantly increased connectivity (Student's t: 2.58, P=0.03) within the hippocampus but decreased connectivity between the hippocampus and amygdala (Student's t: 3.33, P=0.01), particularly for MRI-negative HS patients. Quantitative structural changes, including hippocampal atrophy and temporal pole blurring, are present in both MRI-positive and MRI-negative HS patients, suggesting the potential usefulness of incorporating quantitative analyses into clinical practice. HS is characterized by increased intra-hippocampal EEG synchronization and decreased coupling between the hippocampus and amygdala.

P300 in mesial temporal lobe epilepsy and its correlation with cognition – A MEG based prospective case-control study

PurposeTo assess the role of P300 in patients with temporal lobe epilepsy (TLE) with unilateral hippocampal sclerosis (HS) using magnetoencephalography (MEG) based auditory and visual oddball tasks, and to assess its correlation with neuropsychological tests. MethodsThirty-patients (M:F-17:13, onset-11.77 ± 8.75 years, duration-16.10 ± 9.61 years) with TLE-HS (Left:15, Right:15) and fifteen-healthy age, gender and years of education matched controls (M:F-10:5, age-28.13 ± 4.76 years) underwent auditory and visual oddball tasks in MEG and cognition assessment using Indian Council of Medical Research (ICMR)-cognitive test battery. Independent component analysis (ICA) was applied to the magnetic evoked field responses for the detection of the P300 component. Source localization of P300 was performed with Classical LORETA Analysis Recursively Applied (CLARA). The latency and amplitude of P300 were estimated and subsequently correlated with cognitive scores. ResultsThe visual P300 amplitude in the TLE group was lower when compared to the control group. In subgroup comparison (controls vs. right HS vs. left HS), visual P300 amplitudes were lower in the right HS group compared to both left HS and control groups (p-value = 0.014). On the other hand, no significant difference for auditory P300 latency or amplitude was noted between patients and controls as well as between subgroups. A negative correlation found between the MEG visual P300 amplitude and Indian Trial Making Test (TMT)-B duration in the patient group. ConclusionPatients with TLE-HS have decreased visual-P300 amplitude. A significant correlation found between visual P300 amplitude and cognitive tests of visuospatial attention and working memory. Overall, MEG based visual P300 amplitude can be further explored with large sample size studies to establish as a complementary objective test for cognitive assessment in TLE.

Consanguinity in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis in a Saudi population.

Objectives:To investigate if there is an association between consanguinity and hippocampal sclerosis (HS) in the Saudi population.Methods:A retrospective case-control study was conducted by assessing the prevalence of consanguinity in patients with pathologically proven HS, who underwent epilepsy surgery at King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, between January 2004 and December 2015. We reviewed the medical records to extract data, which included; age, gender, duration of epilepsy, history of febrile seizure, family history of epilepsy in a first or second-degree relative, and pathology reports.Results:A total of 120 patients, out of which 40 patients (65% male) having mesial temporal lobe epilepsy due to HS, and 80 controls (56% male) with cryptogenic epilepsy, were identified. Twenty-two patients (53.5%) in the HS group had a history of consanguinity. In the control group, 30 patients (37.5%) had a history of consanguinity. The odds ratio was 2.04 (95% confidence interval = 0.94 - 4.4, p = 0.052). A family history of epilepsy was found in 28% of the patients with HS and 32.5% cryptogenic epilepsy. Only 8 patients (19.5%) with HS reported a history of febrile seizure.Conclusion:Our retrospective case-control study suggests that consanguinity might increase the likelihood of developing HS.

Investigation of microstructural abnormalities in white and gray matter around hippocampus with diffusion tensor imaging (DTI) in temporal lobe epilepsy (TLE)

ObjectiveThe objective of this study was to apply diffusion tensor imaging (DTI) to investigate microstructural abnormalities in temporal lobe epilepsy (TLE) with and without hippocampal sclerosis (HS). MaterialsTotally, 19 patients with TLE with HS and 23 patients with TLE without HS were included. Fiber tracking fibers focused on the parahippocampal cingulum (PHC), cingulate gyrus (CG), and fornix (FORX). Fractional anisotropy (FA) and mean diffusivity (MD) values were obtained, and hippocampal volumes were measured. ResultsCompared with the contralateral side, for the HS group, FA values of ipsilateral CG and FORX were significantly decreased, and MD value of ipsilateral hippocampus was significantly higher, with significantly declined ipsilateral hippocampal volume. For the MRI-Neg group, FA values of ipsilateral CG, FORX, and hippocampus were significantly decreased, while MD values of ipsilateral FORX and hippocampus were significantly higher. Moreover, for the MRI-Neg group, the FA value of contralateral PHC was significantly decreased. Fractional anisotropy values of ipsilateral CG for both groups were significantly decreased, and FA value of ipsilateral FORX for the HS group was significantly decreased. Furthermore, MD value of ipsilateral hippocampus for the HS group was significantly higher, and FA value of ipsilateral hippocampus for the MRI-Neg group was significantly decreased. In addition, ipsilateral hippocampal volumes for both groups were significantly decreased. Fractional anisotropy value of ipsilateral CG and FORX had a correlation with the seizure frequency. ConclusionDiffusion tensor imaging can detect microstructural abnormalities in brain from patients with TLE, which might be hard to find with routine Magnetic Resonance Imaging (MRI) sequence.

Comparison of Cognitive Parameters Between Bilateral and Unilateral Hippocampal Sclerosis.

Recent studies showed that hippocampal sclerosis (HS) patients with unilateral involvement had more diffuse cognitive impairment than expected. Therefore, we aimed to compare the cognitive profiles of bilateral HS (BHS) patients with unilateral HS (UHS) patients. Consecutive patients, diagnosed with epilepsy, who fulfilled two major magnetic resonance imaging (MRI) criteria (T1 atrophy and T2-FLAIR hyperintensity) for HS were included. Standard neuro-psychological test (NPT) battery consisted of the Turkish version of 15-word verbal memory processes test, Wechsler memory scale visual reproduction subtest, forward and backward digit span, phonemic and semantic fluency, and Stroop test were applied; and the groups with right HS, left HS, and bilateral HS were compared statistically. Ninety-one patients, completing the NPT (34 males, 57 females)-16 with BHS, 36 with right HS, and 39 with left HS-were included. Six out of 43 operated patients had BHS. There were no significant differences in education and handedness of the groups. Even though NPT performances of the BHS group were found to be poor compared to UHS subgroups, this was beyond statistical significance. Comparison of BHS with the right HS group showed a significant difference in the learning score of the Verbal Memory Processes Test, but recognition scores were found to be similar in all groups. Compared to the BHS group, both right and left HS groups revealed a significant difference in delayed recall score of the Verbal Memory Processes Test. Although there were no significant differences in the postoperative parameters of the BHS group, UHS subgroups had deficits in many postoperative parameters. Our study revealed that bilateral involvement of the hippocampi was correlated with a poor cognitive performance. Retrieval failure, rather than a total recall problem, in the memory of the patients resembles a more diffuse involvement not only limited to limbic structures.

Long-term outcome and neuroradiologic changes after multiple hippocampal transection combined with multiple subpial transection or lesionectomy for temporal lobe epilepsy.

Multiple hippocampal transection (MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy (MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation. Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy (mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit (LV). Three subgroups were evaluated as well: magnetic resonance imaging (MRI) negative (MN), hippocampal sclerosis (HS), and normal hippocampus with extrahippocampal lesion (NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume (HV), diffusion tensor parameters (DTP), and glucose utilization (GU) were determined from MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) studies performed before and >6 months after surgery. Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level. The long-term outcome for complex partial seizures after MHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI.

Distinct white matter integrity in glutamic acid decarboxylase and voltage-gated potassium channel-complex antibody-associated limbic encephalitis.

Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI). Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups. Voxelwise statistical analysis was carried out using tract-based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance. We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD-associated limbic encephalitis, whereas no changes were found in VGKC-complex-associated limbic encephalitis. The changes observed in the GAD group were even more extensive when compared against those of the hippocampal sclerosis group, although the disease duration was markedly shorter in patients with GAD antibodies. Correlation analysis revealed areas with a trend toward a negative correlation of diffusivity parameters with figural memory performance located mainly in the right temporal lobe in the GAD group as well. The present study provides further evidence that, depending on the associated antibody, limbic encephalitis features clearly distinct imaging characteristics by showing widespread white matter changes in GAD-associated limbic encephalitis and preserved white matter integrity in VGKC-complex-associated limbic encephalitis. Furthermore, our results contribute to a better understanding of the specific pathophysiologic properties in these two subforms of limbic encephalitis by revealing that patients with GAD antibodies show widespread affections of white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC-complex-associated limbic encephalitis, primarily affecting mesiotemporal gray matter.

Hippocampal GABA transporter distribution in patients with temporal lobe epilepsy and hippocampal sclerosis

PurposeTo determine hippocampal expression of neuronal GABA-transporter (GAT-1) and glial GABA-transporter (GAT-3) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). MethodsHippocampal sections were immunohistochemically stained for GABA-transporter 1 and GABA-transporter-3, followed by quantification of the immunoreactivity in the hilus by optical density measurements. GABA-transporter 3 positive hilar cells were counted and GABA-transporter protein expression in sections that included all hippocampal subfields was quantified by Western blot. ResultsThe hilar GABA-transporter 1 expression of patients with severe hippocampal sclerosis was about 7% lower compared to that in the mild hippocampal sclerosis/control group (p<0.001). The hilar GABA-transporter 3 expression was about 5% lower in the severe hippocampal sclerosis group than in the mild hippocampal sclerosis/control group (non-significant). Also, severe hippocampal sclerosis samples contained 34% less (non-significant) GABA-transporter 3 positive cells compared to that of controls.Protein expression as assessed by Western blot showed that GABA-transporter 1 was equally expressed in mild and severe hippocampal sclerosis samples, whereas GABA-transporter 3 was reduced by about 62% in severe hippocampal sclerosis samples (p<0.0001). ConclusionThese data confirm that GABA-transporter expression is spatially and isoform-specific reduced and GABA-transporter 3 positive cell numbers are unchanged in hippocampal sclerosis. Implications for the use of GABAergic antiepileptic therapies in hippocampal sclerosis vs non-hippocampal sclerosis patients remain to be studied.

Quantitative peri-ictal electrocorticography and long-term seizure outcomes in temporal lobe epilepsy

We analyzed peri-ictal electrocorticography below 70 Hz by a semiautomatic quantitative method. Thirty-four patients with medically intractable temporal lobe epilepsy underwent chronic electrocorticography using subdural electrodes. The resection extent of cortices with maximum amplitude activities were compared between seizure outcome groups. In detected activity significantly related to seizure outcome, we analyzed waveforms with automated waveform amplitude analysis. Mann-Whitney U tests were used. Mean follow-up duration was 49.7 ± 18.2 months. The resection extents of maximum amplitude activities in theta bands during the period between -10 and -5s from the ictal onset were significantly different between seizure outcome groups (adjusted p=0.01, the Benjamini-Hochberg correction). Delta, alpha and beta bands were related to seizure outcome only without multiple comparison corrections (unadjusted p=0.02, 0.03 and 0.04). Waveform peak amplitudes greater than 200 μV tended to be more common in the seizure free group than in the non-seizure-free group (unadjusted p=0.06). Waveform peak amplitudes greater than 350 μV were significantly more common in the cortical dysplasia type I group than in the hippocampal sclerosis group (unadjusted p=0.03). The resection of theta band activities during the preictal period was most important for good seizure outcome in temporal lobe epilepsy.

Quantification of subfield pathology in hippocampal sclerosis: A systematic review and meta-analysis

BackgroundThe utility of MRI-based hippocampal subfield volumetry as a diagnostic test for hippocampal sclerosis (HS) is based on the hypothesis that specific hippocampal subfields are differentially affected in HS. While qualitative studies suggest selective involvement of certain hippocampal subfields in this condition, whether quantifiable differences exist remains unclear. Neuronal density measurement is the most widely used technique for measuring subfield pathological change in HS. Therefore, a systematic review and meta-analysis of studies reporting neuronal densities in temporal lobe epilepsy was performed in order to quantify subfield pathology in hippocampal sclerosis. MethodsStudies were identified by searching the Medline and Embase databases using the search terms: cell count, hippocampus, and epilepsy. Of the 192 studies identified by the literature search, seven met all inclusion and exclusion criteria. Random effects meta-analyses were performed, comparing: (i) neuronal densities in control (n=121) versus HS (n=371) groups for subfields CA1-4; and (ii) amount of neuronal loss in HS between subfields CA1-4. ResultsStatistically significant neuronal loss was observed comparing HS to control groups in all subfields CA1-4 (p<0.001 for all comparisons). Significantly greater neuronal loss was demonstrated in HS comparing CA1 versus CA2 (p<0.001), CA3 (p=0.005), and CA4 (p=0.003). Greater pyramidal cell loss was also demonstrated in CA3 relative to the CA2 subfield (p=0.003). No significant differences were identified comparing CA2 and CA4 (p=0.39); or comparing CA3 and CA4 (p=0.64). ConclusionsHS is characterized by pathology in all hippocampal subfields. Quantifiable differences exist in the involvement of specific hippocampal subfields in HS. Neuronal loss is greatest in CA1, intermediate in CA3 and CA4, and least in CA2. Further studies are required to determine if this pattern can be detected using in vivo MRI.