Cognitive decline in adult-onset temporal lobe epilepsy: Insights from aetiology.

PURPOSE: To identify patients with adult-onset temporal lobe epilepsy (TLE) at risk of developing cognitive decline. Detecting which patients, aetiologies, or factors are most closely related with memory decline would allow us to identify patients that would eventually benefit from more specific treatment. METHODS: Single centre, retrospective analysis of a prospectively followed-up cohort study, including all patients with the diagnosis of adult-onset TLE during 2013, with a minimum follow-up of five years. Memory and cognitive decline were analysed at 5 years and at last follow-up. RESULTS: Of 89 initially selected patients, 71 were included. After 5 years, 11/71 (15.5%) patients suffered cognitive decline, of which 1/71 (4%) developed dementia. At last follow-up (range 65-596 m) a total of 34/71 (47.8%) patients were diagnosed with cognitive decline, specifically either memory decline or dementia. Cognitive decline at 5 years was related to: 1. Age at onset: 62.65 years (SD 9.04) in the group with cognitive decline vs 50.33 y. (SD 13.02 in the group without cognitive decline; p=0.004); 2. Onset as status epilepticus (3/6 in patients with memory decline vs 8/65 in patients without cognitive decline; p=0.04); 3. Immune aetiology: 42% compared with unknown (10%) and structural (10%) aetiologies; p=0.036; 4. Hippocampal sclerosis on MRI: 5/11 patients with cognitive decline vs 9/51 patients without cognitive decline; p=0.035. Cognitive decline was not related to seizure frequency, sex, or age (p=0.78; p=0.40; p=0.95, respectively). CONCLUSIONS: Older age at epilepsy onset, onset as status epilepticus, immune aetiology, and hippocampal sclerosis are risk factors for developing cognitive decline in patients with adult-onset temporal lobe epilepsy.

A comparison of comorbid headache between patients with temporal lobe epilepsy and juvenile myoclonic epilepsy.

Headache is one of the most common symptoms of epilepsy comorbidities. However, the relationship between the epilepsy and headache still needs clarification. Previous studies mostly investigated the overall incidence and clinical features of the headache in patients with the epilepsy. Temporal lobe epilepsy (TLE) and juvenile myoclonic epilepsy (JME) are the common types of focal epilepsy and generalized epilepsy, respectively. Nevertheless, there was no study comparing the clinical features of headache between TLE and JME. This study aimed to analyze the headache features of these two types of epilepsy. Patients with either TLE or JME diagnosed with headache and referred to the West China Hospital of Sichuan University were consecutively recruited from June 2021 to June 2022. The duration of epilepsy was longer than 6 months in these patients. Data on headache and epilepsy were obtained through face-to-face questionnaires. The headache was classified according to the International Classification Headache Disorders-3rd edition (ICHD-III) criteria. χ2-test, t-test, rank-sum test, logistic regression modeling and Mann Whitney test were used to compare the clinical differences of the headache in TLE and JME. A total of 151 TLE patients and 30 JME patients were enrolled in this study. There was no significant difference in the family history of headache, epilepsy durations, headache types, proportion receiving analgesic therapy, the frequency of inter-ictal headache (inter-IH), and the quality of life in epilepsy -10 inventory (QOLIE-10) between the TLE and JME patients. Patients in the TLE group were significantly older (p = 0.004), and a lower percentage of them had a family history of epilepsy (p = 0.007) compared with the JME patients. The proportion of cases with refractory epilepsy was higher in the TLE group than that in the JME group (p < 0.001). The types of seizures in the TLE group varied from those in the JME group (p < 0.001). The composition of the antiseizure medications (ASM) applied in the TLE group differed from that in the JME group (p = 0.047), and the usage of oxcarbazepine was more frequently in the TLE group than in the JME group (p = 0.003). There was no difference in the headache types among patients with TLE or JME. Specifically, 67 (44.37%), 12 (7.95%), and 118 (7.95%) patients were found with inter-IH, pre-ictal headache (Pre-IH) and post-ictal headache (Post-IH) in the TLE group; while 8 (26.67%), 4 (13.33%) and 26 (86.67%) patients had inter-IH, Pre-IH and Post-IH in the JME group. Thirty-nine patients in the TLE group and 4 patients in the JME group were identified with more than one type of headaches, respectively. Tension-type headache (TTH) were found in 38 patients (25.17%) in the TLE group and 3 patients (10.00%) in the JME group, respectively; migraines were found in 10 patients (6.62%) in the TLE group and in 2 patients (6.67%) in the JME group. Patients in the TLE group had a higher headache-attributed lost time-90 days (HLT-90) score than those in the JME group (p = 0.019). The proportion of patients with inter-IH accompanied by nausea in the TLE group was higher than that in the JME group (p = 0.029), while the proportion of patients with frontal headache was lower than that in the JME group (p < 0.05). There was no significant difference in headache severity, quality, headache nature, unilateral/bilateral, and headache duration either in inter-IH or peri-ictal headache (Peri-IH) between the two groups. The logistic regression analysis suggested that except for HLT-90 (AUC = 0.622, p = 0.027), other factors were not found to be correlated with refractory epilepsy. The clinical features of headache differed between TLE and JME patients. TLE patients had a higher ratio of refractory epilepsy, more headache time loss compared with JME patients. HLT-90 was associated with the occurrence of refractory epilepsy in TLE patients. Taken together, we suggested that the comorbid headache may essentially be different between TLE and JME patients.

Association of neighborhood deprivation with white matter connectome abnormalities in temporal lobe epilepsy.

OBJECTIVE: Social determinants of health, including the effects of neighborhood disadvantage, impact epilepsy prevalence, treatment, and outcomes. This study characterized the association between aberrant white matter connectivity in temporal lobe epilepsy (TLE) and disadvantage using a US census-based neighborhood disadvantage metric, the Area Deprivation Index (ADI), derived from measures of income, education, employment, and housing quality. METHODS: Participants including 74 TLE patients (47 male, mean age = 39.2 years) and 45 healthy controls (27 male, mean age = 31.9 years) from the Epilepsy Connectome Project were classified into ADI-defined low and high disadvantage groups. Graph theoretic metrics were applied to multishell connectome diffusion-weighted imaging (DWI) measurements to derive 162 × 162 structural connectivity matrices (SCMs). The SCMs were harmonized using neuroCombat to account for interscanner differences. Threshold-free network-based statistics were used for analysis, and findings were correlated with ADI quintile metrics. A decrease in cross-sectional area (CSA) indicates reduced white matter integrity. RESULTS: Sex- and age-adjusted CSA in TLE groups was significantly reduced compared to controls regardless of disadvantage status, revealing discrete aberrant white matter tract connectivity abnormalities in addition to apparent differences in graph measures of connectivity and network-based statistics. When comparing broadly defined disadvantaged TLE groups, differences were at trend level. Sensitivity analyses of ADI quintile extremes revealed significantly lower CSA in the most compared to least disadvantaged TLE group. SIGNIFICANCE: Our findings demonstrate (1) the general impact of TLE on DWI connectome status is larger than the association with neighborhood disadvantage; however, (2) neighborhood disadvantage, indexed by ADI, revealed modest relationships with white matter structure and integrity on sensitivity analysis in TLE. Further studies are needed to explore this relationship and determine whether the white matter relationship with ADI is driven by social drift or environmental influences on brain development. Understanding the etiology and course of the disadvantage-brain integrity relationship may serve to inform care, management, and policy for patients.

Psychiatric outcomes after temporal lobe surgery in patients with temporal lobe epilepsy and comorbid psychiatric illness: A systematic review and meta-analysis.

BACKGROUND: The currently available evidence is unclear in regard to psychiatric outcomes of temporal lobe epilepsy (TLE) in patients with comorbid psychiatric disorders (PD). AIM: To identify and synthesize psychiatric outcomes in patients with TLE and comorbid psychiatric illnesses before and after TLE surgery. METHODS: Studies were included if participants were adults and/or children with temporal epilepsy and comorbid psychiatric illness. Surgical interventions included focal resection (e.g., lobectomy, selective amygdalohippocampectomy) or stereotactic laser ablation. Included studies reported on pre- and post- surgery data of comorbid psychiatric illness (e.g., mood and anxiety disorders, depression, psychosis, adjustment disorders, non-epileptic seizures, and personality disorders). RESULTS: Ten studies were included in the review. The proportion of patients achieving PD resolution or improvements after surgery varied widely between studies, ranging from 15 % to 57 % at the reported follow-up time. Three studies reported on PD symptom worsening after surgery, with considerable variations of patient proportions across studies. Meta-analysis suggests that 43 % of patients demonstrated improvement and 33 % of patients showed a worsening in psychiatric scores across all studies. Preliminary data from three studies suggest that seizure control may be associated with favourable psychiatric outcomes. CONCLUSION: A considerable proportion of reported TLE patients with comorbid psychiatric illnesses have improvement in their psychiatric symptoms after temporal lobe epilepsy surgery. There is scarcity of detailed outcome reporting including symptom scores, and to date, predictive factors for favourable vs unfavourable outcomes in this patient population are not clear. Further research on the topic is warranted.

Increased prevalence of minor physical anomalies in patients with epilepsy.

Our aim was to investigate the rate and topological profile of minor physical anomalies (MPAs) in adult patients with epilepsy with the use of the Méhes Scale, a comprehensive modern scale of dysmorphology. Consecutive epilepsy patients admitted for outpatient evaluation were included. Patients with comorbidities of neurodevelopmental origin (such as autism, severe intellectual disability, attention deficit hyperactivity disorder, schizophrenia, tic disorder, Tourette syndrome, bipolar disorder, specific learning disorder and specific language impairment) were excluded. All participants underwent physical examination with the use of the Méhes Scale for evaluation of MPAs, including 57 minor signs. The frequency and topological profile of MPAs were correlated to clinical patient data using Kruskal-Wallis, chi2 tests and logistic regression model. 235 patients were included, according to the following subgroups: acquired epilepsy (non-genetic, non-developmental etiology) [N = 63], temporal lobe epilepsy with hippocampal sclerosis (TLE with HS) [N = 27], epilepsy with cortical dysgenesis etiology [N = 29], cryptogenic epilepsy [N = 69] and idiopathic generalized epilepsy (IGE) [N = 47]. As controls, 30 healthy adults were recruited. The frequency of MPAs were significantly affected by the type of epilepsy [H(6) = 90.17; p < 0.001]. Pairwise comparisons showed that all patient groups except for acquired epilepsy were associated with increased frequency of MPAs (p < 0.001 in all cases). Furrowed tongue and high arched palate were more common compared to controls in all epilepsy subgroup except for TLE (p < 0.001 or p = 0.001 in all cases). A positive association was detected between the occurrence of MPAs and antiepileptic drug therapy resistance [Exp(B) = 4.19; CI 95% 1.37-12.80; p = 0.012]. MPAs are more common in patients with epilepsy, which corroborates the emerging concept of epilepsy as a neurodevelopmental disorder. Assessment of these signs may contribute to the clarification of the underlying etiology. Moreover, as increased frequency of MPAs may indicate pharmacoresistance, the identification of patients with high number of MPAs could allow evaluation for non-pharmacological treatment in time.

The impact of one-year COVID-19 containment measures in patients with mesial temporal lobe epilepsy: A longitudinal survey-based study.

BACKGROUND: We assessed levels of depression, anxiety, stress, anhedonia, somatization, psychological distress, sleep, and life quality in patients with mesial temporal lobe epilepsy (MTLE) after one year of containment measures started in Italy to stem the COVID-19 pandemic. METHODS: We consecutively enrolled 51 patients with MTLE, administering an online survey that compared the year before and after the COVID-19 propagation. We analyzed clinical data (e.g., seizure frequency, life quality) and neuropsychological assessment through Somatic Symptom Scale-8 (SSS-8), Beck Depression Inventory (BDI-2), State-Trait Anxiety Inventory (STAI-Y), Depression, Anxiety and Stress Scale (DASS-21), Pittsburgh Sleep Quality Index (PSQI), Snaith-Hamilton Pleasure Scale (SHAPS), Impact of Event Scale-Revised (IES-R). The BDI-2 and STAI-Y scores were compared to those acquired in the same patients before the COVID-19 outbreak. RESULTS: Comparing our population with MTLE before and after COVID-19 outbreak, we found a significant worsening in life quality (p = 0.03), SSS-8 (p = 0.001), BDI-2 (p = 0.032), and STAI-Y scores (p < 0.001). After one year of pandemic, 88.2% of patients obtained pathological scores at PSQI, 19.6% at SHAPS, 29.4% at IES-R. Reduction of life quality correlated with anxiety, depression, stress, and somatization. Higher levels of anhedonia correlated with stress, depression, and anxiety. Somatization correlated with depression, anxiety, and sleep quality. Distress levels correlated with anxiety, somatization, and depression. CONCLUSIONS: We demonstrated a significant worsening of depression, anxiety, life quality, and somatization in patients with MTLE after one year of COVID-19 beginning. Concomitantly, results suggest that the pandemic had a negative impact on sleep quality, psychological distress, and anhedonia, but not on epilepsy itself.

Decreased hippocampal serotonin 5HT1A expression in mesial temporal lobe of epilepsy patients.

INTRODUCTION: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is a surgically remediable epilepsy with a relatively high prevalence and psychiatric comorbidities. Depressive disorders may occur in up to 25% of MTLE-HS patients suggesting a common molecular mechanism underlying both conditions. OBJECTIVE: To compare the gene expression comprising serotonin 5HT1A and 5HT2A, noradrenaline (NA) ADRA1A, and ADRA2A receptors in the hippocampus of MTLE-HS patients with and without major depression. METHODS: A cross-sectional study allocated 31 patients in three groups: MTLE-HS without psychiatric diagnosis (MTLE-HS group), MTLE-HS with major depression (MTLE-HS-D group) and a control group consisting of healthy volunteers without any neurological or psychiatric disorders. Demographic and clinical characteristics were compared among groups. Gene expression of receptors were analyzed using general linear mixed models (GLMM), with an unstructured matrix, normal link. RESULTS: The three groups showed a similar distribution regarding age, gender (p > 0.16), history of initial precipitating injury, family history of epilepsy, monthly frequency of seizures, side of hippocampal sclerosis, interictal spike distribution and anti-seizure medications did not differ between MTLE-HS and MTLE-HS-D groups (p > 0.05). We observed a greater expression of the 5HT1A receptor in the control group when compared to the MTLE-HS (P = .004) and MTLE-HS-D (P = .007). Nevertheless, we did not observe any difference when MTLE-HS and MTLE-HS-D groups were compared to the controls for the ADRA1A (P = .931; P = .931), ADRA2A (P = .120; P = .121) and 5HT2A (P = .638; P = .318, respectively) gene expression. CONCLUSION: Mesial temporal lobe epilepsy related to hippocampal sclerosis and MTLE-HS-D patients showed a lowered expression of the 5HT1A receptors when compared with the controls adjusted for age and schooling. Data suggest that temporal lobe epilepsy plasticity may affect serotonin receptors, which may lead to more frequent cases of major depression in this population. More studies comprising wider samples are necessary to confirm these results; they also should investigate serotonin reuptake drugs as an adjuvant therapeutic option for MTLE-HS disorder.

Low prevalence of amyloid and tau pathology in drug-resistant temporal lobe epilepsy.

OBJECTIVE: Cognitive impairment is common in patients with chronic drug-resistant temporal lobe epilepsy (TLE). Hyperphosphorylated tau (pTau) and amyloid-ß (Aß) plaques, pathological hallmarks of Alzheimer disease, have been hypothesized to play a mechanistic role. We investigated Aß plaques and pTau prevalence in TLE patients who underwent resective surgery and correlated their presence with preoperative psychometric test scores and clinical factors. METHODS: Patients were retrospectively selected from the epilepsy surgery register of the Royal Melbourne Hospital, Australia. Sections from the resected temporal lobe were immunostained for pTau and Aß plaques (antibodies: AT8, 1E8). The presence and severity of pathology were correlated with clinical characteristics, and verbal and visual learning functions as measured by the Verbal Pair Associates (VPA) test and Rey Complex Figure Test. RESULTS: Fifty-six patients (55% female) aged 20-68 years (median = 34 years) at surgery were included. Aß plaques were detected in four patients (7%), all at the moderate level. There was no difference in duration, age at onset of epilepsy, or side of resection between patients with and without Aß plaques. Sparse pTau was found in two patients (3.5%). Both had moderate Aß plaques and were >50 years of age. Patients with Aß plaques had a lower median score for the VPA hard assessment compared to those without (0 vs. 4; p = .02). There was otherwise no correlation between pathology and psychometric test scores. SIGNIFICANCE: Aß plaques and pTau were uncommon in the resected brain tissue of patients who have undergone temporal lobectomy, and did not correlate with clinical characteristics or preoperative psychometric test scores, except for a lower VPA median score in patients with Aß plaques. Therefore, considering the low prevalence of Aß plaques and pTau herein observed, it is unlikely that cognitive impairment in TLE is driven by the same mechanisms as in Alzheimer disease.

Occult focal cortical dysplasia may predict poor outcome of surgery for drug-resistant mesial temporal lobe epilepsy.

PURPOSE: The results of surgery in patients with mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) are favorable, with a success rate over 70% following resection. An association of HS with focal cortical dysplasia (FCD) in the temporal lobe is one of the potential causes for poor surgical outcome in MTLE. We aimed to analyzed seizure outcome in a population of MTLE patients and recognize the role of occult FCD in achieving postoperative seizure control. METHODS: We retrospectively analyzed postoperative outcomes for 82 consecutive adult patients with the syndrome of MTLE due to HS, who had no concomitant lesions within temporal lobe in MRI and who underwent surgical treatment in the years 2005-2016, and correlated factors associated with seizure relapse. RESULTS: At the latest follow-up evaluation after surgery, 59 (72%) were free of disabling seizures (Engel Class I) and 48 (58,5%) had an Engel Class Ia. HS associated with FCD in neocortical structures were noted in 33 patients (40%). Analyzes have shown that dual pathology was the most significant negative predictive factor for Engel class I and Engel class Ia outcome. CONCLUSIONS: The incidence of dual pathology in patients with temporal lobe epilepsy seems to be underestimated. An incomplete epileptogenic zone resection of occult focal temporal dysplasia within temporal lobe is supposed to be the most important negative prognostic factor for seizure freedom after epilepsy surgery in MTLE-HS patients. The study indicates the need to improve diagnostics for other temporal lobe pathologies, despite the typical clinical and radiological picture of MTLE-HS.

Seizure and social outcomes in patients with non-surgically treated temporal lobe epilepsy.

OBJECTIVES: To investigate the seizure outcome with medical treatment in patients with temporal lobe epilepsy (TLE) and its associated factors. We also investigated the social outcome of the patients. METHODS: This was a retrospective study of a prospectively built electronic database of patients with epilepsy. All patients with a diagnosis of TLE were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2019. In a phone call to the patients, at least 24 months after their diagnosis at our center, we investigated their current seizure control and social status. RESULTS: Two hundred and twenty-two patients were studied; 101 patients (45.5%) were seizure free. A lower number of the prescribed drugs was the only factor with a significant association with the seizure-free outcome (Odds Ratio: 1.460; p = 0.001). At the time of the phone call, 76 patients (37.6%) reported having a college education, 103 patients (51%) were employed, 146 patients (72.3%) were married, and 81 patients (40%) reported driving a motor vehicle. The employment status, college education, and driving a motor vehicle were significantly associated with a seizure-free outcome status. The social achievements of the patients, who were partially responsive to medical therapy, were significantly worse than those who were seizure free. CONCLUSION: Many patients with TLE may suffer from drug-resistant seizures. Ongoing seizures in these patients may affect their social lives substantially. Seizure reduction (not freedom) is not good enough to help the patients with TLE enjoy a healthy life with satisfactory social achievements.

Headache in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: It is remarkable that epilepsy and migraine are similar diseases with many parallel clinical features, as well as sharing common pathophysiological mechanisms. However, the pathogenetic role of hippocampal sclerosis (HS) in epilepsy and headache coexistence has not been clarified. In this study, we aimed to investigate the frequency of headache/migraine and the relationship between headache and HS lateralizations in patients with mesial temporal lobe epilepsy (MTLE), accompanied by HS. METHODS: Consecutive patients with mesial temporal lobe epilepsy with hippocampal sclerosis (HS-MTLE) followed up in epilepsy outpatient clinic were included in this study, with their demographic and clinical characteristics, HS lateralization, and side (unilateral-right-left, bilateral), which were recorded. Using the questionnaires, the type of headache [migraine, tension headache (TTH)] was determined. Patients in whom migraine and TTH could not be completely separated were recruited for the unclassified group. The temporal relationship of headache and seizures (peri-ictal and/or interictal), pain lateralization, and side (unilateral-right-left, bilateral, unilateral + bilateral) were likewise determined. RESULTS: There were 56 patients (30 females, 26 males; mean age 36.9 ±â€¯12.1 years; mean epilepsy duration 19.3 ±â€¯12.5 years) included in the study. Thirty-one patients (55.4%) stated they had a headache: of these, eighteen (32.1%) had migraine and 9 (16.1%) had TTH. Migraine accounted for 58.1% of headaches and TTHs was 29%. Headache was unilateral in 15 patients, and bilateral or bilateral + unilateral in 16 patients. Of patients with migraine, pain was unilateral in 10, and bilateral or bilateral + unilateral in 8. HS was right-sided in 24 patients, left-sided in 30 patients, and bilateral in 2 patients. In patients with right-sided HS, it was an ipsilateral headache; bilateral headache was found to be more common in patients with left-sided HS (p = 0.029). No relationship was found between the lateralization of the headache and the side of HS in patients with migraine. CONCLUSION: The results of our study showed that approximately half the patients with HS-MTLE did have a headache, with one third noting migraine type headache; this highlighted that HS may play a pathogenetic role in the development of headache, especially migraine, in patients with epilepsy. Further comprehensive studies will enable us to understand whether accompanying headache, especially migraine attacks in patients with epilepsy, can be determinant for HS-MTLE, as well as if it has a lateralizing value for HS.

Regulation of TWIK-related K+ channel 1 in the anterior hippocampus of patients with temporal lobe epilepsy with comorbid depression.

Epilepsy with comorbid depression has recently attracted increasing attention. Temporal lobe epilepsy (TLE) may represent an increased risk of developing depression, especially if the seizures do not generalize. The two-pore domain potassium channel-TWIK-related K+ channel (TREK-1) plays important roles in both epilepsy and depression. However, the changes in its expression in patients with epilepsy with comorbid depression remain unclear. In the present study, we analyzed depressive symptoms using neuropsychiatric scales in forty-two patients with drug-resistant TLE, who also underwent EEG in waking and sleeping states, as well as 3.0 T brain MRI. We tested for TREK-1 positive neurons and microglial cells in the anterior hippocampi of patients with drug-resistant TLE with and without comorbid depression (n=5/group). Approximately 31% of patients with TLE had comorbid depression (13/42). Meanwhile, the patients who had hippocampal sclerosis had much higher scores on the depression rating scale. The results indicated the contribution of hippocampal sclerosis to the development of depression. Immunostaining of TREK-1 channels was observed in neurons and glia in the anterior hippocampus. Increased immunoreactivity of TREK-1 neurons was observed in the hippocampi of patients with TLE with comorbid depression compared with nondepressed patients with TLE. TREK-1 was expressed in almost all microglia. Curiously, more activated TREK-1-positive microglia were observed in patients with TLE with depression than in those without depression. The results suggested that a change in TREK-1 immunoreactivity was involved, at least partly, in the development of depression as a comorbidity of TLE. Imbalance of the TREK-1 channel may be a potential target for the treatment of patients with epilepsy with comorbid depression.

Investigation of long interspersed element-1 retrotransposons as potential risk factors for idiopathic temporal lobe epilepsy.

OBJECTIVE: To determine if long interspersed element-1 (L1) retrotransposons convey risk for idiopathic temporal lobe epilepsy (TLE). METHODS: Surgically resected temporal cortex from individuals with TLE (N = 33) and postmortem temporal cortex from individuals with no known neurological disease (N = 33) were analyzed for L1 content by Restriction Enzyme Based Enriched L1Hs sequencing (REBELseq). Expression of three KCNIP4 splice variants was assessed by droplet digital PCR (ddPCR). Protein ANalysis THrough Evolutionary Relationships (PANTHER) was used to determine ontologies and pathways for lists of genes harboring L1 insertions. RESULTS: We identified novel L1 insertions specific to individuals with TLE, and others specific to controls. Although there were no statistically significant differences between cases and controls in the numbers of known and novel L1 insertions, PANTHER analyses of intragenic L1 insertions showed statistically significant enrichments for epilepsy-relevant gene ontologies in both cases and controls. Gene ontologies "neuron projection development" and "calcium ion transmembrane transport" were among those found only in individuals with TLE. We confirmed novel L1 insertions in several genes associated with seizures/epilepsy, including a de novo somatic L1 retrotransposition in KCNIP4 that occurred after neural crest formation in one patient. However, ddPCR results suggest this de novo L1 did not alter KCNIP4 mRNA expression. SIGNIFICANCE: Given current data from this small cohort, we conclude that L1 elements, either rare heritable germline insertions or de novo somatic retrotranspositions, may contribute only minimally to overall genetic risk for idiopathic TLE. We suggest that further studies in additional patients and additional brain regions are warranted.

A pioneering FreeSurfer volumetric study of a series of patients with mesial temporal lobe epilepsy and hippocampal sclerosis with comorbid depression.

Depression is the most frequent psychiatric comorbidity in patients with mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). This study aimed to confirm whether patients with comorbid depression have different volumetric patterns on magnetic resonance imaging, analysing the influence of HS sides. Psychiatrists conducted semi-structured interviews with 75 patients, who were divided into non-depression group (NDG, n = 52) and depression group (DG, n = 23), and compared with 98 controls. The FreeSurfer software was used in the volumetric analysis of the estimated total intracranial volume (eTIV), bilateral cortical and subcortical regions of interest (ROIs), and for presence of left (L-, n = 41) or right (R-, n = 34) MTLE-HS. Twenty-three (30.7%) patients had depression, of whom 14 (34.1%) had l-MTLE-HS and 9 (26.5%) had R-MTLE-HS. No difference was observed between DG and NDG vs. controls in terms of eTIV and cortical ROIs, regardless of the severity of depression. In patients with l-MTLE-HS, the eTIV in the DG was reduced in comparison with that in the NDG and control group, with a small effect size. Hippocampal reduction occurred ipsilateral to HS in the l-MTLE-HS and R-MTLE-HS subgroups when DG and NDG were compared with controls, as expected according to Enhancing Neuro Imaging Genetics through Meta-Analysis (2018).

Psychiatric disorders in patients with resistant temporal lobe epilepsy two years after undergoing elective surgery. A longitudinal study.

PURPOSE: Psychiatric morbidity in temporal lobe epilepsy (TLE) is frequent and negatively affects patients' life quality. Surgery is the procedure of choice when treating seizures, although the effects on psychiatric disorders remain unclear. We evaluate the effect of surgery on psychiatric disorders in patients with TLE two years after the intervention, to then shed light on how these are related to anxiety and depression symptoms, and Interictal Dysphoric Disorder (IDD). METHODS: We included data from 65 patients with TLE whose psychiatric evaluations were performed according to DSM-IV criteria. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) test. RESULTS: At 2-year follow-up, anxiety and depressive disorders decreased, and psychotic disorders augmented without statistical significance. Baseline psychiatric disorders predisposed to psychiatric pathology at 2-year follow-up and did not correlate with epilepsy outcome after surgery. Postoperative psychiatric disorders correlated with the seizure incidence two years after the intervention, suggesting that epilepsy and psychiatric disorders were associated in processes such as surgery. De novo psychiatric disorders represented 52% of postoperative psychiatric pathology, 62% being psychotic disorders. De novo psychiatric disorders became more frequent from the first year of surgery, occurring mainly in patients free of seizures. The HADS test scores and IDD correlated with psychiatric disorders at 2-year follow-up. CONCLUSIONS: Baseline psychiatric disorders did not influence surgery outcome, but correlated with psychiatric disorders' prevalence two years after surgery. Despite not finding statistical significance, surgery reduced the prevalence of psychiatric disorders, and de novo psychiatric disorders were associated with an improvement in the epilepsy course at 2-year follow-up.

Initiating an epilepsy surgery program with limited resources in Indonesia.

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999-2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005-2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures were 9, 11 and 11 years (95% CI: 8.170-9.830, 10.170-11.830, and 7.265-14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.

The relation of major depression, OCD, personality disorders and affective temperaments with Temporal lobe epilepsy.

BACKGROUND: In patients with temporal lobe epilepsy (TLE), studies demonstrate frequent comorbidity with mood disorders, personality disorders (especially obsessive-compulsive disorder) and major depression, but there are conflicting findings. This study aimed to investigate psychiatric comorbidities and affective temperament among TLE patients and to explore the relationships between obsessive compulsive disorder, other personality disorders, major depression and affective temperament in order to clarify the mediator effect of TLE in these relationships. METHODS: Thirty patients with TLE and 30 healthy volunteers were included. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), the Structured Clinical Interview for DSM III-R Axis II Disorders (SCID-II), Hamilton Anxiety (HAM-A) scale, Hamilton Depression (HAM-D) scale, Beck Suicidal Ideation Scale (BSSI) and Yale Brown Obsession Compulsion Scale (YBOCS) were applied and evaluated by a psychiatrist. Additionally, all individuals completed The Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A). RESULTS: Patients with temporal lobe epilepsy had higher scores in TEMPS-A, HAM-A, HAM-D, YBOCS and BSSI. Major depression, obsessive compulsive disorder and dependent and antisocial personality disorders were prevalent in patients. With respect to affective temperaments, depressive, cyclothymic and anxious temperaments were associated with obsessive compulsive disorder comorbidity; whereas, depressive and anxious temperaments were found to be associated with major depression comorbidity in patients with TLE. Furthermore, cluster A and cluster C personality disorders were associated with affective temperaments in patients with TLE. Affective temperaments had no correlation with illness duration, seizure frequency, depression severity and suicidal thoughts, but obsessions and compulsions. Suicidal thoughts were associated with obsessions and compulsions. CONCLUSION: Affective temperaments are core personality traits with biological background and they may provide a foundation for psychiatric disorders, especially mood disorders. Considering that TLE originates from abnormalities in brain circuitry, it may form a basis for psychiatric disorders. Therefore, psychiatric evaluation to determine comorbidities may be beneficial to increase the quality of life of patients with TLE.

Predicting mood decline following temporal lobe epilepsy surgery in adults.

OBJECTIVE: To develop a model to predict the probability of mood decline in adults following temporal lobe resection for the treatment of pharmacoresistant epilepsy. METHODS: Variable selection was performed on 492 patients from the Cleveland Clinic using best subsets regression. After completing variable selection, a subset of variables was requested from four epilepsy surgery centers across North America (n = 100). All data were combined to develop a final model to predict postoperative mood decline (N = 592). Internal validation with bootstrap resampling was performed. A clinically significant increase in depressive symptoms was defined as a 15% increase in Beck Depression Inventory-Second Edition score and a postoperative raw score > 11. RESULTS: Fourteen percent of patients in the Cleveland Clinic cohort and 22% of patients in the external cohort experienced clinically significant increases in depressive symptoms following surgery. The final prediction model included six predictor variables: psychiatric history, resection side, relationship status, verbal fluency score, age at preoperative testing, and presence/absence of malformation of cortical development on magnetic resonance imaging. The model had an optimism-adjusted c-statistic of .70 and good calibration, with slight probability overestimation in higher risk patients. SIGNIFICANCE: Clinicians can utilize our nomogram via a paper tool or online calculator to estimate the risk of postoperative mood decline for individual patients prior to temporal lobe epilepsy surgery.

Diversified social cognition in temporal lobe epilepsy.

OBJECTIVES: In an integrated model of social cognition (SC), the theory of mind (ToM), the recognition of behavior in social situations (RBSS), empathy, and sensitivity to moral and conventional rules (SMCR) cooperate in generating mental representations of the interpersonal relationships. The aim of this study was to extend our knowledge of the SC of temporal lobe epilepsy (TLE) patients by characterizing its various aspects and predictors. MATERIALS AND METHODS: Fifty adult patients with TLE and 50 healthy controls were assessed using ToM, RBSS and SMCR neuropsychological tests, the Empathy Questionnaire, and the psychopathology Symptoms Check List 90R (SCL90-R). RESULTS: Patients and controls were similar in terms of occupation, income level, age, sex, marital status and the number of family members. Multivariate analysis of variance with demographic variables as the covariates showed that they were similar in SMCR and empathy. The patients, conversely, had lower ToM and RBSS scores, and higher scores on the SCL90-R psychoticism, depression, paranoid ideation, obsessive-compulsive, somatization and anxiety scales. Impaired RBSS was predicted by psychopathological symptoms, income level, schooling and the duration of epilepsy; ToM related to TLE laterality, seizure frequency and epilepsy duration. CONCLUSIONS: In adult patients with TLE, SC is simultaneously partially impaired and partially preserved, and the fact this is associated with clinical, demographic and psychological variables suggests that SC depends on the integrity of the temporal lobe and the interconnected brain regions, as well as psychosocial stimuli. This approach may contribute to clarify the neurobehavioural phenotype of TLE.

Absolute spike frequency and different comorbidities in temporal lobe epilepsy.

OBJECTIVE: The objective of this study was to examine if the absolute number of interictal epileptiform discharges (IED) is related to the presence of different comorbidities and refractivity in patients with temporal lobe epilepsy. METHODS: Analysis with scalp EEG of the IED of 30 patients with temporal epilepsy. The analysis was performed in three selected periods of the record during N2-N3 sleep. We analyzed the number of IED and the sum of the values obtained in the three selected segments to determine the absolute interictal spike frequency. RESULTS: The number of IED for patients varied from 11 to 450. The absolute interictal spike frequency showed a statistically significant relation with the presence of refractivity (p < 0.05), and neurological and/or psychiatric comorbidity (p < 0.05). Patients with an absolute interictal spike frequency ≤ 60 showed little refractoriness and no comorbidity. Patients with an absolute interictal spike frequency > 60 were mostly refractory and with neurological and/or psychiatric comorbidity. No significant relation was found of absolute interictal spike frequency with age at the onset of epilepsy, number of anticonvulsant drugs used, or base pathology (MRI). CONCLUSIONS: The absolute interictal spike frequency is capable of differentiating patients with temporal lobe epilepsy, identifying those with temporal lobe epilepsy according to the severity of the condition. Only those patients with non-frequent spikes (≤60 over the affected temporal lobe) have a low percentage of refractoriness with little or no presence of comorbidity.