Symptoms In Temporal Lobe Epilepsy Research Articles

Correlation between fluorodeoxyglucose positron emission tomography brain hypometabolism and posttraumatic stress disorder symptoms in temporal lobe epilepsy.

The relationship between posttraumatic stress disorder (PTSD) and focal epilepsy is poorly understood. It has been hypothesized that there is a complex and reciprocal potential reinforcement of the symptoms of each condition. In this study, we investigated whether there are PTSD‐specific brain changes in temporal lobe epilepsy (TLE). Brain fluorodeoxyglucose positron emission tomography (PET) metabolism was compared between controls and two groups of TLE patients: one group of 15 patients fulfilling the criteria for a potential diagnosis of PTSD (TLE‐PTSD+), another group of 24 patients without a diagnosis of PTSD (TLE‐PTSD‐), and a group of 30 healthy control participants. We compared the differences in brain PET metabolism among these three groups, and we studied their correlations with interictal and peri‐ictal scales of PTSD symptoms. TLE‐PTSD+ patients showed more significant hypometabolism involving right temporal and right orbitofrontal cortex in comparison to TLE‐PTSD‐ patients and healthy subjects. Moreover, degree of reduced metabolism in these brain areas correlated with interictal and peri‐ictal PTSD questionnaire scores. PTSD in temporal epilepsy is associated with specific changes in neural networks, affecting limbic and paralimbic structures. This illustrates the close intertwining of epileptogenic and psychogenic processes in these patients.

Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy.

In temporal lobe epilepsy, the ability of the dentate gyrus to limit excitatory cortical input to the hippocampus breaks down, leading to seizures. The dentate gyrus is also thought to help discriminate between similar memories by performing pattern separation, but whether epilepsy leads to a breakdown in this neural computation, and thus to mnemonic discrimination impairments, remains unknown. Here we show that temporal lobe epilepsy is characterized by behavioral deficits in mnemonic discrimination tasks, in both humans (females and males) and mice (C57Bl6 males, systemic low-dose kainate model). Using a recently developed assay in brain slices of the same epileptic mice, we reveal a decreased ability of the dentate gyrus to perform certain forms of pattern separation. This is because of a subset of granule cells with abnormal bursting that can develop independently of early EEG abnormalities. Overall, our results linking physiology, computation, and cognition in the same mice advance our understanding of episodic memory mechanisms and their dysfunction in epilepsy.SIGNIFICANCE STATEMENT People with temporal lobe epilepsy (TLE) often have learning and memory impairments, sometimes occurring earlier than the first seizure, but those symptoms and their biological underpinnings are poorly understood. We focused on the dentate gyrus, a brain region that is critical to avoid confusion between similar memories and is anatomically disorganized in TLE. We show that both humans and mice with TLE experience confusion between similar situations. This impairment coincides with a failure of the dentate gyrus to disambiguate similar input signals because of pathologic bursting in a subset of neurons. Our work bridges seizure-oriented and memory-oriented views of the dentate gyrus function, suggests a mechanism for cognitive symptoms in TLE, and supports a long-standing hypothesis of episodic memory theories.

Surgical Treatment of Temporal Lobe Epilepsy and Micro-Neuroanatomical Details of the Medial Temporal Region.

To evaluate the long-term efficacy of temporal lobe epilepsy (TLE) surgery, and to emphasize the factors affecting seizure outcomes such as surgical technique nuances and micro-neuroanatomical details in TLE cases. In this retrospective analysis, 238 patients who underwent epilepsy surgery at Ankara University (Faculty of Medicine, Department of Neurosurgery) between 1990 and 2019 were included. All patients presented with symptoms of TLE. They were divided into two groups: those with neoplastic lesions and those with non-neoplastic brain lesions presenting with medically intractable epilepsy. In the non-neoplastic group, the patients underwent anterior temporal lobectomy with amygdalohippocampectomy (ATL+AH), whereas in the neoplastic group, the patients underwent tumor resection in addition to ATL+AH. This study included 126 female (52.9%) and 112 male (47.1%) patients. The mean duration of epilepsy was 14.65 ± 9.29 years (0.08?46 years). The number of patients in the non-neoplastic and neoplastic groups was 190 and 48, respectively. The mean duration of follow-up was 15.82 ± 6.55 years (1?28 years). In the neoplastic and non-neoplastic groups, the Engel I seizure-free rates were 91.6% (44/48) and 90.5% (172/190), respectively. Furthermore, no mortality was observed among the groups. Overall, effective seizure control was achieved with acceptable morbidity and complication rates in the neoplastic and non-neoplastic groups with surgical and micro-neuroanatomical nuances.

Resting state functional network disruptions in a kainic acid model of temporal lobe epilepsy.

We studied the graph topological properties of brain networks derived from resting-state functional magnetic resonance imaging in a kainic acid induced model of temporal lobe epilepsy (TLE) in rats. Functional connectivity was determined by temporal correlation of the resting-state Blood Oxygen Level Dependent (BOLD) signals between two brain regions during 1.5% and 2% isoflurane, and analyzed as networks in epileptic and control rats. Graph theoretical analysis revealed a significant increase in functional connectivity between brain areas in epileptic than control rats, and the connected brain areas could be categorized as a limbic network and a default mode network (DMN). The limbic network includes the hippocampus, amygdala, piriform cortex, nucleus accumbens, and mediodorsal thalamus, whereas DMN involves the medial prefrontal cortex, anterior and posterior cingulate cortex, auditory and temporal association cortex, and posterior parietal cortex. The TLE model manifested a higher clustering coefficient, increased global and local efficiency, and increased small-worldness as compared to controls, despite having a similar characteristic path length. These results suggest extensive disruptions in the functional brain networks, which may be the basis of altered cognitive, emotional and psychiatric symptoms in TLE.

Predicting seizures in untreated temporal lobe epilepsy using point-process nonlinear models of heartbeat dynamics.

Symptoms of temporal lobe epilepsy (TLE) are frequently associated with autonomic dysregulation, whose underlying biological processes are thought to strongly contribute to sudden unexpected death in epilepsy (SUDEP). While abnormal cardiovascular patterns commonly occur during ictal events, putative patterns of autonomic cardiac effects during pre-ictal (PRE) periods (i.e. periods preceding seizures) are still unknown. In this study, we investigated TLE-related heart rate variability (HRV) through instantaneous, nonlinear estimates of cardiovascular oscillations during inter-ictal (INT) and PRE periods. ECG recordings from 12 patients with TLE were processed to extract standard HRV indices, as well as indices of instantaneous HRV complexity (dominant Lyapunov exponent and entropy) and higher-order statistics (bispectra) obtained through definition of inhomogeneous point-process nonlinear models, employing Volterra-Laguerre expansions of linear, quadratic, and cubic kernels. Experimental results demonstrate that the best INT vs. PRE classification performance (balanced accuracy: 73.91%) was achieved only when retaining the time-varying, nonlinear, and non-stationary structure of heartbeat dynamical features. The proposed approach opens novel important avenues in predicting ictal events using information gathered from cardiovascular signals exclusively.

Psychiatric Symptoms in Temporal Lobe Epilepsy with Left Mesial Hippocampal Sclerosis

A 16-year-old woman was referred to us for depression and persistent suicidal and homicidal ideation. From 2010, the patient visited a neurologist due to recurrent grand mal epilepsy, auditory and visual hallucinations, episodic memory loss, and persistent depression. Upon admission, it was revealed through clinical history taking that she had suffered from chronic bullying from same-sex peers and sexual abuse, twice, from an adult male in the neighborhood when she was 10 years old. A brain magnetic resonance imaging study showed left mesial hippocampal sclerosis. The patient exhibited improvement of her psychiatric symptoms after treatment with a combination of fluoxetine (30 mg) and aripiprazole (10 mg). Children and adolescents with epilepsy experience conflicts in the family, challenges at school, stigma, and psychosocial limitations or deprivations due to their comorbid psychiatric symptoms and hence, psychiatric evaluation and early intervention is important when treating these patients.

Frontolimbic brain networks predict depressive symptoms in temporal lobe epilepsy

Psychiatric co-morbidities in epilepsy are of great concern. The current study investigated the relative contribution of structural and functional connectivity (FC) between medial temporal (MT) and prefrontal regions in predicting levels of depressive symptoms in patients with temporal lobe epilepsy (TLE). Twenty-one patients with TLE [11 left TLE (LTLE); 10 right TLE (RTLE)] and 20 controls participated. Diffusion tensor imaging was performed to obtain fractional anisotropy (FA) of the uncinate fasciculus (UF), and mean diffusivity (MD) of the amygdala (AM) and hippocampus (HC). Functional MRI was performed to obtain FC strengths between the AM and HC and prefrontal regions of interest including anterior prefrontal (APF), orbitofrontal, and inferior frontal regions. Participants self-reported depression symptoms on the Beck Depression Inventory-II. Greater depressive symptoms were associated with stronger FC of ipsilateral HC-APF, lower FA of the bilateral UF, and higher MD of the ipsilateral HC in LTLE, and with lower FA of the contralateral UF in RTLE. Regression analyses indicated that FC of the ipsilateral HC-APF was the strongest contributor to depression in LTLE, explaining 68.7% of the variance in depression scores. Both functional and microstructural measures of frontolimbic dysfunction were associated with depressive symptoms. These connectivity variables may be moderating which patients present with depression symptoms. In particular, FC MRI may provide a more sensitive measure of depression-related dysfunction, at least in patients with LTLE. Employing sensitive measures of frontolimbic network dysfunction in TLE may help provide new insight into mood disorders in epilepsy that could eventually guide treatment planning.

Is interictal EEG activity a biomarker for mood disorders in temporal lobe epilepsy?

ObjectivePsychiatric comorbidities are frequent in temporal lobe epilepsy (TLE), and symptoms of these comorbidities may be related to epilepsy activity. Here we evaluated interictal EEG activity in TLE patients with or without psychiatric comorbidities. MethodsA cohort study of 78 patients with TLE, with evaluation of wake/sleep interictal scalp EEG. All subjects were submitted to a psychiatric structured clinical interview (SCID) for the diagnosis of lifetime psychiatric comorbidities. Three major diagnostic categories were studied: mood disorders, anxiety disorders, and psychosis. We then evaluated differences in interictal EEG activity between patients with and without these psychiatric comorbidities. ResultsInfrequent EEG interictal spikes, defined as less than one event per minute, were significantly associated with mood disorders in TLE (p=0.02). ConclusionsLow intensity seizure disorder has been associated with a decrease in interictal EEG discharges and with an increase in psychiatric symptoms in TLE, a phenomenon known as forced normalization. In our study, we observed a low interictal spike frequency on EEG in TLE patients with mood disorders. SignificanceA low spike index might be a neurophysiological marker for depression in temporal lobe epilepsy.

Alterations in functional connectivity between the hippocampus and prefrontal cortex as a correlate of depressive symptoms in temporal lobe epilepsy

Depression is a common comorbidity in temporal lobe epilepsy (TLE) that is thought to have a neurobiological basis. This study investigated the functional connectivity (FC) of medial temporal networks in depression symptomatology of TLE and the relative contribution of structural versus FC measures. Volumetric MRI and functional connectivity MRI (fcMRI) were performed on nineteen patients with TLE and 20 controls. The hippocampi and amygdalae were selected as seeds, and five prefrontal and five cingulate regions of interest (ROIs) were selected as targets. Low-frequency blood-oxygen-level-dependent signals were isolated from fcMRI data, and ROIs with synchronous signal fluctuations with the seeds were identified. Depressive symptoms were measured by the Beck Depression Inventory—II. The patients with TLE showed greater ipsilateral hippocampal atrophy (HA) and reduced FC between the ipsilateral hippocampus and the ventral posterior cingulate cortex (vPCC). Neither HA nor hippocampal–vPCC FC asymmetry was a robust contributor to depressive symptoms. Rather, hippocampal–anterior prefrontal FC was a stronger contributor to depressive symptoms in left TLE (LTLE). Conversely, right amygdala FC was correlated with depressive symptoms in both patient groups, with a positive and negative correlation in LTLE and right TLE (RTLE), respectively. Frontolimbic network dysfunction is a strong contributor to levels of depressive symptoms in TLE and a better contributor than HA in LTLE. In addition, the right amygdala may play a role in depression symptomatology regardless of the side of the epileptogenic focus. These findings may inform the treatment of depressive symptoms in TLE and inspire future research to help guide surgical planning.

Impaired D-Serine-Mediated Cotransmission Mediates Cognitive Dysfunction in Epilepsy

The modulation of synaptic plasticity by NMDA receptor (NMDAR)-mediated processes is essential for many forms of learning and memory. Activation of NMDARs by glutamate requires the binding of a coagonist to a regulatory site of the receptor. In many forebrain regions, this coagonist is d-serine. Here, we show that experimental epilepsy in rats is associated with a reduction in the CNS levels of d-serine, which leads to a desaturation of the coagonist binding site of synaptic and extrasynaptic NMDARs. In addition, the subunit composition of synaptic NMDARs changes in chronic epilepsy. The desaturation of NMDARs causes a deficit in hippocampal long-term potentiation, which can be rescued with exogenously supplied d-serine. Importantly, exogenous d-serine improves spatial learning in epileptic animals. These results strongly suggest that d-serine deficiency is important in the amnestic symptoms of temporal lobe epilepsy. Our results point to a possible clinical utility of d-serine to alleviate these disease manifestations.

Pathophysiology of Mood Disorders in Temporal Lobe Epilepsy

There is accumulating evidence that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological, neurochemical and electrophysiological aspects might contribute to the development of psychiatric symptoms in TLE and the putative neurobiological mechanisms that cause mood disorders in this patient subgroup. In this review, clinical, experimental and neuropathological findings, as well as neurochemical features of the limbic system were examined together to enhance our understanding of the association between TLE and psychiatric comorbidities. Finally, the value of animal models in epilepsy and mood disorders was discussed. TLE and psychiatric symptoms coexist more frequently than chance would predict. Alterations and neurotransmission disturbance among critical anatomical networks, and impaired or aberrant plastic changes might predispose patients with TLE to mood disorders. Clinical and experimental studies of the effects of seizures on behavior and electrophysiological patterns may offer a model of how limbic seizures increase the vulnerability of TLE patients to precipitants of psychiatric symptoms.

Cortical thickness abnormalities associated with depressive symptoms in temporal lobe epilepsy

Depression in patients with temporal lobe epilepsy (TLE) is highly prevalent and carries significant morbidity and mortality. Its neural basis is poorly understood. We used quantitative, surface-based MRI analysis to correlate brain morphometry with severity of depressive symptoms in 38 patients with TLE and 45 controls. Increasing severity of depressive symptoms was associated with orbitofrontal cortex (OFC) thinning in controls, but with OFC thickening in TLE patients. These results demonstrate distinct neuroanatomical substrates for depression with and without TLE, and suggest a unique role for OFC, a limbic region for emotional processing strongly interconnected with medial temporal structures, in TLE-related depressive symptoms.

Occurrence and lateralizing value of “rare” peri-ictal vegetative symptoms in temporal lobe epilepsy

We retrospectively investigated rare peri-ictal vegetative symptoms (PIVS) in 380 seizures of 97 patients with temporal lobe epilepsy (TLE): 234 seizures of 60 patients with TLE with mesiotemporal sclerosis (TLE/MTS) and 146 seizures of 37 patients with TLE with other lesions (TLE/non-MTS) who were at least 2 years after epilepsy surgery and classified as Engel I. We assessed the following PIVS: peri-ictal cough (pC), peri-ictal water drinking (pWD), peri-ictal vomiting (pV), and peri-ictal spitting (pS). We observed pC in 24.7% of patients and 10% of seizures; pWD in 14.4% of patients and 5.9% of seizures; pV and pS occurred more rarely. Both pWD and pC occurred significantly more often in those with TLE of the non- language-dominant hemisphere. The limited occurrence of pV and pS made it impossible to perform statistical analysis for these symptoms. In patients with TLE, pC and pWD were quite frequent; we observed pV and pS less frequently. Both pC and pWD have a significant lateralizing value in TLE.

Ictal affective symptoms in temporal lobe epilepsy are related to gender and age

We systematically analyzed the video-recorded and patient-reported, as well as positive and negative ictal affective symptoms (IAS) in temporal lobe epilepsy (TLE). Our aim was to assess (1) frequency, (2) gender effect, (3) lateralizing significance, (4) localizing value, and (5) prognostic significance in epilepsy surgery of IAS in patients with video-registered seizures. We reviewed ictal video recordings of 184 patients (99 women, aged 16-63). All patients had surgery for intractable TLE with video-recorded complex partial seizures (CPS) due to temporal lobe lesions visualized by high-resolution magnetic resonance imaging (MRI). Affective auras (AAs) were categorized into two groups: positive or negative. We registered AAs in 18% of patients: positive in 3%, negative in 15%. We saw ictal affective behavior (IAB) in 22% of patients; 10% had positive, whereas 14% had negative IAB. Two patients had both positive and negative IAB. AAs showed an association with IAB in case of fear expression versus fear auras (p = 0.018). IAB, especially negative IAB, occurred more often in women than in men. Patients with negative IAB were younger than others. We could not demonstrate an association between IAS and the localization, lateralization, or hemispheric dominance. Surgical outcome did not associate with IAS. Patient-reported and video-recorded negative-but not positive-affective signs are related to each other. Video-recorded negative AAs occur more often in women and young patients.

110. Occurrence and lateralizing value of “rare” peri-ictal vegetative symptoms in temporal lobe epilepsy

Objective: The aim of this work is to identify the occurrence of so-called “rare” vegetative symptoms in temporal lobe epilepsy with mesiotemporal sclerosis (TLE MTS) or with other lesions of temporal lobe (TLE non-MTS) and their possible lateralizing value in relation to the speech-nondominant hemisphere.

Atrophy of Basal Ganglia Nuclei and Negative Symptoms in Temporal Lobe Epilepsy

Recent work has identified the presence of negative symptoms in a subset of temporal lobe epilepsy (TLE) patients. The authors hypothesized that negative symptoms in TLE are associated with disruption in the mesolimbic system. Basal ganglia and anterior cingulate region of interest volumes were compared between 22 TLE patients with negative symptoms, 22 TLE patients without negative symptoms, and 22 comparison subjects. The negative symptom group showed significantly reduced volumes in the putamen and globus pallidus. It appears that these structures within the broader mesolimbic system contribute to the phenomenon of negative symptoms in TLE.

Imaging Depression in Epilepsy: Hints at the Biology of Despair

Major Depression in Temporal Lobe Epilepsy with Hippocampal Sclerosis: Clinical and Imaging Correlates. Briellmann RS, Hopwood MJ, Jackson GD. J Neurol Neurosurg Psychiatry 2007 Jan 26; [Epub ahead of print] PURPOSE: Refractory temporal lobe epilepsy (TLE) is often associated with hippocampal sclerosis (HS). Patients with Major Depression (MD) may also show structural abnormalities in the limbic system. Co-occurrence of TLE with HS and MD is not uncommon. We investigate clinical and morphological characteristics of TLE patients in relation to MD. METHODS: Thirty-four TLE patients with HS were assessed at a Comprehensive Epilepsy Program. All relevant clinical data were obtained, including the history of antecedent events to epilepsy. MD was diagnosed based on detailed psychiatric investigation. MRI was used to measure the volume and tissue signal (T2-relaxometry) of the hippocampus and amygdala. The imaging data were expressed as percentage of the values obtained in a series of 55 controls. RESULTS: A history of MD was present in 15 (44%) of the 34 patients. Patients with MD had a longer duration of their epilepsy ( p < 0.05), and a lower frequency of antecedent events (13% with MD, 58% without MD, p < 0.05). Both groups had a similar degree of ipsilateral HS (small hippocampal volume, increased hippocampal T2-relaxation time), and demonstrated bilateral amygdaloid atrophy. However, the contralateral amygdala showed lower signal in presence of MD (97 ± 9 msec; no MD: 103 ± 8 msec, ANCOVA, p < 0.05). CONCLUSION: The integrity of the amygdala may influence mood disturbances in TLE patients with HS, as depression was associated with a relative preservation of the contralateral amygdala. In contrast, hippocampal abnormalities were not related to the presence of depression. Hippocampal 1H-MRSI Correlates with Severity of Depression Symptoms in Temporal Lobe Epilepsy. Gilliam FG, Maton BM, Martin RC, Sawrie SM, Faught RE, Hugg JW, Viikinsalo M, Kuzniecky RI. Neurology 2007;68(5):364–368. OBJECTIVE: To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. METHODS: We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/ N-acetylaspartate ratio maps derived from a previously validated 1H magnetic resonance spectroscopic imaging (1H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. RESULTS: The extent of hippocampal 1H-MRSI abnormalities correlated with severity of depression (Spearman rho = 0.65, p value < 0.001), but other clinical factors did not. CONCLUSION: The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability.

Peri-ictal vegetative symptoms in temporal lobe epilepsy

We investigated peri-ictal vegetative symptoms (PIVS) in 141 patients with adult temporal lobe epilepsy (TLE) and assessed frequency, gender effect, and lateralizing value of peri-ictal autonomic signs. We recorded abdominal auras in 62%, goosebumps in 3%, hypersalivation in 12%, spitting in 1%, cold shivering in 3%, urinary urge in 3%, water drinking in 7%, postictal nose wiping (PNW) in 44%, and postictal coughing in 16%. At least one vegetative sign appeared in 86% of the patients. The presence of PIVS did not have a significant lateralizing value. PNW occurred in 52% of women and in 33% of men, whereas any PIVS was present in 93% of women and 77% of men. In summary, contradictory to previous studies, the presence of PIVS has no lateralizing value, which may be linked to a low frequency of occurrence of PIVS. PIVS, especially PNW, occurred more frequently in women, supporting the gender differences in epilepsy.

Hippocampal 1 H-MRSI correlates with severity of depression symptoms in temporal lobe epilepsy

To investigate the association of an indicator of hippocampal function with severity of depression symptoms in temporal lobe epilepsy. We evaluated 31 patients with video/EEG-confirmed temporal lobe epilepsy using creatine/N-acetylaspartate ratio maps derived from a previously validated (1)H magnetic resonance spectroscopic imaging ((1)H-MRSI) technique at 4.1 T. We also assessed depression symptoms, epilepsy-related factors, and self-perceived social and vocational disability. We used conservative nonparametric bivariate procedures to determine the correlation of severity of depression symptoms with imaging and clinical variables. The extent of hippocampal (1)H-MRSI abnormalities correlated with severity of depression (Spearman rho = 0.65, p value < 0.001), but other clinical factors did not. The extent of hippocampal dysfunction is associated with depression symptoms in temporal lobe epilepsy and may be a more important factor than seizure frequency or degree of disability.

The Role of Aura in Psychopathology and Dissociative Experiences in Epilepsy

Cognitive auras seem to be associated with depression and anxiety, especially in patients with temporal lobe epilepsy (TLE). Dissociative symptoms may occur as an aura or in the context of psychiatric disorders such as depression, anxiety or schizophrenia. This is a cross-sectional study of 62 patients with TLE, using personality and dissociation measures to investigate their relationship with the presence of aura and its different subtypes. Our findings show no difference in psychopathology in patients with different types of aura and reveal that dissociative symptoms correlate with specific measures of anxiety, suggesting a possible link between these experiences and anxiety disorders.