Interictal depression, anxiety, personality traits, and psychological dissociation in patients with temporal lobe epilepsy (TLE) and extra-TLE

PURPOSE: This study was performed to investigate the relation between symptoms of interictal depression, anxiety, personality traits, and psychological dissociation with the localization and lateralization of the epileptogenic zone in patients with partial epilepsy. METHODS: All patients were diagnosed according to the localization-related concept of the 1989 International League Against Epilepsy (ILAE) Classification of Epilepsies and Epileptic Syndromes, and the localization and lateralization of the epileptogenic zone was established by using the clinical criteria for noninvasive presurgical evaluation. This resulted in 67 patients with temporal lobe epilepsy (TLE) and 64 patients with extra-TLE. All patients were assessed on the various aspects of psychopathology by using a comprehensive battery of standardized diagnostic instruments. RESULTS: We did not find the hypothesized excess of psychiatric symptoms in patients with (mesial) TLE in comparison with patients with extra-TLE. We also found no differences between patients with the lateralization of epilepsy in the left versus the right hemisphere. CONCLUSIONS: TLE per se cannot be considered a risk factor in developing more or more severe symptoms of psychopathology in patients with partial epilepsy. Concomitant factors, such as the duration of epilepsy, seizure frequency, and frontal lobe dysfunction may play an additional role. Our findings support the hypothesis of a multifactorial explanation for the psychiatric symptoms in patients with epilepsy.     

Alzheimer's disease and epilepsy: insight from animal models

Alzheimer's disease (AD) and epilepsy are separated in the medical community, but seizures occur in some patients with AD, and AD is a risk factor for epilepsy. Furthermore, memory impairment is common in patients with epilepsy. The relationship between AD and epilepsy remains an important question because ideas for therapeutic approaches could be shared between AD and epilepsy research laboratories if AD and epilepsy were related. Here we focus on one of the many types of epilepsy, temporal lobe epilepsy (TLE), because patients with TLE often exhibit memory impairment, depression and other comorbidities that occur in AD. Moreover, the seizures that occur in patients with AD may be nonconvulsive, which occur in patients with TLE. Here we first compare neuropathology in TLE and AD with an emphasis on the hippocampus, which is central to both AD and TLE research. Then we compare animal models of AD pathology with animal models of TLE. Although many aspects of the comparisons are still controversial, there is one conclusion that we suggest is clear: some animal models of TLE could be used to help address questions in AD research, and some animal models of AD pathology are bona fide animal models of epilepsy.     

Obsessionality, obsessive-compulsive disorder, and temporal lobe epilepsy

We evaluated the prevalence of obsessive-compulsive disorder (OCD) in patients with temporal lobe epilepsy (TLE) and we investigated the hypothesis that obsessionality may represent a trait in TLE. Eighty-two consecutive patients with epilepsy, 62 with TLE and 20 with idiopathic generalized epilepsy (IGE), and 82 matched healthy controls were evaluated using the SCID-IP, Y-BOCS, MMPI-2 (specifically the Psychasthenia and Obsessiveness scales), BDI, and STAI Y1 and Y2. Nine of the TLE patients, none of the IGE patients, and one of the controls had a diagnosis of OCD. Psychasthenia and Obsessiveness scores were significantly higher in the TLE than in the IGE and control groups. Patients with TLE and OCD differed significantly with respect to history of depression when compared with patients with TLE without OCD, whereas there were no differences in age at onset and duration of epilepsy, seizure pattern and frequency, MRI features, laterality of the EEG focus, antiepileptic drug therapy and combinations, and BDI scores.     

Postictal nose-rubbing in the diagnosis, lateralization, and localization of seizures

BACKGROUND: Semiology is very useful in the diagnosis and classification of seizures. Some clinical signs occur primarily with specific localization-related epilepsies. OBJECTIVE: To evaluate postictal nose-rubbing as a potential diagnostic sign and a potential lateralizing or localizing indicator. METHODS: We reviewed presurgical prolonged video-EEG results of 50 consecutive patients with right temporal lobe epilepsy (TLE), 50 consecutive patients with left TLE, 50 consecutive patients with frontal lobe epilepsy, 11 consecutive patients with generalized epilepsy, and 100 consecutive patients with nonepileptic events. Videotapes of all events were reviewed independently by two investigators who were blinded to the results of the monitoring. The episodes of nose-rubbing and the hand with which the patient rubbed the nose were recorded. RESULTS: Nose-rubbing occurred in 25 of 50 (50%) right TLE patients and in 21 of 50 (42%) left TLE patients. Approximately 90% of patients rubbed his or her nose with the ipsilateral hand. Nose-rubbing occurred in 5 of 50 (10%) frontal lobe epilepsy patients. Nose-rubbing was not seen in any patient with generalized epilepsy or nonepileptic events. Postictal nose-rubbing did not occur after secondarily generalized seizures. CONCLUSIONS: Nose-rubbing is an easily observed phenomenon, has high interobserver reliability, and provides useful lateralizing information in patients with TLE. It was less frequently seen in extratemporal lobe epilepsy and was not seen after generalized seizures or nonepileptic events.     

Epilepsy and obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) has long been associated with epilepsy. The link with temporal lobe (usually refractory) epilepsy (TLE) is particularly prominent. Of TLE patients, 10% to 22% of patients may have OCD, often underdiagnosed in the outpatient clinic. Data on the links include case reports, case series, and controlled studies. Three larger, controlled studies in TLE patients, using comprehensive epilepsy and OCD classifications, in aggregate, have noted the obsessive qualities of washing, symmetry/exactness, and ordering, with a greater preoccupation with certain aspects of religion, compared with controls or patients with idiopathic generalized epilepsy. TLE foci may be either left- or right-sided. Social and neurobiological factors are involved in OCD in TLE. The neurobiology implicates a pathophysiological or structural impairment of the orbitofrontal-thalamic, and frontothalamic-pallidal-striatal-anterior cingulate-frontal circuits. Discrete anatomic lesions in these pathways, or their surgical removal, may induce (or conversely) improve OCD in TLE patients.     

Functional connectivity homogeneity correlates with duration of temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is often associated with progressive changes to seizures, memory, and mood during its clinical course. However, the cerebral changes related to this progression are not well understood. Because the changes may be related to changes in brain networks, we used functional connectivity MRI (fcMRI) to determine whether brain network parameters relate to the duration of TLE. Graph theory-based analysis of the sites of reported regions of TLE abnormality was performed on resting-state fMRI data in 48 subjects: 24 controls, 13 patients with left TLE, and 11 patients with right TLE. Various network parameters were analyzed including betweenness centrality (BC), clustering coefficient (CC), path length (PL), small-world index (SWI), global efficiency (GE), connectivity strength (CS), and connectivity diversity (CD). These were compared for patients with TLE as a group, compared to controls, and for patients with left and right TLE separately. The association of changes in network parameters with epilepsy duration was also evaluated. We found that CC, CS, and CD decreased in subjects with TLE compared to control subjects. Analyzed according to epilepsy duration, patients with TLE showed a progressive reduction in CD. In conclusion, we found that several network parameters decreased in patients with TLE compared to controls, which suggested reduced connectivity in TLE. Reduction in CD associated with epilepsy duration suggests a homogenization of connections over time in TLE, indicating a reduction of the normal repertoire of stronger and weaker connections to other brain regions.     

Event-related potential (P300) in epilepsy

The P300 component of auditory event-related potential was studied in 39 patients with temporal lobe epilepsy (TLE), 26 with idiopathic generalized epilepsy (IGE) and 28 controls. The age-corrected P300 latencies were significantly longer in TLE patients compared with those in IGE patients and controls. Neither the duration of epilepsy nor clinical manifestation was related to the P300 component in the same epileptic syndrome. The age-corrected P300 latencies recorded from Cz were significantly prolonged in TLE patients with bilateral temporal EEG foci compared with those with unilateral focus. The effects of anti-epileptic drugs on the P300 component were not significant. Our findings imply that prolonged P300 latency in TLE patients, especially in those with bilateral EEG foci is due to damage of the hippocampus, which is potentially an epileptogenic focus.     

Response inhibition and set shifting in patients with frontal lobe epilepsy or temporal lobe epilepsy

Patients with frontal lobe epilepsy (FLE), patients with temporal lobe epilepsy (TLE), and matched controls were administered a test of response inhibition and set shifting (switching) (Color Word Interference Test, CWIT). Patients with FLE were impaired relative to the controls across all conditions of the CWIT, with the FLE patients showing disproportionate impairment in the Inhibition and Inhibition/Switching conditions. In contrast, the TLE patients did not differ from controls. Further analysis of the patient groups revealed that patients with left FLE were impaired relative to those with right FLE, left TLE, and right TLE in the Inhibition condition. In the Inhibition/Switching condition, patients with left FLE and left TLE were impaired relative to their right-sided counterparts. Finally, performance by the TLE group in the Inhibition/Switching condition was correlated with seizure frequency. These data suggest that patients with FLE, but not TLE, show impaired inhibition and set shifting relative to controls. In addition, side of the seizure focus and seizure frequency may contribute to executive dysfunction in patients with epilepsy.     

A comparison of emotional and cognitive intelligence in people with and without temporal lobe epilepsy

Medial temporal lobe structures have been hypothesized to be important in emotional intelligence (EI) and social cognition. There is some evidence associating temporal lobe epilepsy (TLE) with impairments in social cognition. This study aimed to establish whether TLE is also associated with deficits in EI. Sixteen patients with TLE and 14 controls without epilepsy matched for age and current intelligence quotient were compared on measures of EI, recognition of facial expressions of emotion, and distress. Results indicated that patients with TLE showed both impaired EI and impaired recognition of facial expressions. They also reported greater psychological distress, which correlated negatively with EI. It is suggested that some of the psychosocial problems experienced by patients with TLE can be conceptualized as the consequences of deficits in EI, possibly resulting from epilepsy-related disruption to medial temporal lobe functioning.     

The localizing value of the abdominal aura and its evolution: a study in focal epilepsies.

OBJECTIVE: To evaluate the localizing value of abdominal aura and its evolution into other seizure types. METHODS: The seizures of 491 consecutive patients with focal epilepsies were prospectively classified according to a recently introduced semiologic seizure classification. All patients underwent prolonged EEG video monitoring and MRI scan. Two hundred twenty-three patients (45%) had temporal lobe epilepsies (TLE); 113 patients (23%) had extratemporal epilepsies; and for 155 (32%) patients, the epilepsy could not be localized to one lobe. RESULTS: Abdominal auras were more frequent with TLE (117 of 223 patients, 52%) than in extratemporal epilepsy (13 of 113 patients, 12%, p < 0.0001) and more frequent in mesial TLE (70 of 110 patients, 64%) than in neocortical TLE (16 of 41 patients, 39%, p = 0.007). No preponderance to one side existed. Abdominal auras were followed by ictal oral and manual automatisms (automotor seizure) in at least one seizure evolution in all patients with TLE (117 patients, 100%). In contrast, only two patients with extratemporal epilepsy (2 of 13 patients, 15%, p < 0.0001) had abdominal auras evolving into automotor seizures. An abdominal aura is associated with TLE with a probability of 73.6%. The evolution of an abdominal aura into an automotor seizure, however, increases the probability of TLE to 98.3%. CONCLUSIONS: These results demonstrate that evolution of abdominal aura into automotor seizure permits differentiation between temporal lobe epilepsy and extratemporal epilepsy, showing that analysis of seizure evolution provides more localizing information than does the frequency of particular seizure types.     

Entorhinal cortex MRI assessment in temporal,extratemporal, and idiopathic generalized epilepsy

PURPOSE: We previously showed a reduction in the volume of the entorhinal cortex (EC) ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy (TLE). The purpose of this study was to examine the specificity of EC atrophy in epilepsy. METHODS: We performed volumetric measurement of the EC on high-resolution magnetic resonance imaging (MRI) in patients with TLE (n = 70), extratemporal lobe epilepsy (ETE; n = 18), and idiopathic generalized epilepsy (IGE; n = 20). EC volumes of epilepsy patients were compared with those of 48 age- and sex-matched normal controls. Within the TLE group, 63 patients were selected prospectively with hippocampal atrophy ipsilateral to the seizure focus. The remaining seven patients were chosen retrospectively based on normal volumetric MRI of the hippocampus and amygdale, as well as normal histopathologic examination of the resected tissue. RESULTS: Compared with normal controls, EC volume was smaller ipsilateral but not contralateral to the seizure focus in patients with TLE (p < 0.001). No difference in the EC volumes ipsilateral and contralateral to the seizure focus was seen in patients with ETE and IGE compared with normal controls. The individual analysis showed that the EC was atrophic in 73% of TLE patients with hippocampal atrophy. Three of the seven TLE patients with normal volumetric MRI of the hippocampus and amygdala and normal histopathologic examination had EC atrophy ipsilateral to the seizure focus. In no patient with ETE or IGE was the EC found to be atrophic. CONCLUSIONS: EC atrophy ipsilateral to the seizure focus appears to be specific to mesial temporal lobe structural damage associated with TLE.     

A visual learning and memory test for preoperative evaluation of patients with temporal lobe epilepsy

We used a modified version of the visual DCS (mDCS) test to study patterns of learning, free recall, and recognition capacity in patients with temporal lobe epilepsy (TLE) (N = 24) and controls (N = 38). The patients were under consideration for epilepsy surgery. The mDCS differentiated left from right TLE patients in all aspects of visuospatial learning and delayed recall. The mDCS revealed lower performance for TLE patients as compared with controls. The present results indicate that the mDCS may be a preoperative tool to differentiate left from right TLE.     

Childhood febrile convulsions--which factors determine the subsequent epilepsy syndrome? A retrospective study

To analyze the spectrum of epilepsy syndromes which follow childhood febrile convulsions (FC) and to examine whether retrospective analysis of clinical features of the FC enables discrimination of patients who develop temporal lobe epilepsy (TLE) from those who develop generalized epilepsy (GE). One hundred and thirteen patients with epilepsy and antecedent FC were retrospectively analyzed. We inquired in detail about the clinical characteristics of FC (age, duration, number, focal symptoms) as well as family history, birth history, neurological status, and psychomotor development before onset of FC. Forty five (39.8%) patients had TLE, 41 (36.6%) GE, and 27 (23.9%) had extratemporal epilepsy (ETE). Patients with TLE had a significantly longer duration of FC (P≤0.001), more often focal features (P≤0.001), and febrile status epilepticus (P≤0.001) than patients with GE. Age at FC, Number of FC, family history, birth history and neurological status at FC did not differ between groups. A stepwise discriminant model allowed correct assignment after cross validation in 84.2% to TLE and in 100% to GE. A broad spectrum of epilepsy syndromes follow FC. We found a strong association of prolonged and focal FC with later development of TLE. Short generalized FC were associated with GE.     

Depression and Anxiety in Patients with Epilepsy

The aim of this investigation was to study the interaction between depression/anxiety and epilepsy. One hundred fifty individuals with partial epilepsy, 70 with idiopathic generalized epilepsy, and 100 controls were administered two self-rating mood questionnaires (Zung and Stai) for the evaluation of depression and anxiety, respectively. The group with epilepsy was much more severely impaired than the controls according to both mood questionnaires; the patients with partial epilepsy, especially those with temporal lobe epilepsy (TLE), were more depressed and anxious than the patients with generalized epilepsy. The group with left TLE appeared to have the highest levels of depression and anxiety. The final results of our study confirmed that some mood disorders are common throughout the epilepsy population, especially in patients with left TLE. No correlation was noted between the frequency of seizures and onset of epilepsy and the results of the mood questionnaires. Moreover, no differences were found in depression and anxiety between males and females among both left focus and right focus epilepsy patients.     

Is impairment in set-shifting specific to frontal-lobe dysfunction? Evidence from patients with frontal-lobe or temporal-lobe epilepsy.

Frontal-lobe epilepsy (FLE), temporal-lobe epilepsy (TLE), and matched-control subjects were administered the Trail Making Test (TMT) of the Delis-Kaplan Executive Function System (D-KEFS; Delis et al., 2001), which assesses set-shifting on a visuomotor sequencing task. Results indicated that patients with FLE were impaired in both speed and accuracy on the switching condition relative to patients with TLE and controls. The two patient groups did not differ from controls on the four baseline conditions of the test, which assess visual scanning, motor speed, number sequencing, and letter sequencing. In addition, seizure-related variables (i.e., age of seizure onset, duration of epilepsy, and seizure frequency) failed to correlate with set-shifting performance in patients with FLE. These results suggest that patients with FLE can be reliably distinguished from those with TLE and control subjects on set-shifting as measured by the DKEFS TMT.     

Blood and cerebrospinal fluid immune cell profiles in patients with temporal lobe epilepsy of different etiologies

Inflammation plays a role in the pathogenesis of immune-mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age-matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n = 26), TLE due to hippocampal sclerosis (n = 14), or limbic encephalitis with antibodies against the 65-kDa isoform of glutamic acid decarboxylase (GAD65-LE; n = 11). TLE patients showed increased proportions of human leukocyte antigen–DR isotype (HLA-DR)-expressing CD4⁺ T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14^lowCD16⁺ cells in the PB and blood/CSF-barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65-LE differed from other TLE patients by increased proportions of HLA-DR–expressing CD8⁺ T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other.     

Differential aberrant sprouting in temporal lobe epilepsy with psychiatric co-morbidities

Psychiatric co-morbidities in epilepsy are common in patients with temporal lobe epilepsy (TLE). Pathological alterations in TLE are well characterised; however, neuropathologic data are relatively scale regarding the association between psychiatric diseases and epilepsy. Our objective was to evaluate the clinical data of 46 adult TLE patients with and without psychiatric co-morbidities and to correlate the data with hippocampal neuronal density and mossy fiber sprouting. Accordingly, patients were grouped as follows: TLE patients without history of psychiatric disorder (TLE, n=16), TLE patients with interictal psychosis (TLE+P, n=14), and TLE patients with major depression (TLE+D, n=16). Hippocampi from autopsies served as non-epileptic controls (n=10). TLE+P exhibited significantly diminished mossy fiber sprouting and decreased neuronal density in the entorhinal cortex when compared with TLE. TLE+P showed significantly poorer results in verbal memory tasks. TLE+D exhibited significantly increased mossy fiber sprouting length when compared with TLE and TLE+P. Further, a higher proportion of TLE+D and TLE+P presented secondarily generalised seizures than did TLE. Our results indicate that TLE patients with psychiatric disorders have distinct features when compared with TLE patients without psychiatric co-morbidities and that these changes may be involved in either the manifestation or the maintenance of psychiatric co-morbidities in epilepsy.     

Depression and anxiety before and after temporal lobe epilepsy surgery.

PURPOSE: To examine the course of depression and anxiety in patients with temporal lobe epilepsy (TLE) treated with epilepsy surgery (and anticonvulsant drugs) or medical means alone. METHODS: Of 94 TLE patients evaluated for epilepsy surgery, 76 underwent a resective procedure, 18 continued on medical treatment alone. Depression (Beck Depression Inventory (BDI)) and anxiety scores (Self-Rating Anxiety Scale (SRAS)) were examined during presurgical evaluation (T1) and after a mean of 16 months (T2), or 12 months after surgery. Depression and anxiety scores were related to type of intervention, underlying epileptogenic lesion, change of seizure control and anticonvulsant therapy. RESULTS: At T1, depression and anxiety scores were higher in patients with TLE than scores in published normal populations. At T2, depression but not anxiety scores were significantly lower than at T1. Change of depression scores interacted with improvements of seizure control. CONCLUSIONS: Evidence of depression and anxiety is commonly found in patients with TLE. Depression improves not because of epilepsy surgery per se, but because of improved seizure control. This is more commonly achieved by surgery than medical treatment. The results are consistent with the hypothesis that depression in TLE is caused by pathological epileptic activity rather than a fixed structural defect.     

A comparison of post-ictal headache between patients with occipital lobe epilepsy and temporal lobe epilepsy.

We investigated post-ictal headaches (PIH) using a questionnaire to ascertain their characteristics and compare them among different types of epilepsy. The subjects consisted of 34 patients with occipital lobe epilepsy (OLE) and 75 patients with temporal lobe epilepsy (TLE). PIH occurred in 62% of OLE and 23% of TLE (P < 0.05). The quality of pain in PIH was 'steady' in 71% of OLE and 29% of TLE (P < 0.05) as opposed to 'pounding'. Other factors, such as frequency, severity, duration, and accompanying symptoms showed no significant differences. We found very few patients with migraine-like headaches. Analyses of clinical factors, such as age at onset, duration of epilepsy, seizure frequency, family history of headache, and interictal headache did not reveal any relationship to PIH, although generalized tonic-clonic seizures are associated with PIH in TLE (P < 0.05). These results suggest that the nature of PIH may be different between OLE and TLE, and that the region of epileptic focus or spreading area of epileptic discharge may have a close relation to the induction of PIH. An association with migraine, which has been reported previously, was unclear in our study.     

Preictal headache in partial epilepsy

The authors studied clinical characteristics in 11 patients with intractable focal epilepsy and preictal headache (PIHA) using a standardized interview. Headache was frontotemporal, ipsilateral to the focus, in nine patients with temporal lobe epilepsy (TLE) and contralateral in one with TLE and in one with frontal seizures. Migrainous features were found in four. After surgery, all seven seizure-free patients and two with rare seizures were free of PIHA. It may be a useful lateralizing sign in patients with TLE.