Depressive Symptomatology in a General Hospital Sample of Outpatients with Temporal Lobe Epilepsy: A Controlled Study

Summary: We compared temporal lobe epilepsy (TLE) outpatients attending a general hospital with depressed psychiatric patients and normal control subjects to investigate depressive symptomatology. Both clinicianrated measures and self-report questionnaires were used. Rates of depressive and anxious symptomatology in TLE subjects were higher than those in a normal control sample, but TLE subjects did not differ significantly from controls on anxiety measures. The depressed psychiatric group scored higher than the TLE and control groups on both depression and anxiety measures. Rates of depressive symptomatology in the TLE group were lower than those reported in previous studies for persons attending specialist epilepsy clinics, but similar to the findings of one community study.     

The perception of memory failures in patients with epilepsy

The aim of the study is to evaluate the correlation between subjective memory complaints and neuropsychological tests in the epilepsy population. We administered a Self Report Memory Questionnaire, based on possible everyday memory failures, two questionnaires on anxiety and depression and a battery of cognitive tests to 150 patients with epilepsy (n=100 with partial epilepsy, n=50 with idiopathic generalized epilepsy) and a control group (n=50). A discrepancy between the results of the memory questionnaire and the cognitive tests was found in the epilepsy patients: the Self Report Memory Questionnaire did not show any correlation with the psychological tests. The same discrepancy was not seen in the controls, where the memory questionnaire was related to two verbal memory tests. Furthermore, patients with epilepsy reported greater difficulties on the Self Report Memory Questionnaire than the controls (P < 0.05). It appeared that the tendency to overstate memory problems was mainly related to anxiety and depression, but was not connected with the type of epilepsy, nor with its duration (in years). Seizure frequency, on the other hand, seemed to greatly influence mood, which in turn is probably affect subjective memory perception.     

The relationship of seizure focus with depression,anxiety, and health-related quality of life in children and adolescents with epilepsy

For youth with epilepsy, comorbid psychiatric conditions, such as depression and anxiety, require further examination as they carry increased risk for reduced health-related quality of life (HRQOL). The current study assessed whether rates of depression, anxiety, and withdrawal behaviors differed based on seizure location. Data included parental ratings on the Behavior Assessment System for Children (BASC-2) and the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire for 132 children and adolescents (mean age = 11.34, SD = 3.95) with generalized or partial (i.e., frontal [FLE] or temporal lobe epilepsy [TLE]) epilepsy. Our results identified clinically significant internalizing psychopathology in nearly half of our sample (41%). Although rates of internalizing behavior were similar between generalized and partial groups, children and adolescents with TLE demonstrated higher rates of depression compared to youth with FLE. No effects of laterality on internalizing behaviors were identified between TLE and FLE groups. Finally, for youth with TLE, parental depression ratings along with current number of antiepileptic medications (AEDs) were found to be significant barriers to HRQOL above and beyond anxiety, withdrawal, and epilepsy-specific variables. Temporal lobe epilepsy was associated with a two-fold risk of clinically significant depression ratings. These findings highlight the high prevalence of internalizing psychopathology features in pediatric epilepsy and offer further support for the relationship between depression and TLE in children and adolescents with epilepsy.     

Preoperative amygdala fMRI in temporal lobe epilepsy

Purpose:   Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery.
Methods:   We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale.
Results:   On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients.
Discussion:   The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR.     

Psychiatric disorders in temporal lobe epilepsy: An overview from a tertiary service in Brazil

PurposeTo evaluate the frequency and intensity of psychiatric disorders in a group of temporal lobe epilepsy (TLE) patients from a tertiary-care center.MethodsClinical and sociodemographic data of 73 patients were collected and a neuropsychiatric evaluation was performed with the following instruments: Mini-Mental State Examination (MMSE), structured clinical interview (MINI-PLUS), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), Brief Psychiatric Rating Scale (BPRS).ResultsPatients with TLE showed a high frequency of lifetime psychiatric disorders (70%), the most frequent being mood disorders (49.3%). At assessment, 27.4% of the patients were depressed and 9.6% met criteria for bipolar disorder. Nevertheless, depression had not been properly diagnosed nor treated. Anxiety disorders were also frequent (42.5%), mainly generalized anxiety disorder (GAD) (21.9%). Obsessive compulsive disorder (OCD) was present in 11.0% and psychotic disorders in 5.5% of the sample. Patients with left mesial temporal sclerosis (LMTS) exhibited more psychopathologic features, mainly anxiety disorders (p = 0.006), and scored higher on HAM-A and HAM-D (p < 0.05 in both).ConclusionTLE is related to a high frequency of psychiatric disorders, such as anxiety and depression, which are usually underdiagnosed and undertreated. Damage to the left mesial temporal lobe, seen in LMTS, seems to be an important pathogenic lesion linked to a broad range of psychopathological features in TLE, mainly anxiety disorders. The present study prompts discussion on the recognition of the common psychiatric disorders in TLE, especially on the Brazilian setting.     

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.     

Mood state in unilateral temporal lobe epilepsy

The purpose of this investigation was to reexamine the relationship between self-reported depression and laterality of temporal lobe epilepsy and to determine the contribution of associated frontal lobe dysfunction in predisposing patients to depression. Sixty-four patients with complex partial seizures of left (n = 26) or right (n = 38) temporal lobe origin were administered several self-report measures of mood state (Beck Depression Inventory, Center for Epidemiological Studies-Depression scale, Beck Anxiety Inventory), and a test of frontal lobe function [Wisconsin Card Sorting Test (WCST)]. There were no overall differences between the left and right temporal lobe groups on the measures of depression and anxiety. However, the left temporal lobe group exhibited a significant relationship between the degree of associated frontal lobe dysfunction (as indicated by increased perseverative responding on the WCST) and dysphoric mood state. For the right temporal lobe group there was a nonsignificant inverse relationship between mood state and indices of frontal lobe dysfunction. These results (1) are consistent with the broader psychiatric literature, which has implicated a relationship between depression and left frontal lobe dysfunction, (2) suggest that previous conflicting reports of depression/left temporal lobe epilepsy relationship are due in part to variations in the intactness of frontal lobe function, and (3) suggest that the presence of associated frontal lobe dysfunction may be a consideration in understanding interictal psychopathology in epilepsy.     

Depressed mood and memory impairment in temporal lobe epilepsy as a function of focus lateralization and localization

OBJECTIVE: Memory disorders and depressed mood are prominent psychological symptoms of temporal lobe epilepsies (TLEs). We examined the interaction of depressive mood and memory as a function of focus localization. METHODS: One hundred fifty-two TLE patients with right mesial (n=37, RTLE-AHS), right lateral (n=31, RTLE-LAT), left mesial (n=42, LTLE-AHS), and left lateral (n=42, LTLE-LAT) lesions and epilepsies underwent comprehensive presurgical evaluation and neuropsychological assessment of mood and memory. Univariate and multivariate analyses of covariance (ANCOVAs) and partial correlation analyses were performed to reveal interactions of depression and memory as a function of focus localization. RESULTS: No differences between the study groups were revealed for depression, indicating a general risk of 30% for depressed mood (BDI>12) in patients with TLE. ANCOVAs revealed significant main effects of focus side (left: verbal learning deficits; right: figural learning deficits) and site (mesial at disadvantage) on learning and memory scores. Correlation analyses revealed interactions between memory and mood only in LTLE-LAT patients. CONCLUSIONS: Although the data provide evidence that side and site of the epileptogenic region differentially affect material specific memory performance, there was no evidence of a specific temporal target region for depressive mood. In the majority of the patients, depressed mood and memory impairment appeared as independent rather than as related symptoms of TLE. In LTLE-LAT, however, mood was significantly related to verbal and figural memory performance. Epilepsy-driven pathological left temporofrontal circuits are discussed as a prerequisite for the coupling of mood disorders and memory impairment in this specific patient subgroup which is also known from the psychiatric major depression syndrome.     

Prevalence of Psychopathology in Dutch Epilepsy Inpatients: A Comparative Study

The purpose of this study was to determine the prevalence of psychiatric disorders in Dutch patients with epilepsy in comparison with epidemiological data on a representative sample of the Dutch population. The Composite International Diagnostic Interview (CIDI) was used to determine the prevalence of psychiatric disorders in 209 epilepsy patients and compared with findings in the general Dutch population. The prevalence in temporal lobe epilepsy (TLE) and extra-temporal lobe epilepsy (extra-TLE) was also compared. Psychiatric disorders most frequently found in patients with epilepsy were anxiety and mood disorders. The last-year prevalence of these disorders was 25% for anxiety disorders and 19% for mood disorders. Compared with the general Dutch population, the prevalence of these disorders was significantly higher in epilepsy. No differences were found between patients with TLE and extra-TLE. It can be concluded that patients with epilepsy admitted to a tertiary epilepsy center suffer more often from mood and anxiety disorders than the general population.     

A componential analysis of proverb interpretation in patients with frontal lobe epilepsy and temporal lobe epilepsy: relationships with disease-related factors

The ability to interpret nonliteral, metaphoric language was explored in patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), and matched control participants, to determine (1) if patients with FLE were impaired in their interpretations relative to those with TLE and controls, and (2) if disease-related variables (e.g., age of seizure onset) predicted performances in either patient group. A total of 22 patients with FLE, 20 patients with TLE, and 23 controls were administered a test of proverb interpretation to assess their ability to grasp the abstract meaning of nonliteral language. Participants were presented with a series of proverbs and asked to provide an oral interpretation of each. Responses to each proverb were scored according to their accuracy and level of abstractness. Patients with FLE, but not TLE, were impaired relative to controls in their overall interpretation of proverbs. However, a subgroup analysis revealed that only patients with left FLE showed impaired interpretation accuracy relative to the other groups, whereas patients with both left FLE and left TLE showed impaired abstraction. Patients with FLE were also impaired when they were asked to select the best interpretation of the proverb from response alternatives. In patients with FLE, only a left-sided seizure focus was associated with poorer performance. In patients with TLE, both an early age of onset and a left-sided seizure focus predicted poorer performance. Overall, FLE patients exhibit greater impairment than TLE patients in interpreting proverbs. However, the nature and disease-specific correlates of impaired performances in proverb interpretation differ between the groups.     

Hyperreligiosity in temporal lobe epilepsy: redefining the relationship

Seventy-six subjects with the primary diagnosis of complex partial seizures with a unilateral temporal lobe focus were examined for the presence of hyperreligiosity. Fifty-one subjects had a left temporal lobe seizure focus and 25 had a right temporal lobe seizure focus. In addition to the temporal lobe epilepsy (TLE) groups, two reference groups were also examined. The first consisted of 31 subjects with primary generalized seizures. The second control group consisted of 27 subjects with documented pseudoseizures and no objective evidence of recurrent epileptic seizures. In all cases, the documentation of seizures or pseudoseizures as well as the localization of the seizure focus was accomplished through simultaneous videotaped recording of the 16-channel scalp EEG tracing and the concurrent overt behavior during the ictal phase. The results of this study fail to support the hypothesis that individuals with TLE are characteristically hyperreligious during the interictal state. There were no significant group differences between the left vs. the right TLE groups, nor were there any significant group differences between the two TLE groups vs. the two comparison groups.     

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.     

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.     

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.     

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.     

Contribution of the μ-opioid receptor system to affective disorders in temporal lobe epilepsy: A bidirectional relationship?

Objective

Affective disorders are frequent comorbidities of temporal lobe epilepsy (TLE). The endogenous opioid system has been implicated in both epilepsy and affective disorders, and may play a significant role in their bidirectional relationship. In this cross-sectional study, we investigated the association between μ-opioid receptor binding and affective disorders in patients with TLE.

Methods

Nine patients with TLE and depression/anxiety underwent ¹¹C-carfentanil positron emission tomography (CFN PET) and neuropsychiatric assessment, including the Hospital Anxiety and Depression Scale and the Positive and Negative Affect Schedule. The normalized CFN PET scans were compared with those of 26 age-matched healthy controls. Correlation analyses with affective symptoms were performed by region of interest-based analysis focusing on the limbic circuit and orbitofrontal cortex.

Results

We observed widely reduced CFN binding potential (BP) in bilateral frontal lobes and striata in patients with TLE compared to healthy controls. In the TLE group, more severe anxiety and negative affect were associated with decreased CFN BP in the posterior cingulate gyrus.

Significance

In patients with TLE, interictally reduced binding in the opioid system was associated with higher levels of anxiety and negative affect. We speculate that seizure-related agonist-driven desensitization and downregulation of opioid receptors could be a potential underlying pathomechanism.     

Mismatch negativity is abnormal but not lateralizing in temporal lobe epilepsy

We investigated the changes of mismatch negativity (MMN) in patients with temporal lobe epilepsy (TLE) and explored the possible role of MMN in lateralizing their seizure focus. Thirty patients with TLE and thirty healthy controls were included. MMN was elicited in each subject. Patients with TLE were divided into three subgroups: unilateral left TLE; unilateral right TLE, and bilateral TLE. MMN amplitudes and latencies were compared between the patients with TLE and the control group, and also among the three subgroups of TLE, using repeated measures analyses of variance (ANOVA). To assess the lateralizing value of MMN, MMN latencies and amplitudes at the mastoid sites between the ipsilateral and contralateral sides of epileptic focus in patients with unilateral TLE were compared using t-test. Compared with controls, each subgroup of patients with TLE had longer latencies of MMN at both fronto-central and mastoid sites, but the amplitudes of MMN were not significantly different. The amplitudes and latencies of MMN were not significantly different between the ipsilateral and contralateral sides of seizure focus at mastoid sites. The present findings of prolonged latencies of MMN are suggestive of cognitive impairment in TLE. Both the mastoid sites and the fronto-central sites are involved, which likely reflect widespread cortical abnormalities in TLE. However, the changes of MMN during the interictal phase are not useful for lateralizing the seizure focus in patients with TLE.     

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.     

Diagnosis and treatment of temporal lobe epilepsy

Of the 1,200,000 Americans with partial epilepsy, temporal lobe epilepsy (TLE) occurs in more than 400,000. Temporal lobe seizures are usually stereotypic in their symptoms and duration. A typical sequence is an aura followed by arrest of motor behavior, blank stare, and automatisms. Patients with TLE often show impairments in attention, memory, mental processing speed, executive functions, mood, personality, and drive-related behaviors. Interictal depression occurs in approximately one third of TLE patients. TLE is diagnosed by a history of characteristic partial seizure symptoms. The diagnosis is confirmed by the capture of a typical episode during an electroencephalogram (EEG) or video-EEG, with epileptiform activity over one or both temporal regions. Video-EEG monitoring has revolutionized diagnosis and should be considered in patients in whom diagnosis is uncertain. TLE is treated with medications, resective surgery, and vagus nerve stimulation. Epilepsy surgery should be considered in all patients with refractory partial epilepsy.     

Depression, anxiety, and temporal lobe epilepsy. Laterality of focus and symptoms

The association between anxiety, depression, and lateralization of an epileptogenic focus was explored in 18 adult patients with a left temporal lobe focus, 21 with a right focus, 20 with bilateral temporal foci, and 16 individuals with absence seizures. No significant difference in the level of anxiety was found among the groups. However, patients with left-sided temporal lobe epilepsy scored significantly higher than other groups on self-ratings for depression. This could not be accounted for by factors such as duration of epilepsy, employment status, education, age at seizure onset, or medication status. The left temporal lobe epilepsy group had a nonsignificantly larger number of males and left-handed subjects. The possible interactions between gender, handedness, seizure focus, and vulnerability to depression are described.