Disorder In Temporal Lobe Epilepsy Research Articles

Cognitive impairment in temporal lobe epilepsy

Cognitive impairment (CI) is a common comorbid pathology in epilepsy patients that exerts profound negative impact on quality of life. The CI causes may be due to various factors related to etiology, clinical manifestations, and treatment of epilepsy. A typical disorder in temporal lobe epilepsy is memory impairment. However, neuropsychological impairments may be more extensive and involve other neuropsychological domains. The risk of CI in patients with temporal lobe epilepsy may increase in structural brain disorders such as hippocampal sclerosis as well as in frequent seizures, early onset and long course of the disease. Surgical treatment of epilepsy may positively or negatively impact the cognitive function. In recent years, due to development of neurosciences as well as advances in the field of medical technologies, particularly neuroimaging, genetics, immunology, and biochemistry, new data emerged regarding potential mechanisms for developing CI in patients with epilepsy. The aim of the review is to assess available ideas about neurophysiological mechanisms of CI development, cues influencing emergence of neuropsychological disorders in patients with temporal lobe epilepsy.

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

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. Nine patients with TLE and depression/anxiety underwent 11 C-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. 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. 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.

Personality disorders in temporal lobe epilepsy: What do they signify?

To estimate the prevalence of personality disorders in patients with temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and compare it with general population and analyze their implications on treatment outcome. TLE was diagnosed based on clinical history, MRI, and Video EEG data. IPDE-ICD10 screening questionnaire was applied to investigate personality disorder in 120 subjects, 60 cases, and 60 normal controls. Bear-Fedio inventory (BFI) was used to study different behavior traits in patients with TLE and controls. Prevalence of personality disorders was higher (71.7% in cases versus 38.3% in controls) in patients with TLE compared to controls (P<.001). Some personality traits like schizoid (P=.002), dissocial (P=.001), impulsive (P=.003), anankastic (P<.001), anxious (P<.001), and dependent (P<.001) personalities were found to have high prevalence in TLE. Personality disorder was higher among those cases who had been tried on more than two antiepileptic drugs (AEDs) (P=.033) and in those with duration of illness more than 10years (P=.026). Cases also showed significantly higher score in BFI for all behavioral traits except for aggression. No significant difference of BFI score was seen based on laterality of epileptic focus, gender, duration of illness, or number of AEDs tried. There is a significantly higher prevalence of personality disorders in patients with TLE. Specific interventions for these disorders should be considered at the earliest pari passu with AEDs and surgery.

Mental and behavioral disorders in temporal lobe epilepsy

The evolution of temporal lobe epilepsy often implies complex psychiatric manifestations, as the elements can be part of an aura, as well as of a psychiatric pathology of its own. This paper presents the case of a patient diagnosed with focal epilepsy of the right mesial temporal lobe, who subsequently developed psychotic disorder due to a general medical condition with medico-legal implications, treatment noncompliance and difficulties in controlling epileptic seizures.

Neuroanatomical correlates of personality traits in temporal lobe epilepsy: Findings from the Epilepsy Connectome Project

Behavioral and personality disorders in temporal lobe epilepsy (TLE) have been a topic of interest and controversy for decades, with less attention paid to alterations in normal personality structure and traits. In this investigation, core personality traits (the Big 5) and their neurobiological correlates in TLE were explored using the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) and structural magnetic resonance imaging (MRI) through the Epilepsy Connectome Project (ECP). NEO-FFI scores from 67 individuals with TLE (34.6 ± 9.5 years; 67% women) were compared to 31 healthy controls (32.8 ± 8.9 years; 41% women) to assess differences in the Big 5 traits (agreeableness, openness, conscientiousness, neuroticism, and extraversion). Individuals with TLE showed significantly higher neuroticism, with no significant differences on the other traits. Neural correlates of neuroticism were then determined in participants with TLE including cortical and subcortical volumes. Distributed reductions in cortical gray matter volumes were associated with increased neuroticism. Subcortically, hippocampal and amygdala volumes were negatively associated with neuroticism. These results offer insight into alterations in the Big 5 personality traits in TLE and their brain-related correlates.

Tyrosine receptor kinase B gene variants (NTRK2 variants) are associated with depressive disorders in temporal lobe epilepsy.

Psychiatric comorbidities are highly prevalent in epilepsy, adding an important burden to the disease and profoundly affecting the quality of life of these individuals. Patients with temporal lobe epilepsy (TLE) are especially at risk to develop depression and several lines of evidence suggest that the association of depression with epilepsy might be related to common biological substrates. In this study, we test whether NTRK2 allele variants are associated with mood disorders or depressive disorders in patients with TLE. An association study of 163 patients with TLE. The NTRK2 variants studied were rs1867283, rs10868235, rs1147198, rs11140800, rs1187286, rs2289656, rs1624327, rs1443445, rs3780645, and rs2378672. All patients were submitted to the Structured Clinical Interview for DSM-IV (SCID) and epilepsy patients with mood disorders or depressive disorders were compared to epilepsy patients without mood disorders or depressive disorders. In our TLE cohort, 76 patients (46.6%) showed mood disorders. After logistic regression, independent risk factors for mood disorders in TLE were female sex, presence of concomitant anxiety disorders, and genetic variations in rs1867283 and rs10868235 NTRK2 variants. Depressive disorders accounted for this results and independent variables associated with depressive disorders in TLE were female sex (OR=2.59; 95%CI=1.15-5.82; p=0.021), presence of concomitant anxiety disorders (OR=3.72; 95%CI=1.71-8.06; p=0.001) or psychotic disorders (OR=3.86; 95%CI=1.12-13.25; p=0.032), A/A genotype in the rs1867283 NTRK2 gene (OR=3.06; 95%CI=1.25-7.50; p=0.015) and C/C genotype in the rs10868235 NTRK2 gene (OR=3.54; 1.55-8.08; p=0.003). Similarly, these genotypes also remained independently and significantly associated with depressive disorders when patients with depressive disorders were compared to TLE patients without any psychiatric comorbidity. In the present study, female sex, presence of concomitant anxiety or psychotic disorders, and specific allelic variations in the NTRK2 gene were independently associated with mood disorders or depressive disorders in TLE. If our results were confirmed, variants in the NTRK2 gene could be considered as risk factors or biomarkers for depressive disorders in patients with TLE.

Characterization and prediction of theory of mind disorders in temporal lobe epilepsy.

Patients with temporal lobe epilepsy (TLE) have impaired theory of mind (ToM). However, ToM involves a variety of processes, such as understanding a person's intentions ("cognitive" ToM) and emotional states ("affective" ToM). The objectives of the present study were to characterize ToM disorders in TLE patients, identify patients at risk of ToM disorders, and study the relationships between psychobehavioral and quality of life factors and ToM disorders. Fifty TLE patients and 50 controls performed ToM tasks assessing their understanding of verbal clumsiness (faux pas), sarcastic remarks, and mentalistic actions. Demographic, cognitive, and psychobehavioral data, and (for TLE patients) clinical and quality of life factors, were recorded. Compared with controls, TLE patients showed impairments in all ToM tasks: 84% misunderstood faux pas, and around 50% misunderstood sarcasm. A long duration of epilepsy and young age at onset were risk factors for ToM impairments. In TLE patients, ToM impairments were associated with impaired empathy and anhedonia. Their affective states were less positively and more negatively valenced than in controls. Low positive affectivity was predictive of greater cognitive and affective ToM impairments for the faux pas task, and high negative affectivity was predictive of greater cognitive ToM abilities for the sarcasm task. The lack of social support was correlated with impaired ToM but was not a predictive factor. Both cognitive and affective ToM processes are impaired in TLE patients. Impaired ToM has an impact on empathy abilities and is related to affective disturbances in TLE patients.

Supplemental Material for Characterization and Prediction of Theory of Mind Disorders in Temporal Lobe Epilepsy

Supplemental Material for Characterization and Prediction of Theory of Mind Disorders in Temporal Lobe Epilepsy

P789: Interictal EEG activity is associated with mood disorders in temporal lobe epilepsy

P789: Interictal EEG activity is associated with mood disorders in temporal lobe epilepsy

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.

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.

Common factors among Alzheimer’s disease, Parkinson’s disease, and epilepsy: Possible role of the noradrenergic nervous system

The neurodegenerative disorders Alzheimer's disease (AD) and Parkinson's disease (PD) share in common the neuropathologic loss of locus coeruleus (LC) noradrenergic neurons. In addition, these two neurodegenerative disorders share two symptoms that define these disorders: cognitive impairment and depression. The hippocampus is a region that is known to play a role in cognition and depression, and the hippocampus receives sole noradrenergic innervation from LC neurons. However, it is unclear how the loss of LC noradrenergic neurons contributes to these common symptoms in these two disorders. Epilepsy is not considered a neurodegenerative disorder, but the hippocampus is severely affected in temporal lobe epilepsy. Of interest, cognitive impairment and depression are also common comorbid disorders in temporal lobe epilepsy. This article describes common symptoms among these three neurologic disorders and a possible role of the noradrenergic nervous system.

Serotonin gene polymorphisms and psychiatry comorbidities in temporal lobe epilepsy

Neuropsychiatric comorbidities are frequent in temporal lobe epilepsy (TLE). It is biologically plausible that alterations in serotonin-related genes may be involved in higher susceptibility to psychiatric disease in these individuals. Here we report results of an association study of serotonin gene polymorphisms and psychiatry comorbidities in TLE. Case-control study of 155 patients with temporal lobe epilepsy. We evaluate the influence of 5-HTTLPR and 5-HTTVNTR polymorphisms in the 5-HTT gene and the C-1019G polymorphism in the 5-HT1A gene in psychiatric comorbidities of TLE. After logistic regression, female sex (OR=2.34; 95% CI 1.06-5.17; p=0.035) and the presence of C allele of 5-HT1A C-1019G polymorphism (OR=2.77; 95% CI 1.01-7.63; p=0.048) remained independent risk factors for anxiety disorders in temporal lobe epilepsy. C allele of 5-HT1A C-1019G polymorphism might be an independent risk factor for anxiety disorders in temporal lobe epilepsy. We believe that other studies in this venue will shade some light on molecular mechanisms involved in psychiatric comorbidities in epilepsy.

The neurobiology of cognitive disorders in temporal lobe epilepsy

Cognitive impairment, particularly memory disruption, is a major complicating feature of epilepsy. This Review will begin with a focus on the problem of memory impairment in temporal lobe epilepsy (TLE). We present a brief overview of anatomical substrates of memory disorders in TLE, followed by a discussion of how our understanding of these disorders has been improved by studying the outcomes of anterior temporal lobectomy. The clinical efforts made to predict which patients are at greatest risk of experiencing adverse cognitive outcomes following epilepsy surgery are also considered. Finally, we examine the vastly changing view of TLE, including findings demonstrating that anatomical abnormalities extend far outside the temporal lobe, and that cognitive impairments extend beyond memory function. Linkage between these distributed cognitive and anatomical abnormalities point to a new understanding of the anatomical architecture of cognitive impairment in epilepsy. Clarifying the origin of these cognitive and anatomical abnormalities, their progression over time and, most importantly, methods for protecting cognitive and brain health in epilepsy, present a challenge to neurologists.

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

To evaluate the frequency and intensity of psychiatric disorders in a group of temporal lobe epilepsy (TLE) patients from a tertiary-care center. Clinical 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). Patients 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). TLE 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.

Left-sided EEG focus and positive psychiatric family history are independent risk factors for affective disorders in temporal lobe epilepsy

To identify independent risk factors for affective disorders in temporal lobe epilepsy. We studied 97 patients with temporal lobe epilepsy (TLE) exploring variables like age, gender, family history of epilepsy and psychiatric disorders, duration of epilepsy, control of seizures, presence of aura and initial precipitant insult, abuse of substances, neuroimaging and EEG features. Forty-one patients (42.3% of the total population) had affective disorders. A positive family history of psychiatric disorders (O.R.=3.8; p=0.003) and interictal EEG epileptiform discharges involving the left temporal lobe (O.R.=2.9; p=0.041) were significantly associated with an increased risk for an affective disorder. These associations remained significant after logistic regression, confirming the independent effects of the risk factors observed. Moreover, a binary logistic regression model obtained was able to correctly predict presence or absence of a life-time affective disorder in 71.1% of patients. This study points out that a positive family history of psychiatric disorders and interictal EEG epileptiform discharges involving the left temporal lobe are isolated risk factors for affective disorders in TLE. Our results suggest that biological factors are crucial for affective disorders development in TLE. Further studies are necessary to better specify the genetic and anatomical substracts involved and how they come together to generate affective disorders in those patients.

Prevalence and risk factors for psychiatric disorders in temporal lobe epilepsy

Prevalence and risk factors for psychiatric disorders in temporal lobe epilepsy

Focus laterality and interictal psychiatric disorder in temporal lobe epilepsy

The current study was carried out in order to find the possible associations between foci laterality and kind of prevailed psychopathological disorder in patients with temporal lobe epilepsy (TLE). One hundred and ten patients with TLE (40 men and 70 women) were included into the study. Among all studied patients the left-focus activity was detected in 67 patients, right-sided foci—in 43 patients. No relationships between chronology variables of epilepsy (age, age at epilepsy onset, epilepsy duration) and different subtypes of psychopathology in studied patients were revealed. Diagnosis of organic affective disorder was observed more frequently in patients with right-sided foci, while diagnosis of organic anxiety disorder—in patients with left-sided foci ( χ 2 = 7.0, p = 0.0081; Fisher's exact test p = 0.018). The comparison of dysphoric disorder with anxiety or affective disorder could not reveal any statistically significant association with focus laterality. Obtained results are discussed in terms of association between the different subtypes of studied psychiatric disorders and foci laterality in patients with TLE.

Neural responses associated with positive and negative emotion processing in patients with left versus right temporal lobe epilepsy

Studies on emotion processing in patients with temporal lobe epilepsy have dealt mainly with the processing of negative emotions. To further understand the neural basis of emotional disorders in temporal lobe epilepsy, we studied patterns of brain activation induced by implicit processing of negative and positive emotions perceived through facial expressions and emotionally salient stimuli in candidates for surgical treatment of intractable epilepsy. Using functional MRI, we compared, in patients with mesial temporal lobe epilepsy and healthy subjects, the patterns of brain activation elicited by the implicit processing of fearful, sad, and happy faces and pleasant and unpleasant scenes. The results revealed different patterns of activation in patients with left and right mesial temporal lobe epilepsy, compared with healthy subjects, suggesting that the left and right mesial temporal regions are involved differently in emotion processing, which could be related to different contributions in emotional arousal.

Pathogenic significance of neuronal migration disorders in temporal lobe epilepsy

To assess the epileptogenic lesions, a series of 202 cases with temporal lobectomy were analyzed histopathologically. The severity of hippocampal neuronal loss in patients with temporal lobe epilepsy was quantitatively analyzed and compared against autopsy controls of patients who died of nonneurologic disorders. For the histopathologic diagnosis of neuronal migration disorder (NMD), immunohistochemical stains for neurofilament protein (NF-M/H) and microtubule-associated protein 2 (MAP2) and Bielschowsky silver stains were routinely performed. Histopathology of NMD was classified by the 4-grade system. MAP2 immunoreactivity was useful in the identification of loss of normal polarization of dendrites in the abnormal neurons. NF-M/H immunohistochemistry and silver stains effectively labeled microscopic or occult lesions of NMD (grade II and III). Ammon hom sclerosis (AHS) was identified in 73.3% and NMD in 57.9%. There was more than 50% neuronal cell loss in 82.8% of AHS, and variable degrees of cell loss were observed in the dual-pathology groups. The frequency of dual pathology (both AHS and NMD) was 65.0% and showed relatively equal distributions in grades I, II, III, whereas the pure NMD group were classified predominantly as grades II and III. NMD might be a basic pathogenic substrate causing temporal lobe epilepsy. The dual pathology may indicate the presence of epileptogenic lesions in the neocortical and temporolimbic areas. HUM PATHOL 32:643-648. Copyright © 2001 by W.B. Saunders Company