The role of the thalamus in modular functional networks in temporal lobe epilepsy with cognitive impairment.

OBJECTIVE: Cognitive deficit is common in patients with temporal lobe epilepsy (TLE). Here, we aimed to investigate the modular architecture of functional networks associated with distinct cognitive states in TLE patients together with the role of the thalamus in modular networks. METHODS: Resting-state functional magnetic resonance imaging scans were acquired from 53 TLE patients and 37 matched healthy controls. All patients received the Montreal Cognitive Assessment test and accordingly were divided into TLE patients with normal cognition (TLE-CN, n = 35) and TLE patients with cognitive impairment (TLE-CI, n = 18) groups. The modular properties of functional networks were calculated and compared including global modularity Q, modular segregation index, intramodular connections, and intermodular connections. Thalamic subdivisions corresponding to the modular networks were generated by applying a 'winner-take-all' strategy before analyzing the modular properties (participation coefficient and within-module degree z-score) of each thalamic subdivision to assess the contribution of the thalamus to modular functional networks. Relationships between network properties and cognitive performance were then further explored. RESULTS: Both TLE-CN and TLE-CI patients showed lower global modularity, as well as lower modular segregation index values for the ventral attention network and the default mode network. However, different patterns of intramodular and intermodular connections existed for different cognitive states. In addition, both TLE-CN and TLE-CI patients exhibited anomalous modular properties of functional thalamic subdivisions, with TLE-CI patients presenting a broader range of abnormalities. Cognitive performance in TLE-CI patients was not related to the modular properties of functional network but rather to the modular properties of functional thalamic subdivisions. CONCLUSIONS: The thalamus plays a prominent role in modular networks and potentially represents a key neural mechanism underlying cognitive impairment in TLE.

Neuropsychological features of mind wandering in left-, right- and extra temporal lobe epilepsy.

PURPOSE: Mind wandering, i.e. mental time-travelling and imagery unrelated to the current situation has recently been related to mesial temporal lobe (memory) function. In this regard we evaluated as to whether parameters of mind wandering are related to material specific memory in patients with a left-, right-, or extra- temporal lobe epilepsy. METHODS: In this prospective controlled study we analyzed mind wandering, material specific memory, and executive functions in 29 right-handed patients with right-, left-, or extra-temporal lobe epilepsies. Mind wandering was assessed with a sustained attention to response task containing embedded inquiries on mind wandering. In addition, verbal list learning and memory (VLMT), design list learning (DCS-R), and executive function (EpiTrack) were assessed. RESULTS: In patients with right temporal lobe epilepsy, the propensity to mind wander was positively related to verbal memory performance, while in left temporal lobe epilepsy, the propensity and future related mind wandering were positively correlated to the performance in visual/figural memory. Generally, the propensity of MW was related to executive function as well. CONCLUSION: The results suggest that mind wandering in lateralized temporal lobe epilepsy appears to be non-specifically driven by executive function and specifically by the mode and functionality of the memory system of the non-epileptic hemisphere. Repeated assessments would be required to discern as to how much such patterns depend on lesions versus epileptic dysfunction and whether they change with successful medical or surgical treatment.

Acupuncture, seizure frequency, and quality of life in temporal lobe epilepsy.

OBJECTIVE: To assess seizure frequency and quality of life (QOL) in a group of adults with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) before and after 10 weeks of systemic acupuncture sessions and compare the results with a group of patients with TLE-HS not undergoing acupuncture. METHODS: The Quality of Life in Epilepsy Inventory (QOLIE-31) and the initial and final seizure frequency of 26 adult patients with TLE-HS who underwent acupuncture sessions for 10 consecutive weeks were assessed. The data were compared to those of 26 patients with TLE-HS not submitted to acupuncture, with p < 0.05. RESULTS: There was a clinically significant effect in reducing the mean number of seizures per month in the follow-up period of patients submitted or not to acupuncture (no intervention group and intervention group, effect size: -0.94 and -1.01, respectively). In the last four weeks of follow-up, there was a significant difference between the no intervention and intervention groups (0.5 [0-2] and 0 [0-4]; p = 0.018). When using minimally important change (MIC) threshold data for the QOLIE-31 between the final and initial scores, with the Cantril Ladder Scale as anchoring, it was observed that, in the intervention group, large clinically significant effects were seen for all dimensions, except for cognitive function, medication effect, and social function, which presented medium effects. In the follow-up, the variation of the QOLIE-31 scores was positive for both groups; however, it was higher in all dimensions in the intervention group, indicating a better QOL. CONCLUSION: There was a reduction in the mean number of seizures per month in all patients during the follow-up period. Acupuncture significantly reduced the number of seizures in the intervention group in the final phase of the study. QOL improvements occurred in all patients, however, more significantly in the intervention group.

People with mesial temporal lobe epilepsy have altered thalamo-occipital brain networks.

While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention and learning in TLE may be related to thalamic arousal nuclei connectivity. Our prior preliminary work in a smaller patient cohort suggests that patients with TLE demonstrate abnormal functional connectivity between central lateral (CL) thalamic nucleus and medial occipital lobe. Others have shown pulvinar connectivity disturbances in TLE, but it is incompletely understood how TLE affects pulvinar subnuclei. Also, the effects of epilepsy surgery on thalamic functional connectivity remains poorly understood. In this study, we examine the effects of TLE on functional connectivity of two key thalamic arousal-nuclei: lateral pulvinar (PuL) and CL. We evaluate resting-state functional connectivity of the PuL and CL in 40 patients with TLE and 40 controls using fMRI. In 25 patients, postoperative images (>1 year) were also compared with preoperative images. Compared to controls, patients with TLE exhibit loss of normal positive connectivity between PuL and lateral occipital lobe (p < 0.05), and a loss of normal negative connectivity between CL and medial occipital lobe (p < 0.01, paired t-tests). FMRI amplitude of low-frequency fluctuation (ALFF) in TLE trended higher in ipsilateral PuL (p = 0.06), but was lower in the lateral occipital (p < 0.01) and medial occipital lobe in patients versus controls (p < 0.05, paired t-tests). More abnormal ALFF in the ipsilateral lateral occipital lobe is associated with worse preoperative performance on Rey Complex Figure Test Immediate (p < 0.05, r = 0.381) and Delayed scores (p < 0.05, r = 0.413, Pearson's Correlations). After surgery, connectivity between PuL and lateral occipital lobe remains abnormal in patients (p < 0.01), but connectivity between CL and medial occipital lobe improves and is no longer different from control values (p > 0.05, ANOVA, post hoc Fischer's LSD). In conclusion, thalamic arousal nuclei exhibit abnormal connectivity with occipital lobe in TLE, and some connections may improve after surgery. Studying thalamic arousal centers may help explain distal network disturbances in TLE.

Radiosurgery versus open surgery for mesial temporal lobe epilepsy: The randomized, controlled ROSE trial.

OBJECTIVE: To compare stereotactic radiosurgery (SRS) versus anterior temporal lobectomy (ATL) for patients with pharmacoresistant unilateral mesial temporal lobe epilepsy (MTLE). METHODS: This randomized, single-blinded, controlled trial recruited adults eligible for open surgery among 14 centers in the USA, UK, and India. Treatment was either SRS at 24 Gy to the 50% isodose targeting mesial structures, or standardized ATL. Outcomes were seizure remission (absence of disabling seizures between 25 and 36 months), verbal memory (VM), and quality of life (QOL) at 36-month follow-up. RESULTS: A total of 58 patients (31 in SRS, 27 in ATL) were treated. Sixteen (52%) SRS and 21 (78%) ATL patients achieved seizure remission (difference between ATL and SRS = 26%, upper 1-sided 95% confidence interval = 46%, P value at the 15% noninferiority margin = .82). Mean VM changes from baseline for 21 English-speaking, dominant-hemisphere patients did not differ between groups; consistent worsening occurred in 36% of SRS and 57% of ATL patients. QOL improved with seizure remission. Adverse events were anticipated cerebral edema and related symptoms for some SRS patients, and cerebritis, subdural hematoma, and others for ATL patients. SIGNIFICANCE: These data suggest that ATL has an advantage over SRS in terms of proportion of seizure remission, and both SRS and ATL appear to have effectiveness and reasonable safety as treatments for MTLE. SRS is an alternative to ATL for patients with contraindications for or with reluctance to undergo open surgery.

The role of rosemary extract in degeneration of hippocampal neurons induced by kainic acid in the rat: A behavioral and histochemical approach.

Systemic Kainic Acid (KA) administration has been used to induce experimental temporal lobe epilepsy in rats. The aim of this study was to evaluate the neuroprotective effect of rosemary extract (RE, 40% Carnosic acid) against KA-induced neurotoxicity in hippocampus and impaired learning and memory. Animals received a single dose of KA (9.5 mg/kg) intraperitoneally (i.p.) (KA group) and were observed for 2 h and were scored from 0 (for normal, no convulsion) to 5 (for continuous generalized limbic seizures). RE (100 mg/kg, orally) was administered daily for 23 days, starting a week before KA injection (KA+RE group). Neuronal degeneration in hippocampus was demonstrated by using Fluoro-Jade B immunofluorescence. The number of pyramidal cells in hippocampus was evaluated by Nissl staining. Also, the Morris Water Maze and Shuttle box have been used to assess spatial memory and passive avoidance learning, respectively. Our results revealed that, after treatment with RE, neuronal loss in CA1 decreased significantly in the animals in KA+RE group. The Morris water navigation task results revealed that spatial memory impairment decreased in the animals in KA+RE group. Furthermore, results in Shuttle box test showed that passive avoidance learning impairment significantly, upgraded in the animals in KA+RE group. These results suggest that RE may improve the spatial and working memory deficits and also neuronal degeneration induced by toxicity of KA in the rat hippocampus, due to its antioxidant activities.

Effective connectivity in temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: We hypothesized that temporal lobe epilepsy (TLE) patients with and without hippocampal sclerosis (HS) showed differences in their limbic networks. This study aimed to evaluate the role of the thalamus in TLE patients with HS. MATERIALS AND METHODS: Twenty-nine TLE patients with HS and 30 controls were enrolled in this study. In addition, we included eight TLE patients without HS as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the limbic structures, including the hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. Moreover, we quantified correlations between epilepsy duration and the volumes of these structures. RESULTS: There was a statistically significant effective connectivity from the hippocampus to the thalamus in TLE patients with HS. Moreover, the volumes of the left and right thalamus were negatively correlated with epilepsy duration (r=-.42, P=.0315 and r=-.52, P=.0062, respectively). However, neither TLE patients without HS nor normal controls had a significant effective connectivity from the hippocampus to the thalamus. CONCLUSIONS: The limbic networks of TLE patients with and without HS could be different, and the thalamus might play a critical role in TLE patients with HS.

[Resting-state functional magnetic resonance study of the brain's network of the temporal lobe epilepsy patients with depression].

OBJECTIVE: To study brain networks of temporal lobe epilepsy (TLE) to investigate whether TLE brain dysfunction have an impact on depression, using resting state functional magnetic resonance (RS-fMRI) detection technology. METHODS: A total of 18 patients with TLE were included in this study. According to Beck Depression Inventory (BDI) and Hamilton's Depression Scale (HAMD)-17 score, we divided them into two groups: depression group 9 cases, non-depression group 9 cases. All patients underwent 3.0T MRI , RS-fMRI and magnetic resonance spectroscopy (MRS) examinations and then the results were analyzed. RESULTS: Disease course of depression group was longer than non-depression group and the difference was statistically significant (P<0.05). RS-fMRI examination showed that depression group had more active brain areas and more extral temporal active areas than non-depression group (P<0.05). By compared with the non-depression group, we found more strong active brain areas including thalamus, and the default-mode network which involved in prefrontal cortex, precuneus, ventral anterior cingulate and hippocampus. We found the NAA and NAA/Cho+ Cr of the hippocampus which were ipsilateral to the advantage discharge side were decreased in 5/9 cases with depression in MRS and 3/5 cases had hippocampal atrophy, while the non-depression group had no obvious abnormalities. CONCLUSION: The brain default-mode network activity in TLE patients with depression is increased and there is more extral temporal activation than the non-depression group; furthermore abnormal hippocampus structure is more common in depression group, which suggests that epileptic brain dysfunction may affect the development of depression.

Characterization and prediction of the recognition of emotional faces and emotional bursts in temporal lobe epilepsy.

INTRODUCTION: The present study sought to characterize and predict the recognition of emotional stimuli (presented in a visual or auditory modality) by patients with temporal lobe epilepsy (TLE). METHOD: Fifty TLE patients and 50 matched controls performed two emotion recognition tasks (emotional faces and emotional bursts). Neutral stimuli were also presented, and emotional biases were monitored by analyzing errors. Demographic, cognitive, psychobehavioral and (in TLE patients only) clinical and quality of life data were also recorded. RESULTS: Compared with controls, TLE patients were impaired in the recognition of fear expressions in both visual and auditory modality tasks. However, impairments in the two channels were not always concomitant on the individual level. In the visual modality, recognition of disgust and neutral expressions was significantly worse in TLE patients. In the auditory modality, nonsignificant trends toward poor recognition of disgust and neutral expressions were observed. Negative biases were noted in TLE patients; expressions of fear (faces and bursts) were more frequently misinterpreted as disgust, and neutral facial expressions were more frequently misinterpreted as sadness. Impairments in the recognition of facial fear were less pronounced in left TLE patients who (according to structural magnetic resonance imaging, MRI) did not have any brain lesions. In TLE patients, low levels of social support (a quality of life parameter) were associated with worse recognition of facial disgust, and higher levels of apathy were associated with better recognition of neutral faces. CONCLUSIONS: TLE patients are impaired in some aspects of emotion recognition with both visual and auditory stimuli, although the differential impact of TLE on these modalities requires further research. These emotional impairments are related to quality of life and psychobehavioral parameters.

Thalamotemporal alteration and postoperative seizures in temporal lobe epilepsy.

OBJECTIVE: There are competing explanations for persistent postoperative seizures after temporal lobe surgery. One is that 1 or more particular subtypes of mesial temporal lobe epilepsy (mTLE) exist that are particularly resistant to surgery. We sought to identify a common brain structural and connectivity alteration in patients with persistent postoperative seizures using preoperative quantitative magnetic resonance imaging and diffusion tensor imaging (DTI). METHODS: We performed a series of studies in 87 patients with mTLE (47 subsequently rendered seizure free, 40 who continued to experience postoperative seizures) and 80 healthy controls. We investigated the relationship between imaging variables and postoperative seizure outcome. All patients had unilateral temporal lobe seizure onset, had ipsilateral hippocampal sclerosis as the only brain lesion, and underwent amygdalohippocampectomy. RESULTS: Quantitative imaging factors found not to be significantly associated with persistent seizures were volumes of ipsilateral and contralateral mesial temporal lobe structures, generalized brain atrophy, and extent of resection. There were nonsignificant trends for larger amygdala and entorhinal resections to be associated with improved outcome. However, patients with persistent seizures had significant atrophy of bilateral dorsomedial and pulvinar thalamic regions, and significant alterations of DTI-derived thalamotemporal probabilistic paths bilaterally relative to those patients rendered seizure free and controls, even when corrected for extent of mesial temporal lobe resection. INTERPRETATION: Patients with bihemispheric alterations of thalamotemporal structural networks may represent a subtype of mTLE that is resistant to temporal lobe surgery. Increasingly sensitive multimodal imaging techniques should endeavor to transform these group-based findings to individualize prediction of patient outcomes.

Cognitive rehabilitation in epilepsy: An evidence-based review.

AIM OF THE STUDY: To review the modalities of cognitive rehabilitation (CR), outcome endpoints, and the levels of evidence of efficacy of different interventions. METHODS: A systematic research in Pubmed, Psychinfo, and SCOPUS was performed assessing the articles written in the entire period covered by these databases till December 2013. Articles in English, Spanish or French were evaluated. A manual research evaluated the references of all of the articles. The experimental studies were classified according to the level of evidence of efficacy, using a standardized Italian method (SPREAD, 2007), adopting the criteria reported by Cicerone et al. (2000, 2011). RESULTS: Eighteen papers were classified into two reviews, four papers dealing with the principles and efficacy of CR in epilepsy, a methodological paper, a single-case report, a multiple-case report, and nine experimental papers. Most studies involved patients with temporal lobe epilepsy. Different types of CR were used to treat patients with epilepsy. A holistic rehabilitation approach was more useful than selective interventions to treat memory and attention disturbances. CONCLUSIONS: CR may be a useful tool to treat cognitive impairment in patients with epilepsy. However, the modalities of treatment and outcome endpoints are important concerns of clinical care and research. Controlled studies are needed to determine the efficacy of rehabilitation in well-defined groups of patients with epilepsy.

[Successful treatment with anti-epileptic-drug of an 83-year-old man with musical hallucinosis].

An 83-year-old man with 3 years symptomatic hearing loss suddenly experienced musical hallucinosis. He heard children's songs, folk songs, military songs, and the Japanese national anthem for seven months every day. He sometime had paroxysmal nausea, dull headaches and depressive mood. On examination he had no psychosis or neurological symptoms except sensorineural hearing loss in both ears. MRI brain imaging and electroencephalography showed no significant abnormalities, however 123I-IMP brain SPECT showed decreased activity in the right temporal lobe and increased activity in the left temporal and parietal lobes. Late phase 123I-iomazenil brain SPECT showed decreased accumulation in the right temporal lobe compared to the early phase. This indicates right temporal lobe epilepsy. He was diagnosed with epilepsy because of paroxysmal nausea and headache and the laterality of 123I-IMP brain SPECT and 123I-iomazenil brain SPECT. The musical hallucinosis was much reduced by carbamazepine 200mg per day. Nine months after beginning carbamazepine we detected decreased activity in the right temporal lobe and increased activity in left temporal and parietal lobes was improved. We do not believe he had epileptogenic musical hallucinosis because his musical hallusinosis was neither paroxysmal nor lateral. We diagnosed auditory Charles Bonnet syndrome with onset 3 years after sensorineural hearing loss due to reversible epileptic like discharge in temporal and parietal lobes. There is no established treatment for musical hallucinosis, but anti-epileptic drugs may be of some help.

Temporal and spatial increase of reactive nitrogen species in the kainate model of temporal lobe epilepsy.

Steady-state levels of reactive oxygen species (ROS) and oxidative damage to cellular macromolecules are increased in the rodent hippocampus during epileptogenesis. However, the role of reactive nitrogen species (RNS) in epileptogenesis remains to be explored. The goal of this study was to determine the spatial and temporal occurrence of RNS i.e. nitric oxide levels in a rat model of temporal lobe epilepsy (TLE). Rats were injected with a single high dose of kainate and monitored by video for behavioral seizures for 6weeks to determine the onset and severity of chronic seizures. RNS and tissue/mitochondrial redox status (glutathione redox couple and coenzyme A:glutathione redox couple) were measured in the hippocampus at 8h, 24h, 48h, 1wk, 3wk and 6wk following kainate to assess the level of reactive species in subcellular compartments. We observed a biphasic increase in RNS levels with a return to control values at the 48h time point. However, both tissue and mitochondrial redox status showed permanent and significant decreases during the entire time course of epilepsy development. 3 nitrotyrosine (3NT) protein adducts were found to gradually increase throughout epileptogenesis, conceivably as a result of the local environment under oxidative and nitrosative stress. Colocalization of 3NT immunostaining with neuron- or astrocyte-specific markers revealed neuron-specific localization of 3NT in hippocampal principal neurons. Persistent and concurrent glutathione oxidation and nitrosative stress occur during epileptogenesis suggesting a favorable environment for posttranslational modifications.

Impaired motor learning attributed to altered AMPA receptor function in the cerebellum of rats with temporal lobe epilepsy: ameliorating effects of Withania somnifera and withanolide A.

The aim of this study was to investigate the effect of Withania somnifera (WS) extract, withanolide A (WA), and carbamazepine (CBZ) on cerebellar AMPA receptor function in pilocarpine-induced temporal lobe epilepsy (TLE). In the present study, motor learning deficit was studied by rotarod test, grid walk test, and narrow beam test. Motor learning was significantly impaired in rats with epilepsy. The treatment with WS and WA significantly reversed the motor learning deficit in rats with epilepsy when compared with control rats. There was an increase in glutamate content and IP3 content observed in rats with epilepsy which was reversed in WS- and WA-treated rats with epilepsy. alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor dysfunction was analyzed using radiolabeled AMPA receptor binding assay, AMPA receptor mRNA expression, and immunohistochemistry using anti-AMPA receptor antibody. Our results suggest that there was a decrease in Bmax, mRNA expression, and AMPA receptor expression indicating AMPA receptor dysfunction, which is suggested to have contributed to the motor learning deficit observed in rats with epilepsy. Moreover, treatment with WS and WA resulted in physiological expression of AMPA receptors. There was also alteration in GAD and GLAST expression which supplemented the increase in extracellular glutamate. The treatment with WS and WA reversed the GAD and GLAST expression. These findings suggest that WS and WA regulate AMPA receptor function in the cerebellum of rats with TLE, which has therapeutic application in epilepsy.

A retrospective diagnosis of epilepsy in three historical figures: St Paul, Joan of Arc and Socrates.

It has been suggested that undiagnosed epilepsy profoundly influenced the lives of several key figures in history. Historical sources recounting strange voices and visions may in fact have been describing manifestations of epileptic seizures rather than more supernatural phenomena. Well-documented accounts of such experiences exist for three individuals in particular: Socrates, St Paul and Joan of Arc. The great philosopher Socrates described a 'daimonion' that would visit him throughout his life. This daimonion may have represented recurrent simple partial seizures, while the peculiar periods of motionlessness for which Socrates was well known may have been the result of co-existing complex partial seizures. St Paul's religious conversion on the Road to Damascus may have followed a temporal lobe seizure which would account for the lights, voices, blindness and even the religious ecstasy he described. Finally, Joan of Arc gave a detailed narrative on the voices she heard from childhood during her Trial of Condemnation. Her auditory hallucinations appear to follow sudden acoustic stimuli in a way reminiscent of idiopathic partial epilepsy with auditory features. By analysing passages from historical texts, it is possible to argue that Socrates, St Paul and Joan of Arc each had epilepsy.

Concomitant fractional anisotropy and volumetric abnormalities in temporal lobe epilepsy: cross-sectional evidence for progressive neurologic injury.

BACKGROUND: In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI). METHODOLOGY/PRINCIPAL FINDINGS: For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures. CONCLUSIONS/SIGNIFICANCE: Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients.

Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) is a common form of focal epilepsy. Serum biomarkers to predict cognitive performance in TLE patients without psychiatric comorbidities and the link with gray matter (GM) atrophy have not been fully explored. METHODS: Thirty-four patients with TLE and 34 sex - and age-matched controls were enrolled for standardized cognitive tests, neuroimaging studies as well as measurements of serum levels of heat shock protein 70 (HSP70), S100ß protein (S100ßP), neuronal specific enolase (NSE), plasma nuclear and mitochondrial DNA levels. RESULTS: Compared with the controls, the patients with TLE had poorer cognitive performances and higher HSP70 and S100ßP levels (p < 0.01). The patients with higher frequencies of seizures had higher levels of HSP70, NSE and S100ßP (p < 0.01). Serum HSP70 level correlated positively with duration of epilepsy (σ = 0.413, p < 0.01), and inversely with memory scores in the late registration (σ = -0.276, p = 0.01) and early recall score (σ = -0.304, p = 0.007). Compared with the controls, gray matter atrophy in the hippocampal and parahippocampal areas, putamen, thalamus and supplementary motor areas were found in the patient group. The HSP70 levels showed an inverse correlation with hippocampal volume (R square = 0.22, p = 0.007) after controlling for the effect of age. CONCLUSIONS: Our results suggest that serum biomarkers were predictive of higher frequencies of seizures in the TLE group. HSP70 may be considered to be a stress biomarker in patients with TLE in that it correlated inversely with memory scores and hippocampal volume. In addition, the symmetric extratemporal atrophic patterns may be related to damage of neuronal networks and epileptogenesis in TLE.

Mapping thalamocortical network pathology in temporal lobe epilepsy.

OBJECTIVE: Although experimental work has provided evidence that the thalamus is a crucial relay structure in temporal lobe epilepsy (TLE), the relation of the thalamus to neocortical pathology remains unclear. To assess thalamocortical network pathology in TLE, we mapped pointwise patterns of thalamic atrophy and statistically related them to neocortical thinning. METHODS: We studied cross-sectionally 36 patients with drug-resistant TLE and 19 age- and sex-matched healthy control subjects using high-resolution MRI. To localize thalamic pathology, we converted manual labels into surface meshes using the spherical harmonic description and calculated local deformations relative to a template. In addition, we measured cortical thickness by means of the constrained Laplacian anatomic segmentation using proximity algorithm. RESULTS: Compared with control subjects, patients with TLE showed ipsilateral thalamic atrophy that was located along the medial surface, encompassing anterior, medial, and posterior divisions. Unbiased analysis correlating the degree of medial thalamic atrophy with cortical thickness measurements mapped bilateral frontocentral, lateral temporal, and mesiotemporal cortices. These areas overlapped with those of cortical thinning found when patients were compared with control subjects. Thalamic atrophy intensified with a longer duration of epilepsy and was more severe in patients with a history of febrile convulsions. CONCLUSION: The degree and distribution of thalamic pathology relates to the topography and extent of neocortical atrophy, lending support to the concept that the thalamus is an important hub in the pathologic network of TLE.

Central auditory processing impairment in patients with temporal lobe epilepsy.

In temporal lobe epilepsy (TLE) there may be functional abnormalities or structural lesions that can manifest as a central auditory processing disorder, which is defined as a disorder in the recognition, discrimination, ordering, grouping, and localization of sounds, with emphasis on the processing of nonspeech sounds. We performed frequency pattern, duration pattern, and dichotic tests in 28 patients with TLE with normal hearing on pure tone audiometry. The scores on the frequency pattern, duration pattern, and dichotic tests were abnormal in 78.6, 57.1, and 20.6% of patients, respectively, with no significant differences with the laterality of TLE. Patients with hippocampal sclerosis performed significantly worse than patients with normal MRI findings in frequency tests. Longer duration of epilepsy is negatively correlated with both the duration pattern and dichotic tests (P<0.05). Our results suggest that patients with TLE may be at risk for impairment of central auditory processing, which is increased in patients with hippocampal sclerosis or a longer duration of epilepsy.