Late-onset Temporal Lobe Epilepsy Research Articles

Gut microbiome diversity in a febrile seizure mouse model.

Febrile seizures at a young age can provoke late-onset temporal lobe epilepsy. Since recent evidence has suggested that the gut microbiome affects central nervous system pathology across the blood-brain barrier, we hypothesized that febrile seizures alter the composition of the gut microbiome to provoke epilepsy. Third-generation C57BL/6 mice were separated into two groups (n = 5 each), and hot air was applied to only one group to cause febrile seizures. After two weeks of heat challenge, the fecal pellets acquired from each group were analyzed. The gut microbiota of fecal pellets from each group revealed five taxa at the genus level and eight taxa at the species level that were significantly different in proportion between the groups. Although there was no significant difference in the overall diversity of the gut microbiota between the two groups, the identified heterogeneity may imply the pathognomonic causative relevance of febrile seizures and the development of epilepsy.

Cognitive dysfunction in drug-naïve late-onset temporal lobe epilepsy

ObjectivesTo evaluate cognitive functions including memory in middle-aged and elderly patients with antiseizure drug-naïve late-onset temporal lobe epilepsy (TLE). MethodsWe performed assessments with the Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-Revised (WMS-R) in 26 antiseizure drug-naïve patients with late-onset TLE, in comparison to 30 healthy subjects. We investigated the relationships between these cognitive function scores and clinical characteristics, seizure frequency, and frequency of interictal epileptic discharges (IEDs). ResultsPatients with epilepsy had a significantly lower score than healthy controls in the verbal intelligence quotient (IQ), the performance IQ, and full-scale IQ in intelligence testing. Patients showed significantly decrease in the verbal memory scores, visual memory scores, general memory scores, and delayed recall scores compared with those in the control subjects.Delayed recall scores were significantly negatively correlated with recent seizure frequency and the total IEDs count per minute, but not with age of onset or duration of illness. SignificancePatients with antiseizure drug-naïve late-onset TLE displayed cognitive deficits including the domains of memory by using standard clinical neuropsychological test.Patients with late-onset epilepsy need to be considered for cognitive dysfunction at the time of diagnosis of TLE because they may have their daily life and work affected not only by epileptic seizures but also by cognitive deficits. Appearance of seizures and EEG abnormalities may affect the memory function in patients with late-onset TLE.

Heart rate variability modifications in adult patients with early versus late-onset temporal lobe epilepsy: A comparative observational study

ObjectivesTemporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy. TLE is associated with cardio-autonomic dysfunction and increased cardiovascular (CV) risk in patients over the fifth decade of age. In these subjects, TLE can be classified as early-onset (EOTLE; i.e., patients who had developed epilepsy in their youth) and late-onset (LOTLE; i.e., patients who developed epilepsy in adulthood). Heart rate variability (HRV) analysis is useful for assessing cardio-autonomic function and identifying patients with increased CV risk. This study compared changes in HRV occurring in patients over the age of 50, with EOTLE or LOTLE. MethodsWe enrolled twenty-seven adults with LOTLE and 23 with EOTLE. Each patient underwent a EEG and EKG recording during 20-minutes of resting state and a 5-minutes hyperventilation (HV). Short-term HRV analysis was performed both in time and frequency domains. Linear Mixed Models (LMM) were used to analyze HRV parameters according to the condition (baseline and HV) and group (LOTLE and EOTLE groups). ResultsCompared to the LOTLE group, the EOTLE group showed significantly decreased LnRMSSD (natural logarithm of the root mean square of the difference between contiguous RR intervals) (p-value=0.05), LnHF ms2 (natural logarithm of high frequency absolute power) (p-value=0.05), HF n.u. (high frequency power expressed in normalized units) (p-value=0.008) and HF% (high frequency power expressed in percentage) (p-value=0.01). In addition, EOTLE patients exhibited increased LF n.u. (low frequency power expressed in normalized units) (p-value=0.008) and LF/HF (low frequency/high frequency) ratio (p-value=0.007). During HV, the LOTLE group exhibited a multiplicative effect for the interaction between group and condition with increased LF n.u. (p = 0.003) and LF% (low frequency expressed in percentage) (p = 0.05) values. ConclusionsEOTLE is associated with reduced vagal tone compared to LOTLE. Patients with EOTLE may have a higher risk of developing cardiac dysfunction or cardiac arrhythmia than LOTLE patients.

Volumetric and shape analysis of the hippocampus in temporal lobe epilepsy with GAD65 antibodies compared with non-immune epilepsy

Glutamic acid decarboxylase 65 antibodies (anti-GAD65) have been found in patients with late-onset chronic temporal lobe epilepsy (TLE). No prior neuroimaging studies have addressed how they affect hippocampal volume and shape and how they relate to cognitive abnormalities. We aimed to investigate both brain structure and function in patients with isolated TLE and high anti-GAD65 levels (RIA ≥ 2000 U/ml) compared to 8 non-immune mesial TLE (niTLE) and 8 healthy controls (HC). Hippocampal subfield volume properties were correlated with the duration of the disease and cognitive test scores. The affected hippocampus of GAD-TLE patients showed no volume changes to matched HC whereas niTLE volumes were significantly smaller. Epilepsy duration in GAD-TLE patients correlated negatively with volumes in the presubiculum, subiculum, CA1, CA2–3, CA4, molecular layer and granule cell-molecular layer of the dentate nucleus. We found differences by advanced vertex-wise shape analysis in the anterior hippocampus of the left GAD-TLE compared to HC whereas left niTLE showed bilateral posterior hippocampus deformation. Verbal deficits were similar in GAD-TLE and niTLE but did not correlate to volume changes. These data might suggest a distinct expression of hippocampal structural and functional abnormalities based on the immune response.

Atrophy and cognitive profiles in older adults with temporal lobe epilepsy are similar to mild cognitive impairment.

Epilepsy incidence and prevalence peaks in older adults yet systematic studies of brain ageing and cognition in older adults with epilepsy remain limited. Here, we characterize patterns of cortical atrophy and cognitive impairment in 73 older adults with temporal lobe epilepsy (>55 years) and compare these patterns to those observed in 70 healthy controls and 79 patients with amnestic mild cognitive impairment, the prodromal stage of Alzheimer's disease. Patients with temporal lobe epilepsy were recruited from four tertiary epilepsy surgical centres; amnestic mild cognitive impairment and control subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Whole brain and region of interest analyses were conducted between patient groups and controls, as well as between temporal lobe epilepsy patients with early-onset (age of onset <50 years) and late-onset (>50 years) seizures. Older adults with temporal lobe epilepsy demonstrated a similar pattern and magnitude of medial temporal lobe atrophy to amnestic mild cognitive impairment. Region of interest analyses revealed pronounced medial temporal lobe thinning in both patient groups in bilateral entorhinal, temporal pole, and fusiform regions (all P < 0.05). Patients with temporal lobe epilepsy demonstrated thinner left entorhinal cortex compared to amnestic mild cognitive impairment (P = 0.02). Patients with late-onset temporal lobe epilepsy had a more consistent pattern of cortical thinning than patients with early-onset epilepsy, demonstrating decreased cortical thickness extending into the bilateral fusiform (both P < 0.01). Both temporal lobe epilepsy and amnestic mild cognitive impairment groups showed significant memory and language impairment relative to healthy control subjects. However, despite similar performances in language and memory encoding, patients with amnestic mild cognitive impairment demonstrated poorer delayed memory performances relative to both early and late-onset temporal lobe epilepsy. Medial temporal lobe atrophy and cognitive impairment overlap between older adults with temporal lobe epilepsy and amnestic mild cognitive impairment highlights the risks of growing old with epilepsy. Concerns regarding accelerated ageing and Alzheimer's disease co-morbidity in older adults with temporal lobe epilepsy suggests an urgent need for translational research aimed at identifying common mechanisms and/or targeting symptoms shared across a broad neurological disease spectrum.

CASPR2 antibody encephalitis presenting as transient epileptic amnesia

Transient epileptic amnesia (TEA) is an underrecognized form of late-onset temporal lobe epilepsy, generally occurring between the ages of 50 and 70, and manifesting as ictal episodes of transient amnesia, either retro- and/or anterograde, of variable duration. The episodes are mostly short (≤ 1 h), but can last for hours and thereby mimic benign transient global amnesia (TGA) [1]. In addition to episodic amnesia, the diagnosis of TEA may be suggested by complaints of interictal cognitive problems.

Emotional Processing in Patients With Early- and Late-Onset Temporal Lobe Epilepsy

ObjectiveTemporal Lobe Epilepsy (TLE) could cause various emotional symptoms due to the damages imposed on the temporal lobe. This study aimed at comparing emotional processing between patients with early- and late-onset TLE and a healthy group.MethodsIn a cross-sectional study, after a definitive diagnosis of TLE, 60 patients were compared with 60 healthy controls without any epilepsy to identify emotional-processing styles in them. The research instruments were the Emotional Processing Scale and the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)-based psychiatric interview. The obtained data were analyzed using a multivariate analysis of variance by SPSS.ResultsThe present study results suggested significant differences in emotional processing between the investigated epileptic and non-epileptic groups (P<0.01). Besides, emotional processing indicated significant differences in intrusion, the lack of attunement, and dissociation subscales between patients with early-onset TLE, compared to those with late-onset TLE.ConclusionThe obtained data revealed more emotional processing dysfunction in patients affected by TLE, compared to the non-epileptics. Besides, in some subscales of emotional processing, there was more malfunctioning in the early-onset TLE group, compared to the late-onset TLE group.

Brain morphological and microstructural features in cryptogenic late-onset temporal lobe epilepsy: a structural and diffusion MRI study.

Although epilepsy in the elderly has attracted attention recently, there are few systematic studies of neuroimaging in such patients. In this study, we used structural MRI and diffusion tensor imaging (DTI) to investigate the morphological and microstructural features of the brain in late-onset temporal lobe epilepsy (TLE). We recruited patients with TLE and an age of onset > 50years (late-TLE group) and age- and sex-matched healthy volunteers (control group). 3-Tesla MRI scans, including 3D T1-weighted images and 15-direction DTI, showed normal findings on visual assessment in both groups. We used Statistical Parametric Mapping 12 (SPM12) for gray and white matter structural normalization and comparison and used Tract-Based Spatial Statistics (TBSS) for fractional anisotropy and mean diffusivity comparisons of DTI. In both methods, p< 0.05 (family-wise error) was considered statistically significant. In total, 30 patients with late-onset TLE (mean ± SD age, 66.8 ± 8.4; mean ± SD age of onset, 63.0 ± 7.6years) and 40 healthy controls (mean ± SD age, 66.6 ± 8.5years) were enrolled. The late-onset TLE group showed significant gray matter volume increases in the bilateral amygdala and anterior hippocampus and significantly reduced mean diffusivity in the left temporofrontal lobe, internal capsule, and brainstem. No significant changes were evident in white matter volume or fractional anisotropy. Our findings may reflect some characteristics or mechanisms of cryptogenic TLE in the elderly, such as inflammatory processes.

Language treatment prior to anterior temporal lobe surgery: Can naming skills be preserved?

Epilepsy affects 1% of the general population and is highly prevalent among Veterans. The purpose of this phase I study was to investigate a presurgical linguistically distributed language treatment program that could potentially diminish effects of proper-name retrieval deficits following left anterior temporal lobe resection for intractable epilepsy. A single-subject multiple-baseline design was employed for three individuals with late-onset chronic left temporal lobe epilepsy. Word retrieval treatment was administered prior to anterior temporal lobe resection. The primary outcome measure was confrontation naming of proper nouns. Immediately posttreatment (before surgery), there was a positive effect for all trained stimuli in the form of improved naming as compared with pretreatment. In addition, trained stimuli were found to be better after surgery than they were at pretreatment baseline, which would not be expected had language treatment not been provided. This series of case studies introduces two fundamentally novel concept: that commonly occurring deficits associated with left temporal lobe epilepsy can be treated despite the presence of damaged neural tissue and that providing this treatment prior to surgery can lead to better preservation of language function after surgery than would be expected if the treatment were not provided.

Community structure analysis of transcriptional networks reveals distinct molecular pathways for early- and late-onset temporal lobe epilepsy with childhood febrile seizures.

Age at epilepsy onset has a broad impact on brain plasticity and epilepsy pathomechanisms. Prolonged febrile seizures in early childhood (FS) constitute an initial precipitating insult (IPI) commonly associated with mesial temporal lobe epilepsy (MTLE). FS-MTLE patients may have early disease onset, i.e. just after the IPI, in early childhood, or late-onset, ranging from mid-adolescence to early adult life. The mechanisms governing early (E) or late (L) disease onset are largely unknown. In order to unveil the molecular pathways underlying E and L subtypes of FS-MTLE we investigated global gene expression in hippocampal CA3 explants of FS-MTLE patients submitted to hippocampectomy. Gene coexpression networks (GCNs) were obtained for the E and L patient groups. A network-based approach for GCN analysis was employed allowing: i) the visualization and analysis of differentially expressed (DE) and complete (CO) - all valid GO annotated transcripts - GCNs for the E and L groups; ii) the study of interactions between all the system’s constituents based on community detection and coarse-grained community structure methods. We found that the E-DE communities with strongest connection weights harbor highly connected genes mainly related to neural excitability and febrile seizures, whereas in L-DE communities these genes are not only involved in network excitability but also playing roles in other epilepsy-related processes. Inversely, in E-CO the strongly connected communities are related to compensatory pathways (seizure inhibition, neuronal survival and responses to stress conditions) while in L-CO these communities harbor several genes related to pro-epileptic effects, seizure-related mechanisms and vulnerability to epilepsy. These results fit the concept, based on fMRI and behavioral studies, that early onset epilepsies, although impacting more severely the hippocampus, are associated to compensatory mechanisms, while in late MTLE development the brain is less able to generate adaptive mechanisms, what has implications for epilepsy management and drug discovery.

Antithyroid antibodies as a potential marker of autoimmune-mediated late onset temporal lobe epilepsy

In one third of patients with epilepsy starting in adulthood the aetiology remains undetermined. Some patients with late onset temporal lobe epilepsy (TLE) together with memory decline have elevated antithyroid antibodies. PurposeTo compare the prevalence of antithyroid antibodies (aTR-ab) in adult onset temporal lobe epilepsy (TLE) patients with known and unknown TLE aetiology (N=42). Moreover, the sera of these patients was also assayed for antinuclear antibodies (ANA), anticardiolipin antibodies (ACL), anti glutamic acid decarboxylase antibodies (GAD) and antiglidadin antibodies. ResultsPositive aTR-ab in the sera of patients with unknown aetiology was 11/23 (47.8%) vs. 1/19 (4.3%) in the group with known aetiology (p=0.005). In 9/11 (81%) a pre-existing autoimmune disease was confirmed. Nine (81%) were women and five (45%) had memory impairment. There were 5/11 (45%) pharmacoresistant patients, and corticosteroid treatment was initiated in 3/5 with cognitive and seizure improvement. The results of other immunological tests were only remarkable for antiGAD antibodies with 3/11 (27%) positive patients, but this subgroup does not have any significant clinical differential feature. ConclusionsLate-onset TLE with positive aTR-ab tends to be middle-aged women with nonpharmacoresistant cryptogenic epilepsy plus cognitive decline and other associated autoimmune diseases. It could be advisable to test aTR-ab in TLE patients with an unknown aetiology, in order to improve diagnosis and resulting treatment.

Epileptic Amnesic Syndrome revealing Alzheimer's disease

To describe the aetiology of a particular form of late-onset temporal lobe epilepsy (TLE) - the Epileptic Amnesic Syndrome (EAS) - that can be responsible for cognitive decline. The syndrome is considered as a reversible cause of memory disturbances, but some patients remain unrelieved despite anticonvulsants. 4 case-reports and a brief discussion. University Hospital. 4 patients fulfilling the diagnosis criteria of EAS but for whom a progressive causative disease was suspected because they still complained from their memory after antiepileptic treatment. All patients had characteristics suggesting Alzheimer's disease. Memory disturbances were systematically combined with other non-episodic cognitive impairments. CSF biomarkers were compatible with AD pathological changes. Moreover, brain MRI showed temporal lobe atrophy and neurological examination showed subtle abnormalities in all 4. AD should be kept in mind even though the patients meet the clinical criteria of EAS. This short series highlights the clinical characteristics that should be considered as "red-flags" in EAS patients because their presence makes the diagnosis of EAS improbable. In such a situation, particularly when cognitive improvement is lacking under treatment, a lumbar puncture is warranted.

Late-onset temporal lobe epilepsy with unilateral mesial temporal sclerosis and cognitive decline: A diagnostic dilemma

We present a patient with new onset temporal lobe epilepsy and cognitive decline in his sixth decade with unilateral hippocampal atrophy on structural brain imaging, compatible with mesial temporal sclerosis. This unusual clinical scenario presented a challenging differential diagnosis since it may overlap with primary cognitive disorders, including early-onset Alzheimer's disease and some forms of frontotemporal dementia, and the recently elucidated syndrome of non-paraneoplastic limbic encephalitis associated with voltage-gated potassium channel antibodies.

Ipsilateral Reorganization of Language in Early-Onset Left Temporal Lobe Epilepsy

Purpose. Decline in confrontation naming ability occurs in a subset of temporal lobe epilepsy (TLE) patients following left (dominant) anterior temporal lobectomy (ATL). Patients with late age of onset of seizures are most vulnerable to such decline. In addition, object names typically acquired later in language development are the words most likely to be inaccessible after ATL. Early-onset left TLE patients may be at lower risk for post-ATL dysnomia either because they have a limited preoperative lexicon that does not include most late-age-of-acquistion names or they undergo early ipsilateral language reorganization, which results in a lexicon similar to that of late-onset TLE patients but offers protection from post-ATL naming decline.Methods. Sixty-five left hemisphere speech dominant left TLE patients who had undergone ATL were assessed pre- and postoperatively on the Boston Naming Test (BNT).Results. The early- and late-onset groups performed similarly across three BNT age-of-acquisition categories at the preoperative assessment. Words acquired relatively later in life were most likely to become inaccessible postoperatively for both groups, but the early-onset patients showed significantly less overall postoperative decline in naming ability compared with the late-onset group.Conclusions. The more stable pre- to postoperative naming performance exhibited by early-onset patients cannot be attributed to lack of acquisition of the words shown to be most vulnerable to postoperative decline (i.e., late-age-of-acquisition words). Their object naming stability suggests that early-onset left TLE patients undergo intrahemispheric reorganization of language early in life that provides protective benefits.

Late Onset Temporal Lobe Epilepsy: Possible Etiology and Postsurgical Seizure Outcome

Purpose: Patients with temporal lobe epilepsy usually have initial seizures during childhood. Of 256 patients who underwent surgical resection of the temporal lobe, however, 55 (21%) had initial seizures at 16 years of age or older, We tentatively designated these 55 patients the late onset (LO) type. The purpose of this study was to examine the possible etiology and post‐surgical seizure outcome in LO patients compared to patients who had initial seizures at &gt;15 years of age (childhood onset: CO). Methods: Thirty‐four LO patients were inale and 21 were female. Age at seizure onset ranged from 16 to 4.5 years (mean 2 1.3 years). To obtain information on past illness, we retrospectively reviewed the clinical records of all the patients. Status epilepticus was defined as seizures lasting &gt;30 minutes with or without fever. Complex febrilc convulsions were defined according to Nelson. Prior to resection surgery, 30 of 55 LO patients underwent long‐term invasive EEG/video monitoring. Their age at surgery ranged from 17 to 55 years (mcan 33.2 years). Post‐surgical seizure outcome was compared between 46 LO patients and 141 CO patients who had been followed for &gt;2 years after surgery. Results: Thirty‐nine of 55 LO patients (7 I %) had no relevant past illness, but CT/MRI revealed localized lesions in 82% (32/39), comprising dysembryoplastic epithelial tumor (N = 17), focal cortical dysplasia (N = 3), cavernous angionia (N = 10). and arteriovenous malformation (N = 2). The remaining 16 patients had a history of head trauma (N = 6), CNS infection (N = 3), convulsive status (N = 4), complex febrile convulsions (N=I), or nephrosis (N=2). On the contrary, 101 of 201 CO patients (50%) had no relevant past illness, and CTiMRI revealed localized lesions in 44% (44/101), whereas 73 of 201 CO patients (36%) had a history of convulsive status or complex febrile convulsions. Thirty‐three (72%) of 46 LO patients were in Class I of Engel's outcome classification, although 5 of 8 patients with a history of head trauma or CNS infection were in Class I1 ‐ IV. On the contrary, I14 (81%) of 141 CO patients were in Class I, including 8 of 12 with a history of head trauma or CNS infection. Conclusions: I. Approximately 21 %I of patients who underwent surgical resection of the temporal lobe were late onset patients in whom initial seizures begin at 16 years of age or older. 2. Most of the LO patients had no relevant past illness but had localized lesions detected by CT or MRI. 3. The post‐surgical seizure outcome in LO patients was slightly worse than that in CO patients, although the difference was not statistically significant. 4. Surgical indication for LO patients with a history of head trauma or CNS infection should be carefully considered.

Developmental anterobasal temporal encephalocele and temporal lobe epilepsy

The authors describe the association between an antero-basal temporal lobe encephalocele and medically intractable temporal lobe epilepsy in three patients treated successfully by surgery. Two men and one woman, aged 26 to 37 years (mean 31 years), had onset of complex automatism and generalized seizures in their second and fourth decades (mean age 22.7 years). They had been epileptic for 6 to 14 years (mean 8.3 years) before surgery. Preoperative electroencephalograms localized ictal epileptic activity to the left mesial temporal lobe in all cases, and neuropsychological testing revealed dominant temporal lobe dysfunction. Magnetic resonance (MR) imaging demonstrated an anteromedial basal temporal encephalocele extending into the pterygopalatine fossa through a bone defect at the base of the greater sphenoid wing in the region of the foramen rotundum and pterygoid process, a discrete center of embryonal chondrification. At surgery, the encephaloceles were found in front of the uncus, and an area of gliosis extended from the encephalocele to the amygdalohippocampal region. All patients have been seizure-free following anterior temporal resection and amygdalohippocampectomy including the encephalocele. These three cases delineate a condition of disordered embryogenesis wherein a developmental anterobasal temporal encephalocele acts as the substrate for temporal lobe epilepsy. This lesion may be diagnosed preoperatively with MR imaging and should be considered in the differential diagnosis of late-onset temporal lobe epilepsy.