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Progressive inflammation of one hemisphere characterises Rasmussen's encephalitis (RE), but contralesional epileptiform activity has been repeatedly reported. We aimed to quantify contralesional epileptiform activity in RE and uncover its functional and structural underpinnings. We retrospectively ascertained people with RE treated between 2000 and 2018 at a tertiary centre (Centre 1) and reviewed all available EEG datasets. The temporal occurrence of preoperative contralesional epileptiform activity (interictal/ictal) was evaluated using mixed-effects logistic regression. Cases with/without contralesional epileptiform activity were compared for cognition, inflammation (ipsilesional brain biopsies), and MRI (cortical and fixel-based morphometry). EEG findings were validated in a second cohort treated at another tertiary centre (Centre 2) between 1995 and 2020. We included 127 people with RE and 687 EEG samples. Preoperatively, contralesional epileptiform activity was seen in 30/68 (44%, Centre 1) and 8/59 (14%, Centre 2). In both cohorts, this activity was associated with younger onset age (OR = 0.9; 95% CI 0.83-0.97; P = 0.006). At centre 1, contralesional epileptiform activity was associated with contralesional MRI alterations, lower intelligence (OR = 5.19; 95% CI 1.28-21.08; P = 0.021), and impaired verbal memory (OR = 10.29; 95% CI 1.97-53.85; P = 0.006). After hemispherotomy, 11/17 (65%, Centre 1) and 28/37 (76%, Centre 2) were seizure-free. Contralesional epileptiform activity was persistent postoperatively in 6/12 (50%, Centre 1) and 2/34 (6%, Centre 2). Preoperative contralesional epileptiform activity reduced the chance of postoperative seizure freedom in both cohorts (OR = 0.69; 95% CI 0.50-0.95; P = 0.029). Our findings question the concept of strict unilaterality of RE and provide the evidence of contralesional epileptiform activity as a possible EEG predictor for persisting postoperative seizures.
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OBJECTIVE: Screening for depression in people with epilepsy (PWE) is highly recommended in order to avoid underdiagnosis, misdiagnosis, or delayed diagnosis of this highly impacting comorbidity. Here we evaluated the impact of reporting and suggesting depression via the Beck Depression Inventory (BDI) on medical decision-making, and thereby the value of a depression screening for good medical practice. METHODS: Of 445 BDI data sets, PWE with scores indicating moderate (BDI 19-29) to severe depressive disorder (BDI >29) were extracted and clinical reports were retrospectively reviewed regarding decisions on antidepressants, anti-seizure medications (ASMs), and non-pharmaceutical interventions. RESULTS: Sixty-four PWE (14%; 56% female; mean age 39.7 years) showed elevated BDI scores, with 40 (63%) categorized as moderate depression and 24 (37%) as severe depression. Thirty-nine percent of PWE already had a pre-existing diagnosis of depression and 53% left the clinic with the diagnosis of depression, half of them with antidepressants. High depression scores were associated with any intervention in 53%, interventions with potentially mood affecting ASM in 19%, treatment with antidepressants in 11%, and non-pharmaceutical interventions in 41%. Non-pharmaceutical interventions were related to BDI scores. Changes of potentially mood-affecting ASMs were more frequent in PWE with moderate scores, and introduction of antidepressants appeared as a trend related to higher depression scores. SIGNIFICANCE: The finding of an only weak relation between high depression scores, diagnoses of depression, and treatment consequences questions the diagnosis and treatment pathway and the clinical value of the BDI screening in PWE. Prospective standard procedures need to be established for depression diagnosis and treatment including follow-up evaluations of the validity of the diagnosis and effectiveness of the decisions taken.
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Epilepsy is an inherently dynamic disease and neuropsychology plays a key role in the formulation, monitoring and management of the condition. Teleneuropsychology provides an opportunity for neuropsychology to increase its accessibility, reach and efficiency, using focussed assessments to target epilepsy relevant domains at critical timepoints in the disease trajectory. Neuropsychologists working with epilepsy have, however, been comparatively slow to adopt telehealth methods. Here we review recent developments in teleneuropsychology, with particular reference to applications and considerations in Late Onset Epilepsy. Three different approaches to remote assessment of cognition are discussed: unsupervised, computer-administered assessments; telephone-based assessments; and videoconference-based assessments. Uptake of unsupervised, computer-administered (browser or app-based) assessments has been strongest in aging research, where there is now evidence of feasibility, reliability, and validity, especially for measures of speed and working memory. Telephone-based assessments are well established in older aged cohorts and have recently been applied in epilepsy. Such assessments are widely accessible from a technology perspective, though reliance on a purely oral medium limits cognitive domain coverage. Videoconference based assessments have partially addressed this limitation, though continue to rely largely upon finding ways to administer legacy materials via the medium rather than intrinsically exploiting the technology. We argue that the future of neuropsychology requires development of integrated videoconference-based, computer-assisted cognitive testing, combining the benefits of computerised assessments with the advantages of human led assessments. Such an approach will be applicable across neuropsychological conditions, from childhood through to older adults.
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Cenobamate (CNB) is one of the newer antiseizure medications for the treatment of focal-onset seizures. The cognitive profile of CNB is not yet known in detail. Here we present the case of an 18-year-old male high school student with epilepsy who received adjunctive CNB. Under 400 mg/d of CNB in combination with lamotrigine, a neuropsychological reassessment revealed a severe deterioration of the formerly normal episodic memory functions, while executive functions remained unaffected. The de novo memory deficit had already led to a collapse in school performance and he unexpectedly failed to obtain the general qualification for university entrance. Given the beneficial effect of CNB on seizure control, a dose reduction of CNB to 200 mg/d and introduction of valproic acid was performed. This led to a full recovery of objective memory performance. To our knowledge this is the very first report of a dose-dependent, selective and severe decline in episodic memory performance under CNB, potentially impeding academic achievement. The findings call for a cognitive monitoring of CNB which also addresses episodic memory in addition to executive functions. Systematic studies on episodic memory upon CNB treatment would help to appreciate the scope of this apparently reversible adverse effect.
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OBJECTIVE: Temporal lobe epilepsy (TLE) is typically associated with pathology of the hippocampus, a key structure involved in relational memory, including episodic, semantic, and spatial memory processes. While it is widely accepted that TLE-associated hippocampal alterations underlie memory deficits, it remains unclear whether impairments relate to a specific cognitive domain or multiple ones. METHODS: We administered a recently validated task paradigm to evaluate episodic, semantic, and spatial memory in 24 pharmacoresistant TLE patients and 50 age- and sex-matched healthy controls. We carried out two-way analyses of variance to identify memory deficits in individuals with TLE relative to controls across different relational memory domains, and used partial least squares correlation to identify factors contributing to variations in relational memory performance across both cohorts. RESULTS: Compared to controls, TLE patients showed marked impairments in episodic and spatial memory, with mixed findings in semantic memory. Even when additionally controlling for age, sex, and overall cognitive function, between-group differences persisted along episodic and spatial domains. Moreover, age, diagnostic group, and hippocampal volume were all associated with relational memory behavioral phenotypes. SIGNIFICANCE: Our behavioral findings show graded deficits across relational memory domains in people with TLE, which provides further insights into the complex pattern of cognitive impairment in the condition.
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Epilepsia do Lobo Temporal , Transtornos da Memória , Memória Episódica , Humanos , Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/complicações , Masculino , Feminino , Adulto , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Hipocampo/patologia , Adulto Jovem , Memória Espacial/fisiologia , SemânticaRESUMO
OBJECTIVE: Interictal blood-brain barrier dysfunction in chronic epilepsy has been demonstrated in animal models and pathological specimens. Ictal blood-brain barrier dysfunction has been shown in humans in vivo using an experimental quantitative magnetic resonance imaging (MRI) protocol. Here, we hypothesized that interictal blood-brain barrier dysfunction is also present in people with drug-resistant epilepsy. METHODS: Thirty-nine people (21 females, mean age at MRI ± SD = 30 ± 8 years) with drug-resistant epilepsy were prospectively recruited and underwent interictal T1-relaxometry before and after administration of a paramagnetic contrast agent. Likewise, quantitative T1 was acquired in 29 people without epilepsy (12 females, age at MRI = 48 ± 18 years). Quantitative T1 difference maps were calculated and served as a surrogate imaging marker for blood-brain barrier dysfunction. Values of quantitative T1 difference maps inside hemispheres ipsilateral to the presumed seizure onset zone were then compared, on a voxelwise level and within presumed seizure onset zones, to the contralateral side of people with epilepsy and to people without epilepsy. RESULTS: Compared to the contralateral side, ipsilateral T1 difference values were significantly higher in white matter (corrected p < .05), gray matter (uncorrected p < .05), and presumed seizure onset zones (p = .04) in people with epilepsy. Compared to people without epilepsy, significantly higher T1 difference values were found in the anatomical vicinity of presumed seizure onset zones (p = .004). A subgroup of people with hippocampal sclerosis demonstrated significantly higher T1 difference values in the ipsilateral hippocampus and in regions strongly interconnected with the hippocampus compared to people without epilepsy (corrected p < .01). Finally, z-scores reflecting the deviation of T1 difference values within the presumed seizure onset zone were associated with verbal memory performance (p = .02) in people with temporal lobe epilepsy. SIGNIFICANCE: Our results indicate a blood-brain barrier dysfunction in drug-resistant epilepsy that is detectable interictally in vivo, anatomically related to the presumed seizure onset zone, and associated with cognitive deficits.
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Barreira Hematoencefálica , Epilepsia Resistente a Medicamentos , Imageamento por Ressonância Magnética , Humanos , Barreira Hematoencefálica/fisiopatologia , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/diagnóstico por imagem , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Adulto Jovem , Estudos Prospectivos , Epilepsia/fisiopatologia , Epilepsia/diagnóstico por imagemRESUMO
Given the demographic change with an aging society in Germany, cognitive performance assessment of the elderly is of great importance. The Viacogscreen developed by us is a computer- and web-based brain performance screening for older adults that not only meets the criteria of a measurement instrument, but is also economical and repeatable. The test captures interlocking word list learning with delayed free recall and recognition, semantic word selection and fluidity, phonemic word fluidity and inverted number range, as well as incidental memory, resulting in a total of 17 performance parameters that provide a quick orientation (approximate test duration: 10-12 minutes) regarding the cognitive performance of a test subject. Three performance areas are depicted: executive functions, episodic and semantic memory. The test was standardized for 200 healthy test subjects in 6 different age groups (range: 50-85 years). For the first clinical validation, the test was used in the memory clinics in Bonn and Ulm, where 33 patients with MCI (mild cognitive impairment) and 42 patients with suspected Alzheimer's disease (VAD) were tested. A control group of 42 healthy people of approximately the same age served as the control group. With regard to the cognitive test procedure, all three groups showed significantly different results regarding the overall score (ANOVA F=73.9, p<0.001), executive functions (F=27.6 p<0.001) and semantic memory (F=54.4 p<0.001). Regarding episodic memory, both clinical groups differed significantly from the control group, but not from each other (F=48.7, p<0.001). The Viacogscreen thus produced very good results in its first validation in two memory clinics with regard to differentiation of VAD, and good results with regard to MCI. In addition to use in neurodegenerative diseases, the Viacogscreen is also suitable for other neurological and neuro-oncological diseases, as well as for use in large clinical studies since it enables electronic data collection.
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BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.
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Epilepsias Parciais , Epilepsia do Lobo Temporal , Epilepsia , Humanos , Estudos de Coortes , Eletroencefalografia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/cirurgia , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Convulsões , Resultado do TratamentoRESUMO
PURPOSE: The Liverpool Adverse Event Profile (L AEP) is commonly used in clinical practice and pharmacological trials for the monitoring of side effects of anti-seizure medication (ASM). However potentially unrelated, additional symptoms and normative data should be considered to put patients´ complaints into perspective. METHODS: An extended 32-item AEP (E AEP) was given to 537 healthy subjects and 1,605 patients with epilepsy as part of the Bonn ASM side effect registry. The tool was factor-analyzed, corrected for age, gender, and repeated application, and related to drug load and individual substances (with N> 100) on item and scale level (total E AEP and its subscales cognition, dizziness, energy, mood, bodily symptoms, aggression, and sexuality). RESULTS: Compared to non-normalized results, at item level, between one and two-thirds of responses suggesting impairment were found to be unlikely to be related to ASM treatment after normalization. Binary regression analyses revealed differential effects of medication choice, but also of antidepressants and neuroleptics on complaint domains. The explained variance was better for physical than psychological domains. The results reflect both known drug side effects and indications. Patients´ explicit attribution of problems to their medications barely improved the correlation of the E AEP and treatment parameters. CONCLUSION: Application of a norm-referenced AEP is highly recommended to avoid overestimation of treatment related problems in patients with epilepsy. It allows evaluation on item and scale level for individuals as well as groups in drug trials. Plausible relations to individual drugs and to drug load can be demonstrated. The explanatory power was better for physical than psychological domains. Drug-related complaint patterns reflect known drug side effects (e.g. perampanel and brivaracetam with aggression) as well as drug indications (e.g. lamotrigine for depression). This is likely to be particularly relevant when side effects may have affected treatment decisions. Longitudinal evaluation with repeated application of the E AEP with changes of drug treatment is in progress.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Epilepsia , Humanos , Estudos Transversais , Epilepsia/diagnóstico , Anticonvulsivantes/efeitos adversos , Lamotrigina/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológicoRESUMO
Rasmussen's encephalitis is characterized by drug-resistant focal seizures and chronic inflammation of one hemisphere leading to progressive loss of hemispheric volume. In this cohort study, we aimed to investigate subcortical grey matter volumes and asymmetries in Rasmussen's encephalitis longitudinally in clinically relevant subgroups. We retrospectively included all T1-weighted MRI scans of all people with Rasmussen's encephalitis who were treated at the University Hospital Bonn between 1995 and 2022 (n = 56, 345 scans, median onset 8 years, 36 female). All cases were classified as type 1 (onset ≤ 6 years) or type 2 (onset > 6 years). Subcortical segmentations were performed using FreeSurfer. Longitudinal trajectories of subcortical volumes and hemispheric ratios (ipsi-/contralesional) were assessed using linear mixed-effect models. Unihemispheric cortical degeneration was accompanied by ipsilesional atrophy of the nucleus accumbens, caudate nucleus, putamen, thalamus and contralesional atrophy of the nucleus accumbens and caudate nucleus both in type 1 (all P ≤ 0.014) and type 2 (all P < 0.001). In type 1, however, contralesional volume increase of the amygdala, hippocampus, pallidum and thalamus was found (all P ≤ 0.013). Both ipsilesional and contralesional subcortical atrophies, like cortical atrophy, are most probably caused by neurodegeneration following chronic neuroinflammation. We speculate that contralesional volume increase in type 1 could be related to either neuroplasticity or ongoing acute neuroinflammation, which needs to be investigated in further studies.
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Background: The relationship between epilepsy and dementia is currently a topic of great interest. Our study aimed to determine the prevalence of dementia diagnoses among patients of a large level 4 university epilepsy center. Methods: In this retrospective monocentric study conducted at the Department of Epileptology of the University Hospital Bonn, we searched for dementia-related terms in a total of 145,501 medical letters from 40,360 adult patients who were seen between 2003 and 2021. Files with at least one hit were selected and analyzed with regard to diagnoses, age, age at epilepsy onset, and the question as to whether epilepsy preceded or followed the dementia diagnosis. Results: Among the medical letters of 513 patients, dementia-related terms were found. The letters of 12.7% of these patients stated a dementia diagnosis, 6.6% were suspected of having dementia, 4.9% had mild cognitive impairment, and 6.6% had other neurodegenerative diseases without dementia. Taking all 40,360 patients into account, the prevalence of diagnosed or suspected dementia was 0.25%. An older age (≥60 years) and late-onset epilepsy (≥60 years), but not a longer epilepsy duration, increased the odds of dementia by 6.1 (CI 3.5-10.7) and 2.9 (CI 1.7-4.7), respectively. Additionally, vascular, metabolic, inflammatory, and behavioral mood-related comorbidities were commonly observed. Epilepsy tended to precede (23.2%) rather than follow (8.1%) the dementia diagnosis. Conclusion: Despite the clear limitations of a selection bias and the potential underdiagnosis of dementia and underestimation of its prevalence when relying on the medical letters from a specialized center which rather focuses on epilepsy-related issues, the findings of this study offer valuable insights from the perspective of an epilepsy center. In this setting, the prevalence of dementia in epilepsy is rather low. However, physicians should be aware that the risk of dementia is higher in the elderly, in late-onset epilepsies, and when comorbid risk factors exist. Seizures can also be an early sign of a neurodegenerative disease. Future research should explicitly screen for dementia in patients with epilepsy and stratify them according to their underlying pathologies and comorbidities.
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Rasmussen's encephalitis is an immune-mediated brain disorder characterised by progressive unilateral cerebral atrophy, neuroinflammation, drug-resistant seizures and cognitive decline. However, volumetric changes and epileptiform EEG activity were also observed in the contralateral hemisphere, raising questions about the aetiology of contralateral involvement. In this study, we aim to investigate alterations of white matter integrity, structural network topology and network efficiency in Rasmussen's encephalitis using diffusion-tensor imaging. Fourteen individuals with Rasmussen's encephalitis (11 female, median onset 6 years, range 4-22, median disease duration at MRI 5 years, range 0-42) and 20 healthy control subjects were included. All subjects underwent T1-weighted structural and diffusion-tensor imaging. Diffusion-tensor images were analysed using the fixel-based analysis framework included in the MRtrix3 toolbox. Fibre density and cross-section served as a quantitative measure for microstructural white matter integrity. T1-weighted structural images were processed using FreeSurfer, subcortical segmentations and cortical parcellations using the Desikan-Killiany atlas served as nodes in a structural network model, edge weights were determined based on streamline count between pairs of nodes and compared using network-based statistics. Global efficiency was used to quantify network integration on an intrahemispheric level. All metrics were compared cross-sectionally between individuals with Rasmussen's encephalitis and healthy control subjects using sex and age as regressors and within the Rasmussen's encephalitis group using linear regression including age at onset and disease duration as independent variables. Relative to healthy control subjects, individuals with Rasmussen's encephalitis showed significantly (family-wise-error-corrected P < 0.05) lower fibre density and cross-section as well as edge weights in intrahemispheric connections within the ipsilesional hemisphere and in interhemispheric connections. Lower edge weights were noted in the contralesional hemisphere and in interhemispheric connections, with the latter being mainly affected within the first 2 years after disease onset. With longer disease duration, fibre density and cross-section significantly (uncorrected P < 0.01) decreased in both hemispheres. In the contralesional corticospinal tract, fibre density and cross-section significantly (uncorrected P < 0.01) increased with disease duration. Intrahemispheric edge weights (uncorrected P < 0.01) and global efficiency significantly increased with disease duration in both hemispheres (ipsilesional r = 0.74, P = 0.001; contralesional r = 0.67, P = 0.012). Early disease onset was significantly (uncorrected P < 0.01) negatively correlated with lower fibre density and cross-section bilaterally. Our results show that the disease process of Rasmussen's encephalitis is not limited to the cortex of the lesioned hemisphere but should be regarded as a network disease affecting white matter across the entire brain and causing degenerative as well as compensatory changes on a network level.
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OBJECTIVE: Executive dysfunction is prevalent in children with epilepsy, and associated with poor psychosocial outcome. Sensitive and time effective tools are needed, which capture executive dysfunction across a wide range of impairment. The present study evaluates the applicability of EpiTrack Junior® (EpiTrackJr) as a screening tool at a tertiary epilepsy center, and explore how EpiTrackJr in combination with a subjective measure of everyday attention and executive functions (EFs) may provide clinically important information. METHODS: Retrospective study including 235 pediatric patients admitted to the Norwegian National Centre for Epilepsy. EpiTrackJr and Behavioral Rating Inventory of Executive Functioning (BRIEF) were used to assess attention and EFs. RESULTS: 27,7% obtained a score categorized as "average/unimpaired", 23% as "mildly impaired", and 47.7% as "significantly impaired" on EpiTrackJr. The distribution of age-corrected EpiTrackJr scores was satisfactory. Performance was related to numbers of anti-seizure medication (ASM load), comorbidity and IQ. We found a significant, but weak correlation between EpiTrackJr performance and the BRIEF Metacognitive Index (r = -0.236, n = 108, p=.014), but no significant correlation with the Behavioral Regulation Index (r = -0.178, n = 108, p=.065). SIGNIFICANCE: Our results indicate that EpiTrackJr is applicable as a screening tool for attention and EFs in pediatric patients at a tertiary epilepsy center. Impaired test performance was associated with greater ASM load, comorbidity and lower IQ. Performance based measures and behavior ratings likely capture different aspects of EFs. In combination, the two provide important and nonredundant information about the child's EFs in different settings.
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Hippocampal volumetry is an essential tool in researching and diagnosing mesial temporal lobe epilepsy (mTLE). However, it has a limited ability to detect subtle alterations in hippocampal morphometry. Here, we establish and apply a novel geometry-based tool that enables point-wise morphometric analysis based on an intrinsic coordinate system of the hippocampus. We hypothesized that this point-wise analysis uncovers structural alterations not measurable by volumetry, but associated with histological underpinnings and the neuropsychological profile of mTLE. We conducted a retrospective study in 204 individuals with mTLE and 57 age- and gender-matched healthy subjects. FreeSurfer-based segmentations of hippocampal subfields in 3T-MRI were subjected to a geometry-based analysis that resulted in a coordinate system of the hippocampal mid-surface and allowed for point-wise measurements of hippocampal thickness and other features. Using point-wise analysis, we found significantly lower thickness and higher FLAIR signal intensity in the entire affected hippocampus of individuals with hippocampal sclerosis (HS-mTLE). In the contralateral hippocampus of HS-mTLE and the affected hippocampus of MRI-negative mTLE, we observed significantly lower thickness in the presubiculum. Impaired verbal memory was associated with lower thickness in the left presubiculum. In HS-mTLE histological subtype 3, we observed higher curvature than in subtypes 1 and 2 (all p < .05). These findings could not be observed using conventional volumetry (Bonferroni-corrected p < .05). We show that point-wise measures of hippocampal morphometry can uncover structural alterations not measurable by volumetry while also reflecting histological underpinnings and verbal memory. This substantiates the prospect of their clinical application.
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Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/complicações , Estudos Retrospectivos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Lobo Temporal/patologia , Memória , Imageamento por Ressonância Magnética/métodos , Transtornos da Memória/patologia , Esclerose/patologiaAssuntos
Epilepsia , Neoplasias , Complicações na Gravidez , Gravidez , Feminino , Humanos , Criança , Ácido Fólico/efeitos adversos , Mães , Epilepsia/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Neoplasias/tratamento farmacológico , Suplementos Nutricionais , Complicações na Gravidez/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVES: Limbic encephalitis (LE) is an autoimmune disease often associated with temporal lobe epilepsy and subacute memory deficits. It is categorized into serologic subgroups, which differ in clinical progress, therapy response, and prognosis. Using longitudinal MRI analysis, we hypothesized that mesiotemporal and cortical atrophy rates would reveal serotype-specific patterns and reflect disease severity. METHODS: In this longitudinal case-control study, all individuals with antibody-positive (glutamic acid decarboxylase 65 [GAD], leucine-rich glioma-inactivated protein 1 [LGI1], contactin-associated protein 2 [CASPR2], and N-methyl-d-aspartate receptor [NMDAR]) nonparaneoplastic LE according to Graus' diagnostic criteria treated between 2005 and 2019 at the University Hospital Bonn were enrolled. A longitudinal healthy cohort was included as the control group. Subcortical segmentation and cortical reconstruction of T1-weighted MRI were performed using the longitudinal framework in FreeSurfer. We applied linear mixed models to examine mesiotemporal volumes and cortical thickness longitudinally. RESULTS: Two hundred fifty-seven MRI scans from 59 individuals with LE (34 female, age at disease onset [mean ± SD] 42.5 ± 20.4 years; GAD: n = 30, 135 scans; LGI1: n = 15, 55 scans; CASPR2: n = 9, 37 scans; and NMDAR: n = 5, 30 scans) were included. The healthy control group consisted of 128 scans from 41 individuals (22 female, age at first scan [mean ± SD] 37.7 ± 14.6 years). The amygdalar volume at disease onset was significantly higher in individuals with LE (p ≤ 0.048 for all antibody subgroups) compared with that in healthy controls and decreased over time in all antibody subgroups, except in the GAD subgroup. We observed a significantly higher hippocampal atrophy rate in all antibody subgroups compared with that in healthy controls (all p ≤ 0.002), except in the GAD subgroup. Cortical atrophy rates exceeded normal aging in individuals with impaired verbal memory, while those who were not impaired did not differ significantly from healthy controls. DISCUSSION: Our data depict higher mesiotemporal volumes in the early disease stage, most likely due to edematous swelling, followed by volume regression and atrophy/hippocampal sclerosis in the late disease stage. Our study reveals a continuous and pathophysiologically meaningful trajectory of mesiotemporal volumetry across all serogroups and provides evidence that LE should be considered a network disorder in which extratemporal involvement is an important determinant of disease severity.
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Encefalite Límbica , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Encefalite Límbica/diagnóstico , Estudos de Casos e Controles , Anticorpos , Imageamento por Ressonância Magnética , Glutamato Descarboxilase , Transtornos da MemóriaRESUMO
In response to the recent review by Zawar and Kapur on the overlap between mesial temporal lobe epilepsy (MTLE) and Alzheimer's disease (AD), we (1) underscore that the bidirectionality between epilepsy and dementia is of high interest, also from the epileptological perspective; (2) outline the multifactorial etiology of cognitive deficits in epilepsy; (3) emphasize that the most prevalent neuropathological findings in MTLE comprise hippocampal sclerosis, dysplastic lesions, and neurodevelopmental neoplasm; and (4) state that anti-seizure medication can also have adverse effects on cognition. We conclude that the neuropsychology and neuropathology of MTLE is actually more complex than implicated in the review by Zawar and Kapur. Their suggested model may be valid for a small specific subgroup of cases. However, more studies are needed to confirm the role of hyperphosphorylated tau in epilepsy patients with and without AD considering age and age at epilepsy onset as potential moderator variables.
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Transtornos Cognitivos , Disfunção Cognitiva , Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Transtornos Cognitivos/patologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Cognição , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: Pediatric epilepsy surgery yields cure from epilepsy or complete seizure control with continued medication in many patients early in life. This study aimed to evaluate the long-term (>10 years) psychosocial and socioeconomic outcomes of pediatric epilepsy surgery and examine the role of comorbid disability, type of surgery, seizure freedom, and age at surgery. METHODS: A novel ad hoc parent/patient questionnaire was used to assess educational and occupational attainment, marital/familial status, mobility, and other outcomes in patients who underwent unilobar or multilobar surgery for drug-refractory epilepsy during their childhood. The questionnaire also captured information on comorbid disability. RESULTS: Of the 353 eligible patients, 203 could still be contacted and 101 of these (50%) returned appropriately filled-in questionnaires (follow-up intervals: 11-30 [mean: 19.6] years). The cure from epilepsy rate was 53%. Type of surgery was strongly confounded by comorbid disability. Patients with comorbid disabilities had significantly lower rates of regular school degrees, gainful employment, marriage, and driving license (N = 29; 12%, 4%, 0%, 3%) compared with non-disabled patients (N = 69; 89%, 80%, 43%, and 67%, respectively). Patients achieved lower school degrees than their siblings and parents. Non-disabled seizure-free patients had better employment and mobility outcomes compared with non-seizure-free patients. Age at surgery (<10 vs. ≥10 years of age) did not have any effect on any outcome in patients with preschool seizure onset. SIGNIFICANCE: Pediatric epilepsy surgery can lead to permanent relief from epilepsy in many patients, but comorbid disability strongly impacts adult life achievement. In non-disabled patients, favorable outcomes in academic, occupational, marital, and mobility domains were achieved, approaching respective rates in the German population. Complete seizure freedom had additional positive effects on employment and mobility in this group. However, in case of chronic comorbid disability the overall life prospects may be limited despite favorable seizure outcomes.
Assuntos
Epilepsia , Criança , Humanos , Adulto , Pré-Escolar , Seguimentos , Epilepsia/tratamento farmacológico , Convulsões , Emprego , Inquéritos e QuestionáriosRESUMO
Objective: Evaluation of the antiseizure efficacy, side effects and neuropsychological effects of Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT). ANT-DBS is a treatment option for patients with difficult-to-treat epilepsy. Though several works outline the cognitive and/or mood effects of ANT-DBS for the treatment of epilepsy, data on the intersection between antiseizure efficacy, cognitive and undesired effects are scarce. Methods: We retrospectively analyzed the data of our cohort of 13 patients. Post-implantation seizure frequencies were measured at 6 months, 12 months and last follow-up, as well as averaged throughout follow-up. These values were then compared with mean seizure frequencies in the 6 months before implantation. To address acute cognitive effects of DBS a baseline assessment was performed after implantation and before stimulation, and a follow-up assessment was conducted under DBS. The long-term effects of DBS on cognition were assessed by comparing the preoperative neuropsychological profile with a long-term follow-up under DBS. Results: In the entire cohort, 54.5% of patients were responders, with an average seizure reduction of 73.6%. One of these patients achieved temporary seizure freedom and near-total seizure reduction during the entire follow-up. Seizure reduction of <50% was achieved in 3 patients. Non-responders suffered an average seizure increase of 27.3%. Eight of twenty-two active electrodes (36,4%) were off-target. Two of our patients had both electrodes implanted off-target. When removing these two patients from the analysis and averaging seizure frequency during the entire follow-up period, four patients (44.4%) were responders and three experienced a seizure reduction of <50%. Intolerable side effects arose in 5 patients, mostly psychiatric. Regarding acute cognitive effects of DBS, only one patient showed a significant decline in executive functions. Long-term neuropsychological effects included significant intraindividual changes in verbal learning and memory. Figural memory, attention and executive functions, confrontative naming and mental rotation were mostly unchanged, and improved in few cases. Significance: In our cohort, more than half of patients were responders. Psychiatric side effects seem to have been more prevalent compared to other published cohorts. This may be partially explained by a relatively high occurrence of off-target electrodes.