Late-onset Epilepsy Research Articles

Late onset epilepsy in cerebral amyloid angiopathy patients: A case control study

Sporadic cerebral amyloid angiopathy (CAA) is characterized by amyloid deposition in the walls of leptomeningeal and cortical arteries, arterioles of the central nervous system. To date, epileptic seizures at CAA onset have rarely been reported and its prevalence is unknown. In reason of the high frequency of CAA in the elderly population and of the expected epileptogenic role of cortical hemorrhagic lesions, it may be hypothesized that CAA can explain a proportion of late-onset epilepsies with unknown etiology. This study aims to assess the possible correlation between CAA and late onset (>55 years) epilepsy.

Late-onset epilepsy with unknown etiology: Neuropsychological profile, cerebrospinal fluid biomarkers, and quantitative EEG characteristics

Despite epilepsy has been associated with cognitive decline, neuropsychological, neurobiological and neurophysiological features in patients with late-onset epilepsy of unknown etiology (LOEU) are still unknown. This cross-sectional study aims at investigating neuropsychological profile, cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), and resting-state quantitative electroencephalographic (qEEG) cortical rhythms in LOEU patients with mild cognitive impairment (LOEU-MCI) and with normal cognition (LOEU-CN), compared to non-epileptic MCI (NE-MCI) and cognitively normal (CN) controls.

Cognitive decline risk stratification in people with late-onset epilepsy of unknown etiology: An electroencephalographic connectivity and graph theory pilot study

Although people with late onset epilepsy of unknown etiology (LOEU) are at higher risk of cognitive decline compared to the general population, we still lack affordable tools to predict and stratify their risk of dementia. Electroencephalography (EEG) network small-world (SW) analysis has been proven cost-effective, feasible and reliable in predicting cognitive decline in mild cognitive impairment (MCI). This pilot-study investigates the potential application of EEG network SW properties in predicting cognitive decline among patients with LOEU.

Cognitive decline in late-onset epilepsy of undefined etiology: A longitudinal cohort study

Despite recent evidence suggests that amyloid pathology plays a role in epilepsy, little is known about the relationship between beta amyloid and progression to Alzheimer's Disease (AD) among patients with late-onset epilepsy of unknown origin (LOEU). We aimed to define the evolution in cognitive performance in people with LOEU, and identify factors influencing it.

Spotlight on the September 14 Issue

#### Notable in Neurology This Week This issue features an article that investigates the reversibility of CT hypodensity after endovascular treatment; another examines the risk for and causes of death in patients with late-onset epilepsy. A featured Contemporary Issues in Practice, Education, & Research article evaluates innovations in patient selection and analytical strategy to optimize phase 3 clinical trials for amyotrophic lateral sclerosis. ### Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders ![Graphic][1]</img> This article identifies MRI features that help differentiate among myelin oligodendrocyte glycoprotein–immunoglobulin G (IgG)–associated disorder (MOGAD), anti–aquaporin-4 (AQP4)–IgG neuromyelitis optica spectrum disorder (NMOSD), and multiple sclerosis (MS). In patients with different CNS demyelinating disorders, MRI lesion resolution after … [1]: /embed/inline-graphic-1.gif

Effect of late-onset epilepsy on cognitive functioning in patients with small vessel disease

RationaleLate-onset epilepsy (LOE) often has underlying cerebrovascular cause and has been associated with neurocognitive deficits and dementia. Nevertheless, the interplay between these factors has not been studied thus far. Hence, we conducted a retrospective cross-sectional study aimed to explore how unprovoked epileptic seizures along with vascular-related factors contribute to neurocognitive impairments in patients with cerebral small vessel disease. MethodsTwenty-seven patients with LOE aged > 60 years with concomitant cerebral small vessel disease (cSVD) and a matched group of cSVD without epilepsy were cognitively assessed. Demographic, clinical, and vascular information were obtained and vascular burden score was calculated for each patient. Multiple linear regression models were used to explore the relationship between epilepsy and cognitive measures adjusting for demographic and vascular risk factors. ResultsCompared with cSVD, cSVD-LOE group showed a poorer performance on verbal memory measures, visuomotor tracking and speed processing and phonetic fluency. In the multiple regression analysis, the presence of epilepsy was found to be the major predictor for verbal memory dysfunction, specifically in verbal short recall (p = 0.008) and verbal learning (p < 0.001). No interactions between vascular burden and epilepsy were found. ConclusionPatients who had cSVD with concurrent LOE showed poorer performance on memory function compared with patients with cSVD without epilepsy, and they showed a different cognitive profile from that typically manifested by patients with cSVD. The presence of epilepsy, but not seizure localization nor vascular burden, was the major contributor to the decrease in verbal memory.

Predicting the risk of stroke in patients with late-onset epilepsy: A machine learning approach

BackgroundThe goal of this cohort study was to estimate the predictors for ischemic stroke in patients with epilepsy in a large database containing data from general practitioners in Germany using machine learning methods. MethodsThis retrospective cohort study included 11,466 patients aged ≥ 60 years with an initial diagnosis of epilepsy in 1182 general practices in Germany between January 2010 and December 2018 from the IQVIA Disease Analyzer database. The Sub-Population Optimization and Modeling Solutions (SOMS) tool was used to identify subgroups at a higher risk of stroke than the overall population with epilepsy based on 37 different variables. ResultsA total of seven variables were considered important. Four co-diagnoses (diabetes, hypertension, heart failure, and alcohol dependence) were by far the strongest predictors with a combined predictive ability of more than 90%, whereby diabetes (41.4%) was the strongest predictor, followed by hypertension (35.0%) and heart failure (11.8%). The predictive importance of male gender was only 1.5%, and age was not recognized as an important predictor. Finally, the prescribed AEDs levetiracetam, with a predictive importance of 5.0%, and valproate, with 2.7%, were found to be weak predictors. ConclusionThe stroke risk in patients with epilepsy was relatively high and could be predicted based on comorbidities such as diabetes mellitus, hypertension, heart failure, and alcohol dependence. Knowing and addressing these factors may help reduce the risk of stroke in patients with epilepsy.

Mortality in Patients With Late-Onset Epilepsy: Results From the Atherosclerosis Risk in Communities Study.

To determine the risk of mortality and causes of death in persons with late-onset epilepsy (LOE) compared to those without epilepsy in a community-based sample, adjusting for demographics and comorbid conditions. This is an analysis of the prospective Atherosclerosis Risk in Communities study, initiated in 1987-1989 among 15,792 mostly Black and White men and women in 4 US communities. We used Centers for Medicare & Medicaid Services fee-for-service claims codes to identify cases of incident epilepsy starting at or after age 67. We used Cox proportional hazards analysis to identify the hazard of mortality associated with LOE and to adjust for demographics and vascular risk factors. We used death certificate data to identify dates and causes of death. Analyses included 9,090 participants, of whom 678 developed LOE during median 11.5 years of follow-up after age 67. Participants who developed LOE were at an increased hazard of mortality compared to those who did not, with adjusted hazard ratio 2.39 (95% confidence interval 2.12-2.71). We observed excess mortality due to stroke, dementia, neurologic conditions, and end-stage renal disease in participants with compared to without LOE. Only 4 deaths (1.1%) were directly attributed to seizure-related causes. Persons who develop LOE are at increased risk of death compared to those without epilepsy, even after adjusting for comorbidities. The majority of this excess mortality is due to stroke and dementia.

Epilepsy in Down Syndrome: A Highly Prevalent Comorbidity.

Individuals with Down syndrome (DS) have an increased risk for epilepsy during the whole lifespan, but especially after age 40 years. The increase in the number of individuals with DS living into late middle age due to improved health care is resulting in an increase in epilepsy prevalence in this population. However, these epileptic seizures are probably underdiagnosed and inadequately treated. This late onset epilepsy is linked to the development of symptomatic Alzheimer’s disease (AD), which is the main comorbidity in adults with DS with a cumulative incidence of more than 90% of adults by the seventh decade. More than 50% of patients with DS and AD dementia will most likely develop epilepsy, which in this context has a specific clinical presentation in the form of generalized myoclonic epilepsy. This epilepsy, named late onset myoclonic epilepsy (LOMEDS) affects the quality of life, might be associated with worse cognitive and functional outcomes in patients with AD dementia and has an impact on mortality. This review aims to summarize the current knowledge about the clinical and electrophysiological characteristics, diagnosis and treatment of epileptic seizures in the DS population, with a special emphasis on LOMEDS. Raised awareness and a better understanding of epilepsy in DS from families, caregivers and clinicians could enable earlier diagnoses and better treatments for individuals with DS.

Amyloid-β: a potential link between epilepsy and cognitive decline.

People with epilepsy - in particular, late-onset epilepsy of unknown aetiology - have an elevated risk of dementia, and seizures have been detected in the early stages of Alzheimer disease (AD), supporting the concept of an epileptic AD prodrome. However, the relationship between epilepsy and cognitive decline remains controversial, with substantial uncertainties about whether epilepsy drives cognitive decline or vice versa, and whether shared pathways underlie both conditions. Here, we review evidence that amyloid-β (Aβ) forms part of a shared pathway between epilepsy and cognitive decline, particularly in the context of AD. People with epilepsy show an increased burden of Aβ pathology in the brain, and Aβ-mediated epileptogenic alterations have been demonstrated in experimental studies, with evidence suggesting that Aβ pathology might already be pro-epileptogenic at the soluble stage, long before plaque deposition. We discuss the hypothesis that Aβ mediates - or is at least a major determinant of - a continuum spanning epilepsy and cognitive decline. Serial cognitive testing and assessment of Aβ levels might be worthwhile to stratify the risk of developing dementia in people with late-onset epilepsy. If seizures are a clinical harbinger of dementia, people with late-onset epilepsy could be an ideal group in which to implement preventive or therapeutic strategies to slow cognitive decline.

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.

Efficacy of phenobarbital in treating elderly epilepsy patients in rural northeast China: A community-based intervention trial

ObjectTo provide information on the characteristics of elderly epilepsy patients in rural Northeast China. MethodConsecutive patients (aged >60) who were diagnosed with convulsive epilepsy in seven counties in Jilin Province, Northeast China, between January 2010 and December 2019 were included in the program and were divided into the EOE (early-onset epilepsy) group and the LOE (late-onset epilepsy) group. The patients were followed up once a month, and demographics and clinical data were recorded. ResultThere were 471 patients enrolled in this study, with 329 patients classified into the EOE group and 142 patients recruited into the LOE group. At baseline, the EOE group was younger than the LOE group (t=-9.007, p < 0.001). The most common etiologies for the EOE and LOE groups were post-trauma (4.0%, n=13) and stroke (9.2%, n=13). Elderly epilepsy patients had a good response to PB monotherapy, and no significant difference was found between the two groups (p > 0.05). EOE patients complained of more serious adverse events (p < 0.05), and drowsiness (52%) and ataxia (28%) were the most common adverse events reported by the EOE and LOE groups, respectively; however, more LOE patients were prone to withdrawal due to side effects (p = 0.036). A total of 63 patients withdrew from the study, and nonadherence was the commonest cause for withdrawal (56% in EOE and 50% in LOE). In the entire follow-up period, 112 patients (63 in the EOE group and 49 in the LOE group) died; the most common causes of death were stroke (n=44, 39%) and heart disease (n=36, 32%). The LOE group had a shorter survival time than the EOE group (χ2=42.216, p < 0.001). The LOE group (HR=3.47, 95% CI: 2.36-5.09) and higher seizure frequency (HR=1.72, 95% CI: 1.17-2.52) were the risk factors for death. ConclusionElderly epilepsy patients had a good response to PB monotherapy. EOE patients complained of more serious adverse events, but more LOE patients were prone to withdrawal due to side effects. Nonadherence was the commonest cause of drug withdrawal, and it reflects the limited education regarding the impact of seizures and the differences in priorities of rural communities. EOE patients survive longer than LOE patients.

Cognitive Profile of Patients with Late-Onset Unexplained Epilepsy (2530)

Cognitive Profile of Patients with Late-Onset Unexplained Epilepsy (2530)

Association between autophagy-related protein 5 gene polymorphisms and epilepsy in Chinese patients

Autophagy is a highly conserved degradative process that has been associated with a number of neurological diseases. Autophagy-related protein 5 (ATG5) is one of the key genes for the regulation of the autophagy pathway. In this study, we investigated the potential relationship between ATG5 gene polymorphisms and epilepsy in Han Chinese population. We enrolled 112 patients with epilepsy and 100 healthy controls and detected the genotypic and allelic data of 6 single nucleotide polymorphisms (SNPs) in ATG5 (rs2245214, rs510432, rs548234, rs573775, rs6568431 and rs6937876). The associations of 6 SNPs and epilepsy were evaluated. The results revealed the genotypes of overdominant of rs510432 between controls and patients showed significant differences (Poverdominant = 0.003). Subgroup analysis showed a highly significant association of rs510432 with late-onset epilepsy (Poverdominant = 0.006), and rs548234 were associated with the susceptibility to temporal lobe epilepsy (Pcodominant = 0.002, Poverdominant = 0.006). Furthermore, ATG5 was not linked to either early-onset epilepsy or drug-resistant epilepsy (p > 0.0083). These results demonstrated an association of an ATG5 gene variant with epilepsy, and stronger associations with several subgroups of epilepsy were identified. Our study may provide novel evidence for the role of ATG5 in epilepsy, and contribute to our understanding of the molecular mechanisms of this chronic neurological disease.

Onchocerciasis Prevalence among Persons with Epilepsy in an Onchocerciasis Hypo-Endemic Area in the Democratic Republic of Congo: A Cross-Sectional Study.

A high epilepsy prevalence has been reported in onchocerciasis meso- and hyper-endemic regions in sub-Saharan Africa, including in the Democratic Republic of Congo (DRC). We investigated whether onchocerciasis-associated epilepsy can also be suspected in onchocerciasis hypo-endemic regions. Stored serum samples from 342 patients admitted with recent onset neurological symptoms admitted to Mosango general hospital, in the Kwilu province, DRC, between 2012 and 2015 were screened for onchocerciasis (OV16) antibodies by ELISA and Taenia solium antigen (using an in-house B158/B60 antigen test). Eighty-one (23.7%; 95% CI 19.5–28.5%) of these samples were positive for OV16 antibodies and 43/340 (12.6%; 95% CI 9.5–16.6%) were positive for T. solium antigen. Of the 58 persons clinically diagnosed with late onset epilepsy of unknown etiology, 19 (32.8%) were OV16 positive and nine (16%) T. solium antigen positive. In total, 16 persons with epilepsy were OV16 positive and T. solium negative, of whom 12 (75%) were between the ages seven to 31 years old, an age rage in which onchocerciasis-associated epilepsy is observed. Our study suggests that in onchocerciasis hypo-endemic areas, in T. solium antigen negative persons with epilepsy, onchocerciasis should be considered as a potential trigger of epilepsy.

Potential Parasitic Causes of Epilepsy in an Onchocerciasis Endemic Area in the Ituri Province, Democratic Republic of Congo.

A high burden of epilepsy is observed in Africa where parasitological infections are endemic. In 2016, in an Onchocerciasis endemic area in the Logo health zone, in Ituri province in the Democratic Republic of Congo, a door-to-door study showed an epilepsy prevalence of 4.6%, and 50.6% of persons with epilepsy were infected with Onchocerca volvulus. In the current study, the serum of 195 people infected with O. volvulus persons with epilepsy were tested to determine the proportion of co-infections with Taenia solium, Toxocara canis and Strongyloides. These proportions were, respectively, 8.2, 18.5 and 12.8%. Persons with a T. solium co-infection were older than those without co-infection (p = 0.021). In six (37.5%) of the T. solium co-infected persons, the first seizures appeared after the age of 30 years compared to three (2.1%) persons without a co-infection (p < 0.0001). Our study suggests that an O. volvulus infection is the main parasitic cause of epilepsy in the Ituri province, but in some persons, mainly in those with late onset epilepsy and with focal seizures, the epilepsy may be caused by neurocysticercosis. As the population in the area rears pigs, activities to limit T. solium transmission should be implemented.

The syndrome of transient epileptic amnesia: a combined series of 115 cases and literature review.

The term transient epileptic amnesia was coined in 1990 to describe a form of epilepsy causing predominantly amnestic seizures which could be confused with episodes of Transient Global Amnesia. Subsequent descriptions have highlighted its association with ‘atypical’ forms of memory disturbance including accelerated long-term forgetting, disproportionate autobiographical amnesia and topographical amnesia. However, this highly treatment-responsive condition remains under-recognized and undertreated. We describe the clinical and neuropsychological features in 65 consecutive cases of transient epileptic amnesia referred to our study, comparing these to our previous cohort of 50 patients and to those reported in 102 literature cases described since our 2008 review. Findings in our two cohorts are substantially consistent: The onset of transient epileptic amnesia occurs at an average age of 62 years, giving rise to amnestic episodes at a frequency of around 1/month, typically lasting 15–30 min and often occurring on waking. Amnesia is the only manifestation of epilepsy in 24% of patients; olfactory hallucinations occur in 43%, motor automatisms in 41%, brief unresponsiveness in 39%. The majority of patients describe at least one of the atypical forms of memory disturbance mentioned above; easily provoked tearfulness is a common accompanying feature. There is a male predominance (85:30). Epileptiform changes were present in 35% of cases, while suspected causative magnetic resonance imaging abnormalities were detected in only 5%. Seizures ceased with anticonvulsant treatment in 93% of cases. Some clinical features were detected more commonly in the second series than the first, probably as a result of heightened awareness. Neuropsychological testing and comparison to two age and IQ-matched control groups (n = 24 and 22) revealed consistent findings across the two cohorts, namely elevated mean IQ, preserved executive function, mild impairment at the group level on standard measures of memory, with additional evidence for accelerated long-term forgetting and autobiographical amnesia, particularly affecting episodic recollection. Review of the literature cases revealed broadly consistent features except that topographical amnesia, olfactory hallucinations and emotionality have been reported rarely to date by other researchers. We conclude that transient epileptic amnesia is a distinctive syndrome of late-onset limbic epilepsy of unknown cause, typically occurring in late middle age. It is an important, treatable cause of memory loss in older people, often mistaken for dementia, cerebrovascular disease and functional amnesia. Its aetiology, the monthly occurrence of seizures in some patients and the mechanisms and interrelationships of the interictal features—amnestic and affective—all warrant further study.

Late-onset epilepsy: peculiarities of diagnostics and treatment

Резюме. Рост заболеваемости эпилепсией у людей пожилого возраста объясняется увеличением продолжительности жизни и улучшением диагностики эпилептических припадков в пожилом возрасте. Цель работы — изучение данных современной научной литературы об особенностях этиологии, клиники, диагностики и лечения эпилепсии с поздним началом у людей пожилого возраста. Обсуждаются этиологические факторы поздней эпилепсии, роль факторов риска цереброваскулярных заболеваний, которые одновременно влияют и на развитие поздней эпилепсии. Рассматривается возможность возникновения поздней эпилепсии вследствие церебральной болезни мелких сосудов при неизвестной этиологии эпилепсии и при отсутствии четких структурных изменений на магнитно-резонансной томографии. Обсуждается коморбидность поздней эпилепсии с деменцией. Приведены особенности феноменологии эпилептических припадков у лиц пожилого возраста и значение электроэнцефалографии, которая нередко не проявляет эпилептиформных нарушений. Приведен клинический случай трудностей диагностики поздней эпилепсии. Для лечения пациентов с поздней эпилепсией рекомендуются противоэпилептические препараты нового поколения с относительно небольшим количеством лекарственных взаимодействий, такие как ламотриджин, леветирацетам и габапентин, которые в то же время оказывают наименьшее влияние на когнитивные функции пациентов.

Temporal lobe dysfunction in late-onset epilepsy of unknown origin

ObjectiveEpilepsy with onset in the adulthood is an increasing health problem, due to the progressive aging of the worldwide population. Whether the causes remain undetermined, the disease is defined as Late-Onset Epilepsy of Unknown origin (LOEU). The aim of this study was to evaluate the semiological, electroencephalographic, metabolic, and neuropsychological features of LOEU. MethodsWe selected patients with late-onset epilepsy (LOE) (≥55 years), whose causes of the disease have been excluded with a deep clinical-instrumental characterization, including brain MRI, EEG, 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET), and neuropsychological assessment. ResultsTwenty-three LOEU cases were retrospectively recruited. Half presented focal-onset seizures (FOS), the others focal to bilateral tonic-clonic seizures (FBTCS). All demonstrated a mild phenotype, with no recurrence of seizures on single antiseizure treatment at prolonged follow-up. Brain MRI scans were normal in 12 patients (52.3%) and showed nonspecific gliosis or mild atrophy in ten (43.5%); hippocampal sclerosis (HS) was observed in one. In 17/23 (73.9%), the EEG showed slow and/or epileptiform activity of the temporal areas. Brain FDG-PET revealed temporal lobe hypometabolism, mostly ipsilateral to EEG abnormal activity, or multifocal temporal and extra-temporal (cortical, subcortical and subtentorial) clusters of hypometabolism. The neuropsychological analysis demonstrated three different profiles: normal (43.5%), with focal deficits (39.1%) or mild multidomain impairment (17.4%). SignificanceLate-Onset Epilepsy of Unknown origin can present as FOS or FBTCS, both with good prognosis. The application of metabolic imaging and neurophysiology techniques in these patients points to the dysfunction of the temporal structures, whose role in the pathogenetic process of the disease remains to be clarified.

Ten year cumulative incidence of dementia after late onset epilepsy of unknown etiology

Recent epidemiological studies suggest late life onset epilepsy of unknown etiology (LOEU) is a risk factor for future dementia. These studies rely on inclusion and exclusion of multiple diagnostic codes rather than structured data and neuroimaging findings, and thus challenging to interpret clinically. We assessed the cumulative incidence of dementia in patients with LOEU diagnosed through admission data and neuroimaging over a 10-year follow-up and compared baseline characteristics that distinguish group level incident dementia. We screened our hospital records for patients aged 55–69 with new epilepsy, admitted between 2000 and 2008, and excluded patients diagnosed with epilepsy from an underlying cause on medical records or neuroimaging. We used retrospective hospital data to follow patients for incident dementia or mortality at 10 years and compared baseline (demographics, depression or anxiety, vascular risk factors, results of electroencephalogram (EEG) studies, antidepressant use and type of ant seizure medication) and follow up (seizure recurrence, incident cerebrovascular disease) characteristics for patients with and without incident dementia.Fifty-four LOEU cases were screened, age at first seizure was 61 ± 5. The 10-year cumulative incidence of dementia was 22.20% (95% Confidence Interval 22.08–23.10%) and time to dementia diagnosis was 5.4 ± 3.9 years. Patients with incident dementia were more likely to be women (83% vs 38%, p = 0.002), have interictal epileptic form discharges (IED) on baseline EEG (70% vs 29%, p = 0.011) and depression or anxiety (50% vs 18%, p = 0.026). No differences were found in other baseline or follow up characteristics. Our results support recent findings of dementia incidence in LOEU. Prospective studies on LOEU should evaluate phenotypic determinants of individuals with late life epilepsy and the rate of progression to dementia.