The main theme of the congress was “People with epilepsy – seizures and more”. In addition to high-quality scientific and state-of-the-art symposia on current topics relating to the diagnosis and treatment of seizures and epilepsy, the aim was therefore to provide space for contributions focusing on the peripheral areas of epileptology. This included, for example, cognitive and emotional effects, but also aspects of participation in education, work and society.
Previous work suggests that dysfunction of the blood-brain barrier can be both a cause and a consequence of epileptic activity. Dysfunction of the blood-brain barrier is also associated with extravascular accumulation of iron. One study therefore investigated the hypothesis of whether iron accumulates extravascularly in people with focal epilepsy and whether this can be detected using susceptibility-weighted imaging (SWI) in the ultra-high field (7T) [1]. For this purpose, 32 subjects with focal epilepsy were prospectively included. In addition, a healthy cohort was included as a control group. T1-weighted images (0.6 mm voxel size) and SWI (0.4 mm voxel size) were acquired with 7 Tesla MRI. Processing included motion correction, denoising and bias field correction. Susceptibility values were compared between control and epilepsy cohorts using a linear regression model with age and gender as covariates.
Compared to controls, subjects with focal epilepsy showed significantly higher susceptibility in cortical and subcortical regions. Individuals with temporal seizure onset zone showed higher susceptibility in both hippocampi, amygdalae and nuclei caudati as well as in the thalamus and putamen of the affected hemisphere and in cortical regions, predominantly in the affected hemisphere, compared to controls. Individuals with extratemporal seizure origin zone showed significantly higher susceptibility in regions of both cortices equally, as well as in basal ganglia in both hemispheres.
Biomarkers using heart rate analysis
Epileptic arousals are a clinically relevant seizure type that has received little scientific attention to date and is not listed in the current ILAE classification. These are defined as seizures whose only semiological feature is an arousal/awakening from sleep. The ictal activity is not detected with sufficient sensitivity by superficial EEG recordings, so that this type of seizure may erroneously appear as physiological arousals. Simultaneous intracranial and superficial EEGs therefore offer a unique opportunity to investigate neurophysiological mechanisms of epileptic arousals and could enable the development of a quantitative biomarker-based detection method for non-invasive clinical settings. The aim of one study was to identify biomarkers for epileptic and physiological arousals based on heart rate analysis [2].
Simultaneous intracranial and superficial video EEG recordings with electrocardiography (ECG) were performed and epileptic arousals were analyzed patient-specifically. Physiological arousals were matched by date and sleep stage. R-spike detection algorithms were developed to measure heart rate. Quantitative comparisons were applied in defined time windows of 50 seconds before (pre) and after (post) the arousal for epileptic and physiological arousals.
In 190 nights, 135 epileptic arousals were analyzed in 20 patients with focal epilepsies. In 63.7% of epileptic arousals, no ictal pattern could be detected by surface EEG. Heart rate analysis was performed in 13 patients with 83 epileptic arousals and 81 physiological arousals. Both epileptic and physiological arousals showed an increase in heart rate between pre- and post time windows. The latency between arousal and heart rate peak was significantly different between epileptic and physiological arousals.
A clear need for a non-invasive biomarker was demonstrated, as almost two thirds of epileptic arousals were not detectable by surface EEGs. Epileptic and physiological arousals lead to an increase in heart rate, but show different temporal relationships: Physiological arousals show an average later but consistent modulation of heart rate, in contrast to epileptic arousals with average earlier but heterogeneous changes. The variability of heart rate changes during epileptic arousals reflects the diversity of epileptic seizures. The diversity of heart rate dynamics suggests the possibility of developing a biomarker to help improve detection and diagnosis of this subtle epileptic seizure type.
Genetic diagnostics for newborns
Neonatal seizures (estimated frequency: 2.29 cases/1000 live births LG) are defined by the time of occurrence: in mature newborns (1.10 cases/1000 LG) in the first four weeks post partum, in premature infants (14.28 cases/1000 LG) in the first 44 weeks of gestational age. The spectrum of aetiology mainly includes structural, vascular, epileptic, metabolic and genetic causes. With regard to genetic causes, the question of when a corresponding diagnosis is useful after excluding other causes is particularly relevant. A study has taken a closer look at this [3]. In a retrospective cross-sectional study, 19 neonates (male: n=11 [57,9%], female: n=8 [42,8%]; mature babies: n=11 [57,9%], premature babies: n=8 [42,8%]) with neonatal seizures were included in a three-site center analysis (perinatal center level 1 at two sites) with n=12 154 neonates born (including 174 premature babies <1500 g birth weight) from the years 2022-2023. Genetic diagnostics were performed in 15% of the neonates. In addition to the known pathophysiological explanations for seizures around birth, genetic causes also play a role, the early diagnosis of which has therapeutic and prognostic significance. Genetic testing should therefore be initiated at an early stage, especially if no clear pathophysiological connection appears sufficient to explain the symptoms. Particularly in the case of dysmorphia/malformations and epileptic encephalopathies, early aetiological clarification can lead to further treatment and, if necessary, a change in treatment goals. Overall, the indication for genetic diagnostics should be given generously even in the case of pathophysiologically meaningful explanations such as neonatal stroke due to the increasingly relevant mutations in terms of therapeutic consequences.
Functional seizures or epilepsy?
The differential diagnosis of epileptic and functional seizures (EAs or FAs) remains a complex task for epileptologists. Some interesting new screening tools have been developed to speed up the correct diagnosis and appropriate treatment [4]. In summary, the sensitivity of the instruments is 74 %-95 % (n=8), the specificity is %–86% (n=8), the accuracy is between %–87% (n=6), and the AUC values are between 0.74-0.97 (n=6). In terms of statistical criteria, the DDESVSFS risk calculator performed best, which appears to be feasible in clinical practice with eight items and is freely available. Methodologically, stringent statistical validations of all of these still new instruments would be useful as part of independent research projects. In order to further evaluate the reproducibility and generalizability, data from different clinical settings would be of particular interest. With a broader evidence base, some of the instruments described could make a valuable contribution to the more efficient differential diagnosis of EAs and FAs in the future.
Seizure while cycling
In the course of the mobility transition, more and more journeys are being made on bicycles or pedelecs (bicycles with electric pedal assistance up to 25 km/h), which have the same status under traffic law. Therefore, the accident risk of people with epilepsy (PWD) who ride bicycles or pedelecs should be assessed [5]. For this purpose, the general annual risk of serious/fatal bicycle and pedelec accidents (basic risk), differentiated by age group, was determined based on the Mobility Report 2017, the accident statistics for 2017 from DESTATIS and the reports of the Insurers’ Accident Research 2017 and 2022. In addition, an estimate of the epilepsy-specific risk for serious and fatal accidents was made using the methodology developed by the European Commission on Driving Licenses for estimating the risk of motor vehicle accidents (COSY approach). A basic risk for serious or fatal accidents of bicycle 1:3570; pedelec 1: 2940; car 1: 1470 was found. The accident risk for bicycles and pedelecs increases with age; young pedelec riders between 18 and 34 years are a second risk group. The accident risk increases in proportion to the daily riding time. With regular use of a pedelec and a COSY of 20%, the risk accumulates over 5 years from 1:570 to 1:110.
The accident risk of PWD who have a COSY of 20% is similar for cars, bicycles and pedelecs. It increases considerably if ≥1 seizure per year is to be expected. The risk is significantly higher for pedelecs than for bicycles. Patients with ≥1 seizure per year should be offered special advice in which the differences in risk between cycling and pedelec riding, between normal motor vehicle traffic, on roads with cycle paths and on cycle paths in leisure areas, as well as the legal mobility aids are pointed out.
Depressive comorbidity
Many patients experience a significant reduction in their quality of life as a result of epilepsy. Various factors such as medication side effects, high seizure frequency, stigmatization and psychiatric illnesses have been identified as the causes of this. Symptoms of depression are present in around 10% of the German general population in screening tests, and epilepsy patients have a 3-5 times higher risk of developing depression. A cross-sectional cohort of patients with epilepsy was examined for the presence of depression symptoms and characterization of therapy with mood-stabilizing seizure suppressants, antidepressants and neuroleptics as well as access to neurological and psychiatric treatment [6].
A total of 471 adults with epilepsy and a mean age of 40 years (58.4% female) were analyzed. A HADS-D score of ≥8 was found in 34%, indicating the presence of depressive symptoms. Of these patients, only 13.8% had received psychiatric or psychotherapeutic treatment, while around two thirds (68.8%) had received neurological treatment in the previous three months. Mood-stabilizing seizure suppressive therapy with carbamazepine, lamotrigine or valproate was used in 51.3% of patients with symptoms of depression, and did not differ from the frequency (56.3%) of use of mood-stabilizing seizure suppressive therapy in patients without symptoms of depression. Of the patients with symptoms of depression, 15% received antidepressant therapy and 5% received neuroleptic therapy.
Congress: Annual Conference of the German Society for Epileptology (DGfE)
Literature:
- Heldt NR, et al: Susceptibility-weighted ultra-high-field imaging in focal epilepsy indicates cortical and subcortical iron accumulation. Abstract FV01. 62nd Annual Meeting of the German Society for Epileptology (DGfE), June 12-15, 2024, Offenburg.
- Fisel L, et al: Epileptic arousals – heart rate analysis for the detection of biomarkers in simultaneous intracranial and superficial EEGs. Abstract FV05. 62nd Annual Meeting of the German Society for Epileptology (DGfE), June 12-15, 2024, Offenburg.
- Krampe-Heni F, et al.: Genetic diagnostics in neonatal seizures. Abstract FV14. 62nd Annual Meeting of the German Society for Epileptology (DGfE), June 12-15, 2024, Offenburg.
- Rosenkötter U, et al: Epilepsy or functional seizures? A systematic comparison of the latest screening instruments to support differential diagnosis. Abstract FV19. 62nd Annual Meeting of the German Society for Epileptology (DGfE), June 12-15, 2024, Offenburg.
- Thorbecke R, et al: Risk of seizure-related accidents in people with epilepsy who ride a bicycle or pedelec – implications for counseling. Abstract eP71. 62nd Annual Meeting of the German Society for Epileptology (DGfE), June 12-15, 2024, Offenburg.
- Hock S, et al: Frequency of depressive symptoms (HADS-D) in adults with epilepsy and treatment with mood-stabilizing seizure suppressants, antidepressants and neuroleptics and access to neurological and psychiatric treatment. Abstract eP62. 62nd Annual Meeting of the German Society for Epileptology (DGfE), 12-15.06.2024, Offenburg.
InFo NEUROLOGIE & PSYCHIATRIE 2024; 22(4): 24-25 (published on 26.8.24, ahead of print)
