The biennial joint meeting of the professional societies from Germany, Austria and Switzerland is the fourth largest meeting on epilepsy worldwide. In German-speaking countries, both the quality of care for people with epilepsy and scientific research are strongly established and highly visible internationally. Especially for research, transnational cooperation is indispensable.
Two-thirds of patients with epilepsy are seizure-free thanks to effective treatment management. However, this rate has not been reduced over the past 80 years despite a variety of new drugs. The newly developed substances, however, are better tolerated, which contributes to the quality of life of those affected. Nevertheless, new ways of thinking about how to also increase the efficacy of seizure-suppressive medications have been discussed.
Recent research indicates that biomarkers will play an increasing role in the future treatment of people with epilepsy. For example, they should answer the question of how the disease will develop over the years and how stringent treatment is needed. Certain blood values are already established as diagnostic markers for differentiating epileptic seizures from other seizure-like disorders – however, recent studies also show that the consideration of additional parameters can increase the diagnostic discriminatory power. In the future, biomarkers may help to simplify the selection of seizure-suppressive medications or predict which individuals might particularly benefit from epilepsy surgery. Biomarkers are also being developed for more specific questions, such as the treatment of autoimmune-related epilepsies or the indication for neurostimulation procedures.
Neurofilament light chain (Nf-L) is a nerve cell-specific, primarily axonally localized structural protein that is released into the cerebrospinal fluid and blood during neuronal injury. In recent years, Nf-L has been intensively studied as a sensitive biomarker, prognostic and progression parameter of many chronic degenerative, but also acute neurological diseases. However, the evidence on the release of Nf-L as a result of epileptic seizures has been very limited. Therefore, a retrospective cross-sectional study was initiated to investigate whether epileptic seizures of varying duration and semiology induce neuroaxonal damage that can be quantified by measuring Nf-L [1]. In adult patients, Nf-L was determined in serum and/or CSF after an epileptic seizure. In addition, gender, age, CNS comorbidities, and semiology, duration, etiology, and acute therapy of the epileptic seizure were recorded. Nf-L determination was performed in 92 patients, 15 of whom were excluded because of CNS comorbidities with competing causes of Nf-L elevation. After a singular epileptic seizure, no significant Nf-L increase was detectable in either serum or CSF relative to the upper limit of the age-corrected reference range in 44 patients. Similarly, in 10 patients with a series of multiple epileptic seizures and 23 patients with status epilepticus, there was no significant Nf-L elevation in serum or CSF compared with the upper threshold of the physiological range. However, the duration of status epilepticus was highly correlated with serum Nf-L concentration. The data indicate that single epileptic seizures and seizure series do not induce neuronal damage that can be objectified by an Nf-L increase. Status epilepticus, on the other hand, is associated with a time-dependent increase in this sensitive biomarker, reflecting putative seizure-associated cellular and molecular changes and underscoring the emergency situation with the need for consistent treatment.
Seizure duration for classification?
Bilateral tonic-clonic seizures (BTCS) can have both a focal onset (FBTCS) and a generalized onset (GBTCS). Because BTCS represent the greatest risk for patient harm during seizures, their classification assumes a significant role in treatment decisions. Seizure duration, among other semiological signs, has been described as a distinguishing feature between FBTCS and GBTCS. The aim of one study was to calculate the seizure duration of BTCS and to test whether it is possible to distinguish FBTCS from GBTCS on the basis of seizure duration [2]. A retrospective analysis examined consecutive patients who had BTCS on long-term video-EEG monitoring (LT-VEM). A total of 158 patients were included. Eighty-five patients had temporal lobe epilepsy (TLE), 28 had frontal lobe epilepsy (FLE), 8 had parietal or occipital lobe epilepsy, collectively 36 had extratemporal epilepsy (ETLE), 17 had focal epilepsy that could not be confined to a specific lobe (FNE), and 20 had idiopathic generalized epilepsy (IGE). The median seizure duration was significantly longer with FBTCS at 01:38 min than with GBTCS at 01:24. A subgroup analysis, in which the FNE group was excluded, showed that the median BTCS duration was significantly longer in TLE at 1.49 min compared with ETLE at 01:28 min and IGE at 01:24 min. Overall, it was shown that the median seizure duration was significantly longer in FBTCS than in GBTCS, which was due to FBTCS originating in the temporal lobe. However, analysis of the ROC AUC of BTCS duration revealed only weak discriminatory power between FBTCS and GBTCS. Thus, seizure duration is a poor discriminator between FBTCS and GBTCS in our retrospective patient population, contrary to results from other groups.
Differential diagnosis in infancy
Epileptic seizures are among the common neurologic emergencies in young children. This does not make differential diagnosis any easier. The case of an 18-month-old boy who had so far developed in an age-appropriate manner was discussed [3]. From 14 months of age, a total of three unprovoked bilateral tonic-clonic seizures occurred. The first seizure lasted longer than 5 min. lasted. The further seizures were interrupted after every 2 minutes by administration of diazepam rectally. All seizures occurred 15 minutes after morning awakening, before breakfast. Family history was blank for neurologic disease. Awake and sleep EEG and magnetic resonance imaging of the skull provided normal findings. Continuous therapy with valproate and human genetic diagnosis were initiated. No further seizures have occurred under valproate to date. Human genetic diagnostics revealed a mutation in the SLC2A1 gene. This variant has already been described in the literature in connection with glucose transporter 1 deficiency syndrome (GLUT1 defect). Therapy of choice for GLUT1 defect is ketogenic diet therapy. Unfortunately, this was not tolerated by the patient. GLUT1 defect was first described in 1991 and belongs to the group of metabolic epilepsies. The phenotype is variable, ranging from refractory cerebral seizures in the first year of life with microcephalus and severe developmental delay to isolated movement disorders. With the increase of human genetic diagnostics, this diagnosis is also increasingly made in patients with epileptic seizures beyond the neonatal period. Seizures that occur in the morning before breakfast, as in our case, should be cause for appropriate diagnosis.
Effects of surgical therapy
Many patients are not seizure-free despite currently available drug therapy. For this reason, various surgical procedures have been developed to treat these patients, including minimally invasive methods such as magnetic resonance guided laser interstitial thermal therapy (MRgLITT). However, it is not yet known whether patients operated on by MRgLITT have deficits in vestibular-dependent functions such as spatial orientation, rotational memory, and balance. This was investigated in a pilot study in seven patients [4]. For this purpose, free test series were used: Triangular Completion Test (TCT), Rotational Memory Test (RM) and Clinical Balance Test (CBT). None of the three tests showed significant changes postoperatively. However, the calculated effect sizes were in favor of the postoperative assessment for all tests. This pilot study was the first to examine vestibular-related spatial orientation, memory, and balance functions in patients with temporal lobe epilepsy before and after MRgLITT. Prospective studies with a larger number of patients are needed to adequately assess the changes induced by MRgLITT in these functional areas.
Genetic diagnostics in children
Preepilepsy surgical diagnosis in children and adolescents currently does not include genetic testing. A retrospective data analysis was performed to determine whether such an examination should be included as a standard of care [5]. 63 patients were included. In 17 of them, 20 20 variants with ACMG classification between III- V were found in the following genes: TSC, HUWE1, GRIN1, ASH1I, TRIO, KIF5C, CDON, EEF1A2, ANKD11, TGFBR2, ATN1, MECP2, COL4A2, JAK2, KCNQ2, CACNA1E, ATP1A2, Gli3, were found. 9/63 patients are not seizure-free after an average observation period of 27 months. Of these, 6/9 patients had abnormal genetic findings. Accordingly, genetic diagnosis is recommended in children and adolescents before epilepsy surgery. Although the findings did not lead to a change in surgical technique, they did support counseling of families regarding the chance of seizure freedom and continued drug therapy.
Mobile long-term monitoring
Epileptic seizures do not occur purely randomly, but rather in recurrent characteristic cycles at specific times of day or cyclically at daily, weekly, or even annual intervals. This was shown by recent research results from mobile long-term monitoring. These seizure cycles, in combination with the EEG and autonomic parameters recorded during long-term mobile monitoring, could be successfully used for seizure prediction. This approach opens up entirely new dimensions in epilepsy therapy and could be used in the future to prevent seizure-associated injuries, to prevent Sudden Unexpected Death in Epilepsy (SUDEP), and ultimately as a component of innovative demand-controlled drug therapies or stimulation procedures. In recent years, mobile long-term monitoring with the aid of modern technologies has enabled decisive progress to be made. Epileptic seizures are caused by uncontrolled electrical discharges of nerve cell clusters in the human brain, which can be recorded on an electroencephalogram (EEG). However, traditional EEG is unsuitable for long-term derivations because the usual EEG electrodes placed on the scalp cannot be worn outside the clinic. Now, subcutaneous EEG electrodes enable high-quality ultralong-term EEG recordings over months and years.
Congress: 12th Three-Country Meeting 2023
Literature:
- Schlabitz S, Hebel JM, Holtkamp M, Gaus V: Neurofilament light chain (Nf-L) als Biomarker einer neuronalen Schädigung infolge epileptischer Anfälle. FV 06. Dreiländertagung 2023.
- Lang C, Koren J, Hafner S, Baumgartner C: Vergleich der Anfallsdauer bei bilateral tonischklonischen Anfällen mit fokalem und generalisiertem Beginn.
FV 07. Dreiländertagung 2023. - Meedt B, Schmitt J, Vieker S: Eine seltene Differentialdiagnose bei generalisierten Anfällen im Kleinkindalter. eP017. Dreiländertagung 2023.
- Assady Looyeh K, Dordevic M, Düzel E, et al.: Auswirkungen der selektiven Amygdalahippokampektomie durch stereotaktische Laser-Thermoablation auf vestibuläre Funktionen: räumliche Orientierung, Rotationsgedächtnis und Gleichgewicht. eP 102. Dreiländertagung 2023.
- Becker LL, Makridis KL, Kaindl AM. Genetische Diagnostik bei Kindern vo einem epilepsiechirurgischen Eingriff. FV 15. Dreiländertagung 2023.
InFo NEUROLOGIE & PSYCHIATRIE 2023; 21(3): 32–33 (published 6/2/2013, ahead of print).
