16th International Epilepsy Colloqium

Associate Professor

Prof. Dr.

Epileptic Negative Myoclonus with Lateralized Periodic Discharges: Insights into Pathophysiology

Clinical and translational research

Introduction: Negative myoclonus is a jerky movement characterized by a sudden, brief, and involuntary interruption of sustained muscle activity known as a silent period (SP). ENM is defined by the SP being time-locked to an epileptiform discharge, e.g. a spike. ENM has been described in chronic epilepsy syndromes but not in acutely epileptogenic neurological conditions with LPDs.Objective: To report two cases of epileptic negative myoclonus (ENM) associated with lateralized periodic discharges (LPDs).Materal &amp; Methods: We identified two patients admitted to the neurological ICU at University Hospitals Cleveland Medical Center with acute brain injuries (subdural hematoma and viral encephalitis). Both patients were noted to have negative myoclonus on bedside examination. Both patients were monitored with video-EEG. Surface-EMG (sEMG) electrodes were placed on the agonist and antagonistic muscle pairs of the arm affected by the negative myoclonus. EEG-SP latency was calculated using freely available software, BacAv.Results: Both patients had contralateral facial clonic seizures on presentation. The facial clonic contractions were time-locked to LPDs with superimposed fast activity (LPD+F) at ≥2 Hz frequency. As the seizures subsided by day five-six, the LPDs became blunt with a reduced frequency of 0.5-1Hz. With sustained muscle contraction, brief type I SPs were noted on sEMG electrodes of the contralateral arm (Fig.1). These SPs were time-locked to the LPDs. The maximum initial negativity of the LPDs localized to the parieto-central region. The LPD-SP latency varied from 20-25 ms to 50-60 ms.Conclusions: ENM can occur in acute epileptogenic neurological insults like subdural hematoma and encephalitis with the SPs being time-locked to LPDs. The most likely generator is post-central (S1) as indicated by the localization of the LPDs and SPs being type I only. ENM tends to develop late in the course as the LPDs become less frequent and the superimposed fast activity disappears ("improved epileptogenicity"). The appearance of ENM with improvement in LPDs is likely related to inhibition of deeper cortical layers, producing the SPs. Superimposed faster frequencies with LPDs can overcome this inhibition, thus producing a descending pyramidal tract volley (I-waves) causing a muscle twitch (Fig.2).Figure legendsFig.1 EEG with right parasagittal bipolar chain (top four channels) and surface EMG channels—flexor (blue) and extensor (red). EEG channels demonstrate LPDs with maximum negativity at C4 (double head arrow). The EMG channels demonstrate brief SPs, time-locked to the LPDs (black arrows).Fig.2 Schematic showing pathophysiology of + myoclonus and – myoclonus. Left panel- LPDs with superimposed faster frequencies: Depolarization of superficial and deep cortical neurons leading to descending pyramidal I-waves, thus leading to a positive muscle twitch. Right panel- LPDs without superimposed faster frequencies: Depolarization of superficial neurons with hyperpolarization of deeper neurons, thus leading to inhibition of ongoing muscle activity.

Poster

Hippocampal High-Frequency Oscillation in-vivo and ex-vivo: A pilot study combining stereo-EEG and human organotypic slices

IntroductionInvasive video-EEG monitoring using depth electrodes (iEEG) is a reliable and safe method for determining the resection zone in the pre-surgical evaluation of non-lesional epilepsy. Since this examination can only be performed for relatively short period, safe lateralization of the resection zone based solely on electroclinical seizures may be difficult. Invasive recordings also facilitate the examination of high-frequency oscillations (HFOs), with frequencies &gt;80Hz. The role of hippocampal HFOs in the ripple range (frequency 80-250Hz) is controversially discussed in the literature. Moreover, the underlying physiologic and pathophysiologic mechanisms of HFO emergence are not sufficiently understood. Ex-vivo analyses in resected epileptogenic tissue could help elicit this pertinent question.ObjectivesWe aim to investigate the presence and frequency Ripple-HFOs in-vivo and ex-vivo. In iEEG-patients HFO frequency could provide diagnostic benefits for determining the lateralization of the resection zone in temporal lobe epilepsy, especially when comparing the number of HFOs on both sides. In postsurgical resection tissue, we investigate and strive to replicate our in-vivo findings of HFOs, using a multi-electrode array (MEA) system.Material &amp; MethodsWe include subjects undergoing iEEG with bitemporal depth electrodes for presurgical evaluation. We analyze the presence and frequency of Ripple HFOs in hippocampal electrode contact for each hemisphere. Due to lower artifact overlay, evaluation is performed on nocturnal EEG segments from 2 different nights. HFO determination is semi-automated using the Matlab-based program Ripplelab, and the ratio of HFOs/minute between the seizure onset side and the contralateral side, respectively between both side in patients with bilateral seizure onset, is documented. After epilepsy surgery we retrieve tissue specimen from the putative epileptogenic zone and, if available, from access tissue to prepare organotypic slices. Network Activities and HFOs are then examined in a 256-channel MEA system. HFO extraction is performed using Ripplelab. Slice cultures are then exposed to different temperatures and medical agents to induce or inhibit the occurrence of epileptic network activity.ResultsSo far, 5 subjects have been included in the ripple ratio analysis. 3 of them had a unilateral temporal lobe epilepsy and showed a significantly reduced occurrence of interictal Ripple HFOs in the side-by-side comparison across all mesiotemporal depth electrode contacts on the side of the electroclinical seizure onset (Ratio 0.19, 0.21, 0.11). In the 2 patients with bilateral temporal lobe epilepsy the ratio was &gt; 0.25, so we propose a cut-off-ratio of 0.25 to distinguish between these two groups. In organotypic slice cultures, we were able to show the occurrence of HFO in hippocampus tissue, suggesting that the HFO emerge in this area. We could show that treatment with norepinephrine increased the frequency, whereas AMPA-inhibitors decreased HFO-occurrence. Furthermore, HFO frequency increased with elevated temperature.ConclusionsOur data suggests that the Ripple HFO ratio is helpful as an additional diagnostic tool for identifying focal lateralization in temporal lobe epilepsy. We could further show that HFOs are also present in human hippocampal organotypic slices and responsive to temperature and medical treatment. This opens new perspectives to better understand HFO pathophysiology.

Dr. med.

Prof.

Temporal lobe meningoencephaloceles – The Bethel experience

Epilepsy surgery

Introduction: Temporal lobe meningoencephaloceles are identified as potential epileptogenic lesions during presurgical workup. Surface EEG and invasive EEG monitoring are used to prove their epileptogenicity. The extent of surgical resection required to achieve seizure freedom is still unclear.Objectives: To clarify the diagnostic value of invasive EEG monitoring for the detection of epileptogenicity and its significance for an individually adapted extent of surgical resection in patients with temporal meningoencephaloceles.Results: We present the clinical, diagnostic and outcome data of 20 patients who underwent resective neurosurgery for temporal meningoencephalocele at our center.Half of the patients (10/20) were directed straight to surgical treatment based on EEG-data in agreement with imaging findings . Resection was performed as a circumscribed lesionectomy in 8/10 and as an apical partial temporal lobe resection (resection of the pole and corpus amygdaloideum while sparing mesial structures) in 2/10. 6/8 patients in group 1 (circumscribed lesionectomy) were seizure-free and none of the two in group 2.An invasive depth electrode assessment was performed in 10/20. 1 patient received a circumscribed lesionectomy, 5 patients an apical partial temporal lobe resection, 1 patient a modified apical partial temporal lobe resection (additional removal of hippocampal head), 3 patients an anterior TLR (including removal of mesial structures).In the invasive group, 7/8 patients with long running outcome data were seizure-free postoperatively. Two patients had recently undergone surgery, as a matter of fact they had been also seizure-free for 1 and 2 months respectively. Only one patient was not seizure free (he had received an anterior partial temporal lobe resection).After circumscribed lesionectomy (both groups) seizure freedom was achieved in 7/9 patients and after extended lesionectomy in the sense of an apical TLR in 5/7 patients, in addition 1 modified apical partial temporal lobe resection remained seizure free (operated on just 2 months ago). After anterior partial temporal lobe resection 2/3 patients were seizure-free (all oft hem invasively examined).Summary:In patients with temporal lobe meningoencephaloceles and a complex constellation of findings (e.g. bilateral findings) invasive EEG-monitoring with depth electrodes helps to determine the epileptogenicity and extent of neurosurgical resection and therefore improves the outcome.

Prof. Dr. med. habil.

PD Dr. med.

Prof. Dr. med.

Prof. Dr. med. Dr. med. habil.

Impact of seizure outcome and extent of neocortical resection on emotional well-being in patients with epilepsy one year after temporal lobe surgery

BackgroundSeizure frequency and cognitive function are common parameters in assessing epilepsy surgery outcomes. However, psychobehavioral outcomes, such as symptoms of depression and quality of life (QOL), have not found equal attention yet.ObjectiveTo assess the effect of seizure frequency, the extent of resection, and cognitive function on the psychobehavioral outcome of patients after temporal lobe surgery for pharmacoresistant epilepsy.MethodsWe retrospectively reviewed all consecutive patients who underwent surgery for intractable temporal lobe epilepsy between 09/2015 and 07/2019. We examined seizure outcome, surgical plan, resection volume, cognitive functions, and psychobehavioral outcome.ResultsThis study included 77 patients (31 males, 46 females) who underwent temporal lobe surgery. One year after surgery, 92.2% of patients showed a worthwhile improvement in seizure frequency (Engel I-III). Resection volume was significantly negatively correlated with QOL (r = −0.284, p = 0.041). However, after controlling for the effect of seizure outcome, no significant correlation remained. Patients with a worthwhile improvement in seizure frequency showed significantly fewer symptoms of depression (p = 0.024) and a significantly higher QOL (p = 0.012) one year after surgery. The differences in symptoms of depression (p = 0.044) and QOL (p = 0.030) between patients with and without improvements in seizure frequency remained significant after controlling for the effect of resection volume. After procedures sparing the amygdala and hippocampus (neocortical resection), patients presented significantly fewer symptoms of depression (p = 0.044) and significantly better QOL (p = 0.008) than patients after procedures involving mesial-temporal structures, independent of the resection volume, and after controlling for the side of the procedure (dominant vs. non-dominant). After also controlling for seizure outcome, the difference remained for QOL (p = 0.014) but not for symptoms of depression.ConclusionsA patient&quot;s emotional well-being one year after surgery for pharmacoresistant temporal lobe epilepsy strongly depends on their seizure outcome. As an individual factor, the extent of neocortical resection negatively affects postsurgical emotional well-being, but a favorable seizure outcome outweighs this effect, independent of the resection volume. A favorable seizure outcome even outweighs the negative effects of procedures involving mesial-temporal structures on symptoms of depression.

Defining the epileptogenic zone using subdural or depth electrode recordings in a series of 443 consecutive patients undergoing intracranial presurgical evaluation

Intruduction &amp; ObjectivesIntracranial recordings are used to define the epileptogenic region in complex cases with insufficient or inconsistent localizing information from non-invasive studies, and particularly in non-lesional cases to prove uniregional seizure origin and to plan surgical interventions. The type of intracranial investigation differs between centers without universal agreement as to the optimal diagnostic procedure. We here retrospectively analyzed outcomes of subdural and depth electrode recordings at the Freiburg epilepsy center to compare their diagnostic yield.Methods443 consecutive patients (225 female; 227 male; mean age at implantation: 28.6 y (range2-67 y)) undergoing intracranial presurgical evaluation were analyzed using electronic charts and information from MR imaging and intracranial electrophysiology.347 patients were lesional on MRI, 96 non-lesional. 147 patients underwent purely subdural evaluation, 160 patients depth electrode recordings, and 136 a combined approach. Patients were analyzed as to whether (1) the seizure onset region could be identified with certainty or approximately, (2) surgery was recommended, and (3) how the brain region of implantation influenced these results.Results(1)In lesional epilepsy, 63% of patients undergoing subdural recordings, 69% of patients with depth recordings, and 61% ofpatients with combined recordings were considered to have a clear definition of the seizure onset zone. Rates were lower in non lesional epilepsy, with a clear seizure onset zone in 54% of patients undergoing subdural recordings, 55% of patients with depth recordings, and 55% of patients with combined recordings were considered to have a clear definition of the seizure onset zone.(2) In lesional epilepsy, 86% of patients undergoing subdural recordings, 64% of patients with depth recordings, and 83% of patients with combined recordings proceeded to surgery with a mean Engel I outcome of 60.8%. In non-lesional epilepsy, 63% of patients undergoing subdural recordings, 57% of patients with depth recordings, and 55% of patients with combined recordings proceeded to surgery with a mean Engel I outcome of 54.2%.(3)In both temporal and frontal implantations ofl esional patients, the rate of patients proceeding to surgery was higher following subdural recordings than in those undergoing depth recordings only, although the proportion of patients with clearly identified channels with seizure onset was at least as high with depth electrode recordings.ConclusionsIn both, non-lesional and lesional patients and in different rain regions, subdural and depth electrode recordings showed high rates of successful identification of the seizure onset zone.In subdural recordings, patients in whom seizure onset was defined only approximately proceeded to surgery more frequently; resulting proportions of operated patients obtaining complete seizure control were similar with either diagnostic approach and almost as high in non-lesional cases as in patients with imaging-defined lesions.Either implantation strategy thus proved valid and rewarding in properly selected patients, with significantly higher surgical rates when subdural recordings were used.

PD Dr.

Amygdala Enlargement Correlates with Early Seizure Propagation in Temporal Lobe Epilepsy with Hippocampal Gliosis

Introduction: In unilateral mesial temporal lobe epilepsy (TLE) the relation of ipsi- and contralateral amygdala and hippocampus volumes remains unclear. Here we used 3T MRI-volumetry to identify systematic differences between ipsi- and contralateral amygdala and hippocampus volumes with interictal and ictal intracerebral Stereo-EEG (sEEG) findings.Methods: In 64 patients who underwent epilepsy surgery of unilateral TLE including resection of the amygdala and hippocampus between 07/2015 and 03/2023, presurgical amygdala and hippocampal volumes were reconstructed from 3T T1-weighted images. We created z-scores based on normative data from a scanner-specific sample of 781 healthy controls using a generalized additive model. Z-scores of the amygdala and the hippocampus ipsi- and contralateral to the epileptic focus were validated by postsurgical histopathology. sEEG was evaluated if available.Results: Fifty-five out of 64 patients had histopathologically proven hippocampal sclerosis (HS). Nine patients out of 64 had no mesial temporal lesion except hippocampal gliosis (HG) and gliosis of the amygdala. A mixed-effect model showed a significant interaction of groups (HG vs. HS) by side (ipsi- vs. contralateral) in terms of increased ipsilateral amygdala and hippocampus volumes in patients with HG and decreased ipsilateral amygdala and hippocampus volume in patients with HS. Volume increases were more pronounced in the amygdala whereas the volume decrease was more pronounced in the hippocampus. There were no significant deviations from the normal reference data in the contralateral amygdala or hippocampus.In 16 patients (8/9 patients with HG), sEEG was recorded. All 16 patients had an ipsilateral mesial temporal seizure onset. The ipsilateral amygdala was part of the irritative zone (IZ) involved in the seizure onset zone (SOZ) or early seizure propagation (&lt;2s) in all patients, but the ipsilateral amygdala was only enlarged in patients with HG.Conclusion: An increase in ipsilateral mesial temporal volume, particularly pronounced at the amygdala, typically occurs in patients with HG. Ipsilateral volume reduction in HS, notably pronounced at the hippocampus, also involves the amygdala to a lesser extent. sEEG evidence supports the notion that an enlarged amygdala signifies its involvement in the SOZ or early seizure propagation in patients with HG.

"Psychiatric disorders, Cognitive disability &amp; Multiple seizure types" a triad of symptoms in Hypothalamic Hamartoma

Pediatric epilepsy

Introduction: Hypothalamic hamartomas (HH) are congenital benign tumors known to cause gelastic or dacrystic seizures. In 95% of cases they occur sporadically without further abnormalities. Only 5% are associated with Pallister-Hall syndrome (PHS)[1]. PHS is a very rare autosomal dominant genetic disorder due to mutation in GLI3 gene on the short arm of chromosome 7 with variable penetrance and expressivity [2]. There are two subtypes of HH depending on the anatomical location: The first type is the intrahypothalamic lesion that is usually associated with gelastic seizures. The second type is the parahypothalamic lesion, which typically develops multiple seizure types, cognitive decline and psychiatric symptoms [1].We report on a patient (11y) with PHS, associated Panhypopituitarism and HH. She has a developmental delay and cognitive disability. At the age of 9 years she developed anxiety disorder, panic attacks and severe aggressive behaviour towards others as well as disinhibited behaviour. EEG was normal and HH ws stable on MRI. She was in child psychiatric treatment and received atypical neuroleptics, without symptom reduction.Objective: Is this a primary psychiatric case due to cognitive impairment and psychosocial factors on PHS or secondarily induced by the HH?Methods: Diagnostic testing included neurological examination, routine blood test, Electrocardiogramm, Echocardiography, Electroencephalography (EEG), cerebrospinal fluid analysis, including neuronal antibodies and metabolism parameters and cMRI.Results: cMRI showed HH in constant size and all the other examinations- especially repeated EEG- were within normal range. There was no evidence for autoimmune encephalitis. After four month our patient developed her first focal status epilepticus, presenting with myoclonus, crying and anxiety. EEG showed left frontocentral epileptiform discharges and Lacosamid was started. Seizures with clonus stopped and anxiety states were reduced. However aggressive and disinhibited behaviour only became less frequent after increasing Risperidone dose. Freedom of psychiatric symptoms could not be reached so far.Conclusion: Our patient developed psychiatric symptoms and multiple seizure types including psychiatric semiology due to HH. EEG appears normal during gelastic seizures, so the presence of other seizure types , showing focal, multifocal, or general spikes are helpful in attributing psychiatric symptoms to seizure semiology [1]. Epilepsies and severe psychiatric symptoms associated with HH are frequently drug resistant [3, 4]. The gold-standard treatment is surgical resection of the hamartoma via an open technique or by thermoablation [1, 4]. Our patient will proceed to epilepsy monitoring and surgery in an epilepsy surgery center.Our case demonstrates the difficulties of treatment of psychiatric symptoms in patients with PHS, especially if clear seizures are absent and EEG is normal.[1] Carballo Cuello et al, 2024: Hypothalamic Hamartoma, StatPearls, PMID: 32809498[2] Chandra et al, 2017: Pallister-Hall Syndrome, J Pediatr Neurosci. 12(3):276-279[3] Killeen et al, 2017: Psychiatric comorbidity with hypothalamic hamartoma: Systematic review for predictive clinical features. Epilepsy Behav. 73:126-130[4] Régis et al, 2017: Safety and efficacy of Gamma Knife radiosurgery in hypothalamic hamartomas with severe epilepsies: A prospective trial in 48 patients and review of the literature. Epilepsia.58 Suppl 2:60-71

Incidence and characterization of epileptic seizures in patients with brain metastasis: A monocentric retrospective cohort study of 291 patients

Personalized epilepsy treatment

Objective: Understanding the prevalence and impact of epileptic seizures in patients with brain metastases is crucial, yet remains inadequately explored. This study aims to investigate the frequency of seizures in this cohort and assess the efficacy of treatments for brain metastases in mitigating seizure occurrence. Additionally, it seeks to evaluate the consistency of seizure evaluation practices at the initial diagnosis of brain metastases, aiming to enhance patient care and outcomes.Methods: In this retrospective monocentric cohort study, data was analysed from 291 consecutive patients diagnosed with brain metastases from solid tumors. These patients underwent either tumor resection and/or radiation therapy between September 2015 and September 2023.Results: More than half of all patients (median age 64 yrs, range 30-86, 51% male) harboured brain metastasis from lung cancer and 23% experienced at least one seizure. First line treatment was Levetiracetam in most patients (90%). Whole-brain radiation was applied in139 patients, 200 received stereotactic radiosurgery for brain metastases, and 27 underwent hippocampal sparing radiation therapy. Resection of brain metastasis was done in 30% of the patients. Interestingly, there was no standardized evaluation of seizures in more than ¾ of the patients with brain metastasis in the initial diagnostic work up.Conclusion: More than 20% of the patients in our retrospective monocentric study experienced at least one seizure. The origin of brain metastasis in our cohort was lung cancer in most cases. It can be assumed that the number of unreported cases is higher and that a systematic evaluation will further increase the incidence. Taken into account that epileptic seizures are a strong and additional negative factor for the overall quality of life of cancer patients, this data shows the urgent need of further research and the development of interventions to improve the outcome of these patients.

Poster session
Short presentations – Epilepsy surgery

Termin

Vorsitzende

Programm

Poster sessionShort presentations – Epilepsy surgery

Termin

Vorsitzende

Programm

Poster session
Short presentations – Epilepsy surgery