Dirk-Matthias Altenmüller

Objective: Detection of focal cortical dysplasia (FCD) remains a major challenge in presurgical epilepsy diagnostics. Magnetic resonance imaging (MRI) morphometry increasingly improves lesion detection and postsurgical outcomes. The volume‐based Morphometric Analysis Program, version 2018 (MAP18) with integrated artificial neural network and surface‐based Multi‐centre Epilepsy Lesion Detection (MELD; MELD Graph) MRI morphometry algorithms have demonstrated diagnostic utility, but their performance has not been directly compared within a single cohort of surgically treated patients with histopathologically confirmed FCD. Methods: We retrospectively analyzed 3‐T MRIs of 32 FCD patients who underwent epilepsy surgery. MAP18 was applied to MP2RAGE (magnetization‐prepared 2 rapid gradient echo) sequences and MELD to T1MPRAGE (magnetization‐prepared rapid gradient echo) and three‐dimensional FLAIR (fluid‐attenuated inversion recovery) sequences. Binary lesion masks served as ground truth for evaluating detection accuracy, precision, and recall at cluster and voxel levels. Clinical correlation analysis assessed spatial concordance with seizure onset zone (SOZ) and irritative zone (IZ) from video‐electroencephalography (EEG) and postoperative outcome. Results: The cohort included 34 histopathologically proven FCD lesions (91.2% FCD II, 5.8% mild malformation of cortical development, 2.9% unspecified). MELD identified 32 of 34 lesions (94.1%), and MAP18 identified 33 of 34 lesions (97.1%), with concordance in 32 of 34 lesions (94.1%). At the cluster level, MELD showed significantly higher precision ( p < .001) and fewer false positive clusters per patient (median 0 vs. 3, p < .001). Voxelwise analysis revealed that MELD demonstrated significantly higher precision than MAP18 (.42 vs. .13, p < .0001) and recall (.44 vs. .23, p < .01). Lobar concordance with SOZ reached 90.6% and with IZ reached 87.5%. Among invasive EEG patients, overlap with SOZ and IZ was 100%. Seizure freedom (Engel I) was achieved in 87.5% of patients. Significance: Under standardized high‐resolution 3‐T MRI, both algorithms achieved high detection rates with strong concordance. Combined application may enhance presurgical lesion detection, with results limited to surgically treated patients.

Objective: Focal cortical dysplasia (FCD) causes drug‐resistant epilepsy requiring presurgical evaluation. Invasive electroencephalographic (EEG) studies demonstrate that sleep modulates epileptic activity, including interictal epileptiform discharges (IEDs), fast oscillations (FOs) in the beta (14–40 Hz) and gamma (40–80 Hz) frequency bands, and seizures. This study aimed to quantify sleep‐associated changes in IEDs, FOs, and seizures in FCD patients using noninvasive magnetoencephalography (MEG). Methods: Nineteen patients with FCD were prospectively recruited and underwent simultaneous MEG/EEG recordings lasting 89 ± 19 min during daytime sleep. Sleep stages were classified from the EEG. Beamformer source signals were computed from the MEG signal to enhance sensitivity for visual detection of IEDs, FOs in the beta and gamma frequency bands, and seizures. Magnetic source imaging (MSI) was performed using the Maximum Entropy on the Mean (MEM) method, which is particularly sensitive to the spatial extent of sources, enabling accurate localization of epileptic activity. Results: N1 sleep was reached in 17 of 19 patients and N2 sleep in 14 of 19 patients. Compared to wakefulness, sleep recordings showed significantly higher rates of FOs and seizures (both p < .05), whereas IED rates showed nonsignificant trends. Ten patients demonstrated FOs or seizures, and 12 showed IEDs. MSI of IEDs demonstrated consistent accuracy across vigilance states, with median Euclidean distances of 12.74 mm (interquartile range [IQR] = 22.74) in wake and 8.34 mm (IQR = 27.58) in sleep, and no systematic amplitude or spatial extent changes. Wavelet‐MEM enabled frequency‐specific source imaging, with FOs and seizures localizing concordantly to FCD lesions in five of seven and seven of eight patients, respectively. Significance: Daytime sleep MEG recordings are clinically feasible and significantly enhance the detection of seizures (37% of patients) and FOs compared to wakefulness. Sleep protocols enable noninvasive capture of ictal patterns—the gold standard for epileptogenic zone localization—alongside increased FO rates. These findings support incorporating sleep into standard MEG protocols for presurgical epilepsy evaluation.

Objective: To determine the prevalence and possible causes of amygdala enlargement in patients with drug‐resistant temporal lobe epilepsy. Methods: Patients were retrospectively identified via a radiology information system and a large language model. Magnetic resonance imaging scans were visually re‐analyzed and amygdala volumetry applied. Results: The term “amygdala” was used in 89 of 1853 patients. Of those, 54 had lesions in the amygdalae, 20 had isolated amygdala enlargements, and 15 patients had amygdala enlargements and remote epileptogenic lesions. Objective processing of imaging data confirmed higher amygdala volumes of both latter groups (2.09 ± 0.28 mL, 2.23 ± 0.33 mL vs 1.56 ± 0.22 mL). Significance: When amygdala enlargement occurs with remote epileptogenic lesions and patients become seizure‐free after remote lesion resection, amygdala enlargement is likely the consequence of seizures, but not their cause. In addition, isolated amygdala enlargements can be the consequence of epileptic seizures.

Objective: Focal cortical dysplasia ( FCD ) is a leading cause of drug‐resistant epilepsy and is associated with sleep‐related seizures, yet the underlying electrophysiological mechanisms during different brain states remain poorly understood. We investigated whether fast oscillations ( FOs ) within the seizure onset zone ( SOZ ) and irritative zone ( IZ ) change significantly during sleep compared with wake in FCD patients. We analyzed multiple frequency bands—beta (14–20 Hz), gamma (40–80 Hz), ripple (80–250 Hz), and broadband BGR (14–250 Hz) to provide comprehensive information about sleep‐related changes. We hypothesized that sleep‐related FO changes would be associated with sleep‐related epilepsy, frontal location, or FCD type II . Methods: We examined intracranial EEG ( iEEG ) recordings from 22 FCD patients undergoing presurgical evaluation between 2010 and 2023, with a mean age of 25.3 ± 12.8 years and a disease duration of 17.7 ± 12.3 years. Using semiautomated detection, we compared FO rates between wake and sleep epochs, focusing on contacts within IZ and SOZ . Distance‐based multivariate analysis of variance ( MANOVA ) was employed for patient‐level analysis, accounting for spatial organization and enabling multiband evaluation. Results: Analysis of 67 ± 28 bipolar iEEG contact pairs per patient revealed distinct sleep‐related patterns. In SOZ , gamma oscillations showed significant increases in 10/22 patients (45%), followed by BGR in 7/22 patients (32%). IZ exhibited stronger changes, with BGR and gamma showing significance in 13/22 patients each (59%) with high concordance. Gamma oscillation rates in SOZ increased in patients with confirmed sleep‐related epilepsy ( p < 0.05), while no associations were found with frontal location or FCD type II . Significance: Gamma oscillations showed robust sleep‐related increases in SOZ , while gamma and BGR frequencies demonstrated strong changes in IZ , often occurring simultaneously. These findings suggest gamma oscillations, complemented by BGR analysis, may qualify as markers for characterizing sleep‐related changes in FCD patients, potentially advancing understanding of mechanisms underlying sleep‐related seizures. Plain Language Summary: Focal cortical dysplasia (FCD) is a brain malformation that causes difficult‐to‐treat epilepsy, with patients experiencing seizures mainly during sleep. We studied electrical brain waves in 22 FCD patients using electrodes placed directly within or on the brain during pre‐surgery evaluation. We compared brain wave activity between wake and sleep, focusing on fast brain waves. We found that fast brain waves, especially gamma waves, increased significantly during sleep in brain areas where seizures start, particularly in patients whose seizures occur mainly during sleep. These findings potentially help us better understand why seizures happen more often during sleep in FCD patients.

Rationale: Focal cortical dysplasia (FCD) is associated with increased seizure-risk during sleep, yet the underlying mechanisms remain unclear. Previous studies report increased oscillatory patterns during sleep in focal epilepsy patients with FCD. We investigated whether fast oscillations (FOs, 14-250 Hz) within the epileptic focus significantly change during sleep compared to wake, hypothesizing that analyzing broad frequency bands provides more comprehensive information than narrow bands alone. Methods: We retrospectively analyzed intracranial EEG recordings from 22 FCD patients (2010-2023), focusing on contacts within the irritative zone (IZ) and seizure onset zone (SOZ). Using semiautomated detections, we compared FO rates between one-hour wake and sleep epochs across beta (14-40 Hz), gamma (40-80 Hz), and ripple (80-250 Hz) bands. Distance-based Multivariate Analysis of Variance (MANOVA) was applied to integrate the spatial organization of FO changes, enabling simultaneous analysis of individual and combined broadband ranges (BGR) while accounting for neocortical detection rates outside the epileptic focus and eloquent cortex. Results: Analysis of 67 ± 28 (median ± standard deviation) bipolar iEEG contact pairs per patient (SOZ: 14 ± 12, IZ: 29 ± 16) revealed distinct sleep-related patterns. In the SOZ, gamma showed significant increases in 10 patients, followed by BGR in seven patients. The IZ exhibited strong changes in both BGR and gamma (13 patients each) with high concordance (12 matches). Beta and ripple bands showed moderate concordance. Notably, gamma oscillation rates in the SOZ specifically increased in patients with sleep-related epilepsy (p < 0.05). Conclusion: Gamma oscillations showed the most robust sleep-related increases in the SOZ, while both gamma and BGR showed strong changes in the IZ. These findings suggest gamma oscillations, complemented by broadband analysis, may serve as reliable markers for sleep-related changes in FCD patients. Funding: YLH (LI1904/2-1) and MH (HE6844/3-1; project ID for both: 468174690) were funded by the German Research Foundation (DFG) Key points: Within the seizure onset zone, gamma band oscillations (40-80 Hz) followed by combined broadband BGR (14-250 Hz) show more frequent significant increases from wake to sleep across patients Within the irritative zone, gamma band and broadband oscillations BRG show even more frequent increases from wake to sleep across patients Changes occur simultaneously across multiple frequency bands, supporting the value of multi-band analysis Gamma oscillation rates within the seizure onset zone significantly increased from wake to sleep in patients with sleep-related epilepsy (p < 0.05)

Transient global amnesia (TGA) is characterized by sudden and temporary memory impairment, while transient epileptic amnesia (TEA) represents amnestic attacks as the main manifestation of focal epilepsy with presumed temporal origin. We present a 48‐year‐old patient who experienced transient amnesia 10 weeks after right selective amygdalo‐hippocampectomy for right temporal lobe epilepsy. Despite TEA being a plausible explanation for amnesia in patients with temporal lobe epilepsy, no epileptiform discharges were found during the amnestic episode and key features indicative of TGA, including long duration, isolated occurrence, and dense anterograde amnesia of the episode, argued against a diagnosis of TEA in this case. Notably, the patient has remained seizure‐free (now 4,5 years) and stopped taking antiseizure medication 32 months after surgery. Although TGA clinical criteria formally exclude patients with recent active epilepsy, neurologists should be aware that TGA can occur after epilepsy surgery in the temporal lobe. Therefore, we consider it of high clinical relevance to establish a careful differential diagnosis between TGA and epileptic amnestic attacks after epilepsy surgery to avoid unnecessary reintroduction or continuation of antiseizure medication. Additionally, this case presents the first comparison of detailed neuropsychological test results before and after a presumed TGA episode, revealing a complete recovery of anterograde memory functions within 1 day.Plain Language Summary: A 48‐year‐old patient experienced an episode of transient amnesia 10 weeks after epilepsy surgery. Given the patient's history, an epileptic origin of the episode initially seemed likely. However, tests revealed no seizure activity during the episode and the characteristics matched a condition called transient global amnesia. This case highlights the importance of correctly diagnosing memory impairments after epilepsy surgery to prevent unnecessary treatment.

Objective: We aimed to assess the ability of semiautomated electric source imaging (ESI) from long‐term video‐electroencephalographic (EEG) monitoring (LTM) to determine the epileptogenicity of temporopolar encephaloceles (TEs) in patients with temporal lobe epilepsy.Methods: We conducted a retrospective study involving 32 temporal lobe epilepsy patients with TEs as potentially epileptogenic lesions in structural magnetic resonance imaging scans. Findings were validated through invasive intracerebral stereo‐EEG in six of 32 patients and postsurgical outcome after tailored resection of the TE in 17 of 32 patients. LTM (mean duration = 6 days) was performed using the 10/20 system with additional T1/T2 for all patients and sphenoidal electrodes in 23 of 32 patients. Semiautomated detection and clustering of interictal epileptiform discharges (IEDs) were carried out to create IED types. ESI was performed on the averages of the two most frequent IED types per patient, utilizing individual head models, and two independent inverse methods (sLORETA [standardized low‐resolution brain electromagnetic tomography], MUSIC [multiple signal classification]). ESI maxima concordance and propagation in spatial relation to TEs were quantified for sources with good signal quality (signal‐to‐noise ratio > 2, explained signal > 60%).Results: ESI maxima correctly colocalized with a TE in 20 of 32 patients (62.5%) either at the onset or half‐rising flank of at least one IED type per patient. ESI maxima showed propagation from the temporal pole to other temporal or extratemporal regions in 14 of 32 patients (44%), confirming propagation originating in the area of the TE. The findings from both inverse methods validated each other in 14 of 20 patients (70%), and sphenoidal electrodes exhibited the highest signal amplitudes in 17 of 23 patients (74%). The concordance of ESI with the TE predicted a seizure‐free postsurgical outcome (Engel I vs. >I) with a diagnostic odds ratio of 2.1.Significance: Semiautomated ESI from LTM often successfully identifies the epileptogenicity of TEs and the IED onset zone within the area of the TEs. Additionally, it shows potential predictive power for postsurgical outcomes in these patients.

Introduction: Mental health comorbidities such as depression and anxiety are common in epilepsy, especially among people with pharmacoresistant epilepsy who are candidates for epilepsy surgery. The Psychology Task Force of the International League Against Epilepsy advised that psychological interventions should be integrated into comprehensive epilepsy care. Methods: To better understand the psychological impact of epilepsy and epileptic seizures in epilepsy surgery candidates, we analysed interviews with this subgroup of patients using Karl Jaspers’ concept of limit situations, which are characterised by a confrontation with the limits and challenges of life. These are especially chance, randomness, and unpredictability, death and finitude of life, struggle and self-assertion, guilt, failure, and falling short of one’s aspirations. Results: In 43 interviews conducted with 15 people with drug-resistant epilepsy who were candidates for epilepsy surgery, we found that these themes are recurrent and have a large psychosocial impact, which can result in depression and anxiety. For some people, epileptic seizures appear to meet the criteria for traumatic events. Conclusion: Understanding epilepsy and seizures as existential challenges complements the neurobiological explanations for psychological comorbidities and can help tailor psychological interventions to the specific needs of people with epilepsy, especially those who are candidates for surgical treatment.