Brain tumors represent the second most frequent etiology in patients with focal seizure onset before 18 years of age and submitted to epilepsy surgery. Hence, this category of brain tumors, herein defined as low-grade, developmental, epilepsy-associated brain tumors (LEAT) is different from those frequently encountered in adults as (A): 77% of LEAT occur in the temporal lobe; (B): the vast majority of LEAT are of low malignancy and classified as WHO I°; (C): LEAT are often composed of mixed glial and neuronal cell components and present with variable growth patterns including small cysts or nodules; (D): LEAT do not share common gene driving mutations, such as IDH1 or 1p/19q co-deletions. Characteristic entities comprise the ganglioglioma (GG), the dysembryoplastic neuroepithelial tumor (DNT), the angiocentric glioma (AG), the isomorphic diffuse glioma (IDG) and the papillary glio-neuronal tumor (PGNT), representing 73.2% of 1680 tumors collected in a large German series of 6747 patients submitted to epilepsy surgery. In the realm of exciting discoveries of genetic drivers of brain tumors new genes have been also reported for LEAT. BRAF V600E mutations were linked to GG with CD34 expression, FGFR1 mutations to DNT, MYB alterations to AG and also IDG and PRKCA fusions to PGNT, suggesting the possibility to also develop a genetically driven tumor classification scheme for LEAT. Rare availability of LEAT in a single center is a challenging obstacle, however, to systematically unravel the neurobiological nature and clinical behavior of LEAT. Other challenges in need of clarification include malignant tumor progression of LEAT entities, seizure relapse in patients following bulk tumor resection and the controversial issue of associated focal cortical dysplasia as additional pathomechanism. In order to advance our understanding and promote reliable diagnostic work-up of LEAT, we recommend, therefore, international collaboration to achieve our goals.

Periventricular nodular heterotopias (PVNH) are developmental abnormalities with neurons abnormally clustered around the cerebral ventricles. Patients frequently present with focal drug-resistant epilepsy (DRE). However, the relationship between PVNH and the seizure onset zone (SOZ) is complex. Stereo-electroencephalography (SEEG) is an invasive diagnostic procedure for patients with DRE. In selected patients, the SEEG may be converted into a therapeutic procedure, lesioning the probable (SOZ) with pulsed radiofrequency thermocoagulation (RFTC). The aim of our study was to evaluate the efficacy and safety of SEEG-RFTC in a series of DRE patients with PVNH. Twenty-four patients with focal DRE related to PVNH and treated with SEEG-guided-RFTC restricted to nodules were prospectively collected between 2016 and 2023 and retrospectively analyzed after a follow-up of at least 12 months. Seventeen patients (71 %) responded (ILAE class 1-4) after SEEG-guided RFTC of whom eleven (46 %) became seizure-free (class 1) at last follow up, nine (45 %) despite residual PVNH tissue on MRI. SEEG seizure onset was restricted to PVNH in eleven patients (class 1 in 45 %) and simultaneously in PVNH and other cortical areas in thirteen patients (class 1 in 46 %). Out of 31 SEEG-RFTC procedures in twenty-four patients, adverse events, related to RFTC, were recorded in eight (26 %), of which two patients (8 %) had predicted permanent visual complaints whilst the other five had transient complaints. This study demonstrates that a considerable percentage of patients, even with bilateral, multiple PVNH and involvement of adjacent cortical regions can be rendered seizure-free with SEEG-guided-RFTC restricted to the nodules. Furthermore, this study delivers evidence that the complete destruction of the entire nodule is not necessary to render a patient seizure free. This justifies the use of SEEG in patients with single, multiple or bilateral PVNHs to provide insight into the epileptogenic organization in and around these lesions.

Objective: To investigate whether local lesions created by stereo‐electroencephalography (SEEG)–guided radiofrequency thermocoagulation (RFTC) affect distant brain connectivity and excitability in patients with focal, drug‐resistant epilepsy (DRE).Methods: Ten patients with focal DRE underwent SEEG implantation and subsequently 1 Hz bipolar repetitive electrical stimulation (RES) for 30 s before and after RFTC. Root mean square (RMS) of cortico‐cortical evoked potentials (CCEPs) was calculated for 15 ms to 300 ms post‐stimulation with baseline correction. Contact pairs were categorized as both coagulated, hybrid, or both non‐coagulated. The data were divided into nine categories based on the stimulating and recording contact pair combinations. RMS of CCEPs was compared before and after (<12 h) RFTC using a two‐sample t test (Hochberg corrected, p < 0.05) for each patient. Boost score, indicating power increase during seizures before RFTC relative to baseline, was analyzed in 4 s windows with 1 s overlap during seizure duration.Results: RFTC altered connectivity across all categories. Of interest, decreases and increases in RMS were observed in connections between non‐coagulated contacts distant from coagulation site (range: 1.09–85 mm, median = 17.7 mm, interquartile range [IQR] 10.1–32.3). Contact pairs involved in significantly altered non‐coagulated connections showed a higher boost score correlation in the theta, beta, and gamma bands, as well as a stronger maximum correlation with coagulated sites in the delta band than contacts for which connectivity did not change after RFTC.Significance: This study highlights how local lesions alter distant brain connectivity, providing insights for future research on epilepsy network changes and seizure outcomes following RFTC.

: Paraneoplastic neurological syndromes (PNS) can manifest with every type of malignancy. A well-known syndrome is myasthenia gravis (MG) in combination with thymomas. No association between primary brain tumors and neuromuscular disorders has been described. Here, we present a case of a 65-year-old patient who developed MG, following an uncomplicated, gross-total resection of a glioblastoma. To our knowledge, this is the first case describing the onset of MG during the early postoperative phase after glioblastoma resection. Current criteria of PNS are insufficient when the neurological syndrome is diagnosed at the time of a malignancy or shortly thereafter and should be revisited.

Background: Gastrointestinal (GI) complaints are frequently noted in aging dystrophinopathy patients, yet their underlying molecular mechanisms are largely unknown. As dystrophin protein isoform 71 (Dp71) is particularly implicated in the development of smooth muscle cells, we evaluated its distribution in the neonatal and adult rat intestine in this study. Methods: Dp71 expression levels were assessed in the proximal (duodenum, jejunum and ileum) and distal (caecum, colon and rectum) intestine by Western blotting and qPCR. In addition, the cellular distribution of total Dp was evaluated in the duodenum and colon by immunohistochemical colocalization studies with alpha-smooth muscle actin (aSMA), Hu RNA binding proteins C and D (HuC/HuD) for neurons and vimentin (VIM) for interstitial cells. Results: In neonatal and adult rats, the distal intestine expressed 2.5 times more Dp71 protein than the proximal part (p < 0.01). This regional difference was not observed in Dp71 mRNA. During both stages, Dp-immunoreactivity was predominant in the muscularis propria, where it co-localized with aSMA and HuC/HuD. Conclusions: In neonatal and adult rats, Dp71 was expressed highest in the distal intestine. Together with the observation that Dp may be expressed by myenteric neurons, this warrants a paradigm shift in the treatment of GI comorbidities.