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Abstract Background Glioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of the AMPA-receptor subtype form between non-malignant brain neurons and tumor cells. This neuron-tumor network connectivity contributed to glioma progression and could be efficiently targeted with the EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies. The PerSurge trial was designed to test the clinical potential of perampanel to reduce tumor cell network connectivity and tumor growth with an extended window-of-opportunity concept. Methods PerSurge is a phase IIa clinical and translational treatment study around surgical resection of progressive or recurrent glioblastoma. In this multicenter, 2-arm parallel-group, double-blind superiority trial, patients are 1:1 randomized to either receive placebo or perampanel (n = 66 in total). It consists of a treatment and observation period of 60 days per patient, starting 30 days before a planned surgical resection, which itself is not part of the study interventions. Only patients with an expected safe waiting interval are included, and a safety MRI is performed. Tumor cell network connectivity from resected tumor tissue on single cell transcriptome level as well as AI-based assessment of tumor growth dynamics in T2/FLAIR MRI scans before resection will be analyzed as the co-primary endpoints. Secondary endpoints will include further imaging parameters such as pre- and postsurgical contrast enhanced MRI scans, postsurgical T2/FLAIR MRI scans, quality of life, cognitive testing, overall and progression-free survival as well as frequency of epileptic seizures. Further translational research will focus on additional biological aspects of neuron-tumor connectivity. Discussion This trial is set up to assess first indications of clinical efficacy and tolerability of perampanel in recurrent glioblastoma, a repurposed drug which inhibits neuron-glioma synapses and thereby glioblastoma growth in preclinical models. If perampanel proved to be successful in the clinical setting, it would provide the first evidence that interference with neuron-cancer interactions may indeed lead to a benefit for patients, which would lay the foundation for a larger confirmatory trial in the future. Trial registration EU-CT number: 2023-503938-52-00 30.11.2023.

Abstract Background It is difficult to set up a balanced higher-order full-factorial experiment that can capture multiple intricate interactions between cognitive and psycholinguistic factors underlying bilingual speech production. To capture interactions more fully in one study, we analyzed object-naming reaction times (RTs) by using mixed-effects multiple regression. Methods Ten healthy bilinguals (median age: 23 years, seven females) were asked to name 131 colored pictures of common objects in each of their languages. RTs were analyzed based on language status, proficiency, word choice, word frequency, word duration, initial phoneme, time series, and participant’s gender. Results Among five significant interactions, new findings include a facilitating effect of a cross-language shared initial phoneme (mean RT for shared phoneme: 974 ms vs. mean RT for different phoneme: 1020 ms), which profited males less (mean profit: 10 ms) than females (mean profit: 47 ms). Conclusions Our data support language-independent phonological activation and a gender difference in inhibitory cognitive language control. Single word production process in healthy adult bilinguals is affected by interactions among cognitive, phonological, and semantic factors.

Abstract Background Research in migraine points towards central-peripheral complexity with a widespread pattern of structures involved. Migraine-associated neck and shoulder muscle pain has clinically been conceptualized as myofascial trigger points (mTrPs). However, concepts remain controversial, and the identification of mTrPs is mostly restricted to manual palpation in clinical routine. This study investigates a more objective, quantitative assessment of mTrPs by means of magnetic resonance imaging (MRI) with T2 mapping. Methods Ten subjects (nine females, 25.6 ± 5.2 years) with a diagnosis of migraine according to ICHD-3 underwent bilateral manual palpation of the upper trapezius muscles to localize mTrPs. Capsules were attached to the skin adjacent to the palpated mTrPs for marking. MRI of the neck and shoulder region was performed at 3 T, including a T2-prepared, three-dimensional (3D) turbo spin echo (TSE) sequence. The T2-prepared 3D TSE sequence was used to generate T2 maps, followed by manual placement of regions of interest (ROIs) covering the trapezius muscles of both sides and signal alterations attributable to mTrPs. Results The trapezius muscles showed an average T2 value of 27.7 ± 1.4 ms for the right and an average T2 value of 28.7 ± 1.0 ms for the left side (p = 0.1055). Concerning signal alterations in T2 maps attributed to mTrPs, nine values were obtained for the right (32.3 ± 2.5 ms) and left side (33.0 ± 1.5 ms), respectively (p = 0.0781). When comparing the T2 values of the trapezius muscles to the T2 values extracted from the signal alterations attributed to the mTrPs of the ipsilateral side, we observed a statistically significant difference (p = 0.0039). T2 hyperintensities according to visual image inspection were only reported in four subjects for the right and in two subjects for the left side. Conclusions Our approach enables the identification of mTrPs and their quantification in terms of T2 mapping even in the absence of qualitative signal alterations. Thus, it (1) might potentially challenge the current gold-standard method of physical examination of mTrPs, (2) could allow for more targeted and objectively verifiable interventions, and (3) could add valuable models to understand better central-peripheral mechanisms in migraine.

Abstract Background The treatment recommendations for Low-grade Gliomas (LGG) underwent profound changes due to results from RTOG 9802 published in April 2016. This work aims to investigate whether the results from the trial were already incorporated into the treatment recommendations at German oncology centers before an update of the official guidelines. Methods An online based questionnaire with questions covering all aspects of adjuvant treatments of LGGs was generated, including three cases with distinct clinical situations. We contacted all members of the neuro-oncologic working group (NOA) of the German Cancer Society (DKG) as well as all German-speaking members of the European Low-Grade Glioma Network via E-mail. Results We collected 38 responses. All responders were at least specialists; they predominantly worked at tertiary hospitals with a high volume of LGGs treated annually (75% with more than 10 cases per year). All responders stated to consent treatment recommendation for LGGs within interdisciplinary oncologic boards. The treatment recommendations for LGGs changed profoundly between 2015 and 12/2016. There is a trend towards PCV-based multimodal treatments, especially for oligodendroglial LGGs, as well as a trend away from watchful-waiting-policies for astrocytic LGGs. Conclusion Neurooncologists do adapt results from clinical trials quickly. None the less, there is still an immense heterogeneity within the treatment recommendations, predominantly for astrocytic LGGs. Well planned clinical trials and concise treatment recommendations are warranted; additionally, individual counseling of patients is essential.

Abstract Background Visuospatial attention is executed by the frontoparietal cortical areas of the brain. Damage to these areas can result in visual neglect. We therefore aimed to assess a combination of the greyscales task and repetitive navigated transcranial magnetic stimulation (rTMS) to identify cortical regions involved in visuospatial attention processes. This pilot study was designed to evaluate an approach in a cohort of healthy volunteers, with the future aim of using this technique to map brain tumor patients before surgery. Ten healthy, right-handed subjects underwent rTMS mapping of 52 cortical spots in both hemispheres. The greyscales task was presented tachistoscopically and was time-locked to rTMS pulses. The task pictures showed pairs of horizontal rectangles shaded continuously from black at one end to white at the other, mirror-reversed. On each picture the subject was asked to report which of the two greyscales appeared darker overall. The responses were categorized into “leftward” and “rightward,” depending on whether the subject had chosen the rectangle with the darker end on the left or the right. rTMS applied to cortical areas involved in visuospatial attention is supposed to affect lateral shifts in spatial bias. These shifts result in an altered performance on the greyscales task compared to the baseline performance without rTMS stimulation. Results In baseline conditions, 9/10 subjects showed classic pseudoneglect to the left. Leftward effects also occurred more often in mapping conditions. Yet, calculated rightward deviations were strikingly greater in magnitude (p