Cerebral toxoplasmosis is a form of encephalitis caused by Toxoplasma gondii. It typically occurs in immunocompromised individuals and is rarely observed in patients with B‑cell lymphoma. The first two patients of this case series, both previously diagnosed with peripheral B‑cell lymphoma, presented with new-onset neurological symptoms and cerebral mass lesions. Laboratory results indicated latent infection with T. gondii, but the findings in cerebrospinal fluid were unspecific One patient underwent brain biopsy, thereby confirming the diagnosis histologically, while the second patient was classified as having probable cerebral toxoplasmosis. Both patients were treated with pyrimethamine and sulfadiazine, leading to clinical and radiological improvement within weeks. To highlight the diagnostic pitfalls of cerebral toxoplasmosis, we included a third patient in the case series who presented with a cerebral metastasis of peripheral diffuse large B‑cell lymphoma. Additionally, we performed a comprehensive literature review on cerebral toxoplasmosis in patients with peripheral B‑cell lymphoma.

ObjectivesGlioblastoma (GB) is a highly invasive and lethal primary brain tumor, with survival affected by tumor location, clinical factors, and molecular features. White matter (WM) tracts serve as pathways for GB cell migration, but the effects of microstructural integrity within specific fiber subcomponents on overall survival (OS) remain unclear. This study aimed to determine whether correlational tractography can identify WM tract segments whose microstructural integrity correlates with OS in GB patients.Materials and methodsDiffusion tensor imaging and clinical data from 498 GB patients in the UPENN-database were analyzed. Connectometry and correlational tractography were used to reconstruct WM tracts and identify subcomponents whose fractional anisotropy (FA) correlated with OS, controlling for age, sex, and extent of resection. Kaplan–Meier and Cox-proportional-hazards models assessed survival differences based on FA.ResultsNormal FA in reconstructed fiber subcomponents was significantly associated with longer OS across the whole brain (median OS 487 vs. 207 days) and in left- (488 vs. 241 days) and right-hemispheric tumors (493 vs. 216 days). Subclusters of the thalamic radiation and corpus callosum were the major tracts correlating with OS. Lobe-specific patterns reflected normative anatomy: projection fibers predominated in central tumors, commissural fibers in frontal tumors, and association fibers in temporal tumors. Cox-models confirmed FA was independently associated with reduced hazard across the whole brain (HR=0.555) and in both hemispheres (HR=0.589).ConclusionConnectometry and correlational tractography identify WM subcomponents whose microstructural integrity is closely linked to survival in GB, supporting their potential for prognostic modeling and individualized treatment planning.

INTRODUCTION:Posterior circulation (PC) stroke is underrepresented in most large-scale trials. While the importance of the onset-to-needle time (ONT) for intravenous thrombolysis (IVT) in anterior circulation stroke is well established, data on PC stroke are lacking. This study aimed to investigate how ONT affects functional outcome after IVT and to identify additional predictors of outcome in PC stroke. PATIENTS AND METHODS:IVT-treated PC stroke patients included in the nationwide Austrian Stroke Unit Registry between 2003 and 2024 were retrospectively analyzed. The primary outcome measure was the excellent (mRS 0-1) and non-excellent (mRS 2-6) functional outcome at 90 days. The secondary outcome measure was the occurrence of severe intracranial hemorrhage (sICH). Associations between ONT as continuous variable, clinical predictors, and functional outcomes were assessed using ordinal and binomial logistic regression models. A cut-off point for the transition from excellent to non-excellent outcome was determined by maximizing the odds ratio metric. The effect of ONT on sICH was analyzed dichotomously in time intervals of 0-150 min and 151-300 min. RESULTS:Of 11,025 eligible patients with PC stroke, 1,359 (12.3%) were treated with IVT, resulting in more frequent excellent functional outcome in patients treated with IVT compared to best medical treatment (BMT) in the ordinal logistic regression (adjusted odds ratio (aOR) 1.31, 95% CI 1.16-1.47, p < 0.001). Correspondingly, binomial logistic regression showed fewer non-excellent functional outcomes in patients treated with IVT compared to BMT (aOR 0.73, 95% CI 0.63-0.85, p < 0.001). The odds of an excellent functional outcome were increased within the first 282 min, with a pronounced treatment benefit in the first 122 min. The transition cut-off point was found to be at 258 min. sICH occurred in 2.8% and was unrelated to ONT (aOR 1.28, 95% CI 0.55-2.91, p = 0.552). Overall, women had lower IVT rates (11.3% vs 13.0%, p = 0.007) and were more likely to experience a non-excellent outcome (aOR 1.31, 95% CI 1.19-1.45, p < 0.001), but had similar functional outcomes compared to men when treated with IVT (aOR 1.03, 95% CI 0.74-1.43, p = 0.883). DISCUSSION AND CONCLUSION:A treatment benefit of IVT in PC stroke was observed within 4.5 h of stroke onset, with its maximum within the first 2 h. Women should receive special attention as they may be at a prognostic disadvantage due to lower IVT rates and less favorable overall outcomes.

Cerebral toxoplasmosis is a form of encephalitis caused by Toxoplasma gondii. It typically occurs in immunocompromised individuals and is rarely observed in patients with B‑cell lymphoma. The first two patients of this case series, both previously diagnosed with peripheral B‑cell lymphoma, presented with new-onset neurological symptoms and cerebral mass lesions. Laboratory results indicated latent infection with T. gondii, but the findings in cerebrospinal fluid were unspecific One patient underwent brain biopsy, thereby confirming the diagnosis histologically, while the second patient was classified as having probable cerebral toxoplasmosis. Both patients were treated with pyrimethamine and sulfadiazine, leading to clinical and radiological improvement within weeks. To highlight the diagnostic pitfalls of cerebral toxoplasmosis, we included a third patient in the case series who presented with a cerebral metastasis of peripheral diffuse large B‑cell lymphoma. Additionally, we performed a comprehensive literature review on cerebral toxoplasmosis in patients with peripheral B‑cell lymphoma.

Unter paraneoplastischen neurologischen Syndromen (PNS) versteht man verschiedene Erkrankungen des zentralen, peripheren und autonomen Nervensystems sowie der neuromuskulären Übertragung und der Muskulatur. Sie beruhen auf einer Immunreaktion, die sich einerseits gegen Tumorgewebe (Abwehr der Krebserkrankung) und andererseits gegen körpereigenes neuronales Gewebe (Autoimmunreaktion) richtet. Psychiatrische Manifestationen, zu denen affektive Symptome (u. a. Stimmungslabilität, Depression, Angst), kognitive Beeinträchtigungen (u. a. Aufmerksamkeit, Gedächtnis, Sprache), psychotische Symptome (u. a. Halluzination, Realitätsverlust) sowie Wesens- und Verhaltensänderungen zählen, müssen bei PNS im Hinblick auf die Diagnose mitgedacht werden, insbesondere wenn das limbische Netzwerk mitbetroffen ist. Sowohl für das neurologische als auch für das onkologische Outcome ist eine frühzeitige Diagnose entscheidend, speziell bei High-Risk-PNS. Der vorliegende Beitrag thematisiert klinische Syndrome ebenso wie Pathophysiologie und Einteilung, erörtert das klinische Spektrum sowie die klinische Bedeutung psychiatrischer Symptome bei PNS und erläutert Therapiemöglichkeiten.

Background: Glioblastoma is an extremely aggressive brain tumor that diffusely infiltrates white matter and alters large-scale brain connectivity. Most prognostic models focus on localized tumor features and clinical variables, overlooking broader effects on the brain's structural connectome. This study addressed this limitation by integrating graph-theoretical analysis of preoperative diffusion tensor imaging (DTI)-derived structural connectomes with machine learning (ML) to improve prediction of overall survival (OS) in newly diagnosed glioblastoma. Methods: Preoperative DTI data from 871 glioblastoma patients from the UPenn-GBM and UCSF-PDGM cohorts were processed to construct whole-brain structural connectomes weighted by tract count and quantitative anisotropy (QA). Global and nodal graph-theoretical network metrics were extracted and combined with demographic and clinical information. Ten ML models were trained and validated on 784 patients (90% of the cohort). The three best-performing algorithms were tested on a held-out cohort of 87 patients (10%). Results: Random forest, adaptive boosting, and KStar showed the strongest validation performance. In held-out internal testing, random forest models using degree and QA-weighted strength achieved accuracies of 0.862 and 0.874, with AUROCs of 0.929 and 0.909, for predicting OS beyond one year. Strength and clustering coefficient were key predictors, with over two-thirds of significant nodes localized in the temporal lobe, particularly the parahippocampal, and superior, middle, and inferior temporal gyri. Conclusions: Graph-theoretical quantification of structural brain network disruption combined with ML allows accurate prediction of OS in glioblastoma. These results support a network-based conceptualization of the disease and indicate that connectome-derived metrics may complement established prognostic frameworks.

Background:Novel approaches to guide personalized treatment in glioblastoma are urgently needed. Given the poor predictive value of genetic biomarkers in glioblastoma, we are conducting a prospective clinical trial to investigate the novel approach of cultivated patient-derived tumor cells (PDCs) for ex vivo drug screening. Methods:In this randomized phase 2 study, we are testing the ability of PDC-based ex vivo drug screening to formulate a personalized recommendation for maintenance treatment in patients with newly diagnosed glioblastoma with unmethylated MGMT promoter after combined radio-chemotherapy. Based on overall survival as the primary endpoint, we plan to include 240 patients (120 per group) to show with a power of 80% that we can increase the median survival from 12 to 17 months (hazard ratio 0.7). Patients will be randomized 1:1 to either the standard group (no drug screening) or the intervention group (drug screening and personalized recommendation for maintenance treatment). In the intervention group, automated drug screening will be performed on PDCs with 28 drugs used for the treatment of solid tumors and hematological malignancies. Based on the cytotoxic activity of these drugs, as quantified by relative viability based on adenosine triphosphate levels, a molecular tumor board will recommend a personalized treatment regimen. Results:The first patient was enrolled in July 2024. Interim analysis of the ATTRACT study (NCT06512311) is expected in late 2027, and final results in 2030. Trial Registration:The ATTRACT trial is registered under the ID NCT06512311 (https://clinicaltrials.gov/study/NCT06512311).

Im Verlauf der Erkrankung haben Glioblastompatient:innen ein hohes Risiko, kognitive Defizite zu entwickeln, welche sich auf persönliche, soziale und berufliche Lebensbereiche auswirken und die Lebensqualität erheblich beeinträchtigen. Die kognitive Funktionsfähigkeit kann durch direkte tumorbedingte Schädigung, die Störung neuronaler Netzwerke sowie durch patienten- und therapiebezogene Faktoren beeinträchtigt werden, wie Operation, Radiochemotherapie, Alter oder Bildungsniveau. Eine neuropsychologische Verlaufsdiagnostik erlaubt die Erfassung von Veränderungen in der Kognition über die Zeit, die Identifikation von Ursachen sowie die Ableitung alltagsrelevanter Empfehlungen. Zudem bietet sie eine Grundlage für therapeutische Entscheidungen hinsichtlich des Verhältnisses zwischen Behandlungstoxizität und Erhalt kognitiver Funktionsfähigkeit. Neuropsychiatrische Komorbiditäten wie Fatigue, Schlafstörung, Depression und Ängste sollten gezielt behandelt werden, da sie die Kognition negativ beeinflussen können. Daneben stellt auch die konkomitante Medikation einen potenziell modifizierbaren Einflussfaktor dar. Der prä- und postoperative kognitive Status ist ein unabhängiger Prädiktor für das Gesamtüberleben, und eine kognitive Verschlechterung kann ein früher Hinweis auf eine Progression sein. Die medizinische Entscheidungsfähigkeit hängt primär vom Ausmaß der bestehenden kognitiven Beeinträchtigungen ab und wird von Behandler:innen häufig überschätzt. Therapeutische Ansätze hängen von der zugrunde liegenden Ursache ab und umfassen unter anderem kognitive Rehabilitation, die auf Training oder Kompensation beeinträchtigter Funktionen abzielt, sowie pharmakologische Interventionen. Donepezil und Memantin könnten potenziell positive Effekte haben, jedoch bei aktuell begrenzter Evidenz.

BACKGROUND AND PURPOSE:Detecting glioma recurrence is fundamental for clinical patient outcomes; however, conventional MRI (cMRI) techniques may be limited, leading to diagnostic uncertainty relevant for therapeutic intervention. This study aimed to evaluate whether a microvascular perfusion (µPerf) imaging technique based on spin-echo DSC perfusion MRI could support the early detection of glioma recurrence compared with cMRI by characterizing subtle vascular changes preceding macroscopic tumor growth. MATERIALS AND METHODS:A total of 351 patients with gliomas who underwent 2003 follow-up MRI examinations were retrospectively evaluated, with 422 of these examinations subjected to detailed quantitative analysis. The standard cMRI protocol was extended by applying the µPerf approach, with an additional 2 minutes for data acquisition. Custom-made Matlab software was used to generate imaging biomarker maps for microvascular CBV and microvascular type indicator. The clinical utility of µPerf was assessed by comparing its findings with radiologic interpretations of cMRI data, which were reviewed in consensus by at least 2 board-certified radiologists. Statistical analyses included the calculation of diagnostic performance metrics and the area under the receiver operating characteristic curve (AUROC) to evaluate glioma recurrence detection. RESULTS:The µPerf technique exhibited superior diagnostic performance, achieving an accuracy of 97.4% and AUROC values of 0.987 (95% CI, 0.976-0.999) for microvascular type indicator and 0.982 (95% CI, 0.965-0.998) for microvascular CBV, significantly surpassing cMRI (accuracy: 85.1%; AUROC: 0.941; 95% CI, 0.918-0.965 for CBV). µPerf identified glioma recurrence earlier than cMRI in 13.5% of cases, with the time interval ranging from 41 to 353 days (mean, 137 days). During this time, tumor volume increased by 38% to as much as 155-fold (mean, 9.1-fold). Notably, early recurrences of high-grade malignant gliomas were predominantly characterized by microvascular changes compared with later-stage recurrences. CONCLUSIONS:µPerf improves early detection of glioma recurrence and shows a higher sensitivity of microvascular changes compared with cMRI. µPerf has significant potential to promote more timely and personalized treatment strategies, which, in turn, could improve patient outcomes. Notably, µPerf works with standard clinical follow-up protocols, but its integration into clinical practice requires further validation through multicenter studies and long-term outcome analyses.

TPS2097 Background: Targeted therapies used in a personalized treatment concept have revolutionized the management of several solid cancers. So far, various clinical trials aiming to introduce the concept of personalized targeted therapies in glioblastoma have failed, as no clinically meaningful responses were observed. Importantly, most clinical trials investigating molecular targeted therapies included all-comers and concentrated on genetic biomarkers to predict treatment response. Given the biological complexity of glioblastoma, genetic biomarkers might give only an insufficient insight into the response of a given patient, and more personalized approaches are warranted. As novel approaches to guide personalized treatment in glioblastoma are urgently needed, we designed a prospective clinical trial to investigate the novel approach of cultivated patient-derived tumor cells (PDCs) for ex vivo drug screening. Methods: In this randomized phase 2 study, we are testing the ability of PDC-based ex vivo drug screening to formulate a personalized recommendation for maintenance treatment in patients with newly diagnosed glioblastoma with unmethylated MGMT promoter after neurosurgical resection followed by combined radio-chemotherapy. Based on overall survival as the primary endpoint, we plan to include 240 patients (120 per group) to show with a power of 80% that we can increase the median survival from 12 to 17 months (hazard ratio 0.7). Patients are randomized 1:1 to either the standard group (no drug screening) or the intervention group (drug screening and personalized recommendation for maintenance treatment). In the intervention group, automated drug screening is performed on PDCs with 28 drugs used for treatment of solid tumors and hematological malignancies. Based on the cytotoxic/cytostatic activity of these drugs, as quantified by relative viability based on adenosine triphosphate levels, a molecular tumor board recommends a personalized treatment regimen. The first patient was enrolled in July 2024. Interim analysis of the ATTRACT study (NCT06512311) is expected in late 2027, and final results in 2030. Moreover, the clinical trial is accompanied by a comprehensive translational research program to gain insights into the biological underpinnings of treatment response in glioblastoma. Clinical trial information: NCT06512311 .

We present results of a retrospective population-based investigation of patterns of care and outcome of glioblastoma patients in Austria. In this nation-wide cooperative project, all Austrian glioblastoma patients newly diagnosed between 2014 and 2018 and registered in the ABTR-SANOnet database were included. Histological typing used criteria of the WHO classification of CNS tumors, 4th edition 2016. Patterns of care were assessed, and all patients were followed until the end of 2019. 1,420 adult glioblastoma cases were identified. 813 (57.3

Zusammenfassung Eine qualitativ hochwertige Versorgung von Patient:innen mit Glioblastomen erfolgt in Österreich durch die etablierten Neuroonkologischen Zentren (NONKZ, Versorgungsmodell ÖSG). Die interdisziplinäre und fächerübergreifende Zusammenarbeit ist das wesentliche Element für die bestmögliche diagnostische und therapeutische Sicherheit und Effizienz. Vor allem sog. „alternativmedizinische“ u. a. Methoden, angewandt bei Patient:innen mit Glioblastomen, eröffnen ein breites ethisches Spannungsfeld. Diese Patient:innen mit hochmalignen Erkrankungen sind eine besonders vulnerable Personengruppe. Neben dem offensichtlichen Geschäft mit der Hoffnung in einer persönlichen Ausnahmesituation für Patient:innen und Angehörige sind zusätzliche tumorbedingte kognitive Einschränkungen bei dieser Patientengruppe, mit potenziell einhergehender Beeinträchtigung der Entscheidungsfähigkeit, von besonderer Problematik. Ansätze zur Lösung beinhalten eine vermehrte und strukturierte Aufklärung von Patient:innen und Angehörigen zu komplementären/alternativen Praktiken, eine psychoonkologische Betreuung, ausreichende personelle Ressourcen in den neuroonkologischen Zentren, einen kritischen Journalismus und den öffentlicher Diskurs über Ethik in der Medizin.

IntroductionAnti-Xa serves as a clinical surrogate for assessing the efficacy and bleeding risk in patients treated with enoxaparin for thromboembolic events. Evidence from the literature and empirical observations suggest that patients are underdosed in clinical practice to avoid bleeding complications. This study aimed to investigate such underdosing of enoxaparin and its potential impact on achieving therapeutic anti-Xa levels.MethodsThis multicentric, retrospective, observational study included patients with acute ischemic stroke due to atrial fibrillation. All patients received enoxaparin in the therapeutic setting with subsequent anti-Xa measurements. The one-sample, one-tailed Wilcoxon signed-rank test was used to identify a significant difference between the doses administered and the recommended daily dose. Logistic regression model analysis was performed to identify additional predictors affecting achievement of the therapeutic anti-Xa target range. Stepwise forward-backward selection with Akaike’s information criterion as metric was applied to refine the logistic regression model.ResultsA total of 145 patients from the university hospitals of St. Pölten and Tulln in Lower Austria were included. The median daily enoxaparin dose administered was 1.23 mg/kg, resulting in an overall target range achievement rate of 66%. As compared to recommended therapeutic doses, significant underdosing of enoxaparin was evident in both participating centers (p < 0.001). The calculated threshold dose to achieve the therapeutic target range with a 90% probability was 1.5 mg/kg enoxaparin daily. Female sex was found to be a strong independent predictor of achieving a therapeutic target range (OR 9.44; 95% CI 3.40–30.05, p < 0.001).ConclusionDespite the underdosing observed in both centers, therapeutic anti-Xa levels were achieved with lower than recommended doses of enoxaparin, and women required even lower doses than men. These findings warrant further confirmation by prospective studies.

Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8 + /perforin + /granzyme A/B + cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions. Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.

Background ‘Definite Neuroborreliosis (NB)’ is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Objective Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. Design and methods This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. Results We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated ‘definite NB’. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant ( P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Conclusion Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

INTRODUCTION:Acute hyperammonemic encephalopathy is associated with distinct brain MRI findings, namely, hyperintensity in T2-weighted sequences as well as restricted diffusion in diffusion-weighted imaging with accentuation in the insular cortex and cingulate gyrus. The pathophysiology and the histopathological correlates of these characteristic MRI findings are largely unknown. CASE REPORT:We present a 57-year-old male with a history of chronic alcohol abuse, liver cirrhosis and portal hypertension, and a clinical syndrome (variceal bleeding, depression of consciousness, seizures), elevated plasma ammonia levels, and characteristic brain MRI abnormalities suggestive of acute hyperammonemic encephalopathy. A postmortem histopathological examination revealed extensive hypoxic ischemic encephalopathy without evidence for metabolic encephalopathy. No episodes of prolonged cerebral hypoxemia were documented throughout the course of the disease. We conducted a review of the literature, which exhibited no reports of hyperammonemic encephalopathy in association with characteristic brain MRI findings and a consecutive histopathological examination. CONCLUSION:This is the first report of a patient with acute hyperammonemic encephalopathy together with characteristic brain MRI findings and a histopathological correlation. Although characteristic MRI findings of acute hyperammonemic encephalopathy were present, a histopathological examination revealed only hypoxic pathology without signs of metabolic encephalopathy.

The mutational status of the isocitrate dehydrogenase (IDH) gene plays a key role in the treatment of glioma patients because it is known to affect energy metabolism pathways relevant to glioma. Physio-metabolic magnetic resonance imaging (MRI) enables the non-invasive analysis of oxygen metabolism and tissue hypoxia as well as associated neovascularization and microvascular architecture. However, evaluating such complex neuroimaging data requires computational support. Traditional machine learning algorithms and simple deep learning models were trained with radiomic features from clinical MRI (cMRI) or physio-metabolic MRI data. A total of 215 patients (first center: 166 participants + 16 participants for independent internal testing of the algorithms versus second site: 33 participants for independent external testing) were enrolled using two different physio-metabolic MRI protocols. The algorithms trained with physio-metabolic data demonstrated the best classification performance in independent internal testing: precision, 91.7%; accuracy, 87.5%; area under the receiver operating curve (AUROC), 0.979. In external testing, traditional machine learning models trained with cMRI data exhibited the best IDH classification results: precision, 84.9%; accuracy, 81.8%; and AUROC, 0.879. The poor performance for the physio-metabolic MRI approach appears to be explainable by site-dependent differences in data acquisition methodologies. The physio-metabolic MRI approach potentially supports reliable classification of IDH gene status in the presurgical stage of glioma patients. However, non-standardized protocols limit the level of evidence and underlie the need for a reproducible framework of data acquisition techniques.

Zusammenfassung Die Metastasierung in das zentrale Nervensystem (ZNS) bei T‑Zell-Lymphomen ist ein seltenes klinisches Szenario. Zu den häufigsten Subtypen mit ZNS-Beteiligung gehören periphere T‑Zell-Lymphome (PTCL) und anaplastische großzellige Lymphome (ALCL). Neurologische Symptome bei einer sekundären ZNS-Beteiligung entwickeln sich in der Regel subakut bis akut. Die diagnostischen Maßnahmen umfassen die klinisch neurologische Untersuchung, eine Gadolinium-verstärkte MRT der gesamten Neuroachse, eine Liquoranalyse und gegebenenfalls eine Hirnbiopsie. Die ZNS-Metastasierung von T‑Zell-Lymphomen stellt, aufgrund ihrer Seltenheit, eine diagnostische Herausforderung dar und muss von anderen Erkrankungen, wie infektiologischen, autoimmunen oder anderen neoplastischen Ursachen, abgegrenzt werden. Zu den Behandlungsoptionen gehören die systemische Chemotherapie, die intrathekale Chemotherapie und die Strahlentherapie. Die Prognose für eine sekundäre ZNS-Beteiligung bei T‑Zell-Lymphomen ist, trotz der zahlreichen Behandlungsoptionen, in der Regel ungünstig. In diesem Fallbericht wird über eine durch Biopsie nachgewiesene ZNS-Metastase eines peripheren T‑Zell-Lymphoms berichtet. Ziel der Literaturübersicht inklusive des Fallberichts ist es, das Verständnis für die klinischen Merkmale, die diagnostischen Modalitäten, die Behandlungsmöglichkeiten und die Prognose der ZNS-Metastasierung von peripheren T‑Zell-Lymphomen zu verbessern.

Background:The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification. Methods:In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005-2018) and an external validation site in South Korea (44 patients, 2013-2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines. Results:The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64-11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients. Conclusions:The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer.