Cerebral activation patterns and functional connectivity during perception of social cues in people with autism spectrum disorder and typically developed controls - an fMRI study

Als Autismus beschreibt man laut dem Diagnostic and Statistical Manual of Mental Disorders (DSM-V) eine „tiefgreifende Entwicklungsstörung“. Aktuell werden fünf, vormals verschiedene, Diagnosen unter dem Begriff Autismus Spektrum Störung (ASD) zusammengefasst. Dabei ist die Bandbreite der präsentierten Symptome groß und ihre Ausprägung bzw. die Einschränkungen, die betroffene Personen erleben, individuell sehr unterschiedlich. Allen Betroffenen gemeinsam sind Auffälligkeiten in drei Hauptbereichen: Schwierigkeiten in der sozialen Interaktion, auf verschiedene Weise beeinträchtigte Kommunikation und schließlich Verhaltensmuster, die sich in Stereotypien, repetitiven Verhaltensmustern oder in Tiefe und Art ungewöhnlichen Interessen und Beschäftigungen äußern können. Darüber hinaus besteht bei ASD eine hohe Komorbidität mit anderen psychiatrischen Erkrankungen, wie z.B. Depressionen. Insbesondere die Schwierigkeiten in der sozialen Interaktion mit anderen werden oft als belastend empfunden und können hohen Leidensdruck bei den Betroffenen verursachen. ASD Patienten können u.a. nur schwer vom Gesichtsausdruck oder der Prosodie auf die Gefühlslage eines Gegenübers schließen, sie vermeiden Augenkontakt und das Initiieren und die Aufrechterhaltung von sozialen Kontakten fallen ihnen schwerer als Vergleichspersonen. Es existieren verschiedene Theorien darüber, worin die neurologischen Korrelate der sozialen Interaktionsschwierigkeiten bestehen könnten: Zum Einen werden Aktivierungsunterschiede in Hirnregionen, die bei der Verarbeitung sozialer Signale eine Rolle spielen, angenommen, zum Anderen gerät zunehmend die Untersuchung der Verbindung dieser Regionen untereinander in den Fokus der Forschung. Mehrere Studien fanden bei Autisten eine Hypoaktivierung in den Amygdalae und dem fusiformen Gyrus. Bei Untersuchungen der Konnektivität fanden Studien sowohl eine erhöhte als auch eine reduzierte Konnektivität zwischen an der Verarbeitung von sozialen Signalen beteiligten Hirnregionen. Außerdem fanden sich Hinweise, dass das Konnektivitätsmuster bei Autisten individuell sehr unterschiedlich, aber intrapersonell konstant sind - dies wird als Idiosynkrasie bezeichnet. Ziel unserer fMRT-Studie war es, die Aktivierung von Hirnregionen, die an der Wahrnehmung und Verarbeitung sozialer Signale beteiligt sind, zu untersuchen. Der erste Teil der Experimente diente der Identifizierung von Strukturen, die durch die Verarbeitung menschlicher Stimmen, Gesichter und audiovisueller Integration aktiviert werden. Im Fokus lagen dabei die rechte und linke Amygdala, der rechte und linke fusiforme Gyrus, die rechte und linke temporale Sprachregion und ein audio-visuelles Integrationsareal im rechten posterioren superioren temporalen Sulcus. Untersucht wurden Aktivierungsunterschiede während der impliziten Wahrnehmung und Verarbeitung von sozialen Signalen zwischen den Gruppen der Autisten und der neurotypischen Kontrollen. Außerdem wurde eine Konnektivitätsanalyse mit den oben genannten Regionen als Ursprungsregionen durchgeführt. Zudem erfolgte eine Korrelation der Aktivierung und neuronalen Konnektivität mit den Werten des AQ, eines Fragebogens, der die Stärke der Ausprägung autistischer Charakterzüge untersucht. Im zweiten Teil der Studie wurde die Verarbeitung von verschiedenen Lachtypen als nonverbale, audiovisueller Signale untersucht. Außerdem wurden die Probanden mit einem Mentalizing-Task instruiert. Hierbei wurden die Probanden gebeten, mental unterschiedliche Perspektiven einzunehmen - in der einen Kondition sollten sie sich vorstellen, sie selbst seien der Adressat des beobachteten Lachens, und in der anderen Kondition, sie beobachteten eine Schauspieler beim Einüben unterschiedlicher Lachtypen. In diesem experimentellen Teil wurden Aktivierungs- und Konnektivitätsunterschiede zwischen den Gruppen - in Bezug auf Lachtyp und Beobachterperspektive - sowie behaviorale Daten analysiert

Extra cardiac findings by 64-multidetector computed tomography in patients with symptomatic atrial fibrillation prior to pulmonal vein isolation

The aim of this study was to investigate the prevalence of extracardiac findings diagnosed by 64-multidetector computed tomography (MDCT) examinations prior to circumferential pulmonary vein (PV) ablation of atrial fibrillation (AF). A total of 158 patients (median age, 60.5 years; male 68%) underwent 64-MDCT of the chest and upper abdomen to characterize left atrial and PV anatomy prior to AF ablation. MDCT images were evaluated by a thoracic radiologist and a cardiologist. For additional scan interpretation, bone, lung, and soft tissue window settings were used. CT scans with extra-cardiac abnormalities categorized for the anatomic distribution and divided into two groups: Group 1—exhibiting clinically significant or potentially significant findings, and Group 2—patients with clinically non-significant findings. Extracardiac findings (n = 198) were observed in 113/158 (72%) patients. At least one significant finding was noted in 49/158 patients (31%). Group 1 abnormalities, such as malignancies or pneumonias, were found in 85/198 findings (43%). Group 2 findings, for example mild degenerative spine disease or pleural thickening, were observed in 113/198 findings (72%). 74/198 Extracardiac findings were located in the lung (37%), 35/198 in the mediastinum (18%), 8/198 into the liver (4%) and 81/198 were in other organs (41). There is an appreciable prevalence of prior undiagnosed extracardiac findings detected in patients with AF prior to PV-Isolation by MDCT. Clinically significant or potentially significant findings can be expected in ~40% of patients who undergo cardiac MDCT. Interdisciplinary trained personnel is required to identify and interpret both cardiac and extra cardiac findings

Radiotherapy planning parameters correlate with changes in the peripheral immune status of patients undergoing curative radiotherapy for localized prostate cancer

PURPOSE: The influence of radiotherapy on patient immune cell subsets has been established by several groups. Following a previously published analysis of immune changes during and after curative radiotherapy for prostate cancer, this analysis focused on describing correlations of changes of immune cell subsets with radiation treatment parameters. PATIENTS AND METHODS: For 13 patients treated in a prospective trial with radiotherapy to the prostate region (primary analysis) and five patients treated with radiotherapy to prostate and pelvic nodal regions (exploratory analysis), already published immune monitoring data were correlated with clinical data as well as radiation planning parameters such as clinical target volume (CTV) and volumes receiving 20 Gy (V20) for newly contoured volumes of pelvic blood vessels and bone marrow. RESULTS: Most significant changes among immune cell subsets were observed at the end of radiotherapy. In contrast, correlations of age and CD8(+) subsets (effector and memory cells) were observed early during and 3 months after radiotherapy. Ratios of T cells and T cell proliferation compared to baseline correlated with CTV. Early changes in regulatory T cells (Treg cells) and CD8(+) effector T cells correlated with V20 of blood vessels and bone volumes. CONCLUSIONS: Patient age as well as radiotherapy planning parameters correlated with immune changes during radiotherapy. Larger irradiated volumes seem to correlate with early suppression of anti-cancer immunity. For immune cell analysis during normofractionated radiotherapy and correlations with treatment planning parameters, different time points should be looked at in future projects. TRIAL REGISTRATION NUMBER: NCT01376674, 20.06.2011 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-021-03002-6

The role of Simpson grading in meningiomas after integration of the updated WHO classification and adjuvant radiotherapy

Since the introduction of the Simpson grading for the extent of resection in meningiomas in 1957, its usefulness in modern neurosurgery has been challenged. Especially, the updated WHO classification regarding brain invasion and the efficacy of radiation therapy has not been taken into account when evaluating the prognostic role of the Simpson grading in this era. We analyzed the clinical and histopathological data of 1571 meningiomas that were surgically resected in the authors' institution between July 2003 and March 2017. Operative reports were reviewed regarding the extent of resection according to Simpson grading. Meningioma subtype according to the updated WHO classification of 2016 and clinical characteristics and time to tumor progression were analyzed. The mean follow-up was 38.4 months (range 1.2 to 195.6). A higher rate of tumor recurrence was observed for male gender, younger age, recurrent tumors, non-spinal tumor localization, higher WHO, and Simpson grades in the univariate analysis. In the multivariate analysis older age, recurrent tumors and higher WHO grades remained negative prognostic factors. Among the different Simpson grades, the relative risk for recurrence was highest for grade IV compared to all other grades (each p < 0.0001), while there was no difference between Simpson grades I and II. Adjuvant radiotherapy showed lower rates of tumor recurrence. Subtotal microsurgical resection remains an independent prognostic factor with a higher rate of tumor recurrence. The prognostic benefit of radical treatment of the dural attachment is questionable and needs to be considered when weighing the intraoperative risks of radicality

The immunohistochemical expression of SSTR2A is an independent prognostic factor in meningioma

The expression of somatostatin receptors in meningioma is well established. First, suggestions of a prognostic impact of SSTRs in meningioma have been made. However, the knowledge is based on few investigations in small cohorts. We recently analyzed the expression of all five known SSTRs in a large cohort of over 700 meningiomas and demonstrated significant correlations with WHO tumor grade and other clinical characteristics. We therefore expanded our dataset and additionally collected information about radiographic tumor recurrence and progression as well as clinically relevant factors (gender, age, extent of resection, WHO grade, tumor location, adjuvant radiotherapy, neurofibromatosis type 2, primary/recurrent tumor) for a comprehensive prognostic multivariate analysis (n = 666). The immunohistochemical expression scores of SSTR1, 2A, 3, 4, and 5 were scored using an intensity distribution score ranging from 0 to 12. For recurrence-free progression analysis, a cutoff at an intensity distribution score of 6 was used. Univariate analysis demonstrated a higher rate of tumor recurrence for increased expression scores for SSTR2A, SSTR3, and SSTR4 (p = 0.0312, p = 0.0351, and p = 0.0390, respectively), while high expression levels of SSTR1 showed less frequent tumor recurrences (p = 0.0012). In the Kaplan-Meier analysis, a higher intensity distribution score showed a favorable prognosis for SSTR1 (p = 0.0158) and an unfavorable prognosis for SSTR2A (0.0143). The negative prognostic impact of higher SSTR2A expression remained a significant factor in the multivariate analysis (RR 1.69, p = 0.0060). We conclude that the expression of SSTR2A has an independent prognostic value regarding meningioma recurrence

Increased proliferation is associated with CNS invasion in meningiomas

Introduction!#!Meningiomas are the most common benign intracranial neoplasms. CNS invasion in meningiomas has been integrated into the 2016 WHO classification of CNS tumors as a stand-alone criterion for atypia. Since then, its prognostic impact has been debated based on contradictory results from retrospective analyses. The aim of the study was to elucidate whether histopathological evidence of CNS invasion is associated with increased proliferative potential.!##!Methods!#!We have conducted a quantified measurement of the proliferation marker Ki67 and analyzed its association with CNS invasion determined by histology together with other established prognostic markers of progression. Routine, immunohistochemical staining for Ki67 were digitalized and automatic quantification was done using Image J software.!##!Results!#!Overall, 1718 meningiomas were assessed. Histopathological CNS invasion was seen in 108 cases (6.7%). Uni- and multivariate analysis revealed a significantly higher Ki67 proliferation rate in meningiomas with CNS invasion (p < 0.0001 and p = 0.0098, respectively).!##!Conclusions!#!Meningiomas with histopathological CNS invasion show a higher proliferative activity

Retrospective analysis of recurrence patterns and clinical outcome of grade II meningiomas following postoperative radiotherapy

BACKGROUND: Atypical meningiomas exhibit a high tendency for tumor recurrence even after multimodal therapy. Information regarding recurrence patterns after additive radiotherapy is scarce but could improve radiotherapy planning and therapy decision. We conducted an analysis of recurrence patterns with regard to target volumes and dose coverage assessing target volume definition and postulated areas of tumor re-growth origin. Prognostic factors contributing to relapse were evaluated. METHODS: The clinical outcome of patients who had completed additive, somatostatin receptor (SSTR)-PET/CT-based fractionated intensity-modulated radiotherapy for atypical meningioma between 2007 and 2017 was analyzed. In case of tumor recurrence/progression, treatment planning was evaluated for coverage of the initial target volumes and the recurrent tumor tissue. We proposed a model evaluating the dose distribution in postulated areas of tumor re-growth origin. The median of proliferation marker MIB-1 was assessed as a prognostic factor for local progression and new distant tumor lesions. RESULTS: Data from 31 patients who had received adjuvant (n = 11) or salvage radiotherapy (n = 20) were evaluated. Prescribed dose ranged from 54.0 to 60.0 Gy. Local control at five years was 67.9%. Analysis of treatment plans of the eight patients experiencing local failure proved sufficient extent of target volumes and coverage of the prescribed dose of at least 50.0 Gy as determined by mean dose, D98, D2, and equivalent uniform dose (EUD) of all initial target volumes, postulated growth-areas, and areas of recurrent tumor tissue. In all cases, local failure occurred in high-dose volumes. Tumors with a MIB-1 expression above the median (8%) showed a higher tendency for re-growth. CONCLUSIONS: The model showed adequate target volume and relative dose distribution but absolute dose appears lower in recurrent tumors without reaching statistical significance. This might provide a rationale for dose escalation studies. Biological factors such as MIB-1 might aid patients’ stratification for dose escalation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13014-021-01825-2