Notes

Hereditary guidance along with screening regarding genetic hemorrhagic telangiectasia.
Pitch and duration mismatch negativity (pMMN/dMMN) are related to left Heschl's gyrus gray matter volumes in first-episode schizophrenia (FESz). Previous methods were unable to delineate functional subregions within and outside Heschl's gyrus. The Human Connectome Project multimodal parcellation (HCP-MMP) atlas overcomes this limitation by parcellating these functional subregions. Further, MMN has generators in inferior frontal cortex, and therefore, may be associated with inferior frontal cortex pathology. With the novel use of the HCP-MMP to precisely parcellate auditory and inferior frontal cortex, we investigated relationships between gray matter and pMMN and dMMN in FESz.

pMMN and dMMN were measured at Fz from 27 FESz and 27 matched healthy controls. T1-weighted MRI scans were acquired. The HCP-MMP atlas was applied to individuals, and gray matter volumes were calculated for bilateral auditory and inferior frontal cortex parcels and correlated with MMN. FDR correction was used for multiple comparisons.

In FESz only, pMMN was negatively correlated with left medial belt in auditory cortex and area 47L in inferior frontal cortex. Duration MMN negatively correlated with the following auditory parcels left medial belt, lateral belt, parabelt, TA2, and right A5. Further, dMMN was associated with left area 47L, right area 44, and right area 47L in inferior frontal cortex.

The novel approach revealed overlapping and distinct gray matter associations for pMMN and dMMN in auditory and inferior frontal cortex in FESz. Thus, pMMN and dMMN may serve as biomarkers of underlying pathological deficits in both similar and slightly different cortical areas.
The novel approach revealed overlapping and distinct gray matter associations for pMMN and dMMN in auditory and inferior frontal cortex in FESz. Thus, pMMN and dMMN may serve as biomarkers of underlying pathological deficits in both similar and slightly different cortical areas.The onset of several neuropsychiatric disorders including anxiety disorders coincides with adolescence. Consistently, threat extinction, which plays a key role in the regulation of anxiety-related behaviors, is diminished during adolescence. Furthermore, this attenuated threat extinction during adolescence is associated with an altered synaptic plasticity in the infralimbic medial prefrontal cortex (IL-mPFC), a brain region critical for threat extinction. However, the mechanism underlying the altered plasticity in the IL-mPFC during adolescence is unclear. Given the purported role of vasoactive intestinal polypeptide expressing interneurons (VIPINs) in disinhibition and hence their potential to affect cortical plasticity, we examined whether VIPINs exhibit an adolescence-specific plasticity in the IL-mPFC. We observed an increase in GABAergic transmission and a decrease in excitability in VIPINs during adolescence. Male mice show a significantly higher VIPIN-pyramidal neuron GABAergic transmission compared with female mice. The observed increase in GABAergic transmission and a decrease in membrane excitability in VIPINs during adolescence could play a role in the altered plasticity in the adolescent IL-mPFC. Furthermore, the suppression of VIPIN-mediated GABAergic transmission in females might be relevant to sex differences in anxiety disorders.
The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases.

Patients with 4-10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at 3 months post-treatment.

The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range 4-9) and the median total treatment volume was 13.0 cc
(range 1.8-25.9 cc
). QOL at 3 months decreased in the SRS group by 0.1 (SD = 0.2), compared to 0.2 (SD = 0.2) in the WBRT group (
= .23). The actuarial 1-year survival rates were 57% (SRS) and 31% (WBRT) (
= .52). The actuarial 1-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (
= .22).

In patients with 4-10 BM, SRS alone resulted in 1-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.
In patients with 4-10 BM, SRS alone resulted in 1-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.
G lioblastoma (GBM) is associated with poor overall survival. Recently, we showed that androgen receptor (AR) protein is overexpressed in 56% of GBM specimens and AR antagonists induced dose-dependent death in several GBM cell lines and significantly reduced tumor growth and prolonged the lifespan of mice implanted with human GBM. 16β-18F-fluoro-5α-dihydrotestosterone ([
F]-FDHT) is a positron emission tomography (PET) tracer used to detect AR expression in prostate and breast cancers. This study was aimed at exploring the ability of [
F]-FDHT-PET to detect AR expression in high-grade gliomas.

Twelve patients with suspected high-grade glioma underwent a regular workup and additional dynamic and static [
F]-FDHT-PET/CT. Visual and quantitative analyses of [
F]-FDHT kinetics in the tumor and normal brain were performed. Mean and maximum (max) standardized uptake values (SUVs) were determined in selected volumes of interest. The patients had surgery or biopsy after PET/CT. AR protein was analyzed in the tumor samples by western blot. Fold change in AR expression was calculated by densitometry analysis. Correlation between imaging and AR protein samples was determined.

In six of the 12 patients, [
F]-FDHT uptake was significantly higher in the tumor than in the normal brain. These patients also had increased AR protein expression within the tumor. Pearson correlation coefficient analysis for the tumor-to-control normal brain uptake ratio in terms of SUV
versus AR protein expression was positive and significant (R = 0.84;
= .002).

[
F]-FDHT-PET/CT could identify increased AR expression in high-grade glioma.
[18 F]-FDHT-PET/CT could identify increased AR expression in high-grade glioma.The newly discovered functional integration of glioma cells into brain networks in mouse models provides groundbreaking insight into glioma aggressiveness and resistance to treatments, also suggesting novel potential therapeutic avenues and targets. In the context of such neuron-to-glioma communication, noninvasive brain modulation techniques traditionally applied to modulate neuronal function in neurological and psychiatric diseases (eg, increase/decrease cortical excitability and plasticity) could now be tested in patients with brain tumors to suppress glioma's activity and its pathological crosstalk with healthy brain tissue.Glioblastoma (GBM), the most aggressive primary brain tumor, has a dismal prognosis. Despite our growing knowledge of genomic and epigenomic alterations in GBM, standard therapies and outcomes have not changed significantly in the past two decades. There is therefore an urgent unmet need to develop novel therapies for GBM. The inter- and intratumoral heterogeneity of GBM, inadequate drug concentrations in the tumor owing to the blood-brain barrier, redundant signaling pathways contributing to resistance to conventional therapies, and an immunosuppressive tumor microenvironment, have all hindered the development of novel therapies for GBM. Given the high frequency of DNA damage pathway alterations in GBM, researchers have focused their efforts on pharmacologically targeting key enzymes, including poly(ADP-ribose) polymerase (PARP), DNA-dependent protein kinase, ataxia telangiectasia-mutated, and ataxia telangiectasia and Rad3-related. The mainstays of GBM treatment, ionizing radiation and alkylating chemotherapy, generate DNA damage that is repaired through the upregulation and activation of DNA damage response (DDR) enzymes. Therefore, the use of PARP and other DDR inhibitors to render GBM cells more vulnerable to conventional treatments is an area of intense investigation. In this review, we highlight the growing body of data behind DDR inhibitors in GBM, with a focus on putative predictive biomarkers of response. We also discuss the challenges involved in the successful development of DDR inhibitors for GBM, including the intracranial location and predicted overlapping toxicities of DDR agents with current standards of care, and propose promising strategies to overcome these hurdles.
Meningiomas express high levels of somatostatin receptor 2 (SSTR2). SSTR2-targeted PET imaging with [
Ga]-DOTATATE can aid with distinguishing residual meningioma from reactive changes in the postoperative setting. We present initial dosimetric analyses, acute events, and local control data utilizing [
Ga]-DOTATATE PET/MRI-assisted target delineation for prospectively-treated intermediate-risk meningiomas.

Twenty-nine patients underwent DOTATATE PET/MRI meningioma evaluation in 2019. Eight patients with 9 postoperative meningiomas met RTOG 0539 intermediate-risk criteria (recurrent WHO grade I, 1/9; WHO grade II, 8/9). Target volumes were created using DOTATATE PET/MRI to determine residual disease and received a nominal dose of 35.0 Gy over 5 fractions. For comparison, cases were recontoured and planned with MRI alone per RTOG 0539 guidelines. Mean and maximum equivalent 2 Gy doses were generated for target volumes and organs at risk (OAR) within 1 cm of the PTV and compared using Wilcoxon matched pairostoperative meningiomas.
Breast cancer is the second most common cancer associated with brain metastases. The purpose of this study was to identify factors that impact the time to brain metastases in breast cancer patients at a single institution.

Single institution retrospective study that captured all consecutive stage 2 and stage 3 breast cancer patients from 2003 to 2010. Patient characteristics analyzed included age, hormone status, HER2 receptor status, grade, stage, and time from breast cancer diagnosis to brain metastasis.

A total of 1218 patients were eligible for the final analysis. 849 (69.7%) patients were ER+/HER2-, 90 (7.4%) were HER2+, and 279 (22.9%) were triple-negative (TN). Overall, 74 patients (6.1%) developed brain metastases over a median follow up time of 92 months. Median times to brain metastases for HER2+, TN, and ER+/HER2- patients were 20, 26, and 57 months, respectively. Multivariate analysis demonstrated that TN disease (HR = 2.043,
= .015), grade (HR = 1.667,
= .024) and stage (HR = 3.851,
< .001) were independent risk factors for earlier brain metastases. Median times to brain metastases were 34 and 52 months for stage 3 and 2 patients, and 30, 49, and 71 months for grade 3, 2, and 1 tumors, respectively.

This single-institutional case series demonstrates that TN breast cancer, higher stage, and higher histologic grade are associated with earlier brain metastases in multivariate analysis. selleck Additional prospective studies are warranted to investigate the impact of brain metastases screening on survival outcome in this high-risk defined group.
This single-institutional case series demonstrates that TN breast cancer, higher stage, and higher histologic grade are associated with earlier brain metastases in multivariate analysis. Additional prospective studies are warranted to investigate the impact of brain metastases screening on survival outcome in this high-risk defined group.
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