The spectrum of cognitive symptoms in Parkinson's disease (PD) can span various domains, including executive function, language, attention, memory, and visuospatial skills. These symptoms may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. The primary purpose of this study is to find microstructural correlates of impairments across these cognitive domains in PD using diffusion tensor imaging (DTI). Sixteen patients with PD with comprehensive neuropsychological evaluation and DTI data were retrospectively studied. Fractional anisotropy (FA) and mean diffusivity (MD) were assessed using regions‐of‐interest (ROI) analysis and confirmed with a voxel‐based approach. Executive function directly correlated with FA and inversely correlated with MD in mostly frontal white matter tracts, especially the anterior limb of the internal capsule and genu of the corpus callosum. Likewise, language and attentional performance demonstrated correlations with DTI parameters in the frontal regions, but the attention domain additionally recruited regions widespread throughout the brain, with the most significant correlation identified in cingulate gyrus (cingulum). Lastly, memory impairment mainly involved MD alterations within the fornix. No significant correlations were found between visuospatial skills and DTI measures. Despite some overlap, unique patterns of white matter diffusivity underlie impairments in distinct cognitive domains in patients with PD. DTI combined with neurocognitive tests may be a valuable biomarker for identifying cognitive impairments in PD. Hum Brain Mapp 35:1325–1333, 2014.

We recorded the electrocorticogram directly from the exposed cortical surface of awake neurosurgical patients during the presentation of auditory syllable stimuli. All patients were unanesthetized as part of a language-mapping procedure for subsequent left-hemisphere tumor resection. Time–frequency analyses showed significant high-gamma (γ_high: 70–160 Hz) responses from the left superior temporal gyrus, but no reliable response from the left inferior frontal gyrus. Alpha suppression (α: 7–14 Hz) and event-related potential responses exhibited a more widespread topography. Across electrodes, the α suppression from 200 to 450 ms correlated with the preceding (50–200 ms) γ_high increase. The results are discussed in terms of the different physiological origins of these electrocortical signals.

Meningiomas are mostly benign, slow-growing tumors of the CNS that originate from arachnoidal cap cells. While monosomy 22 is the most frequent genetic abnormality found in meningiomas, a multitude of other aberrant chromosomal alterations, signaling pathways, and growth factors have been implicated in its pathogenesis. Losses on 22q12.2, a region encoding the tumor suppressor gene merlin , represent the most common genetic alterations in early meningioma formation. Malignant meningioma progression, however, is associated with more complex karyotypes and greater genetic instability. Cytogenetic studies of atypical and anaplastic meningiomas revealed gains and losses on chromosomes 9, 10, 14, and 18, with amplifications on chromosome 17. However, the specific gene targets in a majority of these chromosomal abnormalities remain elusive. Studies have also implicated a myriad of aberrant signaling pathways involved with meningioma tumorigenesis, including those involved with proliferation, angiogenesis, and autocrine loops. Understanding these disrupted pathways will aid in deciphering the relationship between various genetic changes and their downstream effects on meningioma pathogenesis. Despite advancements in our understanding of meningioma pathogenesis, the conventional treatments, including surgery, radiotherapy, and stereotactic radiosurgery, have remained largely stagnant. Surgery and radiation therapy are curative in the majority of lesions, yet treatment remains challenging for meningiomas that are recurrent, aggressive, or refractory to conventional treatments. Future therapies will include combinations of targeted molecular agents as a result of continued progress in the understanding of genetic and biological changes associated with meningiomas.

Object: Medical and surgical management of low-grade gliomas (LGGs) is complicated by a highly variable clinical course. The authors recently developed a preoperative scoring system to prognosticate outcomes of progression and survival in a cohort of patients treated at a single institution (University of California, San Francisco [UCSF]). The objective of this study was to validate the scoring system in a large patient group drawn from multiple external institutions. Methods: Clinical data from 3 outside institutions (University of Utah, Toronto Western Hospital, and University of California, Los Angeles) were collected for 256 patients (external validation set). Patients were assigned a prognostic score based upon the sum of points assigned to the presence of each of the 4 following factors: 1) location of tumor in presumed eloquent cortex, 2) Karnofsky Performance Scale (KPS) Score ≤ 80, 3) age > 50 years, and 4) maximum diameter > 4 cm. A chi-square analysis was used to analyze categorical differences between the institutions; Cox proportional hazard modeling was used to confirm that the individual factors were associated with shorter overall survival (OS) and progression-free survival (PFS); and Kaplan–Meier curves estimated OS and PFS for the score groups. Differences between score groups were analyzed by the log-rank test. Results: The median OS duration was 120 months, and there was no significant difference in survival between the institutions. Cox proportional hazard modeling confirmed that the 4 components of the UCSF Low-Grade Glioma Scoring System were associated with lower OS in the external validation set; presumed eloquent location (hazard ratio [HR] 2.04, 95% CI 1.28–2.56), KPS score ≤ 80 (HR 5.88, 95% CI 2.44–13.7), age > 50 years (HR 1.82, 95% CI 1.02–3.23), and maximum tumor diameter > 4 cm (HR 2.63, 95% CI 1.58–4.35). The stratification of patients based on scores generated groups (0–4) with statistically different OS and PFS estimates (p < 0.0001, log-rank test). Lastly, the UCSF patient group (construction set) was combined with the external validation set (total of 537 patients) and analyzed for OS and PFS. For all patients, the 5-year survival probability was 0.79; the 5-year cumulative OS probabilities stratified by score group were: score of 0, 0.98; score of 1, 0.90; score of 2, 0.81; score of 3, 0.53; and score of 4, 0.46. Conclusions: The UCSF scoring system accurately predicted OS and PFS in an external large, multiinstitutional population of patients with LGGs. The strengths of this system include ease of use and ability to be applied preoperatively, with the eventual goal of aiding in the design of individualized treatment plans for patients with LGG at diagnosis.

In comparison with responses in recurrent glioblastoma (rGBM), the intracranial response of brain metastases (BrM) to immune checkpoint blockade (ICB) is less well studied. Here, we present an integrated single-cell RNA-Seq (scRNA-Seq) study of 19 ICB-naive and 9 ICB-treated BrM samples from our own and published data sets. We compared them with our previously published scRNA-Seq data from rGBM and found that ICB led to more prominent T cell infiltration into BrM than rGBM. These BrM-infiltrating T cells exhibited a tumor-specific phenotype and displayed greater activated/exhausted features. We also used multiplex immunofluorescence and spatial transcriptomics to reveal that ICB reduced a distinct CD206⁺ macrophage population in the perivascular space, which may modulate T cell entry into BrM. Furthermore, we identified a subset of progenitor exhausted T cells that correlated with longer overall survival in BrM patients. Our study provides a comprehensive immune cellular landscape of ICB’s effect on metastatic brain tumors and offers insights into potential strategies for improving ICB efficacy for brain tumor patients.