Hsiu-Mei Wu

Objective: Stereotactic radiosurgery (SRS) is widely used for the treatment of intracranial dural arteriovenous fistulas (DAVFs); however, the outcomes of repeated SRS to deal with residual DAVFs are unclear. This study assessed the benefits and potential negative consequences of repeated SRS in patients with residual DAVFs. Methods: This retrospective study examined all patients who underwent two SRS procedures for DAVFs in a single academic medical center between January 1998 and December 2022. Information related to patient demography, DAVFs characteristics, and clinical outcomes were obtained from medical records. The objective in this study was to obtain a preliminary overview of the results of repeated SRS for DAVFs. Results: The study cohort of 19 patients included 14 patients with non-cavernous sinus (NCS) DAVFs and 5 patients with cavernous sinus (CS) DAVFs. The NCS group included 8 patients who were categorized as low-grade (Borden grade 1) and 6 as high-grade (Borden grade 2 or 3). The median follow up duration after the second session of SRS was 37 months. Symptomatic improvement was noted in 16 patients (84.2%) and total obliteration was identified in 11 patients (57.9%). No patient suffered from intracranial hemorrhage after the repeated SRS. One patient (5.3%) experienced symptomatic radiation-induced change mandating temporary course of medical treatment. Conclusions: Repeated SRS appears to be a safe and effective approach to deal with residual DAVFs, resulting in symptomatic improvement and complete radiologic obliteration.

Purpose To examine the differential effects of SRS and TKI on EGFR-mutated NSCLC patients with brain metastases (BMs) and outcomes following continuation of the same TKI agent in case of new BMs. Methods This study included 608 NSCLC patients (2,274 BMs) while meta-analyses included 1,651 NSCLC patients (> 3,944 BMs). Overall survival (OS) and intracranial progression free survival (iPFS) were estimated using Kaplan-Meier methods. Hazard ratios (95% CI) of prognostic factors were estimated using Cox regression models. Results The median OS/iPFS (95% CI) (months) for patients with wildtype EGFR/ALK, EGFR mutations, and ALK rearrangements were 17.7 (12.9–23.6)/12.1 (9.8–15.6), 28.9 (23.8–33.3)/17.7 (14.8–21.2), and 118.0 (not reached)/71.7 (15.1–not reached), respectively. In EGFR-mutated patients, meta-analyses combining our data showed significantly improved OS and iPFS of patients who received SRS and TKI (OS:35.1 months, iPFS:20.0 months) when compared to those who have SRS alone (OS:20.8 months, iPFS:11.8 months) or TKI alone (OS:24.3 months, iPFS:13.8 months). Having SRS for newly diagnosed BMs while keeping the existing TKI agent yielded OS (30.0 vs. 32.1 months, p = 0.200) non-inferior to patients who started combined SRS and TKI therapy for their newly diagnosed NSCLC with BMs. Multivariable analyses showed that good performance score and TKI therapy were associated with improved outcomes. Conclusions Combined SRS and TKI resulted in favorable outcomes in EGFR-mutated NSCLC patients with newly diagnosed BMs. Continuation of the same TKI agent plus SRS in case of new brain metastases yielded good clinical outcomes and may be considered a standard-of-care treatment.

(1) Background: Surgical resection for the removal of brain metastases often fails to prevent tumor recurrence within the surgical cavity; hence, researchers are divided as to the benefits of radiation treatment following surgical resection. This retrospective study assessed the effects of post-operative stereotactic radiosurgery (SRS) on local tumor control and overall survival. (2) Methods: This study examined the demographics, original tumor characteristics, and surgical outcomes of 97 patients who underwent Gamma Knife Radiosurgery (GKRS) treatment (103 brain metastases). Kaplan–Meier plots and Cox regression were used to correlate clinical features to tumor control and overall survival. (3) Results: The overall tumor control rate was 75.0% and overall 12-month survival was 89.6%. Tumor control rates in the radiation group versus the non-radiation group were as follows: 12 months (83.1% vs. 57.7%) and 24 months (66.1% vs. 50.5%). During the 2-year follow-up period after SRS, the intracranial response rate was higher in the post-craniotomy radiation group than in the non-radiation group (p = 0.027). Cox regression multivariate analysis determined that post-craniotomy irradiation of the surgical cavity is predictive of tumor control (p = 0.035). However, EGFR mutation was not predictive of overall survival or tumor control. (4) Conclusions: Irradiating the surgical cavity after surgery can enhance local tumor control; however, it does not have a significant effect on overall survival.

Dementia is related to the cellular accumulation of β-amyloid plaques, tau aggregates, or α-synuclein aggregates, or to neurotransmitter deficiencies in the dopaminergic and cholinergic pathways. Cellular and neurochemical changes are both involved in dementia pathology. However, the role of dopaminergic and cholinergic networks in metabolic connectivity at different stages of dementia remains unclear. The altered network organisation of the human brain characteristic of many neuropsychiatric and neurodegenerative disorders can be detected using persistent homology network (PHN) analysis and algebraic topology. We used¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) imaging data to construct dopaminergic and cholinergic metabolism networks, and used PHN analysis to track the evolution of these networks in patients with different stages of dementia. The sums of the network distances revealed significant differences between the network connectivity evident in the Alzheimer’s disease and mild cognitive impairment cohorts. A larger distance between brain regions can indicate poorer efficiency in the integration of information. PHN analysis revealed the structural properties of and changes in the dopaminergic and cholinergic metabolism networks in patients with different stages of dementia at a range of thresholds. This method was thus able to identify dysregulation of dopaminergic and cholinergic networks in the pathology of dementia.

Spinocerebellar ataxia (SCA) and multiple system atrophy-cerebellar type (MSA-C) often present with similar clinical manifestations in the beginning. Magnetic resonance spectroscopy (MRS) has been proved to be a useful tool to help differentiate different types of SCA and MSA-C on cross-sectional studies. However, longitudinal changes of the MRS metabolites in these subjects have never been reported. The purpose of this study was to track the longitudinal evolution of the MRS metabolites in these patients and to ascertain the correlation between clinical severity measured by Scale of the Assessment and Rating of Ataxia (SARA) and MRS metabolites. Significant reductions of NAA/Cr and NAA/Cho in the cerebellar hemispheres in all patients and lower Cho/Cr in the cerebellar hemispheres in patients with SCA2 or MSA-C were found at all times. At initial assessments, patients with MSA-C or SCA2 tended to have lower NAA/Cr and Cho/Cr in the cerebellar hemispheres than those with SCA3 or SCA6. At follow-ups, patients with SCA2 or MSA-C had a lower NAA/Cr in cerebellar hemispheres than those with SCA3 or SCA6. Patients with MSA-C had a lower NAA/Cr in the vermis and Cho/Cr in the cerebellar hemispheres than those with SCA2 at the start, and had a lower NAA/Cr in cerebellar hemispheres than those with SCA2 at follow-ups. Characteristic patterns of neurodegenerative evolution were observed in patients with disparate SCAs and MSA-C using MRS and SARA. A continual impairment of neuronal integrity was observed in all groups of patients. The longitudinal changes of MRS metabolites and SARA scores were most striking in patients with SCA2 and MSA-C. Although the changes in the metabolites on MRS may still be used to help understand the pathophysiology of ataxia disorders, they are short of being a good biomarker.