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Brain Research Bulletin Jul 2024The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions....
INTRODUCTION
The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions. However, how afferent neurons of mPFC are affected by chronic stress needs to be clarified. In this study, the effects of chronic restraint stress (CRS) on the distribution density of mPFC dendrites/dendritic spines and the projections from the cortex and subcortical brain regions to the mPFC were investigated.
METHODS
In the present study, C57BL/6 J transgenic (Thy1-YFP-H) mice were subjected to CRS to establish an animal model of depression. The infralimbic (IL) of mPFC was selected as the injection site of retrograde AAV using stereotactic technique. The effects of CRS on dendrites/dendritic spines and afferent neurons of the mPFC IL were investigaed by quantitatively assessing the distribution density of green fluorescent (YFP) positive dendrites/dendritic spines and red fluorescent (retrograde AAV recombinant protein) positive neurons, respectively.
RESULTS
The results revealed that retrograde tracing virus labeled neurons were widely distributed in ipsilateral and contralateral cingulate cortex (Cg1), second cingulate cortex (Cg2), prelimbic cortex (PrL), infralimbic cortex, medial orbital cortex (MO), and dorsal peduncular cortex (DP). The effects of CRS on the distribution density of mPFC red fluorescence positive neurons exhibited regional differences, ranging from rostral to caudal or from top to bottom. Simultaneously, CRS resulted a decrease in the distribution density of basal, proximal and distal dendrites, as well as an increase in the loss of dendritic spines of the distal dendrites in the IL of mPFC. Furthermore, varying degrees of red retrograde tracing virus fluorescence signals were observed in other cortices, amygdala, hippocampus, septum/basal forebrain, hypothalamus, thalamus, mesencephalon, and brainstem in both ipsilateral and contralateral brain. CRS significantly reduced the distribution density of red fluorescence positive neurons in other cortices, hippocampus, septum/basal forebrain, hypothalamus, and thalamus. Conversely, CRS significantly increased the distribution density of red fluorescence positive neurons in amygdala.
CONCLUSION
Our results suggest a possible mechanism that CRS leads to disturbances in synaptic plasticity by affecting multiple inputs to the mPFC, which is characterized by a decrease in the distribution density of dendrites/dendritic spines in the IL of mPFC and a reduction in input neurons of multiple cortices to the IL of mPFC as well as an increase in input neurons of amygdala to the IL of mPFC, ultimately causing depression-like behaviors.
Topics: Animals; Prefrontal Cortex; Mice, Inbred C57BL; Stress, Psychological; Mice, Transgenic; Mice; Restraint, Physical; Depression; Male; Dendritic Spines; Disease Models, Animal; Afferent Pathways; Dendrites; Neurons, Afferent; Brain
PubMed: 38777132
DOI: 10.1016/j.brainresbull.2024.110981 -
Otolaryngology--head and Neck Surgery :... May 2024To assess the effect of wait and scan (W&S) and stereotactic radiosurgery (SRS) on health-related quality of life (HRQoL) over time in patients with a stable vestibular...
OBJECTIVE
To assess the effect of wait and scan (W&S) and stereotactic radiosurgery (SRS) on health-related quality of life (HRQoL) over time in patients with a stable vestibular schwannoma (VS) and growing VS.
STUDY DESIGN
Longitudinal, multicenter, observational study.
SETTING
Tertiary expert center for VS (Radboudumc Nijmegen) and Gamma-Knife center ETZ Hospital Tilburg.
METHODS
Changes in HRQoL, measured with the Penn Acoustic Neuroma Quality-of-Life (PANQOL), and the physical and mental component summary scores (PCS and MCS, respectively) derived from the 36-Item Short Form Health Survey (SF-36), were compared among patients managed by W&S and SRS between 2017 and 2022. Second, HRQoL over time in patients with a growing VS was compared between W&S and SRS.
RESULTS
Differences in PANQOL total and subdomain scores, PCS and MCS scores over time in the W&S (n = 73) and SRS (n = 170) groups were nonsignificant and on average did not exceed the minimal clinically important differences (mean difference of -2.56 [PANQOL total], 1.22 [PCS], and -1.76 [MCS]; all P > .05). In growing VS, comparison of W&S (n = 29) and SRS (n = 154) also revealed no significant difference (mean difference of 1.19 (PANQOL total), 1.83 (PCS) and -0.12 (MCS); all P > .05).
CONCLUSION
Differences in HRQoL in patients with VS are minor and not significantly different or clinically relevant between patients managed with W&S or SRS. Similarly, patients with a growing VS managed with W&S or SRS exhibit no significant or clinical relevant difference in HRQoL during follow-up. This can aid clinicians in the counseling of patients regarding HRQoL when deciding on a management strategy after diagnosis or documented growth.
PubMed: 38769852
DOI: 10.1002/ohn.814 -
Journal of Medical Imaging and... Jun 2024Contrast-enhanced mammography (CEM) and MRI detect 'contrast-only' lesions (COLs) occult on standard breast imaging (ultrasound and conventional mammography). Until...
INTRODUCTION
Contrast-enhanced mammography (CEM) and MRI detect 'contrast-only' lesions (COLs) occult on standard breast imaging (ultrasound and conventional mammography). Until recently, MRI was the only reliable method of biopsy. This study presents the first Australian experience with CEM-guided biopsy (CEMBx) and the lessons learnt.
METHODS
A prospective audit of the first 15 consecutive patients who underwent CEMBx for COLs was performed. Indications for contrast imaging, patient and lesion characteristics, procedural details, radiation dose and pathology data were collected.
RESULTS
The 15 women were aged 37-81 years (mean 59 years). Indications for contrast imaging were problem solving (n = 3), moderate risk screening (n = 2), cancer staging (n = 9) and symptoms (n = 1). The COLs were non-mass (n = 14), mass (n = 1) and an enhancing asymmetry (n = 1). For one patient, two lesions were sampled during the same event. All lesions enhanced and were successfully sampled followed by marker clip insertion. Most biopsies (87.5%) were performed with the breast in cranio-caudal compression using a horizontal approach. Procedural duration ranged from 13 to 33 min (mean 22 min). Radiation dose was similar to standard stereotactic biopsy. Post-biopsy hematomas occurred in three patients, none required intervention. Clip displacement occurred in three cases. Core biopsy histopathology results were benign (n = 8), malignant (n = 7) and a borderline breast lesion (BBL) (n = 1). Patient satisfaction rates were high. Imaging follow-up is ongoing.
CONCLUSIONS
CEMBx is a quick, safe and reliable alternative to MRIBx to sample COLs.
Topics: Humans; Female; Middle Aged; Aged; Adult; Mammography; Contrast Media; Breast Neoplasms; Aged, 80 and over; Australia; Prospective Studies; Stereotaxic Techniques; Image-Guided Biopsy
PubMed: 38766916
DOI: 10.1111/1754-9485.13663 -
Cureus Apr 2024A 60-year-old male presented with an elevated prostate-specific antigen (PSA) of 10 ng/ml. A transrectal ultrasound-guided prostate biopsy showed prostate adenocarcinoma...
A 60-year-old male presented with an elevated prostate-specific antigen (PSA) of 10 ng/ml. A transrectal ultrasound-guided prostate biopsy showed prostate adenocarcinoma GS 4+3 (grade 3) with 5 out of 12 cores positive for malignancy. He initially planned to have prostate stereotactic body radiation therapy (SBRT) with SpaceOAR gel insertion in his rectoprostatic space to reduce radiation to the rectum. Magnetic resonance imaging (MRI) two months after SpaceOAR insertion showed evidence of infiltration of the SpaceOAR within the anterior rectal wall. This delayed his treatment and he was started on a short course of androgen deprivation therapy with Leuprolide while waiting for absorption of the gel. After completion of androgen deprivation therapy, the patient was treated with external beam radiation therapy (EBRT) to the prostate, seminal vesicles, and pelvis to a total dose of 6000 centigray (cGy) in 20 fractions at a dose per fraction of 300 cGy. He did well after treatment with minimal side effects.
PubMed: 38765433
DOI: 10.7759/cureus.58485 -
Cureus Apr 2024Lung cancer with brain metastasis has a high morbidity and mortality worldwide. Neurocysticercosis is a parasitic infection commonly found in regions with poor...
Lung cancer with brain metastasis has a high morbidity and mortality worldwide. Neurocysticercosis is a parasitic infection commonly found in regions with poor sanitation. We present a case with the coexistence of lung cancer and neurocysticercosis. A 57-year-old Caucasian female, with a history of secondhand smoke exposure, presented with a cough. Further evaluation revealed a lesion in the right upper lobe of the lung on a CT scan, a frontal lobe lesion on brain MRI, and hypermetabolic lymph nodes on a PET scan. Biopsies confirmed invasive moderately differentiated adenocarcinoma, indicating stage 4 lung cancer with a solitary brain metastasis. The patient underwent stereotactic radiosurgery for the brain lesion and subsequently received chemoradiation therapy. Upon completion of therapy, the patient showed improvement in both lung and brain lesions. Durvalumab maintenance therapy was initiated. However, a follow-up MRI of the brain revealed a new lesion in the right lateral ventricle. Stereotactic radiosurgery was performed to target this lesion. Five months later, a repeat MRI showed growth of the brain lesion. Given the atypical image finding, a biopsy of the right lateral ventricle lesion was performed, revealing an unexpected diagnosis of calcified parenchymal neurocysticercosis. The patient was referred to an infectious disease specialist who started the patient on dexamethasone without antiparasitic treatment. The co-occurrence of metastatic lung cancer to the brain and neurocysticercosis presents significant diagnostic and therapeutic complexities. Despite stereotactic radiosurgery, the patient's neurologic symptoms failed to improve, and subsequent radiographic assessments yielded inconclusive results. Consequently, a brain biopsy was performed, deviating from the usual practice in cancer management, revealing the unexpected presence of neurocysticercosis. This unforeseen diagnosis underscores the critical significance of contemplating alternative etiologies in patients exhibiting atypical clinical manifestations, particularly in regions devoid of prevalent parasitic infections. This case highlights the challenges in identifying and managing complex cases involving lung cancer and neurocysticercosis, where treatment decisions must balance the need for oncologic control and the management of parasitic infection.
PubMed: 38765376
DOI: 10.7759/cureus.58456 -
Nature Communications May 2024After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory...
After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.
Topics: Humans; COVID-19; Cognitive Dysfunction; Male; Fatigue; Female; Magnetic Resonance Imaging; Middle Aged; Olfaction Disorders; Adult; SARS-CoV-2; Brain; Post-Acute COVID-19 Syndrome; Aged
PubMed: 38762609
DOI: 10.1038/s41467-024-48651-0 -
PLoS Medicine May 2024Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble...
BACKGROUND
Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to 40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble (FUS-MB) treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitised tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided FUS-MB (MRgFUS-MB) treatment, a radioenhancement therapy for breast cancer.
METHODS AND FINDINGS
This prospective, single-center, single-arm Phase 1 clinical trial included patients with stages I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was deemed adequate by a multidisciplinary team (clinicaltrials.gov identifier: NCT04431674). Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2 to 3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 kHz and 570 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary outcome was acute toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Secondary outcomes were tumour response at 3 months and local control (LC). A total of 21 female patients presenting with 23 primary breast tumours were enrolled and allocated to intervention between August/2020 and November/2022. Three patients subsequently withdrew consent and, therefore, 18 patients with 20 tumours were included in the safety and LC analyses. Two patients died due to progressive metastatic disease before 3 months following treatment completion and were excluded from the tumour response analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n = 8/20), 30 to 35 Gy/5 fractions (35%, n = 7/20), 30 to 40 Gy/10 fractions (15%, n = 3/20), and 66 Gy/33 fractions (10%, n = 2/20). The median follow-up was 9 months (range, 0.3 to 29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were evaluated for response: 9 exhibited complete response (50%, n = 9/18), 6 partial response (33%, n = 6/18), 2 stable disease (11%, n = 2/18), and 1 progressive disease (6%, n = 1/18). Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94% (95% confidence interval [CI] [84%, 100%]), 88% (95% CI [75%, 100%]), and 76% (95% CI [54%, 100%]), respectively. The study's limitations include variable tumour sizes and dose fractionation regimens and the anticipated small sample size typical for a Phase 1 clinical trial.
CONCLUSIONS
MRgFUS-MB is an innovative radioenhancement therapy associated with a safe profile, potentially promising responses, and durable LC. These results warrant validation in Phase 2 clinical trials.
TRIAL REGISTRATION
clinicaltrials.gov, identifier NCT04431674.
Topics: Humans; Breast Neoplasms; Female; Microbubbles; Middle Aged; Aged; Prospective Studies; Adult; Treatment Outcome; Magnetic Resonance Imaging; Aged, 80 and over
PubMed: 38758967
DOI: 10.1371/journal.pmed.1004408 -
JCO Global Oncology May 2024Local ablative therapy, such as radiotherapy or surgery, plays a key role in treatment of patients with oligometastatic disease. Stereotactic ablative body radiotherapy... (Observational Study)
Observational Study
PURPOSE
Local ablative therapy, such as radiotherapy or surgery, plays a key role in treatment of patients with oligometastatic disease. Stereotactic ablative body radiotherapy (SABR) comes to the fore as a safe and effective treatment for patients with a limited number of metastases, even those located in hard-to-reach body sites. Many researchers have suggested that metastatsis-directed therapy could improve long-term progression-free survival (PFS) and overall survival (OS) in patients with oligometastases.
PATIENTS AND METHODS
This was a retrospective, single-arm, observational study conducted between July 2015 and February 2022. In our institute, 60 patients with controlled primary tumors and one to five metastases were treated with SABR. Prescribed radiation doses ranged from 12 to 60 Gy administered in one to seven fractions. We aimed to determine whether metastatic-directed therapy using SABR for all oligometastases affects OS and PFS and whether the primary tumor or metastatic site influences OS/PFS.
RESULTS
The most common primary malignancy types were prostate (n = 14), colorectal (n = 10), lung (n = 7), and breast cancers (n = 6). The median follow-up was 30 months, ranging from 9 to 79. The 1-, 3-, and 5-year PFS and OS rates were 54.9%, 37.0%, and 37.0% and 98.3%, 84.4%, and 73.8%, respectively, and the median time to first progression was 15 (range, 2-32) months. Twenty-four (40%) patients had no recurrence. In our analysis, primary tumor site was not an independent prognostic factor. The metastatic site may influence on patient outcome in cases of localized bone and liver metastases.
CONCLUSION
In our retrospective analysis, SABR was associated with favorable levels of PFS and OS in patients with oligometastases. The limitations of our study were lacking high-level evidence, and randomized studies to compare SABR and palliative standard of care are mandatory.
Topics: Humans; Radiosurgery; Male; Female; Retrospective Studies; Aged; Middle Aged; Neoplasm Metastasis; Aged, 80 and over; Adult; Neoplasms; Progression-Free Survival
PubMed: 38754052
DOI: 10.1200/GO.23.00275 -
Acta Neurochirurgica May 2024The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic...
PURPOSE
The aim of this study was to evaluate the treatment outcomes of neuroendoscopic cyst partial resection (ECPR) combined with stereotactic radiotherapy (SRT) for cystic craniopharyngiomas.
METHODS
In this retrospective study, 22 craniopharyngioma patients undergoing ECPR combined with SRT were included. This combination therapy was indicated for suprasellar cystic craniopharyngiomas in patients whose pituitary function was preserved but would be difficult to preserve in direct surgery. The outcomes of combination therapy, including tumor control and postoperative visual and pituitary functions, were investigated.
RESULTS
ECPR was safely performed, and cyst shrinkage was accomplished in all cases. After ECPR, visual function improved in 12 of 13 patients (92%) with visual field disturbance and did not deteriorate in any patients. Pituitary function was preserved in 14 patients (64%) and deteriorated in eight patients (36%) after ECPR. As a complication of ECPR, meningitis occurred because of a wound infection in one patient. In 18 of 22 patients (82%), the tumor was controlled without further treatment 19 - 87 months (median, 33 months) after SRT. Hypopituitarism was an adverse event after SRT in two of the 18 patients who achieved tumor control. Four patients (18%) had enlarged cysts after SRT. Postoperative pituitary function was significantly more likely to deteriorate in cases of extensive detachment from the ventricular wall, and retreatment was significantly more common in cases with hypothalamic extension.
CONCLUSION
Although limited to some cases, ECPR combined with SRT is a less invasive and useful therapeutic option for suprasellar cystic craniopharyngiomas. However, its long-term prognosis requires further evaluation.
Topics: Humans; Craniopharyngioma; Male; Female; Pituitary Neoplasms; Adult; Middle Aged; Radiosurgery; Neuroendoscopy; Retrospective Studies; Treatment Outcome; Young Adult; Adolescent; Child; Cysts; Aged; Combined Modality Therapy
PubMed: 38750340
DOI: 10.1007/s00701-024-06113-y -
NeuroImage. Clinical 2024The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The...
BACKGROUND AND OBJECTIVES
The intricate relationship between deep brain stimulation (DBS) in Parkinson's disease (PD) and cognitive impairment has lately garnered substantial attention. The presented study evaluated pre-DBS structural and microstructural cerebral patterns as possible predictors of future cognitive decline in PD DBS patients.
METHODS
Pre-DBS MRI data in 72 PD patients were combined with neuropsychological examinations and follow-up for an average of 2.3 years after DBS implantation procedure using a screening cognitive test validated for diagnosis of mild cognitive impairment in PD in a Czech population - Dementia Rating Scale 2.
RESULTS
PD patients who would exhibit post-DBS cognitive decline were found to have, already at the pre-DBS stage, significantly lower cortical thickness and lower microstructural complexity than cognitively stable PD patients. Differences in the regions directly related to cognition as bilateral parietal, insular and cingulate cortices, but also occipital and sensorimotor cortex were detected. Furthermore, hippocampi, putamina, cerebellum and upper brainstem were implicated as well, all despite the absence of pre-DBS differences in cognitive performance and in the position of DBS leads or stimulation parameters between the two groups.
CONCLUSIONS
Our findings indicate that the cognitive decline in the presented PD cohort was not attributable primarily to DBS of the subthalamic nucleus but was associated with a clinically silent structural and microstructural predisposition to future cognitive deterioration present already before the DBS system implantation.
Topics: Humans; Deep Brain Stimulation; Parkinson Disease; Male; Female; Subthalamic Nucleus; Middle Aged; Cognitive Dysfunction; Aged; Magnetic Resonance Imaging; Neuropsychological Tests
PubMed: 38749145
DOI: 10.1016/j.nicl.2024.103617