Stereotactic Laser Ablation (SLA) followed by consolidation stereotactic radiosurgery (cSRS) as treatment for brain metastasis that recurred locally after initial radiosurgery (BMRS): a multi-institutional experience.

INTRODUCTION: The optimal treatment paradigm for brain metastasis that recurs locally after initial radiosurgery remains an area of active investigation. Here, we report outcomes for patients with BMRS treated with stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy, LITT) followed by consolidation radiosurgery. METHODS: Clinical outcomes of 20 patients with 21 histologically confirmed BMRS treated with SLA followed by consolidation SRS and > 6 months follow-up were collected retrospectively across three participating institutions. RESULTS: Consolidation SRS (5 Gy × 5 or 6 Gy × 5) was carried out 16-73 days (median of 26 days) post-SLA in patients with BMRS. There were no new neurological deficits after SLA/cSRS. While 3/21 (14.3%) patients suffered temporary Karnofsky Performance Score (KPS) decline after SLA, no KPS decline was observed after cSRS. There were no 30-day mortalities or wound complications. Two patients required re-admission within 30 days of cSRS (severe headache that resolved with steroid therapy (n = 1) and new onset seizure (n = 1)). With a median follow-up of 228 days (range: 178-1367 days), the local control rate at 6 and 12 months (LC6, LC12) was 100%. All showed diminished FLAIR volume surrounding the SLA/cSRS treated BMRS at the six-month follow-up; none of the patients required steroid for symptoms attributable to these BMRS. These results compare favorably to the available literature for repeat SRS or SLA-only treatment of BMRS. CONCLUSIONS: This multi-institutional experience supports further investigations of SLA/cSRS as a treatment strategy for BMRS.

Peritoneal catheter knot formation in ventriculoperitoneal shunting: an intraoperative artificial phenomenon?

BACKGROUND: Peritoneal catheter knot formation is a rare complication associated with ventriculoperitoneal shunting. In most reports, the knot formation was also considered to be the cause of shunt malfunction. DISCUSSION: In this study, we demonstrate the possible misinterpretation of peritoneal catheter knot formation in ventriculoperitoneal shunting. We found a knot in the peritoneal catheter intraoperatively, while no knot was noted on the abdominal X-ray taken 1 day prior to the operation. Our findings indicate that the knot had actually formed intraoperatively. This case suggests that we should not immediately conclude that a knot is the cause of shunt malfunction in such an operation.

Extracranial glioblastoma diagnosed by examination of pleural effusion using the cell block technique: case report.

Metastatic glioblastoma is a rare condition, and several studies have reported the involvement of multiple organs including the lymph nodes, liver, and lung. The lung and pleura are reportedly the most frequent sites of metastasis, and diagnosis using less invasive tools such as cytological analysis with fine needle aspiration biopsy is challenging. Cytological analysis of fluid specimens tends to be negative because of the small number of cells obtained, whereas the cell block technique reportedly has higher sensitivity because of a decrease in cellular dispersion. Herein, the authors describe a patient with a history of diffuse astrocytoma who developed intractable, progressive accumulation of pleural fluid. Initial cytological analysis of the pleural effusion obtained by thoracocentesis was negative, but reanalysis using the cell block technique revealed the presence of glioblastoma cells. This is the first report to suggest the effectiveness of the cell block technique in the diagnosis of extracranial glioblastoma using pleural effusion. In patients with a history of glioma, the presence of extremely intractable pleural effusion warrants cytological analysis of the fluid using this technique in order to initiate appropriate chemotherapy.

Choroid Plexus Hyperplasia with Intractable Ascites and a Resulting Communicating Hydrocele following Shunt Operation for Hydrocephalus.

Choroid plexus hyperplasia/papilloma and resulting hyperproduction of cerebrospinal fluid is a rare cause of hydrocephalus. In these patients, intractable ascites can occur after a ventriculoperitoneal (VP) shunting operation. However, shunt-related hydrocele is a rare complication of VP shunting. Previous reports have indicated catheter-tip migration to the scrotum as a cause of hydrocele. Here, we present the first documented case of choroid plexus hyperplasia that led to intractable ascites after shunting and a resulting hydrocele without catheter-tip migration into the scrotum.

Hypertensive Cerebral Hemorrhage in a Patient with Turner Syndrome Caused by Deletion in the Short Arm of the X Chromosome.

Turner syndrome is a chromosomal disorder usually caused by complete deletion of an X chromosome, with deletion in the short arm of the X chromosome being a rare cause of the condition. Patients with Turner syndrome commonly develop hypertension, and associated vascular complications such as aortic dissection or cerebral hemorrhage have been reported. Cerebral hemorrhage in Turner syndrome is a rare complication, and only a few reports have been published. In these reports, all patients have XO karyotypes or a mosaic type as the cause of Turner syndrome, while no other Turner syndrome types have been documented. In this report, we present for the first time a patient with Turner syndrome caused by deletion in the short arm of the X chromosome who experienced hypertensive hemorrhage as a late complication.

Adult-Onset Hemorrhagic Quasi-Moyamoya Disease with Unilateral Steno-occlusive Lesion in a Patient with Neurofibromatosis Type 1.

BACKGROUND: Quasi-moyamoya disease is a condition that occurs in association with a specific underlying condition or disease such as atherosclerotic disease or neurofibromatosis type 1 (NF1). Pediatric cases are frequently reported, and an ischemic and bilateral presentation is more common than a hemorrhagic and unilateral presentation. CLINICAL PRESENTATION: A 39-year-old woman previously diagnosed with NF1 presented to our department with nausea and left hemiparesis. She was diagnosed with right temporal intracerebral hemorrhage by initial computed tomography. Subsequent angiography showed an occlusion of the terminal portion of the right internal carotid artery, and magnetic resonance imaging showed multiple flow voids in the right basal ganglia, suggesting quasi-moyamoya disease. The hematoma was surgically removed, and her neurological condition improved after the operation. CONCLUSIONS: This is the first reported case of quasi-moyamoya disease with a rare combination of characteristics, including an adult-onset, hemorrhagic presentation and a unilateral lesion in a patient previously diagnosed with NF1.

A Novel Association between the 27-bp Deletion and 538G>A Mutation in the ABCC11 Gene.

A single nucleotide polymorphism in the ABCC11 gene, 538G>A (rs17822931), is known to determine human ear wax type. The G/G and G/A genotypes correspond to the wet type, while the A/A genotype corresponds to the dry type. Another earwax determinant, a 27-bp deletion (Δ27) downstream from the rs17822931 site, is a rare variant that leads to the dry phenotype. In a previous report, we found an individual with the G allele who unexpectedly showed the dry type of earwax, leading to the identification of Δ27. We also demonstrated that the Δ27 allele was present in individuals of Japanese, Thai, native North American, Andean, and Bolivian ancestry but absent in those of European and African ancestry. Here, we assessed the Δ27 allele frequency among Japanese and Ukrainian individuals and identified a novel association between the Δ27 and 538G>A mutations. The Δ27 allele frequency was 0.002 (3/1,520; one individual is heterozygous, and another is homozygous) among Japanese individuals and 0 (0/794) among Ukrainians. We also found a previously unreported homozygous genotype for both the Δ27 and A alleles. Our findings suggest that the Δ27 deletion may have occurred in an ABCC11 gene with the 538G>A mutation.

Intrathecal Baclofen Pump Implantation for Type 2 Gaucher Disease.

Gaucher disease (GD) is the most common type of lysosomal storage disease, with type 2 being the most severe subtype. Type 2 GD patients suffer significant progressive neurological impairment, including spasticity, opisthotonus, seizure, and apnea. The recently developed enzyme replacement therapy (ERT) has shown therapeutic benefit for GD. However, as the enzymes do not cross the blood-brain barrier, ERT does not ameliorate neurological impairment in GD. Intrathecal baclofen therapy (IBT) is indicated for spastic neurological diseases, such as cerebral palsy, and studies have shown its therapeutic benefit in improving several manifestations of GD, such as scoliosis caused by muscle spasticity and respiratory function. To date, the potential benefits of IBT for treating lysosomal storage diseases such as GD have not been examined. Here we provide the first report of a patient with type 2 GD treated with IBT, and demonstrate its therapeutic benefit in ameliorating the neurological aspects of this disease.

Eosinopenia in Children following Traumatic Intracranial Hemorrhage Is Associated with Poor Prognosis and Prolonged Hospital Admission.

BACKGROUND: Neutrophilia is associated with brain injury and is frequently accompanied by eosinopenia. Although eosinopenia is a poor prognostic indicator for various diseases, its significance in intracranial events has not been investigated. METHODS: We retrospectively included 22 pediatric patients (≤18 years old) who experienced traumatic intracranial hemorrhage between 2002 and 2015. Patients were divided into two groups based on the presence or absence of eosinopenia on admission, i.e. the proportion of eosinophils to total white blood cells <1.0%. RESULTS: The mean Glasgow Coma Scale score was marginally lower in the eosinopenia group (14.1 vs. 12.0, p = 0.06). The mean Glasgow Outcome Scale-Extended (GOSE) score was significantly lower in the eosinopenia group (7.5 vs. 5.7, p = 0.02), and the mean length of hospital stay tended to be longer in patients with eosinopenia (7.8 vs. 28.4, p = 0.10). In our multivariate logistic regression analysis, eosinopenia was the only significant risk factor for poor outcome (GOSE score 1-7, OR 29.7, p = 0.03) and prolonged hospital stay (>2 weeks, OR 7.1, p = 0.047). CONCLUSION: These results demonstrate the significance of eosinopenia as a novel prognostic factor in traumatic intracranial hemorrhage in children.

Eosinopenia as a Predictive Factor of the Short-Term Risk of Mortality and Infection after Acute Cerebral Infarction.

BACKGROUND: Eosinopenia has been shown to be a prognostic factor in bacteremia, chronic obstructive pulmonary disease, and myocardial infarction, but studies focusing on cerebral infarction are lacking. METHODS: We conducted a retrospective study of 405 patients admitted to the Asahi General Hospital from June 2011 to September 2014 with a diagnosis of cerebral infarction within 24 hours after symptom onset. Differences in mortality, mortality associated with infection, and the prevalence of infection within 2 months of hospital admission were assessed between patients with and without eosinopenia at presentation. RESULTS: Patients with eosinopenia had a significantly higher mortality rate (hazard ratio (HR) 2.54, 95% confidence interval (CI) 1.17-5.21, P = .01), mortality associated with infection (HR 28.7, 95% CI 4.9-542.2, P <.0001), and an increased prevalence of infection (HR 1.83, 95% CI 1.12-2.89, P = .01) than patients without eosinopenia. Patients with neutrophilia and eosinopenia showed a significantly higher mortality rate than patients without neutrophilia (HR 3.15, 95% CI 1.40-6.92, P = .007), whereas patients with neutrophilia without eosinopenia showed no significant difference in mortality compared with patients without neutrophilia (HR 1.57, 95% CI .56-3.93, P = .37). Eosinopenia was a significant risk factor in 2-month mortality rate in multivariate analyses (HR 2.34, 95% CI 1.05-4.95, P = .04). CONCLUSIONS: Eosinopenia is a novel predictive factor for complications after acute cerebral infarction. Stroke patients with eosinopenia should be monitored carefully for infection.

Chloroquine potentiates temozolomide cytotoxicity by inhibiting mitochondrial autophagy in glioma cells.

Mitochondrial autophagy eliminates damaged mitochondria and decreases reactive oxygen species (ROS). The autophagy inhibitor chloroquine (CQ) potentiates temozolomide (TMZ) cytotoxicity in glioma cells, but it is not known whether CQ does this by inhibiting mitochondrial autophagy. The effects of CQ and TMZ on MitoSOX Red fluorescence, a mitochondrial ROS indicator, and cell death were examined in rat C6 glioma cells. Mitochondrial autophagy was monitored by the colocalization of MitoTracker Red fluorescence and EGFP-LC3 dots. Mitochondrial content was measured by MitoTracker Green fluorescence and immunoblotting for a mitochondrial protein. Finally, CQ's effects on tumor cells derived from a glioblastoma patient and human U87-MG glioblastoma cells were assessed. TMZ (100-1,000 µM) alone did not affect mitochondrial ROS or cell death in C6 cells, but when administered with CQ (10 µM), it increased mitochondrial ROS and cell death. Antioxidants significantly suppressed the CQ-augmented cell death in TMZ-treated cells, indicating that mitochondrial ROS were involved in this cell death. TMZ treatment reduced MitoTracker Green fluorescence and mitochondrial protein levels, and these effects were inhibited by CQ. TMZ also increased the colocalization of EGFP-LC3 dots with mitochondria, and CQ enhanced this effect. CQ potentiated TMZ-induced cytotoxicity in patient-derived glioblastoma cells as well as human U87-MG glioblastoma cells. These results suggest that CQ increases cellular ROS and augments TMZ cytotoxicity in glioma cells by inhibiting mitochondrial autophagy.

Resveratrol improves cardiomyopathy in dystrophin-deficient mice through SIRT1 protein-mediated modulation of p300 protein.

Cardiomyopathy is the main cause of death in Duchenne muscular dystrophy. Here, we show that oral administration of resveratrol, which leads to activation of an NAD(+)-dependent protein deacetylase SIRT1, suppresses cardiac hypertrophy and fibrosis and restores cardiac diastolic function in dystrophin-deficient mdx mice. The pro-hypertrophic co-activator p300 protein but not p300 mRNA was up-regulated in the mdx heart, and resveratrol administration down-regulated the p300 protein level. In cultured cardiomyocytes, cardiomyocyte hypertrophy induced by the α(1)-agonist phenylephrine was inhibited by the overexpression of SIRT1 as well as resveratrol, both of which down-regulated p300 protein levels but not p300 mRNA levels. In addition, activation of atrial natriuretic peptide promoter by p300 was inhibited by SIRT1. We found that SIRT1 induced p300 down-regulation via the ubiquitin-proteasome pathway by deacetylation of lysine residues for ubiquitination. These findings indicate the pathological significance of p300 up-regulation in the dystrophic heart and indicate that SIRT1 activation has therapeutic potential for dystrophic cardiomyopathy.

Stereotactic radiosurgery for facial nerve hemangioma: Case report and systematic review.

BACKGROUND: Facial nerve hemangiomas (FNHs) are rare tumors that primarily occur near the geniculate ganglion in the temporal bone. Despite their rarity, they can cause significant facial nerve dysfunction. The optimal management approach for FNHs remains uncertain, with surgery being the mainstay but subject to debate regarding the extent of resection and preservation of the facial nerve. METHODS: Systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We queried the PubMed/Medline (accessed on 5 March 2024) electronic database using combinations of the following search terms and words text: "geniculate ganglion hemangioma", "ganglional hemangioma", "hemangioma of the facial nerve", "facial hemangioma", and "intratemporal hemangioma". RESULTS: We identified a total of 30 literatures (321 patients). The most common site involved for the facial nerve hemangioma was the geniculate ganglion area followed by internal auditory canal, tympanic segment, labyrinthine segment and mastoid involvement. All patients were treated with conservative management or surgery. We report a 48-year-old female patient with HB grade 2 facial palsy and hemifacial spasm underwent SRS using Cyberknife technology. The treatment targeted the FNH in the left internal acoustic canal near the geniculate ganglion. Six months post-treatment, clinical improvement was evident, and lesion control was confirmed in a follow-up brain MRI. CONCLUSION: The rarity of FNHs contributes to the lack of consensus on optimal management. This illustrative case demonstrates the feasibility of SRS as a standalone treatment for FNHs.

Automatic Segmentation of Vestibular Schwannomas: A Systematic Review.

BACKGROUND: Vestibular schwannomas (VSs) are benign tumors often monitored over time, with measurement techniques for assessing growth rates subject to significant interobserver variability. Automatic segmentation of these tumors could provide a more reliable and efficient for tracking their progression, especially given the irregular shape and growth patterns of VS. METHODS: Various studies and segmentation techniques employing different Convolutional Neural Network architectures and models, such as U-Net and convolutional-attention transformer segmentation, were analyzed. Models were evaluated based on their performance across diverse datasets, and challenges, including domain shift and data sharing, were scrutinized. RESULTS: Automatic segmentation methods offer a promising alternative to conventional measurement techniques, offering potential benefits in precision and efficiency. However, these methods are not without challenges, notably the "domain shift" that occurs when models trained on specific datasets underperform when applied to different datasets. Techniques such as domain adaptation, domain generalization, and data diversity were discussed as potential solutions. CONCLUSIONS: Accurate measurement of VS growth is a complex process, with volumetric analysis currently appearing more reliable than linear measurements. Automatic segmentation, despite its challenges, offers a promising avenue for future investigation. Robust well-generalized models could potentially improve the efficiency of tracking tumor growth, thereby augmenting clinical decision-making. Further work needs to be done to develop more robust models, address the domain shift, and enable secure data sharing for wider applicability.

Dosimetric Comparison of Dedicated Radiosurgery Platforms for the Treatment of Essential Tremor: Technical Report.

Essential tremor (ET) is one of the most common adult movement disorders. As the worldwide population ages, the incidence and prevalence of ET is increasing. Although most cases can be managed conservatively, there is a subset of ET that is refractory to medical management. By virtue of being "reversible", deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is one commonly accepted intervention. As an alternative to invasive and expensive DBS, there has been a renaissance in treating ET with lesion-based approaches, spearheaded most recently by high-intensity focused ultrasound (HIFU), the hallmark of which is that it is non-invasive. Meanwhile, stereotactic radiosurgical (SRS) lesioning of VIM represents another time-honored lesion-based non-invasive treatment of ET, which is especially well suited for those patients that cannot tolerate open neurosurgery and is now also getting a "second look". While multiple SRS platforms have been and continue to be used to treat ET, there is little in the way of dosimetric comparison between different technologies. In this brief technical report we compare the dosimetric profiles of three major radiosurgical platforms (Gamma Knife, CyberKnife Robotic Radiosurgery, and Zap-X Gyroscopic Radiosurgery (GRS)) for the treatment of ET. In general, the GRS and Gamma Knife were shown to have the best theoretical dosimetric profiles for VIM lesioning. Nevertheless the relevance of such superiority to clinical outcomes requires future patient studies.

Primary Stereotactic Body Radiotherapy for Spinal Bone Metastases From Lung Adenocarcinoma.

OBJECTIVE: This study aimed to assess the results of primary stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM) originating from lung adenocarcinoma (ADC). We considered the revised Tokuhashi score (rTS), Spinal Instability Neoplastic Score (SINS), and genetic characteristics. METHODS: We examined adult patients with lung ADC who underwent primary SBRT (using the CyberKnife System) for SBM between March 2012 and January 2023. RESULTS: We analyzed data from 99 patients, covering 152 SBM across 194 vertebrae. The overall local control (LC) rate was 77.6% for SBM from lung ADC, with a LC rate of 90.7% at 1 year. The median period for local progression (LP) occurrence was recorded at 10.0 (3-52) months. Additionally, Asian patients demonstrated higher LC rates than White patients. Utilizing the rTS and SINS as predictive tools, we revealed that a poor survival prognosis and an unstable spinal structure were associated with increased rates of LP. Furthermore, the presence of osteolytic bone destructions and pain complaints were significantly correlated with the occurrence of LP. In the cohort of this study, 108 SBM underwent analysis to determine the expression levels of programmed cell death ligand 1 (PD-L1). Additionally, within this group, 60 showed mutations in the epidermal growth factor receptor (EGFR) alongside PD-L1 expression. Nevertheless, these genetic differences did not result in statistically significant differences in the LC rate. CONCLUSION: The one-year LC rate for primary SBRT targeting SBM from lung ADC stood at 90.7%, particularly with the use of the CyberKnife System. Patients achieving LC exhibited significantly longer survival times compared to those with LP.

Differential cell-protective function of two resveratrol (trans-3,5,4'-trihydroxystilbene) glucosides against oxidative stress.

Resveratrol (trans-3,5,4'-trihydroxystilbene; RSV), a natural polyphenol, exerts a beneficial effect on health and diseases. RSV targets and activates the NAD(+)-dependent protein deacetylase SIRT1; in turn, SIRT1 induces an intracellular antioxidative mechanism by inducing mitochondrial superoxide dismutase (SOD2). Most RSV found in plants is glycosylated, and the effect of these glycosylated forms on SIRT1 has not been studied. In this study, we compared the effects of RSV and two glycosyl RSVs, resveratrol-3-O-ß-d-glucoside (3G-RSV; polydatin/piceid) and resveratrol-4'-O-ß-d-glucoside (4'G-RSV), at the cellular level. In oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, the antioxidant activity of 3G-RSV was comparable to that of RSV, whereas the radical-scavenging efficiency of 4'G-RSV was less than 50% of that of RSV. However, 4'G-RSV, but not 3G-RSV, induced SIRT1-dependent histone H3 deacetylation and SOD2 expression in mouse C2C12 skeletal myoblasts; as with RSV, SIRT1 knockdown blunted these effects. RSV and 4'G-RSV, but not 3G-RSV, mitigated oxidative stress-induced cell death in C2C12 cells and primary neonatal rat cardiomyocytes. RSV and 4'G-RSV inhibited C2C12 cell proliferation, but 3G-RSV did not. RSV was found in both the intracellular and extracellular fractions of C2C12 cells that had been incubated with 4'G-RSV, indicating that 4'G-RSV was extracellularly deglycosylated to RSV, which was then taken up by the cells. C2C12 cells did not deglycosylate 3G-RSV. Our results point to 4'G-RSV as a useful RSV prodrug with high water solubility. These data also show that the in vitro antioxidative activity of these molecules did not correlate with their ability to protect cells from oxidative stress-induced apoptosis.

Adjuvant Stereotactic Radiosurgery With or Without Postresection Fractionated Radiation Therapy for the Management of Clival Chordomas in Adults: An International Multicenter Case Series.

BACKGROUND: Clival chordomas are challenging because of their proximity to critical neurovascular structures. Stereotactic radiosurgery (SRS) has been proven effective with minimal adverse effects. OBJECTIVE: To compare the outcomes of histologically confirmed primary clival chordomas in adults who underwent SRS alone (SRS group) vs SRS after fractionated radiotherapy (FRT+SRS group). METHODS: We collected patient data from 10 institutions affiliated with the International Radiosurgery Research Foundation. We evaluated overall survival, tumor control, and freedom from additional treatment (FFAT). RESULTS: Fifty-seven (77%) patients were included in the SRS group and 17 (23%) in the FRT+SRS group. The median radiological follow-up was 48 months (IQR, 24-85) in the SRS group and 36 months (IQR, 25-41) in the FRT+SRS group. During the follow-up, 8 SRS and 2 FRT+SRS patients died ( P = .80). The groups had comparable 10-year overall survival (SRS: 76% vs FRT+SRS: 80%; logrank test, P = .75) and tumor control rates (SRS: 34% vs FRT+SRS: 45%; logrank test, P = .29). The SRS group had a superior 10-year FFAT rate (40%) compared with FRT+SRS (23%; logrank test, P = .02). This finding persisted in the multivariate analysis of the Cox proportional hazards illustrating a 2.40-fold increase in the relative risk of requiring additional treatment among the FRT+SRS group ( P = .04). CONCLUSION: Adjuvant FRT with subsequent boost SRS did not provide superior overall survival or tumor control compared with patients who underwent adjuvant SRS alone. Further studies are required to refine management guidelines among adults with clival chordomas.