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NPJ Precision Oncology Feb 2024Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of...
Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.
PubMed: 38388726
DOI: 10.1038/s41698-024-00541-w -
Cureus Jan 2024Image guidance technologies can significantly improve the accuracy and safety of intracranial catheter insertions. Augmented reality (AR) allows surgeons to visualize 3D...
Image guidance technologies can significantly improve the accuracy and safety of intracranial catheter insertions. Augmented reality (AR) allows surgeons to visualize 3D information overlaid onto a patient's head. As such, AR has emerged as a novel image guidance technology that offers unique advantages when navigating intracranial targets. A 71-year-old woman with a history of brain metastasis from breast cancer and prior resection surgery and chemotherapy presented with altered mental status and generalized weakness worse on her left side. Magnetic resonance imaging (MRI) demonstrated right frontotemporoparietal edema with a contrast-enhancing mass. MR perfusion confirmed an active tumor with an enlarging right temporal pole cyst. A cyst aspiration was performed via Ommaya reservoir placement. Neuro-navigation (BrainLab, Munich, Germany) and AR navigation were used to plan the trajectory from the temporal gyrus to the cyst. Post-operative computed tomography (CT) demonstrated good placement of the reservoir, reconstitution of the temporal horn of the lateral ventricle with decreased external mass effect, and no areas of hemorrhage. AR has tremendous potential in the field of neurosurgery for improving the accuracy and safety of procedures. This case demonstrates an encouraging application of AR and can serve as an example to drive expanded clinical use of this technology.
PubMed: 38371146
DOI: 10.7759/cureus.52383 -
Molecular Therapy. Methods & Clinical... Dec 2023Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome...
Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking. The use of intracerebroventricular (i.c.v.) catheters offers a solution for repeated dosing; however, fixation techniques in large animal models are not standardized and are not reliable. Here we describe a novel surgical technique in a sheep model for i.c.v. delivery of neurotherapeutics based on the fixation of the i.c.v. catheter with a 3D-printed anchorage system composed of plastic and ceramic parts, compatible with magnetic resonance imaging, computed tomography, and electroencephalography (EEG). Our technique allowed tracking electrical brain activity in awake animals via EEG and video recording during and for the 24-h period after administration of a novel oligonucleotide in sheep. Its anchoring efficiency was demonstrated for at least 2 months and will be tested for up to a year in ongoing studies.
PubMed: 37920238
DOI: 10.1016/j.omtm.2023.101122 -
Frontiers in Neurology 2023Hydrocephalus with intracranial infection (HII) may cause pathological changes in brain tissue structure and irreversible damage to the nervous system. However,...
BACKGROUND
Hydrocephalus with intracranial infection (HII) may cause pathological changes in brain tissue structure and irreversible damage to the nervous system. However, intracranial infection is a contraindication to ventriculo-peritoneal (VP) shunt surgery, and the prognosis is improved by early infection control and intracranial pressure reduction. This study evaluated the safety and efficacy of the Ommaya reservoir vs. modified external ventricular drainage (M-EVD) in the management of HII in pediatric patients.
METHODS
This retrospective controlled study included 45 pediatric patients with HII treated with an Ommaya reservoir ( = 24) or M-EVD ( = 21) between January 2018 and December 2022. Clinical outcomes, cerebrospinal fluid (CSF) test results, complications, and outcomes were compared between the Ommaya reservoir and M-EVD groups.
RESULTS
No patient died during the follow-up period. The two groups were similar regarding age, sex, admission temperature, weight, preoperative serum protein and albumin concentrations, CSF analysis (white blood cell count, glucose concentration, and protein content), and clinical symptoms ( > 0.05). Both groups had significant changes in the CSF test results postoperatively compared with preoperatively ( < 0.05). In the M-EVD group, the median days for 13 children to remove the external drainage tube and receive VP shunt was 19 days. The longest drainage tube retention time was 61 days, and there was no intracranial infection or serious complication related to the drainage tube. After the placement of the Ommaya, the median time required for CSF to return to normal was 21 days, and a total of 15 patients underwent VP shunt surgery.
CONCLUSION
The Ommaya reservoir and M-EVD are safe and effective for pediatric patients with HII. Both methods reduce the intracranial pressure and alleviate the symptoms of hydrocephalus, although there are differences between the two methods.
PubMed: 38274873
DOI: 10.3389/fneur.2023.1303631 -
Child's Nervous System : ChNS :... May 2024Mucopolysaccharidosis type II (MPS II) results from the genetic deficiency of a lysosomal enzyme and is associated with central nervous system (CNS) dysfunction. In... (Review)
Review
Ommaya reservoir placement using ultrasound guidance via anterior fontanelle combined with frameless electromagnetic neuronavigation in patients with mucopolysaccharidosis type 2: Case reports and review of the literature.
Mucopolysaccharidosis type II (MPS II) results from the genetic deficiency of a lysosomal enzyme and is associated with central nervous system (CNS) dysfunction. In Japan, in addition to intravenous enzyme administration, intracerebroventricular enzyme delivery through the Ommaya reservoir has recently gained approval. Nevertheless, the ideal approach for safely implanting the reservoir into the narrow ventricles of infantile MPS II patients remains uncertain. In this report, we present two cases of successful reservoir placement in infantile MPS II patients using ultrasound guidance via the anterior fontanelle, coupled with flameless electromagnetic neuronavigation.
Topics: Humans; Neuronavigation; Mucopolysaccharidosis II; Cranial Fontanelles; Electromagnetic Phenomena; Drug Delivery Systems
PubMed: 38165414
DOI: 10.1007/s00381-023-06265-9 -
Operative Neurosurgery (Hagerstown, Md.) Apr 2024Surface-based facial scanning registration emerged as an essential registration method in the robot-assisted neuronavigation surgery, providing a marker-free way to...
BACKGROUND AND OBJECTIVES
Surface-based facial scanning registration emerged as an essential registration method in the robot-assisted neuronavigation surgery, providing a marker-free way to align a patient's facial surface with the imaging data. The 3-dimensional (3D) structured light was developed as an advanced registration method based on surface-based facial scanning registration. We aspire to introduce the 3D structured light as a new registration method in the procedure of the robot-assisted neurosurgery and assess the accuracy, efficiency, and safety of this method by analyzing the relative operative results.
METHODS
We analyzed the results of 47 patients who underwent Ommaya reservoir implantation (n = 17) and stereotactic biopsy (n = 30) assisted by 3D structured light at our hospital from January 2022 to May 2023. The accuracy and additional operative results were analyzed.
RESULTS
For the Ommaya reservoir implantation, the target point error was 3.2 ± 2.2 mm and the entry point error was 3.3 ± 2.4 mm, while the operation duration was 35.8 ± 8.3 minutes. For the stereotactic biopsy, the target point error was 2.3 ± 1.3 mm and the entry point error was 2.7 ± 1.2 mm, while the operation duration was 24.5 ± 6.3 minutes.
CONCLUSION
The 3D structured light technique reduces the patients' discomfort and offers the advantage of a simpler procedure, which can improve the clinical efficiency with the sufficient accuracy and safety to meet the clinical requirements of the puncture and navigation.
PubMed: 38687040
DOI: 10.1227/ons.0000000000001184 -
Research Square Feb 2024Radiolabeled antibody I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402)....
BACKGROUND
Radiolabeled antibody I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic.
METHODS
Intraventricular radioimmunotherapy (RIT) with 925-1850 MBq (25-50 mCi) of I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 minutes, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3-10 y/o, 10-18 y/o, and 18+.
RESULTS
Post-administration exposure rates for patients ranged from 0.16-0.46 μSv/hr/MBq at 1 ft and 0.03-0.08 μSv/hr/MBq at 1 m. Radiation exposure duration ranged from 1-10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring.
CONCLUSION
I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402.
PubMed: 38464207
DOI: 10.21203/rs.3.rs-3969388/v1 -
Journal of Neurosurgery Mar 2024Radionuclide shuntography (RS) performed using 99mTc-DTPA injected into the reservoir of CSF shunts enables evaluation of CSF flow for suspected shunt malfunctions. The...
OBJECTIVE
Radionuclide shuntography (RS) performed using 99mTc-DTPA injected into the reservoir of CSF shunts enables evaluation of CSF flow for suspected shunt malfunctions. The goal of this study was to report the authors' institutional experience with RS and evaluate its utility and associated complications.
METHODS
The authors retrospectively reviewed all RS studies performed between November 2003 and June 2022. Patients with shunted hydrocephalus who were ≥ 18 years of age were included. Patients undergoing RS for evaluation of Ommaya reservoirs were excluded. Demographics, hydrocephalus etiology, presenting symptoms, study results, subsequent management, complications, and intraoperative diagnoses were recorded. Chi-square tests were reported for categorical variables and standard 2 × 2 contingency methods were used for sensitivity/specificity analysis.
RESULTS
The authors identified 211 RS procedures performed in 142 patients. The mean age at procedure was 55.6 ± 20.9 years (mean ± SD). Normal pressure hydrocephalus was the most common hydrocephalus etiology (37.0%), followed by congenital malformations (26.1%) and idiopathic intracranial hypertension (15.6%). Successful radionuclide injection was achieved in 207 studies (98.1%). Shunt patency was confirmed in 63.8% of successful injections, whereas malfunction was demonstrated in 27.1% and abnormally slow flow was seen in 9.2%. RS studies demonstrating shunt malfunction were more likely to result in subsequent revisions than were studies showing patency (86.6% vs 2.9%; p < 0.0001). The overall sensitivity and specificity of RS for detecting shunt malfunction was 92.3% and 96.2%, respectively. The median follow-up time was 29 months, with 151 cases having ≥ 6 months of follow-up. There were no complications or infections attributable to RS in this cohort.
CONCLUSIONS
RS is a useful and safe tool in the workup of shunt malfunction.
Topics: Adult; Humans; Middle Aged; Aged; Retrospective Studies; Cerebrospinal Fluid Shunts; Hydrocephalus, Normal Pressure; Neurosurgical Procedures; Radioisotopes
PubMed: 37725052
DOI: 10.3171/2023.7.JNS23455 -
Continuous Intrathecal Medication Delivery With the IRRA flow Catheter: Pearls and Early Experience.Operative Neurosurgery (Hagerstown, Md.) Mar 2024Intrathecal (IT) medications are routinely introduced through catheterization of the intraventricular space or subarachnoid space. There has been sporadic use of IT...
BACKGROUND AND OBJECTIVES
Intrathecal (IT) medications are routinely introduced through catheterization of the intraventricular space or subarachnoid space. There has been sporadic use of IT medications delivered directly to the ventricle either by intermittent injection through an external ventricular drain (EVD) or by an Ommaya reservoir with a ventricular catheter. IT medication delivery through EVD has many drawbacks, including the necessary opening of a sterile system, delivery of medication in a bolus form, and requirements to clamp the EVD after medication delivery. Despite these setbacks, IT medications delivered through EVD have been used across a wide range of applications, including antibiotic delivery treatment of vasospasm with nicardipine and delivery of tissue plasminogen activator.
METHODS
We used a newly developed active fluid exchange device to treat various severe conditions involved in the cerebral ventricles. Here, we present our treatment protocols and advice on the techniques related to successful active fluid exchange therapy.
RESULTS
Seventy patients have been treated with our system with various conditions, including subarachnoid hemorrhage, intraventricular hemorrhage, ventriculitis, and cerebral abscess. Total complication rate was 14% with only 1 catheter occlusion and low rates of hemorrhage, infection, and spinal fluid leak.
CONCLUSION
Current continuous IT medication dosages and protocols are based on reports and consensus statements evaluating intermittent instillation of medication boluses. The pharmacokinetics of continuous dosing and the therapeutic and safety profiles of the medications need to be studied in a prospective manner to evaluate the true optimal dosing standards. Furthermore, the ability to deliver continuous, sterile medications directly through an IT route will open new avenues of pharmacotherapy that were previously closed. This report serves as a basic guide for the safe and effective use of the IRRA flow active fluid exchange catheter to deliver IT medications.
Topics: Humans; Tissue Plasminogen Activator; Prospective Studies; Cerebral Ventricles; Cerebral Hemorrhage; Catheters
PubMed: 37819074
DOI: 10.1227/ons.0000000000000940 -
Journal of Neurological Surgery. Part... Apr 2024Introduction Post-Neurosurgical Meningitis (PNM) is a serious medical condition with high mortality and morbidity caused by organisms like Staphylococcus aureus and...
Introduction Post-Neurosurgical Meningitis (PNM) is a serious medical condition with high mortality and morbidity caused by organisms like Staphylococcus aureus and Gram-negative organisms like Acinetobacter baumannii. Optimum concentration of antibiotics in the cerebrospinal fluid (CSF) to treat these infections are difficult to achieve. Intraventricular antibiotic administration bypasses the blood-brain barrier and can achieve high CSF concentration without causing systemic toxicity. Methods Retrospective review of all patient records were done to identify patients who developed post-neurosurgical meningitis and received intraventricular antibiotic therapy during the period of July 2017 to December 2022. Demographic and clinical data along with type of antibiotic, route, dose and duration of administration was collected. CSF parameters before and after intraventricular antibiotic administration were collected and analyzed. Results 26 patients with post-neurosurgical meningitis received intraventricular antibiotic therapy. Intracranial tumors were the most common underlying pathology followed by aneurysms. 17/26 patients had received vancomycin and 9/26 patients had received colistin. External ventricular drain was used in 17/26 cases and Ommaya reservoir was used in 9/26 cases. 6 cases showed growth of organism in CSF before starting intraventricular antibiotics, 1 case remained culture positive despite treatment. 3/26 patients died despite treatment. There were significant changes in the CSF parameters after intraventricular antibiotic therapy. Conclusion Intraventricular administration of antibiotic provides an alternative therapeutic option in the management of patients who are not responding or poorly responding to systemic antibiotics.
PubMed: 38657674
DOI: 10.1055/a-2312-9276