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The blood–cerebrospinal fluid barrier (BCSFB) tightly regulates molecular exchanges between the bloodstream and cerebrospinal fluid (CSF), creating challenges for effective central nervous system (CNS) drug delivery. This review assesses intrathecal (IT) nanoparticle (NP) delivery systems that aim to enhance drug delivery by circumventing the BCSFB, complementing approaches that target the blood–brain barrier (BBB). Active pharmaceutical ingredients (APIs) face hurdles like restricted CNS distribution and rapid clearance, which diminish the efficacy of IT therapies. NPs can be engineered to extend drug circulation times, improve CNS penetration, and facilitate sustained release. This review discusses key pharmacokinetic (PK) parameters essential for the effectiveness of these systems. NPs can quickly traverse the subarachnoid space and remain within the leptomeninges for extended periods, often exceeding three weeks. Some designs enable deeper brain parenchyma penetration. Approximately 80% of NPs in the CSF are cleared through the perivascular glymphatic pathway, with microglia-mediated transport significantly contributing to their paravascular clearance. This review synthesizes recent progress in IT-NP delivery across the BCSFB, highlighting critical findings, ongoing challenges, and the therapeutic potential of surface modifications and targeted delivery strategies.

Tuberculous meningitis (TBM) presents a critical neurologic emergency characterized by high mortality and morbidity rates, necessitating immediate therapeutic intervention, often ahead of definitive microbiological and molecular diagnoses. The primary hurdle in effective TBM treatment is the blood–brain barrier (BBB), which significantly restricts the delivery of anti-tuberculous medications to the central nervous system (CNS), leading to subtherapeutic drug levels and poor treatment outcomes. The standard regimen for initial TBM treatment frequently falls short, followed by adverse side effects, vasculitis, and hydrocephalus, driving the condition toward a refractory state. To overcome this obstacle, intrathecal (IT) sustained release of anti-TB medication emerges as a promising approach. This method enables a steady, uninterrupted, and prolonged release of medication directly into the cerebrospinal fluid (CSF), thus preventing systemic side effects by limiting drug exposure to the rest of the body. Our review diligently investigates the existing literature and treatment methodologies, aiming to highlight their shortcomings. As part of our enhanced strategy for sustained IT anti-TB delivery, we particularly seek to explore the utilization of nanoparticle-infused hydrogels containing isoniazid (INH) and rifampicin (RIF), alongside osmotic pump usage, as innovative treatments for TBM. This comprehensive review delineates an optimized framework for the management of TBM, including an integrated approach that combines pharmacokinetic insights, concomitant drug administration strategies, and the latest advancements in IT and intraventricular (IVT) therapy for CNS infections. By proposing a multifaceted treatment strategy, this analysis aims to enhance the clinical outcomes for TBM patients, highlighting the critical role of targeted drug delivery in overcoming the formidable challenges presented by the blood–brain barrier and the complex pathophysiology of TBM.

Surgical site infections (SSIs) after spinal surgery present significant challenges, including poor antibiotic penetration and biofilm formation on implants, leading to frequent treatment failures. Polymethylmethacrylate (PMMA) is widely used for localized drug delivery in bone infections, yet quantifying individual drug release kinetics is often impractical. This retrospective study analyzed 23 cases of deep SSIs (DSSIs) following spinal surgery treated with antibiotic-loaded PMMA. A mathematical model estimated personalized drug release kinetics from PMMA, considering disease types, pathogens, and various antibiotics. The study found that vancomycin (VAN), ceftriaxone (CRO), and ceftazidime (CAZ) reached peak concentrations of 15.43%, 15.42%, and 15.41%, respectively, within the first two days, which was followed by a lag phase (4.91–4.92%) on days 2–3. On days 5–7, concentrations stabilized, with CRO at 3.22% and CAZ/VAN between 3.63% and 3.65%, averaging 75.4 µg/cm2. Key factors influencing release kinetics include solubility, diffusivity, porosity, tortuosity, and bead diameter. Notably, a patient with a low glomerular filtration rate (ASA IV) was successfully treated with a shortened 9-day intravenous VAN regimen, avoiding systemic complications. This study affirms the effectiveness of local drug delivery systems (DDS) in treating DSSIs and underscores the value of mathematical modeling in determining drug release kinetics. Further research is essential to optimize release rates and durations and to mitigate risks of burst release and tissue toxicity.

Background This study evaluates the conformity of using a computer vision-based posture analysis system as a screening assessment for postural deformity detection in the spine that is easily applicable to clinical practice. Methods One hundred forty participants were enrolled for screening of the postural deformation. Factors that determine the presence or absence of spinal deformation, such as shoulder height difference (SHD), pelvic height difference (PHD), and leg length mismatch (LLD), were used as parameters for the clinical decision support system (CDSS) using a commercial computer vision-based posture analysis system. For conformity analysis, the probability of postural deformation provided by CDSS, the Cobb angle, the PHD, and the SHD was compared and analyzed between the system and radiographic parameters. A principal component analysis (PCA) of the CDSS and correlation analysis were conducted. Results The Cobb angles of the 140 participants ranged from 0° to 61°, with an average of 6.16° ± 8.50°. The postural deformation of CDSS showed 94% conformity correlated with radiographic assessment. The conformity assessment results were more accurate in the participants of postural deformation with normal (0–9°) and mild (10–25°) ranges of scoliosis. The referenced SHD and the SHD of the CDSS showed statistical significance ( p  < 0.001) on a paired t-test. SHD and PHD for PCA were the predominant factors (PC1 SHD for 79.97%, PC2 PHD for 19.86%). Conclusion The CDSS showed 94% conformity for the screening of postural spinal deformity. The main factors determining diagnostic suitability were two main variables: SHD and PHD. In conclusion, a computer vision-based posture analysis system can be utilized as a safe, efficient, and convenient CDSS for early diagnosis of spinal posture deformation, including scoliosis.

This review highlights the need for therapeutic guidelines for syringomyelia associated with tethered cord syndrome (TCS) caused by spinal dysraphism (SD). A comprehensive literature review was conducted, selecting twelve articles to analyze common therapeutic strategies. Surgical cord untethering alone has recently become a preferred treatment, with 45 ± 21.1% of patients experiencing remission or improvement, 47 ± 20.4% unchanged and asymptomatic, and 4 ± 8% worsened. Untethering with direct surgical drainage for the syrinx had better outcomes than untethering alone (78% vs. 45%, p = 0.05). Terminal syringostomy was beneficial for syrinxes extending to the filum terminale but not for asymptomatic small syrinxes with a syrinx index < 0.4. Syrinx shunting was recommended for symptomatic large syrinxes (>2 cm in length and syrinx index > 0.5). Various shunt procedures for syrinxes are still advocated, mainly for refractory syringomyelia in Chiari malformation, posttraumatic cases, SD, or other causes. Personalized surgical methods that address the root cause of syringomyelia, particularly those improving cerebrospinal fluid flow, offer promising results with minimized complications. Ongoing studies are required to enhance management strategies for syringomyelia associated with TCS, optimize patient outcomes, and reduce the risk of recurrent symptoms.

The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.

Cerebral hemorrhages require rapid diagnosis and intensive treatment. This study aimed to detect cerebral hemorrhages and their locations in images using a deep learning model applying explainable deep learning. Normal brain images with no hemorrhages and images with subarachnoid, intraventricular, subdural, epidural, and intraparenchymal hemorrhages according to computed tomography (CT) (n = 200) were analyzed. A ResNet deep learning model, including image processing, was utilized. The visual explanation from a heatmap was made at the hemorrhage location using a gradient-class activation map (Grad-CAM). To evaluate the performance of the deep learning system, the accuracy, sensitivity, and specificity were determined. A hemorrhage prediction system for images of normal brains and brains with subarachnoid, intraventricular, subdural, epidural, and intraparenchymal hemorrhages was built. The Grad-CAM representation indicated the location of the hemorrhages in these images. In the prediction results, accurate predictions of the hemorrhage areas were made and visualizations of the corresponding locations overlapped in the images within (− 4, 1) pixel difference. The evaluation of the system performance showed an accuracy of 0.81 with a sensitivity of 0.67 and specificity of 0.86. These results constitue a proof of concept for the use of explainable artificial intelligence (XAI) to detect cerebral hemorrhages and visualize their locations in medical images, which will allow rapid diagnosis and treatment.

This study aimed to evaluate prognostic factors associated with nidus obliteration following stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations. From January 2001 to January 2018, 119 patients who underwent SRS with AVM were studied to analyze major prognostic factors (age, prescription dose (Gy), volume (mm3), nidus size (cm), and Spetzler–Martin (SM) grade) for nidus obliteration. A random forest and tree explainer was used to construct a predictive model of nidus obliteration. The prognostic factors affecting nidus obliteration from most to least important were age, nidus size, volume, total prescription dose, and SM grade, using a predictive model. In a specific case for nidus size (1.5 cm), total dose (23 Gy), and SM grade (2), the result showed a high obliteration score of 0.75 with the actual obliteration period of 6 months spent; the mean AUC was 0.90 in K-fold cross validation. The predictive model identified the main contributing factors associated with a prognostic of nidus obliteration from linear accelerator-based SRS for cerebral AVM. It was confirmed that the results, including the prognostic factors, are potentially useful for outcome prediction for patient and treatment.

Purpose To evaluate a feasibility of normal distribution transform (NDT) algorithm compared with the iterative closest point (ICP) method as a useful surface registration in stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS). Methods Point cloud images using the 3D triangulation technology were obtained from a depth camera‐based optical imaging (OSI) system equipped in a radiosurgery room. Two surface registration algorithms, NDT and ICP, were used to measure and compare the discrepancy values between the reference and the current surfaces during the positioning of the patient. The performance evaluation was investigated by calculating the registration error and root‐mean‐square (RMS) values for the surface model, reposition, and target accuracy, which were analyzed statistically using a paired t‐test. Results For surface model accuracy, the average of the registration error and RMS values were measured as 3.56 ± 2.20 mm and 6.98 ± 1.89 mm for ICP method, and 1.76 ± 1.32 mm and 3.58 ± 1.30 mm for NDT method (p < 0.05). For reposition accuracy, the average registration error and RMS values were calculated as 1.41 ± 0.98 mm and 2.53 ± 1.64 mm using ICP method, and 0.92 ± 0.61 mm and 1.75 ± 0.80 mm using NDT method (p = 0.005). The overall target accuracy using the NDT method reduced the average of the reposition error and overall RMS value by 0.71 and 1.32 mm, respectively, compared to the ICP method (p = 0.03). Conclusions We found that the surface registration algorithm based on NDT method provides more reliable accuracy in the values of surface model, reposition, and target accuracies than the classic ICP method. The NDT method in OSI systems offers reasonable accuracy in SBRT/SRS.

Severe centrum semiovale perivascular spaces (CSO-PVSs) are associated with the onset of brain atrophy and dementia. This study explored the relationship between severity of CSO-PVS and development of subdural fluid (SDF) in patients with mild traumatic brain injury (TBI), with the aim of investigating independent radiological risk factors for development of SDF. The study cohort comprised 222 patients with a mean age of 51 years (64.0% men) who presented with mild TBI from January 2013 to November 2016. In this study, mild TBI was defined as a Glasgow Coma Scale (GCS) of ≥ 13, Post-Traumatic Amnesia (PTA) of <1 day, and Loss of Consciousness (LOC) of <30 minutes. The severity of CSO-PVS was categorized as low or high-degree. Among the 222 enrolled patients, 38 (17.1%) and 90 (40.5%) had high-degree PVS in the basal ganglia (BG) and centrum semiovale, respectively. Compared with patients who did not develop SDF, the mean age of patients who developed SDF was significantly higher (47.41 years versus 60.33 years, P < 0.0001). The incidence of de novo SDF was significantly higher in men than in women (77.8% versus 59.5%, P = 0.0151). Patients who showed SDF on brain computed tomography at admission more frequently developed de novo SDF (68.5% versus 38.1%, P < 0.0001). In multivariate logistic regression analysis of risk factors, high-degree CSO-PVS, male sex, initial SDF on admission, and old age were independently associated with development of de novo SDF after mild TBI. In Cox proportional hazards models of risk factors for SDF-development free survival rate, high-degree CSO-PVS, old age, and initial subdural hemorrhage showed statistically significant differences. Our study might help neurosurgeons determine the frequency of brain CT or the duration of follow-up for patients who present with mild TBI with high-degree CSO-PVS.