Structural and functional connectivity in hydrocephalus: a scoping review.

Optimizing the treatment of hydrocephalus remains a major challenge in adult and pediatric neurosurgery. Currently, clinical treatment relies heavily on anatomic imaging of ventricular size and clinical presentation. The emergence of functional and structural brain connectivity imaging has provided the basis for a new paradigm in the management of hydrocephalus. Here we review the pertinent advances in this field. Following PRISMA-ScR guidelines for scoping reviews, we searched PubMed for relevant literature from 1994 to April 2023 using hydrocephalus and MRI-related terms. Included articles reported original MRI data on human subjects with hydrocephalus, while excluding non-English or pre-1994 publications that didn't match the study framework. The review identified 44 studies that investigated functional and/or structural connectivity using various MRI techniques across different hydrocephalus populations. While there is significant heterogeneity in imaging technology and connectivity analysis, there is broad consensus in the literature that 1) hydrocephalus is associated with disruption of functional and structural connectivity, 2) this disruption in cerebral connectivity can be further associated with neurologic compromise 3) timely treatment of hydrocephalus restores both cerebral connectivity and neurologic compromise. The robustness and consistency of these findings vary as a function of patient age, hydrocephalus etiology, and the connectivity region of interest studied. Functional and structural brain connectivity imaging shows potential as an imaging biomarker that may facilitate optimization of hydrocephalus treatment. Future research should focus on standardizing regions of interest as well as identifying connectivity analysis most pertinent to clinical outcome.

Natural history of craniovertebral abnormalities in a single-center study in 54 patients with Hurler syndrome.

OBJECTIVE: Craniovertebral junction (CVJ) abnormalities are common and well documented in mucopolysaccharidosis type I-Hurler syndrome (MPS IH), often causing severe spinal canal narrowing. However, the requirement for surgical decompression and/or fusion is uncommon. Although hematopoietic cell transplant (HCT) has been shown to prolong the lives of patients with MPS IH, its effect in halting or reversing musculoskeletal abnormalities is less clear. Unfortunately, there are currently no universal guidelines for imaging or indication for surgical interventions in these patients. The goal of this study was to track the progression of the CVJ anatomy in patients with MPS IH following HCT, and to examine radiographic features in patients who needed surgical intervention. METHODS: Patients with MPS IH treated at the University of Minnesota with allogeneic HCT between 2008 and 2020 were retrospectively reviewed. Patients who underwent CVJ surgery were identified with chart review. All MPS IH cervical scans were examined, and the odontoid retroflexion angle, clivoaxial angle (CXA), canal width, and Grabb-Oakes distance (pB-C2) were measured yearly for up to 7 years after HCT. Longitudinal models based on the measurements were made. An intraclass correlation coefficient was used to measure interrater reliability. Nine children without MPS IH were examined for control CVJ measurements. RESULTS: A total of 253 cervical spine MRI scans were reviewed in 54 patients with MPS IH. Only 4 (7.4%) patients in the study cohort required surgery. Three of them had posterior fossa and C1 decompression, and 1 had a C1-2 fusion. There was no statistically significant difference in the spinal parameters that were examined between surgery and nonsurgery groups. Among the measurements, canal width and CXA varied drastically in patients with different neck positions. Odontoid retroflexion angle and CXA tended to decrease with age. Canal width and pB-C2 tended to increase with age. CONCLUSIONS: Based on the data, the authors observed an increase in canal width and pB-C2, whereas the CXA and odontoid retroflexion angle became more acute as the patients aged after HCT. The longitudinal models derived from these data mirrored the development in children without MPS IH. Spinal measurements obtained on MR images alone are not sufficient in identifying patients who require surgical intervention. Symptom monitoring and clinical examination, as well as pathological spinal cord changes on MRI, are more crucial in assessing the need for surgery than is obtaining serial imaging.

Magnetic Resonance Imaging-Aided SmartFlow Convection Delivery of DNX-2401: A Pilot, Prospective Case Series.

BACKGROUND: The Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE) study is a phase II clinical trial testing the efficacy of a recombinant adenovirus DNX-2401 combined with the immune checkpoint inhibitor pembrolizumab. Here, we report the first patients in this study who underwent viral delivery through real-time magnetic resonance imaging (MRI) stereotaxis-guided SmartFlow convection delivery of DNX-2401. METHODS: Patients who underwent real-time MRI-guided DNX-2401 delivery through the SmartFlow convection catheter were prospectively followed. RESULTS: Precise catheter placement was achieved in all patients treated, and no adverse events were noted. Average radial error from target was 0.9 mm. Average procedural time was 3 hours 16 minutes and was comparable to other convection-enhanced delivery techniques. In 2 patients, delivery of DNX-2401 was visualized as >1 cm maximal diameter of T1 hypointensity infusate on MRI obtained immediately after completion of viral infusion. These patients exhibited partial response based on Response Assessment in Neuro-Oncology assessment. The remaining patient showed <1 cm maximal diameter of infusate on immediate postinfusion MRI and showed disease progression on subsequent MRI. CONCLUSIONS: Our pilot case series supports compatibility of the SmartFlow system with oncolytic adenovirus delivery and provides the basis for future validation studies.

Stereotactic Radiosurgery as Treatment for Brain Metastases: An Update.

Stereotactic radiosurgery (SRS) is a mainstay treatment option for brain metastasis (BM). While guidelines for SRS use have been outlined by professional societies, consideration of these guidelines should be weighed in the context of emerging literature, novel technology platforms, and contemporary treatment paradigms. Here, we review recent advances in prognostic scale development for SRS-treated BM patients and survival outcomes as a function of the number of BM and cumulative intracranial tumor volume. Focus is placed on the role of stereotactic laser thermal ablation in the management of BM that recur after SRS and the management of radiation necrosis. Neoadjuvant SRS prior to surgical resection as a means of minimizing leptomeningeal spread is also discussed.

Advances in Epidural Spinal Cord Stimulation to Restore Function after Spinal Cord Injury: History and Systematic Review.

Epidural spinal cord stimulation (eSCS) has been recently recognized as a potential therapy for chronic spinal cord injury (SCI). eSCS has been shown to uncover residual pathways within the damaged spinal cord. The purpose of this review is to summarize the key findings to date regarding the use of eSCS in SCI. Searches were carried out using MEDLINE, EMBASE, and Web of Science database and reference lists of the included articles. A combination of medical subject heading terms and keywords was used to find studies investigating the use of eSCS in SCI patients to facilitate volitional movement and to restore autonomic function. The risk of bias was assessed using Risk Of Bias In Non-Randomized Studies of Interventions tool for nonrandomized studies. We were able to include 40 articles that met our eligibility criteria. The studies included a total of 184 patient experiences with incomplete or complete SCI. The majority of the studies used the Medtronic 16 paddle lead. Around half of the studies reported lead placement between T11- L1. We included studies that assessed motor (n = 28), autonomic (n = 13), and other outcomes (n = 10). The majority of the studies reported improvement in outcomes assessed. The wide range of included outcomes demonstrates the effectiveness of eSCS in treating a diverse SCI population. However, the current studies cannot definitively conclude which patients benefit the most from this intervention. Further study in this area is needed to allow improvement of the eSCS technology and allow it to be more widely available for chronic SCI patients.

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.

Long-Term Spinal Cord Stimulation After Chronic Complete Spinal Cord Injury Enables Volitional Movement in the Absence of Stimulation.

Background: Chronic spinal cord injury (SCI) portends a low probability of recovery, especially in the most severe subset of motor-complete injuries. Active spinal cord stimulation with or without intensive locomotor training has been reported to restore movement after traumatic SCI. Only three cases have been reported where participants developed restored volitional movement with active stimulation turned off after a period of chronic stimulation and only after intensive rehabilitation with locomotor training. It is unknown whether restoration of movement without stimulation is possible after stimulation alone. Objective: We describe the development of spontaneous volitional movement (SVM) without active stimulation in a subset of participants in the Epidural Stimulation After Neurologic Damage (ESTAND) trial, in which locomotor training is not prescribed as part of the study protocol, and subject's rehabilitation therapies are not modified. Methods: Volitional movement was evaluated with the Brain Motor Control Assessment using sEMG recordings and visual examination at baseline and at follow-up visits with and without stimulation. Additional functional assessment with a motor-assisted bicycle exercise at follow-up with and without stimulation identified generated work with and without effort. Results: The first seven participants had ASIA Impairment Scale (AIS) A or B thoracic SCI, a mean age of 42 years, and 7.7 years post-injury on average. Four patients developed evidence of sustained volitional movement, even in the absence of active stimulation after undergoing chronic epidural spinal cord stimulation (eSCS). Significant increases in volitional power were found between those observed to spontaneously move without stimulation and those unable (p < 0.0005). The likelihood of recovery of spontaneous volitional control was correlated with spasticity scores prior to the start of eSCS therapy (p = 0.048). Volitional power progressively improved over time (p = 0.016). Additionally, cycling was possible without stimulation (p < 0.005). Conclusion: While some SVM after eSCS has been reported in the literature, this study demonstrates sustained restoration without active stimulation after long-term eSCS stimulation in chronic and complete SCI in a subset of participants. This finding supports previous studies suggesting that "complete" SCI is likely not as common as previously believed, if it exists at all in the absence of transection and that preserved pathways are substrates for eSCS-mediated recovery in clinically motor-complete SCI. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03026816.