Faculty Bibliography

BACKGROUND:Middle meningeal artery embolization (MMAE) has emerged as a promising therapy for chronic subdural hematomas (cSDHs). The efficacy of standalone MMAE compared with MMAE with concurrent surgery is largely unknown. METHODS:cSDH patients who underwent successful MMAE from 14 high volume centers with at least 30 days of follow-up were included. Clinical and radiographic variables were recorded and used to perform propensity score matching (PSM) of patients treated with standalone MMAE or MMAE with concurrent surgery. Multivariable logistic regression models were used for additional covariate adjustments. The primary outcome was recurrence requiring surgical rescue, and the secondary outcome was radiographic failure defined as <50% reduction of cSDH thickness. RESULTS:722 MMAE procedures in 588 cSDH patients were identified. After PSM, 230 MMAE procedures remained (115 in each group). Median age was 73 years, 22.6% of patients were receiving anticoagulation medication, and 47.9% had no preoperative functional disability. Median midline shift was 4 mm and cSDH thickness was 16 mm, representing modestly sized cSDHs. Standalone MMAE and MMAE with surgery resulted in similar rates of surgical rescue (7.8% vs 13.0%, respectively, P=0.28; adjusted OR (aOR 0.73 (95% CI 0.20 to 2.40), P=0.60) and radiographic failure (15.5% vs 13.7%, respectively, P=0.84; aOR 1.08 (95% CI 0.37 to 2.19), P=0.88) with a median follow-up duration of 105 days. These results were similar across subgroup analyses and follow-up durations. CONCLUSIONS:Standalone MMAE led to similar and durable clinical and radiographic outcomes as MMAE combined with surgery in select patients with moderately sized cSDHs and mild clinical disease.

Fibrillary aggregation of α-synuclein in Lewy body inclusions and nigrostriatal dopaminergic neuron degeneration define Parkinson's disease neuropathology. Mutations in GBA1, encoding glucocerebrosidase, are the most frequent genetic risk factor for Parkinson's disease. However, the lack of reliable experimental models able to reproduce key neuropathological signatures has hampered the clarification of the link between mutant glucocerebrosidase and Parkinson's disease pathology. Here, we describe an innovative protocol for the generation of human induced pluripotent stem cell-derived midbrain organoids containing dopaminergic neurons with nigral identity that reproduce characteristics of advanced maturation. When applied to patients with GBA1-related Parkinson's disease, this method enabled the differentiation of midbrain organoids recapitulating dopaminergic neuron loss and fundamental features of Lewy body pathology observed in human brains, including the generation of α-synuclein fibrillary aggregates with seeding activity that also propagate pathology in healthy control organoids. Still, we observed that the retention of mutant glucocerebrosidase in the endoplasmic reticulum and increased levels of its substrate glucosylceramide are determinants of α-synuclein aggregation into Lewy body-like inclusions. Consistently, the reduction of glucocerebrosidase activity accelerated α-synuclein pathology by promoting fibrillary α-synuclein deposition. Finally, we demonstrated the efficacy of ambroxol and GZ667161 - two modulators of the glucocerebrosidase pathway in clinical development for the treatment of GBA1-related Parkinson's disease - in reducing α-synuclein pathology in this model, supporting the use of midbrain organoids as a relevant pre-clinical platform for investigational drug screening.

BACKGROUND:Hypoglossal canal dural arteriovenous fistulas (HCDAVFs) are a relatively rare subtype of dural arteriovenous fistula (dAVF), representing 3%-5% of all dAVFs. The complex angio- and venous architecture predisposed to numerous anastomoses and nearby anatomical structures, including the posterior fossa sinuses and cranial nerves, can complicate both the diagnosis and treatment of these lesions. OBSERVATIONS/METHODS:The authors describe the case of HCDAVF in a 74-year-old male who presented with pulsatile tinnitus (PT) lasting 3 months and significant fatigue, headaches, and dizziness. Diagnostic cerebral angiography demonstrated a left-sided HCDAVF with bilateral supply from the ascending pharyngeal arteries and fistulous connection at the level of the left anterior condylar vein (ACV). This lesion was consistent with a Cognard and Borden type I dAVF. LESSONS/CONCLUSIONS:The authors present a case in which transvenous embolization (TVE) with detachable coils via the ipsilateral internal jugular vein successfully occluded the previously visualized shunt to the left ACV and provided a clinical cure for the patient's PT and headaches without complication. Selecting the appropriate treatment strategy for the successful treatment of HCDAVFs is predicated on a comprehensive understanding of the anatomical features of the lesion, namely arterial feeders, venous drainage pattern, and location of the fistulous connection. TVE is a safe and efficacious treatment option for HCDAVFs. https://thejns.org/doi/10.3171/CASE24606.

BACKGROUND:Visual disability is a growing problem for many middle-aged and older adults. Conventional mobility aids, such as white canes and guide dogs, have notable limitations that have led to increasing interest in electronic travel aids (ETAs). Despite remarkable progress, current ETAs lack empirical evidence and realistic testing environments and often focus on the substitution or augmentation of a single sense. OBJECTIVE:This study aims to (1) establish a novel virtual reality (VR) environment to test the efficacy of ETAs in complex urban environments for a simulated visual impairment (VI) and (2) evaluate the impact of haptic and audio feedback, individually and combined, on navigation performance, movement behavior, and perception. Through this study, we aim to address gaps to advance the pragmatic development of assistive technologies (ATs) for persons with VI. METHODS:The VR platform was designed to resemble a subway station environment with the most common challenges faced by persons with VI during navigation. This environment was used to test our multisensory, AT-integrated VR platform among 72 healthy participants performing an obstacle avoidance task while experiencing symptoms of VI. Each participant performed the task 4 times: once with haptic feedback, once with audio feedback, once with both feedback types, and once without any feedback. Data analysis encompassed metrics such as completion time, head and body orientation, and trajectory length and smoothness. To evaluate the effectiveness and interaction of the 2 feedback modalities, we conducted a 2-way repeated measures ANOVA on continuous metrics and a Scheirer-Ray-Hare test on discrete ones. We also conducted a descriptive statistical analysis of participants' answers to a questionnaire, assessing their experience and preference for feedback modalities. RESULTS:Results from our study showed that haptic feedback significantly reduced collisions (P=.05) and the variability of the pitch angle of the head (P=.02). Audio feedback improved trajectory smoothness (P=.006) and mitigated the increase in the trajectory length from haptic feedback alone (P=.04). Participants reported a high level of engagement during the experiment (52/72, 72%) and found it interesting (42/72, 58%). However, when it came to feedback preferences, less than half of the participants (29/72, 40%) favored combined feedback modalities. This indicates that a majority preferred dedicated single modalities over combined ones. CONCLUSIONS:AT is crucial for individuals with VI; however, it often lacks user-centered design principles. Research should prioritize consumer-oriented methodologies, testing devices in a staged manner with progression toward more realistic, ecologically valid settings to ensure safety. Our multisensory, AT-integrated VR system takes a holistic approach, offering a first step toward enhancing users' spatial awareness, promoting safer mobility, and holds potential for applications in medical treatment, training, and rehabilitation. Technological advancements can further refine such devices, significantly improving independence and quality of life for those with VI.

OBJECTIVES/OBJECTIVE:Posterior circulation stroke (PCS) presents diagnostic challenges due to its diverse clinical presentations. Timely detection is crucial, yet a highly sensitive, non-invasive screening tool for PCS is lacking. This study explores gait assessment as a readily accessible diagnostic tool for ruling out PCS in acutely vertiginous patients. MATERIALS AND METHODS/METHODS:In this retrospective case-control study, we examined medical records of 311 acutely vertiginous patients from the Get with the Guidelines Database at an academic hospital in New York City. Of these, 40 were diagnosed with PCS and 271 did not have PCS based on imaging and clinical criteria. We used multivariable logistic regression models and ROC curves to evaluate the association between objective gait abnormality (OGA) and PCS. RESULTS:Objective gait abnormality (OGA) was observed in 38/40 (95 %) posterior circulation stroke (PCS) cases and 57/271 (21 %) controls (adjusted odds ratio 144, 95 %CI 24.4-855, p < 0.0001). In a predictive model, objective gait abnormality (OGA) exhibited excellent discrimination between cases and controls (AUC 0.9599, sensitivity 95.0 %, specificity 75.6 %, positive predictive value 36.5 %, negative predictive value 99.0 %). CONCLUSIONS:Gait assessment emerges as a highly-sensitive screening tool for ruling out posterior circulation stroke (PCS) in acutely vertiginous patients, enabling more efficient triage and patient management. Further prospective research is warranted to validate these findings in larger and more diverse patient populations.

OBJECTIVE:Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure-freedom. We developed an open-source software to characterize and localize HS to aid the presurgical evaluation of children and adults with suspected TLE. METHODS:We included a multicenter cohort of 365 participants (154 HS; 90 disease controls; 121 healthy controls). HippUnfold was used to extract morphological surface-based features and volumes of the hippocampus from T1-weighted MRI scans. We characterized pathological hippocampi in patients by comparing them to normative growth charts and analyzing within-subject feature asymmetries. Feature asymmetry scores were used to train a logistic regression classifier to detect and lateralize HS. The classifier was validated on an independent multicenter cohort of 275 patients with HS and 161 healthy and disease controls. RESULTS:HS was characterized by decreased volume, thickness, and gyrification alongside increased mean and intrinsic curvature. The classifier detected 90.1% of unilateral HS patients and lateralized lesions in 97.4%. In patients with MRI-negative histopathologically-confirmed HS, the classifier detected 79.2% (19/24) and lateralized 91.7% (22/24). The model achieved similar performances on the independent cohort, demonstrating its ability to generalize to new data. Individual patient reports contextualize a patient's hippocampal features in relation to normative growth trajectories, visualise feature asymmetries, and report classifier predictions. INTERPRETATION/CONCLUSIONS:Automated and Interpretable Detection of Hippocampal Sclerosis (AID-HS) is an open-source pipeline for detecting and lateralizing HS and outputting clinically-relevant reports. ANN NEUROL 2024.

BACKGROUND:Health and healthcare disparities for surgical patients with blindness and low vision (pBLV) stem from inaccessible healthcare systems that lack universal design principles or, at a minimum, reasonable accommodations (RA). OBJECTIVES/OBJECTIVE:We aimed to identify barriers to developing and implementing RAs in the surgical setting and provide a review of best practices for providing RAs. METHODS:We conducted a search of PubMed for evidence of reasonable accommodations, or lack thereof, in the surgical setting. Articles related to gaps and barriers to providing RAs for pBLV or best practices for supporting RAs were reviewed for the study. RESULTS:Barriers to the implementation of reasonable accommodations, and, accordingly, best practices for achieving equity for pBLV, relate to policies and systems, staff knowledge and attitudes, and materials and technology. CONCLUSIONS:These inequities for pBLV require comprehensive frameworks that offer, maintain, and support education about disability disparities and RAs in the surgical field. Providing RAs for surgical pBLV, and all patients with disabilities is an important and impactful step towards creating a more equitable and anti-ableist health system.

BACKGROUND:Subdural hematoma is a rare manifestation of hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease. Here, the authors present a patient with HHT and a large chronic subdural hematoma, for whom nonsurgical management was pursued. OBSERVATIONS/METHODS:A 49-year-old right-handed male with a history of hypertension and familial HHT presented with complaints of mild confusion and left hemiparesis over several days. Noncontrast head computed tomography images demonstrated a large chronic right hemisphere subdural hematoma compressing the right cerebral hemisphere and causing a 1.3-cm midline shift. Due to concerns about surgical complications arising from hemorrhages of cryptic telangiectasias, the patient was treated conservatively with middle meningeal artery embolization and adjuvant tranexamic acid. There was clinical and radiological resolution several months later. LESSONS/CONCLUSIONS:This case highlights the rarity of a subdural hematoma as a manifestation of HHT and the nonsurgical treatment strategy as a mechanism to avoid hemorrhagic complications of surgical evacuation. https://thejns.org/doi/10.3171/CASE24483.

The anatomy of vertebrobasilar perforators has been widely studied in human cadavers, with most reports found in the neurosurgical literature. These arterial perforators are extremely hard to visualize consistently with traditional two-dimensional digital subtraction angiography, but are reliably visible with cross sectional cone beam CT techniques. A clear understanding of this specific neurovascular anatomy and pathology is essential for informed treatment decisions. This review analyzes the anatomy of vertebrobasilar perforators with a focus on practical implications for aneurysm treatment, particularly flow diversion.