Faculty Bibliography

INTRODUCTION/BACKGROUND:Cannabis use is rising in the United States. Up to 30 % of individuals who use cannabis develop cannabis use disorder (CUD), for which there are no FDA-approved treatments. This randomized controlled trial (RCT) evaluated the feasibility and efficacy of a novel, one-month telehealth intervention of remotely supervised tDCS (RS-tDCS) paired with mindfulness meditation. This home-based telehealth intervention was evaluated in a cohort of women with multiple sclerosis (MS), a vulnerable subpopulation of adults with high rates of CUD. METHODS:The intervention included 20 home-based RS-tDCS sessions targeting the left DLPFC, delivering 2.0mA for 20minutes, paired with guided mindfulness meditation. Sessions were conducted 5 days per week for four weeks. Fifty-two women with MS and CUD (age: 44 ± 10 years) consented to participate; 47 were randomized 2:1 to active or sham tDCS. Feasibility was assessed via retention and adherence, while preliminary efficacy was measured by cannabis use, withdrawal symptoms, and MS-related symptom scales. RESULTS:Of 47 randomized participants (31 active, 16 sham), 39 (83 %) completed the intervention. The active tDCS group showed significant reductions in weekly cannabis use (Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory, DFAQ-CU: 5.3 ± 2.4 vs. 3.9 ± 2.7 days, p = 0.014) and withdrawal symptoms (CWS: p < 0.001). A trend toward reduced MS-related symptoms was observed (SymptoMScreen: p = 0.031). Cognitive performance improvement at the end of the intervention was significant in the active group (p = 0.011 vs. p = 0.172), supporting functional benefits of reduced cannabis use. CONCLUSIONS:This pilot RCT supports the feasibility and preliminary efficacy of telehealth tDCS in a medical subpopulation. Studying women with MS highlights its potential for large-scale RCTs and clinical use.

Alexia without agraphia is a neurological syndrome characterised by an acquired inability to read with a preserved ability to write. It is caused by the combined effect of two lesions: in the splenium of the corpus callosum and in the occipital lobe of the dominant hemisphere. Splenial lesions disconnect the language areas in the temporal and parietal lobes of the dominant hemisphere from the visual areas in the occipital cortex of the contralateral side, while lesions in the dominant occipital lobe cause homonymous hemianopia. We describe two patients with lesions affecting the splenium and dominant occipital lobe, with different causes. Together, these cases highlight the importance of performing a thorough language evaluation in patients presenting with homonymous visual field deficits, as otherwise, clinicians may overlook impairments in writing (agraphia) or reading (alexia).

The presence of tantalum opacified liquid embolic in incompletely treated dural arteriovenous fistulae (dAVFs) limits visibility of critically important angioarchitectural features. Modern cone beam CT imaging can resolve the anatomy of dAVFs allowing for a targeted embolic approach. However, distortion from beam hardening artifact is particularly limiting in cone beam CT imaging. We present a case of a dAVF embolized 4 times without cure at an outside hospital and ultimately referred to our practice for treatment. In this case, dual volume cone beam CT imaging (versus the traditional single volume technique), combined with post-processing tools on a modern workstation, enabled clear resolution of critical angioarchitectural features of the dAVF leading to a targeted cure. This technique has the potential to vastly improve dAVFs resolution in the context of partial treatment, a challenging and not uncommon diagnostic and treatment challenge.

Tractography is a unique modality for the in vivo measurement of structural connectivity, crucial for understanding brain networks and neurological conditions. With increasing b-value, the diffusion-weighting signal becomes primarily sensitive to the intra-axonal signal. However, it remains unclear how tractography is affected by this observation. Here, using open-source datasets, we showed that at high b-values, DWI reduces the uncertainty in estimating fiber orientations. Specifically, we found the ratio of biologically-meaningful longer-range connections increases, accompanied with downstream impact of redistribution of connectome and network metrics. However, when going beyond b = 6000 s/mm², the loss of SNR imposed a penalty. Lastly, we showed that the data reaches satisfactory reproducibility with b-values above 1200 s/mm². Overall, the results suggest that using b-values above 2500 s/mm² is essential for more accurate connectome reconstruction by reducing uncertainty in fiber orientation estimation, supporting the use of higher b-value protocols in standard diffusion MRI scans and pipelines.

BackgroundMiddle meningeal artery embolization (MMAE) is a promising treatment for chronic subdural hematoma (cSDH). Cancer patients are at risk for cSDH due to thrombocytopenia. The efficacy of MMAE in this population has not been studied.MethodsWe conducted a retrospective analysis of 76 patients who underwent 94 MMAEs for cSDH at 12 tertiary centers across North America and Europe between February 2018 and January 2023. We analyzed patient demographics, clinical profiles, procedural details, and outcomes. The primary outcome was cSDH progression, while secondary outcomes included radiographic resolution, mortality, 90-day functional outcomes, functional improvement, and procedural complications.ResultsRadiographic improvement occurred in 88.5% of patients, and technical success was achieved in 96.8%, with comparable rates between the MMAE-only and MMAE + surgery groups. Complications occurred in five patients (5.3%), with no significant difference between groups (6.0% in MMAE vs. 3.7% in MMAE + surgery, p = 0.658). Hemorrhage was reported in four patients (4.3%), and no cases of stroke were recorded. Mortality was 24.5% overall, with a slightly higher rate in the MMAE + surgery group (29.6%) compared to the MMAE-only group (22.4%, p = 0.460). Functional improvement in modified Rankin Scale (mRS) was seen in 15 patients (24.2%), with a significantly greater improvement in the combined group (Δ mRS = 2.625) versus the MMAE-only group (Δ mRS = 0.348, p < 0.001).ConclusionsMMAE is a safe and effective treatment option for managing cSDH in cancer patients. Higher mortality in this population is likely reflective of underlying cancer and comorbidities.

IntroductionFlow diversion with the pipeline embolization device (PED) is an effective endovascular treatment. However, the metal surface's thrombogenicity and need for dual antiplatelet therapy (DAPT) are notable limitations. Few prior studies have reported specifically on flow diverters' safety in patients with hemoglobinopathies, a population at increased risk of thrombotic and hemorrhagic complications.MethodsNatural language processing queried our institution's medical records for intracranial embolization procedures from 2014 to 2024, screening for "hemoglobinopathy," "thalassemia," and "sickle cell." Patient charts were retrospectively reviewed.ResultsSixteen procedures in 14 patients were identified in which a mean 2.0 PEDs per patient were used. Most patients were female (71.4%). Median age was 48.8 years. Five patients had sickle cell disease, two had sickle cell trait, two had sickle cell or hemoglobin C trait and alpha thalassemia minor, and five had alpha thalassemia minor. The 14 patients were treated for 20 aneurysms; four treatments covered two distinct aneurysms. Median dome size per treatment was 4.0 mm. Of the 16 aneurysm treatments, five (31.2%) treated an irregular aneurysm. Most (56.2%) treatments used multiple PEDs. All patients were discharged on DAPT after verifying effect with P2Y12 assays. Follow-up DSA, CTA, or MRA was obtained in 12/14 (85.7%) patients at a median 1.6 years. Complete occlusion was achieved in all aneurysms. Clinical follow-up was obtained in all patients at a median 2.2 years. There were no thromboembolic or hemorrhagic complications, neurological deficits, or mortalities.ConclusionPipeline embolization can safely and effectively treat patients with hemoglobinopathies.

OBJECTIVE:The application of transcranial direct current stimulation (tDCS) at home for the treatment of depression and other neuropsychiatric disorders presents both significant opportunities and inherent challenges. Ensuring safety and maintaining high-quality stimulation are paramount for the efficacy and safety of at-home tDCS. This study investigates tDCS quality based on its technical parameters as well as safety of at-home and in-clinic tDCS applications comparing the data from two randomized controlled trials in patients with major depressive disorder. METHODS:We analyzed 229 active stimulation sessions from the HomeDC study (at-home tDCS) and 835 sessions from the DepressionDC study (in-clinic tDCS). Notably, five adverse events (skin lesions) were reported exclusively in the at-home cohort, highlighting the critical need for enhanced safety protocols in unsupervised environments. RESULTS:= .097). The at-home tDCS sessions exhibited higher impedance variability (M = 837, SD = 328) compared to in-clinic sessions (M = 579, SD = 309). Furthermore, at-home tDCS sessions resulting in adverse events (AEs) were associated with significantly higher average impedances than sessions without such issues. CONCLUSION/CONCLUSIONS:The study demonstrates that monitoring the technical parameters of at-home tDCS used in this study is essential. However, it may be not sufficient for ensuring safety and promptly detecting or preventing adverse events. Quality control protocols including digital training and monitoring techniques should be systematically developed and tested for a reliable and safe application of at-home tDCS therapies.

The ability to connect the form and meaning of a concept, known as word retrieval, is fundamental to human communication. While various input modalities could lead to identical word retrieval, the exact neural dynamics supporting this process relevant to daily auditory discourse remain poorly understood. Here, we recorded neurosurgical electrocorticography (ECoG) data from 48 patients and dissociated two key language networks that highly overlap in time and space, critical for word retrieval. Using unsupervised temporal clustering techniques, we found a semantic processing network located in the middle and inferior frontal gyri. This network was distinct from an articulatory planning network in the inferior frontal and precentral gyri, which was invariant to input modalities. Functionally, we confirmed that the semantic processing network encodes word surprisal during sentence perception. These findings elucidate neurophysiological mechanisms underlying the processing of semantic auditory inputs ranging from passive language comprehension to conversational speech.

INTRODUCTION/BACKGROUND:While revascularization rates have improved for mechanical thrombectomy (MT) in acute ischemic stroke, advancements in aspiration pumps have been limited. The ALGO Smart Pump (Von Vascular, Sunrise, FL) is a small on-field, operator-driven pump offering two aspiration modes: Adaptive Pulsatile Aspiration (APA™) Mode and a continuous 'Static' mode. This study evaluates the performance of the ALGO Smart Pump's Static Mode compared to a commercially available aspiration pump. METHODS:Operators performed aspiration thrombectomy in a flow model with ALGO and the Penumbra ENGINE (Penumbra, Alameda, CA) using medium (ID.036-.057") to large (ID.068-.071) bore aspiration catheters. Primary endpoint was complete clot ingestion (CCI), defined as the full ingestion of the clot within the catheter or pump's canister, without any clot at the catheter tip or evidence of embolization to new territories (ENT). Secondary endpoints included first pass recanalization, ENT and total aspiration time. RESULTS:When comparing all catheters, ALGO Smart Pump achieved CCI in 154 of 180 thrombectomies (85.6 %) compared to Penumbra ENGINE achieving CCI in 136 of 180 thrombectomies (75.6 %). The CCI rate between pump types across all catheters was statistically significant (p = 0.008), favoring ALGO pump. There was no difference between pump type on aspiration time. CONCLUSION/CONCLUSIONS:The ALGO Smart Pump may represent an alternative in MT, with potential higher effectiveness compared to existing available aspiration pumps with additional user-friendly benefits including a sterile, smaller, on-field apparatus.

Hyperphosphorylated tau (pTau) in Alzheimer's disease (AD) brain tissue is a complex mix of multiple tau species that are variably phosphorylated. The emerging studies suggest that phosphorylation of specific residues may alter the role of tau. The role of specific pTau species can be explored through protein interactome studies. The aim of this study was to analyse the interactome of tau phosphorylated at T217 (pT217), which biomarker studies suggest is one of the earliest accumulating tau species in AD. pT217 interactors were identified in fresh-frozen human brain tissue from 10 cases of advanced AD using affinity purification-mass spectrometry. The cases included a balanced cohort of APOE ε3/ε3 and ε4/ε4 genotypes (n = 5 each) to explore how apolipoprotein E altered phosphorylated tau interactions. The results were compared to our previous interactome dataset that profiled the interactors of PHF1-enriched tau to determine if individual pTau species have different interactomes. 23 proteins were identified as bona fide pT217 interactors, including known pTau interactor SQSTM1. pT217 enriched tau was phosphorylated at fewer residues compared to PHF1-enriched tau, suggesting an earlier stage of pathology development. Notable pT217 interactors included five subunits of the CTLH E3 ubiquitin ligase (WDR26, ARMC8, GID8, RANBP9, MAEA), which has not previously been linked to AD. In APOE ε3/ε3 cases pT217 significantly interacted with 46 proteins compared to 28 in APOE ε4/ε4 cases, but these proteins were significantly overlapped. CTLH E3 ubiquitin ligase subunits significantly interacted with phosphorylated tau in both APOE genotypes. pT217 interactions with SQSTM1, WDR26 and RANBP9 were validated using co-immunoprecipitation and immunofluorescent microscopy of post-mortem human brain tissue, which showed colocalisation of both protein interactors with tau pathology. Our results report the interactome of pT217 in human Alzheimer's disease brain tissue for the first time and highlight the CTLH E3 ubiquitin ligase complex as a significant novel interactor of pT217 tau.