Faculty Bibliography

Fahr disease is a rare neurodegenerative syndrome characterized by abnormal symmetric calcium deposition in the white matter, cerebral cortex, deep gray, and cerebellar nuclei. The characteristic CT pattern is well known, but descriptions of molecular imaging in Fahr disease remain sparse. We present the characteristic imaging patterns of Fahr disease by CT, I-123-Ioflupane SPECT, and integrated FDG PET/MRI in a single patient.

In treating malignant cerebral edema after a large middle cerebral artery stroke, clinicians need quantitative tools for real-time risk assessment. Existing predictive models typically estimate risk at one, early time point, failing to account for dynamic variables. To address this, we developed Hybrid Ensemble Learning Models for Edema Trajectory (HELMET) to predict midline shift severity, an established indicator of malignant edema, over 8-h and 24-h windows. The HELMET models were trained on retrospective data from 623 patients and validated on 63 patients from a different hospital system, achieving mean areas under the receiver operating characteristic curve of 96.6% and 92.5%, respectively. By integrating transformer-based large language models with supervised ensemble learning, HELMET demonstrates the value of combining clinician expertise with multimodal health records in assessing patient risk. Our approach provides a framework for accurate, real-time estimation of dynamic clinical targets using human-curated and algorithm-derived inputs.

Immune-mediated protection generated to COVID-19 mRNA vaccines is associated with anti-Spike (S) protein neutralizing antibodies. However, humoral immunity is compromised in B cell depleting (BCD) therapies, used to treat autoimmune diseases such as Multiple Sclerosis (MS). To study the effect of BCD on the durability and protective efficacy of vaccine-induced immunity, we evaluated S-reactive antibodies and T cell responses 1-70 weeks post-vaccination in MS cohorts treated with BCD compared to non-BCD therapies from four centers. BCD-treated participants had significantly reduced antibody levels and enhanced frequencies of S-reactive CD4⁺ and CD8⁺ memory T cells to COVID-19 vaccination compared to the non-BCD group, with some variations among different BCD formulations. T cell memory responses persisted up to 14 months post-vaccination in both BCD and non-BCD cohorts, who experienced similar clinical protection from COVID-19. Together, our results establish a critical role for T cell-mediated immunity in anti-viral protection independent of humoral immunity.

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.

OBJECTIVE:In traditionally designed randomized clinical trials of antiseizure medications, participants take a blinded treatment for a prespecified number of weeks, irrespective of continued seizures. The alternative design time to prerandomization monthly seizure count (T-PSC) allows participants to end the blinded treatment after an individually prespecified number of seizures, which shortens exposure to placebo and ineffective treatment. Previous reanalyses have shown that T-PSC replicated the efficacy conclusions of trials; therefore, we evaluated whether T-PSC also could replicate tolerability and safety conclusions. METHODS:We retrospectively applied the T-PSC design to analyze treatment-emergent adverse events (TEAEs) from three blinded, placebo-controlled trials of perampanel for focal onset seizures (NCT00699972, NCT00699582, NCT00700310). We evaluated the incidences of TEAEs, treatment-related TEAEs, serious TEAEs, and TEAEs that prompted medication adjustment compared to those observed during the full-length trial. RESULTS:Of the 1480 participants in the three trials, 1093 experienced any TEAE, of whom 1006 (92%) had onset prior to T-PSC. When evaluating the differences in each type of TEAE for each dose of perampanel from placebo within each trial, there was no consistent pattern of under- or overestimation. Across the three studies, 23 of 79 (29%) serious TEAEs, most requiring hospitalization, occurred after T-PSC. SIGNIFICANCE/CONCLUSIONS:Almost all TEAEs occurred before T-PSC. Similar conclusions regarding the tolerability and safety of perampanel would have been reached if the T-PSC design had been used. This suggests that the T-PSC design may potentially benefit participants by allowing earlier change from an ineffective treatment to an alternate treatment, which could reduce the risk of serious consequences of ineffective treatment, such as hospitalization.

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.

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.

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.