Faculty Bibliography

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.

Chronic inflammatory demyelinating polyneuropathy (CIDP) following viral infections and influenza vaccination has been well documented. However, there have been no confirmed natural influenza A infections leading to development of CIDP. Therefore, we present the case of a 6-year-old male who developed CIDP following a confirmed influenza A infection. Initially presenting with typical flu-like symptoms, the patient experienced a gradual onset of gait instability and leg weakness approximately 1 month later. Despite initial improvement with intravenous immunoglobulin therapy following a diagnosis of Guillain-Barré syndrome, his symptoms relapsed, including lower extremity weakness, incontinence, and sensory loss. Electromyography confirmed a demyelinating polyneuropathy, leading to a diagnosis of CIDP.

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.

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.

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.

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.

Resective surgery for drug-resistant temporal lobe epilepsy remains underutilized in the United States. While anteromesial temporal lobectomy consistently achieves the highest rates of long-term seizure freedom, it comes with greater risks for memory and language decline. Magnetic resonance imaging-guided laser interstitial thermal therapy and neuromodulation have gained popularity due to perceived lower surgical risk and faster recovery, although they yield lower rates of sustained seizure freedom. Neuromodulation with vagus nerve, deep brain, or responsive neurostimulation provides an option for patients ineligible for resection or ablation, but overall seizure outcomes remain modest. Balancing improved seizure control with open resection against the potential cognitive advantages of less invasive treatments is complex, requiring careful patient selection. Future research must refine these approaches to optimize results. Thoughtful, individualized decision-making, guided by each patient's clinical scenario and goals, is paramount for achieving the best balance between seizure freedom, cognitive preservation, and overall patient outcome.

OBJECTIVE:To report interim data from an ongoing, open-label extension (OLE) of a Phase 2b study (X-TOLE) of azetukalner in adults with focal onset seizures (FOS) receiving 1-3 antiseizure medications. METHODS:Eligible participants enrolled in the 7-year OLE at 20 mg azetukalner once daily with food. Long-term seizure outcomes included median percentage change (MPC) in monthly (28 days) FOS frequency from the double-blind phase (DBP) baseline and achievement of ≥50%, ≥75%, ≥90%, and 100% seizure reductions. RESULTS:285 participants completed the DBP, and 275 (96.5%) enrolled in the OLE. At the 24-month interim analysis (September 5, 2023), 182 participants had been treated for ≥12 months and 165 for ≥24 months; 152 (55.3%) continued in the study. The median (range) treatment duration in the OLE was 26.3 (0.1-46.6) months. MPC reduction was 83.2% at 24 months in the OLE vs. DBP baseline. For all participants who entered the OLE, 56.4% (155/275) and 44.4% (122/275) achieved a ≥50% seizure reduction, 28.4% (78/275) and 19.6% (54/275) achieved a ≥90% seizure reduction, and 22.2% (61/275) and 14.9% (41/275) achieved seizure freedom (100% seizure reduction) for any consecutive ≥6- and ≥12-month period, respectively. For those who reached ≥24 months in the OLE, seizure freedom was achieved by 34.5% (57/165) and 23.6% (39/165) for any consecutive ≥6- and ≥12-month period, respectively. The majority of treatment-emergent adverse events (TEAEs) were mild or moderate. The most common TEAEs were dizziness (21.8%), headache (15.3%), coronavirus infection (15.3%), somnolence (12.7%), fall (12.7%), and memory impairment (10.9%). Serious AEs were reported in 35 (12.7%) participants. SIGNIFICANCE/CONCLUSIONS:The efficacy demonstrated by azetukalner in reducing FOS seizure frequency in the DBP was sustained in this interim analysis. Azetukalner was generally well tolerated, with no new safety signals compared to the DBP. These data suggest sustained long-term efficacy and safety of azetukalner in a difficult-to-treat population. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:This long-term study assessed the safety and efficacy of azetukalner to treat focal seizures. Patients taking azetukalner daily with food for about 2 years had far fewer focal seizures with azetukalner than before taking the medication. For those who had been treated for 24 months, about a third were seizure-free for a consecutive 6-month period, and about a quarter were seizure-free for a consecutive 12-month period. Most side effects were mild or moderate, and these included dizziness, headache, and somnolence (sleepiness).