Faculty Bibliography

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.

Optic disc swelling, frequently associated with vitamin A toxicity, is infrequently linked to vitamin A deficiency. This report describes a 6-year-old male with autism spectrum disorder (ASD) and avoidant restrictive food intake disorder who presented with xerophthalmia, optic disc swelling, vision changes, and deficiencies in vitamins A, B₁, and iron. The patient's behavioral dysregulation posed important challenges for the evaluation, diagnosis, and treatment of his hypovitaminoses. This case underscores the importance of considering multiple nutritional deficiencies as the etiology of optic disc swelling in pediatric populations with autism spectrum disorder and avoidant restrictive food intake disorder, diagnoses that have increased in frequency. Early recognition and intervention can prevent further complications such as visual loss and improve outcomes.

The incidence of intracerebral hemorrhage (ICH) associated with oral anticoagulants (OAC) is about one in five cases of ICH and associated with severe clinical presentation, frequently rapid clinical deterioration, and 30-days mortality of app 50%. This narrative review gives an overview of presentation and acute treatment of OAC-ICH. Oral anticoagulants do not cause ICH but lead to prolongation of bleeding and higher risk of hematoma expansion (HE). Clinicoradiological characteristics of oral anticoagulant associated ICH are not different from ICH in general. The therapeutic principle of reversal is to prevent or limit HE. The mode of action of the reversal agents for vitamin K antagonists, direct oral thrombin inhibitor and direct oral factor Xa inhibitors are described in the main text. We also discuss the principles of blood pressure lowering in the setting of acute OAC-ICH as it may be the second driving force of HE. Stroke unit care is needed to prevent further complications. Data from randomized controlled trials and observational data from unselected patients are needed to make stronger and more precise recommendations on acute therapy.

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.

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.

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.

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.

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.

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.

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.