Citations

This is the case of a 67-year-old immunocompetent Hispanic male residing in Mexico who presented with acute right lower back and right lateral thigh pain. Initial imaging was unremarkable. He later developed painful vesicular lesions on the right foot and buttock. He was diagnosed with herpes zoster and initiated acyclovir and gabapentin. Ten days later, he developed foot drop, leg weakness, and urinary incontinence. Magnetic resonance imaging (MRI) showed enhancement of the cauda equina, and electrodiagnostic studies demonstrated right lumbar polyradiculopathy. The patient improved significantly with pain medications and physical therapy. After 8 months of physical therapy, he demonstrated significant clinical improvement. This case highlights the uncommon presentation of motor involvement in herpes zoster and emphasizes the role of imaging and electrophysiology in guiding diagnosis and management.

Deep brain stimulation (DBS), a cornerstone neurosurgical intervention for advanced Parkinson’s disease, exerts modulatory effects on aberrant basal ganglia circuitry through continuous high-frequency electrical stimulation. This approach yields sustained amelioration of motor symptoms while concurrently reducing the requisite dosage of dopaminergic pharmacotherapy. Nonetheless, DBS still has its limitations: its efficacy on non-motor symptoms remains limited, electrode implantation leads to biological reactions, and it cannot alter the trajectory of disease progression. Embryonic stem cells and induced pluripotent stem cells can be directed to differentiate into functionally mature nigrostriatal dopaminergic neurons, demonstrating the potential for neuronal replacement and neuroprotective effects in preclinical models and early-phase clinical trials. Mesenchymal stem cells and their derived exosomes mitigate neuroinflammation and impede α-synuclein aggregation through neurotrophic support and immunomodulatory mechanisms. This article reviews two core domains that have achieved breakthroughs in the treatment of Parkinson’s disease—DBS and stem cells—and covers their current status and future prospects. First, this review elucidates the therapeutic mechanisms of DBS, including neurotransmitter release regulation and neuroinflammation suppression, while evaluating its long-term efficacy (e.g., the sustainability of motor improvement and advancements in directional stimulation technology) and safety challenges (e.g., cognitive impairment, mood disturbances, and glial scar formation induced by electrode implantation). Second, it provides an in-depth analysis of the differentiation mechanisms of stem cells from different sources (embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, etc.), preclinical efficacy validation, and early-phase clinical trial outcomes (e.g., the long-term safety and motor function enhancement observed in the transplantation of induced pluripotent stem cell-derived nigrostriatal dopaminergic progenitor cells). Third, the article addresses the standardization of stem cell therapy protocols, strategies for managing immune rejection, and current international regulatory and ethical frameworks. The core challenges of current Parkinson’s disease treatment paradigms are as follows: DBS shows limited efficacy in improving axial symptoms (e.g., freezing of gait), whereas stem cell transplantation faces issues such as low long-term graft survival and insufficient functional integration. Looking ahead, multidisciplinary integration is essential to promote the synergistic application of DBS and stem cell therapy, develop personalized treatment protocols under the guidance of precision medicine, and translate novel neural interface materials and genetic engineering technologies into clinical practice. Ultimately, such integrated strategies hold the promise of advancing Parkinson’s disease therapy from mere symptom control to true disease modification.

Background: Major depressive disorder remains a leading cause of disability. While subgenual cingulate cortex (sgCC) deep brain stimulation (DBS) shows promise for medically refractory depression, clinical outcomes have been heterogeneous, suggesting that individual differences in neural circuitry engagement may critically influence therapeutic efficacy. We aimed to define the electrophysiological signatures of sgCC efferent connectivity using single-pulse electrical stimulation (SPES) with intracranial stereo-EEG (sEEG) to inform rational targeting and physiological biomarkers for sgCC-DBS. Methods: In four patients undergoing clinically indicated sEEG for seizure mapping, SPES was delivered through sgCC pairs, while distributed brain stimulation-evoked potentials (BSEPs) were recorded across cortical and subcortical sites. Responses were characterized using Canonical Response Parameterization to extract reproducible waveforms and per-trial reliability. Results: sgCC stimulation elicited reproducible, spatially organized BSEPs across frontal, limbic, and paralimbic networks, aligning with known anatomical pathways. Frontal recruitment featured robust, lateralized orbitofrontal activation favoring the ipsilateral central, medial OFC and bilateral ventromedial prefrontal responses. Limbic effects demonstrated bilateral cingulate activation with stronger ipsilateral recruitment and lateralized amygdala and hippocampal responses. Paralimbic engagement included insular responses with subject-specific anterior predominance and bi-hemispheric temporal-polar slow-wave deflections. Conclusion: These findings provide direct electrophysiological evidence of distributed, lateralized sgCC divergent network connectivity in the human brain, offering physiologic confirmation of its role in affective circuitry. The observed topography and laterality have direct applications for sgCC-DBS targeting and implicate BSEP signatures as candidate biomarkers to guide patient-specific therapy.

The ever-changing landscape of cardiology necessitates continuous education of healthcare providers. Case-based learning (CBL) provides an inquiry-based form of learning where learners apply knowledge to realistic clinical scenarios under instructor guidance. However, current case-based learning curricula are limited to representing 3-dimensional content in 2-dimensions with distinct modalities utilized for various data sources. Virtual reality (VR) shows promise for CBL given it provides an immersive and interactive 3-dimensional medium in which multi-source content can be incorporated into a unified learning experience, potentially translating to improved learning efficiency and lower cognitive load. With VR case-based learning, learners can view medical imaging in 3-dimensions or seamlessly interact with various 2-dimensional images within one unified medium. Further, additional content including simulated patients or procedures can be incorporated with a higher level of fidelity. Herein, we summarize the current literature exploring VR-CBL, demonstrate a proof-of-concept VR application, and review the implications for cardiology education. The proof-of-concept exemplifies many of the key advantages unique to VR-CBL, such as medical imaging rendered in 3-dimensions, integration of multiple imaging sources, and novel interaction methodologies. Given the importance and rapid evolution of ongoing medical education, VR-CBL, with its immersive and engaging nature, appears to be a promising form of instruction that may serve a larger role in continuing medical education initiatives.

Abstract Background Diabetes mellitus elevates Parkinson’s disease (PD) risk, via hypothesized cerebrovascular mediation. Whether the diabetes/prediabetes vascular-risk phenotype concentrates in cardiometabolic risk or macrovascular events across prodromal and clinically diagnosed PD remains unresolved. Objectives To quantify the vascular-risk burden associated with diabetes/prediabetes across the PPMI diagnostic cohorts to test whether this association differs by cohort. Methods Cross-sectional analysis of 413 PPMI participants (76 healthy controls, 145 prodromal PD, 192 clinically diagnosed PD) examined diabetes/prediabetes (n = 73) and seven vascular risk factors. The Vascular Burden Score (0 to 7) was a priori partitioned into microvascular and macrovascular sub-scores. Modified Poisson regression estimated adjusted prevalence ratios (aPR), adjusted for age, sex, and body mass index. A cohort-by-diabetes interaction tested cross-cohort consistency. Sensitivity analyses incorporated nigral diffusion tensor imaging (PD-risk biomarker) and FreeSurfer white matter hypointensity volume (cerebrovascular marker). Results Diabetes/prediabetes elevated Vascular Burden Score (β = 0.53, 95% CI 0.29 to 0.77, p < 0.001) versus non-diabetic participants, with a non-significant cohort-by-diabetes interaction (F = 0.29, p = 0.747). Three microvascular factors survived false discovery rate correction: obesity (aPR 2.28), hypertension (aPR 1.60), and hyperlipidemia (aPR 1.45). Macrovascular events showed no diabetic amplification (β = −0.06, p = 0.25). In the imaging-phenotyped subset, Vascular Burden Score components contributed classifier variance distinct from nigral microstructure. Conclusions Diabetes/prediabetes operationalize a microvascular cluster stable across prodromal and idiopathic PD. Cardiometabolic phenotyping may complement established PD-risk biomarkers (dopamine transporter SPECT, nigral diffusion), pending longitudinal validation linking vascular phenotype to dopaminergic markers.

Objective: To synthesize the available evidence on medical therapies investigated for the management of NF2-related vestibular schwannomas (VS). Study design: Systematic review. Setting: Not applicable. Patients: NF2-related VS patients. Interventions: Systemic medical therapies. Main outcome measures: Tumor control and hearing outcomes. Results: Thirty studies met inclusion criteria: 18 investigated bevacizumab, 5 mTOR inhibitors, 5 tyrosine kinase inhibitors (TKIs), and 2 the vascular endothelial growth factor receptor (VEGFR) vaccine. Bevacizumab demonstrated the most consistent activity, with hearing improvement in up to 61% of patients, stable hearing in up to 84%, and tumor response in up to 60% (Level 4 evidence). Outcomes for mTOR inhibitors were variable, with 1 study stopped for futility, while others reported up to 100% hearing and tumor stability (Level 4 evidence). Five different TKIs showed hearing improvement rates ranging from 17 to 60% and tumor responses of 10 to 23.5% (Level 4 evidence). The VEGFR vaccine appeared safe and immunologically active, with radiologic and hearing improvement in one-third of patients (Level 4 evidence). Conclusions: Bevacizumab remains the most studied and clinically active systemic therapy for NF2-related VS, although evidence is largely nonrandomized. Other systemic therapies have demonstrated variable results in terms of hearing outcomes or tumor control. High-quality prospective and randomized controlled trials are needed to clarify efficacy, durability, and comparative effectiveness.

Abstract Tandem repeats are highly mutable genomic elements linked to human traits and diseases. Profiling large catalogs of tandem repeats from population-scale long-read sequencing data requires accurate and efficient tools. We introduce inquiSTR, a command-line toolkit for fast genome-wide tandem repeat length genotyping. inquiSTR, with efficient parallel processing and low-memory streaming algorithms, genotypes a genome-wide repeat catalog of 1.78 million loci in less than two minutes. Benchmarking shows high accuracy and significantly faster performance compared to existing tools and truth sets. inquiSTR also provides methods for downstream analyses such as population structure inference, association testing, and outlier detection.

Background: Alcohol-associated hepatitis (AH) is a severe inflammatory liver condition driven by dysregulated immune responses. CD8 T cells accumulate in the liver during AH, yet their functional role remains poorly defined. Methods: A murine NIAAA chronic-binge model with lipopolysaccharide (LPS) challenge was used. Single-cell RNA sequencing of liver and blood immune cells defined CD8 T cell subsets, followed by pathway analysis and reanalysis of human AH datasets. Spatial relationships were validated by immunohistochemistry of human AH liver tissue with CD8 T RM and liver sinusoidal endothelial cell (LSEC) co-staining. LSEC–CD8 T cell interactions were examined using in vitro co-culture, and signaling pathways were assessed by bulk RNA sequencing and phospho-protein analyses. IL15 function was evaluated by in vivo neutralization. Results: Single-cell RNA sequencing in the murine AH model revealed a distinct population of CD8 tissue-resident memory T cells (T RM ) with heightened activation and proinflammatory cytokine production. Analysis of human AH liver single-cell RNA sequencing data, along with immunohistochemistry validation, supported CD8 T RM enrichment in diseased tissue. IL15 emerged as a prominent pathway linked to T RM activation, and IL15 blockade reduced T RM abundance and attenuated EtOH/ lipopolysaccharide-induced liver injury. Mechanistically, LSECs not only provided a structural niche for T RM retention but also amplified IL15 signalling. In vitro, coculture experiments demonstrated that LSECs intensified activation in pre-stimulated CD8 T cells in a stimulus-dependent manner: under IL15 stimulation, LSECs boosted effector function without inducing cell death, whereas under T-cell receptor stimulation, LSECs drove hyperactivation and activation-induced cell death. Bulk RNA-seq and phospho-protein analysis identified the PI3K-AKT pathway as a shared pathway enhanced by LSEC coculture in activated CD8 T cells. These findings define a context-dependent mechanism in which LSECs promote IL15-driven signaling through AKT pathway amplification, promoting T RM persistence and inflammatory activity in AH. Conclusions: IL15-associated signaling within the hepatic microenvironment, shaped by LSEC-CD8 T-cell interactions, promotes activation and persistence of CD8 T RM cells in AH. Targeting the IL15-LSEC-AKT axis may disrupt pathogenic T RM niches and represent a promising therapeutic strategy for severe AH.

Pharmacological plasminogen reduction enhanced liver regeneration experimentally and clinically. siRNA-induced plasminogen deficiency promoted hepatocyte proliferation after partial hepatectomy in mice, contrasting genetic deficiency models. In the HeLiX trial, tranexamic acid reduced post-hepatectomy liver failure odds, suggesting a novel therapeutic strategy.