Phantom Safety Assessment of 3 Tesla Magnetic Resonance Imaging in Directional and Sensing Deep Brain Stimulation Devices.

Introduction: Magnetic resonance imaging (MRI) is both a crucial clinical and research tool for patients with deep brain stimulation (DBS) devices. However, safety concerns predominantly related to device heating have limited such imaging. Rigorous safety testing has demonstrated that scanning outside of vendor guidelines may be both safe and feasible, unlocking unique opportunities for advanced imaging in this patient population.

Evolutionary rate covariation is pervasive between glycosylation pathways and points to potential disease modifiers.

Mutations in glycosylation pathways, such as N-linked glycosylation, O-linked glycosylation, and GPI anchor synthesis, lead to Congenital Disorders of Glycosylation (CDG). CDG typically present with seizures, hypotonia, and developmental delay but display large clinical variability with symptoms affecting every system in the body. This variability suggests modifier genes might influence the phenotypes.

Identification of as a genetic modifier of PIGA-CDG through pedigree analysis of a family with incomplete penetrance and functional testing in .

Loss of function mutations in the X-linked gene lead to PIGA-CDG, an ultra-rare congenital disorder of glycosylation (CDG), typically presenting with seizures, hypotonia, and neurodevelopmental delay. We identified two brothers (probands) with PIGA-CDG, presenting with epilepsy and mild developmental delay. Both probands carry , an ultra-rare variant predicted to be damaging.

Drosophila models of phosphatidylinositol glycan biosynthesis class A congenital disorder of glycosylation (PIGA-CDG) mirror patient phenotypes.

Mutations in the phosphatidylinositol glycan biosynthesis class A (PIGA) gene cause a rare, X-linked recessive congenital disorder of glycosylation. Phosphatidylinositol glycan biosynthesis class A congenital disorder of glycosylation (PIGA-CDG) is characterized by seizures, intellectual and developmental delay, and congenital malformations. The PIGA gene encodes an enzyme involved in the first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis.

A Drosophila screen identifies a role for histone methylation in ER stress preconditioning.

Stress preconditioning occurs when transient, sublethal stress events impact an organism's ability to counter future stresses. Although preconditioning effects are often noted in the literature, very little is known about the underlying mechanisms. To model preconditioning, we exposed a panel of genetically diverse Drosophila melanogaster to a sublethal heat shock and measured how well the flies survived subsequent exposure to endoplasmic reticulum (ER) stress.

models of PIGA-CDG mirror patient phenotypes.

Mutations in the phosphatidylinositol glycan biosynthesis class A (PIGA) gene cause a rare, X-linked recessive congenital disorder of glycosylation (CDG). PIGA-CDG is characterized by seizures, intellectual and developmental delay, and congenital malformations. The gene encodes an enzyme involved in the first step of GPI anchor biosynthesis.

Presumed Silicone Oil Droplets After Intravitreal Pegcetacoplan Injections.

Importance: Recently, intravitreal pegcetacoplan became the first drug to gain US Food and Drug Administration approval for the treatment of geographic atrophy associated with nonexudative age-related macular degeneration, but the administration of this medication may be associated with unanticipated posttreatment complications.

Objective: To assess the prevalence of presumed silicone oil droplets in the vitreous cavity after intravitreal injection of pegcetacoplan.

Design, Setting, And Participants: This case series study involved a retrospective record review of all 55 patients treated with intravitreal pegcetacoplan, 0.

Characterizing genetic variation in the regulation of the ER stress response through computational and cis-eQTL analyses.

Misfolded proteins in the endoplasmic reticulum (ER) elicit the ER stress response, a large transcriptional response driven by 3 well-characterized transcription factors (TFs). This transcriptional response is variable across different genetic backgrounds. One mechanism in which genetic variation can lead to transcriptional variability in the ER stress response is through altered binding and activity of the 3 main TFs: XBP1, ATF6, and ATF4.

Comparative neural correlates of DBS and MRgFUS lesioning for tremor control in essential tremor.

Background: Given high rates of early complications and non-reversibility, refined targeting is necessitated for magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for essential tremor (ET). Selection of lesion location can be informed by considering optimal stimulation area from deep brain stimulation (DBS).

Methods: 118 patients with ET who received DBS (39) or MRgFUS (79) of the ventral intermediate nucleus (VIM) underwent stimulation/lesion mapping, probabilistic mapping of clinical efficacy and normative structural connectivity analysis.

Successful magnetic resonance-guided focused ultrasound treatment of tremor in patients with a skull density ratio of 0.4 or less.

Objective: The use of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor-related disorders and other novel indications has been limited by guidelines advocating treatment of patients with a skull density ratio (SDR) above 0.45 ± 0.05 despite reports of successful outcomes in patients with a low SDR (LSDR).

A screen identifies a role for histone methylation in ER stress preconditioning.

Stress preconditioning occurs when transient, sublethal stress events impact an organism's ability to counter future stresses. Although preconditioning effects are often noted in the literature, very little is known about the underlying mechanisms. To model preconditioning, we exposed a panel of genetically diverse to a sublethal heat shock and measured how well the flies survived subsequent exposure to endoplasmic reticulum (ER) stress.

DIS3 Variants are Associated With Primary Ovarian Insufficiency: Importance of Transcription/Translation in Oogenesis.

Context: A genetic etiology accounts for the majority of unexplained primary ovarian insufficiency (POI).

Objective: We hypothesized a genetic cause of POI for a sister pair with primary amenorrhea.

Design: The study was an observational study.

A genome-wide CRISPR screen identifies DPM1 as a modifier of DPAGT1 deficiency and ER stress.

Partial loss-of-function mutations in glycosylation pathways underlie a set of rare diseases called Congenital Disorders of Glycosylation (CDGs). In particular, DPAGT1-CDG is caused by mutations in the gene encoding the first step in N-glycosylation, DPAGT1, and this disorder currently lacks effective therapies. To identify potential therapeutic targets for DPAGT1-CDG, we performed CRISPR knockout screens in Drosophila cells for genes associated with better survival and glycoprotein levels under DPAGT1 inhibition.

An in vivo drug repurposing screen and transcriptional analyses reveals the serotonin pathway and GSK3 as major therapeutic targets for NGLY1 deficiency.

NGLY1 deficiency, a rare disease with no effective treatment, is caused by autosomal recessive, loss-of-function mutations in the N-glycanase 1 (NGLY1) gene and is characterized by global developmental delay, hypotonia, alacrima, and seizures. We used a Drosophila model of NGLY1 deficiency to conduct an in vivo, unbiased, small molecule, repurposing screen of FDA-approved drugs to identify therapeutic compounds. Seventeen molecules partially rescued lethality in a patient-specific NGLY1 deficiency model, including multiple serotonin and dopamine modulators.

The dynamic effect of genetic variation on the in vivo ER stress transcriptional response in different tissues.

The genetic regulation of gene expression varies greatly across tissue-type and individuals and can be strongly influenced by the environment. Many variants, under healthy control conditions, may be silent or even have the opposite effect under diseased stress conditions. This study uses an in vivo mouse model to investigate how the effect of genetic variation changes with cellular stress across different tissues.

Probing responses to deep brain stimulation with functional magnetic resonance imaging.

Background: Deep brain stimulation (DBS) is an established treatment for certain movement disorders and has additionally shown promise for various psychiatric, cognitive, and seizure disorders. However, the mechanisms through which stimulation exerts therapeutic effects are incompletely understood. A technique that may help to address this knowledge gap is functional magnetic resonance imaging (fMRI).

Global trends in chronic thromboembolic pulmonary hypertension clinical trials and dissemination of results.

Treatment options for chronic thromboembolic pulmonary hypertension (CTEPH) are rapidly expanding. The purpose of this study is to identify trends in CTEPH clinical trials and the publication of results. We performed a worldwide review of completed and ongoing clinical trials through searching the ClinicalTrials.

Causal and Candidate Gene Variants in a Large Cohort of Women With Primary Ovarian Insufficiency.

Context: A genetic etiology likely accounts for the majority of unexplained primary ovarian insufficiency (POI).

Objective: We hypothesized that heterozygous rare variants and variants in enhanced categories are associated with POI.

Design: The study was an observational study.

Focused Ultrasound Thalamotomy Sensory Side Effects Follow the Thalamic Structural Homunculus.

Objective: Focused ultrasound thalamotomy is an effective treatment for tremor; however, side effects may occur. The purpose of the present study was to investigate the spatial relationship between thalamotomies and specific sensory side effects and their functional connectivity with somatosensory cortex and relationship to the medial lemniscus (ML).

Methods: Sensory adverse effects were categorized into 4 groups based on the location of the disturbance: face/mouth/tongue numbness/paresthesia, hand-only paresthesia, hemibody/limb paresthesia, and dysgeusia.

Neuromodulatory treatments for psychiatric disease: A comprehensive survey of the clinical trial landscape.

Background: Numerous neuromodulatory therapies are currently under investigation or in clinical use for the treatment of psychiatric conditions.

Objective/hypothesis: We sought to catalogue past and present human research studies on psychiatric neuromodulation and identify relevant trends in this field.

Methods: ClinicalTrials.

Potential optimization of focused ultrasound capsulotomy for obsessive compulsive disorder.

Obsessive-compulsive disorder is a debilitating and often refractory psychiatric disorder. Magnetic resonance-guided focused ultrasound is a novel, minimally invasive neuromodulatory technique that has shown promise in treating this condition. We investigated the relationship between lesion location and long-term outcome in patients with obsessive-compulsive disorder treated with focused ultrasound to discern the optimal lesion location and elucidate the efficacious network underlying symptom alleviation.

Evolution of the Neurosurgeon's Role in Clinical Trials for Glioblastoma: A Systematic Overview of the Clinicaltrials.Gov Database.

Background: The therapeutic challenge of glioblastoma (GBM) has catalyzed the development of clinical trials to evaluate novel interventions. With increased understanding of GBM biology and technological advances, the neurosurgeon's role in neuro-oncology has evolved.

Objective: To evaluate the current landscape of procedure-based clinical trials for GBM to characterize this evolution, gain insight into past failures, and accordingly outline implications for future research and practice that may inform future studies.