Faculty Bibliography
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school:SOM
Department/Unit:Neurology
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23427
Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development
Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.
PMID: 36635388
ISSN: 1546-1718
CID: 5410502
The Clinical Autonomic Research journal 2022 and onward [Editorial]
PMID: 36580219
ISSN: 1619-1560
CID: 5409682
Enhanced cognitive interference during visuomotor tasks may cause eye-hand dyscoordination
In complex visuomotor tasks, such as cooking, people make many saccades to continuously search for items before and during reaching movements. These tasks require cognitive resources, such as short-term memory and task-switching. Cognitive load may impact limb motor performance by increasing demands on mental processes, but mechanisms remain unclear. The Trail-Making Tests, in which participants sequentially search for and make reaching movements to 25 targets, consist of a simple numeric variant (Trails-A) and a cognitively challenging variant that requires alphanumeric switching (Trails-B). We have previously shown that stroke survivors and age-matched controls make many more saccades in Trails-B, and those increases in saccades are associated with decreases in speed and smoothness of reaching movements. However, it remains unclear how patients with neurological injuries, e.g., stroke, manage progressive increases in cognitive load during visuomotor tasks, such as the Trail-Making Tests. As Trails-B trial progresses, switching between numbers and letters leads to progressive increases in cognitive load. Here, we show that stroke survivors with damage to frontoparietal areas and age-matched controls made more saccades and had longer fixations as they progressed through the 25 alphanumeric targets in Trails-B. Furthermore, when stroke survivors made saccades during reaching movements in Trails-B, their movement speed slowed down significantly. Thus, damage to frontoparietal areas serving cognitive motor functions may cause interference between oculomotor, visual, and limb motor functions, which could lead to significant disruptions in activities of daily living. These findings augment our understanding of the mechanisms that underpin cognitive-motor interference during complex visuomotor tasks.
PMID: 36625969
ISSN: 1432-1106
CID: 5419032
Post-Vaccine Evaluation to Assist with Subsequent COVID-19 Vaccine Administration [Meeting Abstract]
Rationale: During roll-out of Pfizer-BioNTech, Moderna, and Johnson & Johnson (J&J) COVID-19 vaccines, adverse reactions led patients to seek Allergy evaluation following vaccination.
Method(s): We conducted retrospective chart review of patients >= 18 years seeking vaccine counseling between December 1, 2020 - May 1, 2021 after experiencing COVID-19 vaccine reactions. Demographics, atopic history, anaphylaxis history and vaccine administration/reactions were recorded. Follow up phone calls were used to complete data collection.
Result(s): We identified 24 patients (N= 21 Female, 3 Male) reporting reactions to COVID-19 vaccination; 19 after 1st dose, 2 after 2nd dose, and 3 after both. The 27 total reactions were classified as immediate (12), or delayed (15) and subdivided further based on features. Two patients had symptoms consistent with anaphylaxis and were evaluated in the ER, one received epinephrine and subsequently tolerated J+J. The other did not pursue additional vaccination. Among the additional 10 immediate reactions, 6 were cutaneous/mucocutaneous-only and 4 involved subjective systemic symptoms. Six patients were evaluated in the emergency room (3 delayed, 3 immediate). Overall, 22 of 24 patients completed vaccination series (defined as one dose of J&J or 2 doses of an mRNA vaccine).
Conclusion(s): Many patients reported reactions to COVID-19 vaccine, most following first vaccine dose with isolated cutaneous or mucocutaneous symptoms. No patients with delayed cutaneous reactions went on to have more severe reactions and only 1 patient had return cutaneous symptoms with 2nd dose. Patients with adverse reactions may be reluctant to pursue additional vaccination; 2 of our patient cohort remain incompletely vaccinated to COVID-19.
Copyright
Method(s): We conducted retrospective chart review of patients >= 18 years seeking vaccine counseling between December 1, 2020 - May 1, 2021 after experiencing COVID-19 vaccine reactions. Demographics, atopic history, anaphylaxis history and vaccine administration/reactions were recorded. Follow up phone calls were used to complete data collection.
Result(s): We identified 24 patients (N= 21 Female, 3 Male) reporting reactions to COVID-19 vaccination; 19 after 1st dose, 2 after 2nd dose, and 3 after both. The 27 total reactions were classified as immediate (12), or delayed (15) and subdivided further based on features. Two patients had symptoms consistent with anaphylaxis and were evaluated in the ER, one received epinephrine and subsequently tolerated J+J. The other did not pursue additional vaccination. Among the additional 10 immediate reactions, 6 were cutaneous/mucocutaneous-only and 4 involved subjective systemic symptoms. Six patients were evaluated in the emergency room (3 delayed, 3 immediate). Overall, 22 of 24 patients completed vaccination series (defined as one dose of J&J or 2 doses of an mRNA vaccine).
Conclusion(s): Many patients reported reactions to COVID-19 vaccine, most following first vaccine dose with isolated cutaneous or mucocutaneous symptoms. No patients with delayed cutaneous reactions went on to have more severe reactions and only 1 patient had return cutaneous symptoms with 2nd dose. Patients with adverse reactions may be reluctant to pursue additional vaccination; 2 of our patient cohort remain incompletely vaccinated to COVID-19.
Copyright
EMBASE:2022491136
ISSN: 1097-6825
CID: 5509722
Focal epilepsies: update on diagnosis and classification
Correctly diagnosing and classifying seizures and epilepsies is paramount to ensure the delivery of optimal care to patients with epilepsy. Focal seizures, defined as those that originate within networks limited to one hemisphere, are primarily subdivided into focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures. Focal epilepsies account for most epilepsy cases both in children and adults. In children, focal epilepsies are typically subdivided in three groups: self-limited focal epilepsy syndromes (e.g., self-limited epilepsy with centrotemporal spikes), focal epilepsy of unknown cause but which do not meet criteria for a self-limited focal epilepsy syndrome, and focal epilepsy of known cause (e.g., structural lesions - developmental or acquired). In adults, focal epilepsies are often acquired and may be caused by a structural lesion such as stroke, infection and traumatic brain injury, or brain tumors, vascular malformations, metabolic disorders, autoimmune, and/or genetic causes. In addition to seizure semiology, neuroimaging, neurophysiology, and neuropathology constitute the cornerstones of a diagnostic evaluation. Patients with focal epilepsy who become drug-resistant should promptly undergo assessment in an epilepsy center. After excluding pseudo-resistance, these patients should be considered for presurgical evaluation as a means to identify the location and extent of the epileptogenic zone and assess their candidacy for a surgical procedure. The goal of this seminar in epileptology is to summarize clinically relevant information concerning focal epilepsies. This contributes to the ILAE's mission to ensure that worldwide healthcare professionals, patients, and caregivers continue to have access to high-quality educational resources concerning epilepsy.
PMID: 36938903
ISSN: 1950-6945
CID: 5462702
Addressing mental health needs of NCAA student-athletes of colour: foundational concepts from the NCAA Summit on Diverse Student-Athlete Mental Health and Well-Being
We sought to identify concepts that may facilitate National Collegiate Athletic Association efforts to assist member institutions in addressing the mental health needs of student-athletes of colour. A two-step process was followed to generate and refine concepts, guided by Delphi methodology. First, a scoping review was conducted, including original peer-reviewed research articles that quantified or qualitatively described determinant(s) of racial or ethnic differences in athlete mental health or mental healthcare. Next, a multiday virtual meeting was facilitated to review the results of the scoping review, discuss lived experiences and generate potential concepts. Participants included a racially and ethnically diverse group of student-athletes, medical and mental health professionals, athletics administrators, diversity, equity and inclusion experts, health educators and representatives from leading organisations involved in athlete mental health. Through the consensus process, participants identified 42 concepts that member institutions might consider implementing on their campuses. Concepts were largely focused on organisational policies and practices such as staffing diversity and inclusion, expanded options for clinical support (ie, identity-relevant support groups) and within-organisation accountability. Concepts related to specific areas for stakeholder education were also identified. Institutions have the potential to play an important role in supporting the mental well being of student-athletes of colour, and the present concepts can help inform institutional action. While concepts proposed are believed to be broadly relevant across athletics settings, they would need to be further considered and tailored to reflect setting-specific organisational structures, resources and needs.
PMID: 36657824
ISSN: 1473-0480
CID: 5775042
Where's the Vision? The Importance of Visual Outcomes in Neurologic Disorders: The 2021 H. Houston Merritt Lecture
Neurologists have long-recognized the importance of the visual system in the diagnosis and monitoring of neurological disorders. This is particularly true since approximately 50% of the brain's pathways subserve afferent and efferent aspects of vision. During the past 30 years, researchers and clinicians have further refined this concept to include investigation of the visual system for patients with specific neurologic diagnoses, including multiple sclerosis (MS), concussion, Parkinson's disease (PD) and conditions along the spectrum of Alzheimer's disease (AD, mild cognitive impairment [MCI] and subjective cognitive decline [SCD]). This review, highlights the visual "toolbox" that has been developed over the past three decades and beyond to capture both structural and functional aspects of vision in neurologic disease. While the efforts to accelerate the emphasis on structure-function relationships in neurological disorders began with MS during the early 2000's, such investigations have broadened to recognize the need for outcomes of visual pathway structure, function and quality of life for clinical trials of therapies across the spectrum of neurological disorders. This review begins with a patient case study highlighting the importance utilizing the most modern technologies for visual pathway assessment, including optical coherence tomography (OCT). We emphasize that both structural and functional tools for vision testing can be used in parallel to detect what might otherwise be sub-clinical events or markers of visual and, perhaps, more global neurological, decline. Such measures will be critical as clinical trials and therapies become more available across the neurological disease spectrum.
PMID: 36522160
ISSN: 1526-632x
CID: 5382402
Author Correction: Federated learning enables big data for rare cancer boundary detection
PMID: 36702828
ISSN: 2041-1723
CID: 5426632
Neural stem cells and oligodendrocyte progenitor cells compete for remyelination in the corpus callosum
A major therapeutic goal in demyelinating diseases, such as Multiple Sclerosis, is to improve remyelination, thereby restoring effective axon conduction and preventing neurodegeneration. In the adult central nervous system (CNS), parenchymal oligodendrocyte progenitor cells (pOPCs) and, to a lesser extent, pre-existing oligodendrocytes (OLs) and oligodendrocytes generated from neural stem cells (NSCs) in the sub-ventricular zone (SVZ) are capable of forming new myelin sheaths. Due to their self-renewal capabilities and the ability of their progeny to migrate widely within the CNS, NSCs represent an additional source of remyelinating cells that may be targeted to supplement repair by pOPCs. However, in demyelinating disorders and disease models, the NSC contribution to myelin repair is modest and most evident in regions close to the SVZ. We hypothesized that NSC-derived cells may compete with OPCs to remyelinate the same axons, with pOPCs serving as the primary remyelinating cells due to their widespread distribution within the adult CNS, thereby limiting the contribution of NSC-progeny. Here, we have used a dual reporter, genetic fate mapping strategy, to characterize the contribution of pOPCs and NSC-derived OLs to remyelination after cuprizone-induced demyelination. We confirmed that, while pOPCs are the main remyelinating cells in the corpus callosum, NSC-derived cells are also activated and recruited to demyelinating lesions. Blocking pOPC differentiation genetically, resulted in a significant increase in the recruitment NSC-derived cells into the demyelinated corpus callosum and their differentiation into OLs. These results strongly suggest that pOPCs and NSC-progeny compete to repair white matter lesions. They underscore the potential significance of targeting NSCs to improve repair when the contribution of pOPCs is insufficient to affect full remyelination.
SCOPUS:85147662714
ISSN: 1662-5102
CID: 5424962
Assessment of learning and memory impairments in adults with predominately inattentive versus combined presentation attention-deficit/hyperactivity disorder
This cross-sectional study compared adults diagnosed with Attention-Deficit/Hyperactivity Disorder-Inattentive (ADHD-I) and ADHD-Combined (ADHD-C) presentations with a non-ADHD group on verbal and visual learning and delayed recall using the Rey Auditory Verbal Learning Test (RAVLT) and Brief Visuospatial Memory Test-Revised (BVMT-R), respectively. Data from 380 predominately college student adult outpatients were used, with 155 who met criteria for ADHD-I, 165 who met criteria for ADHD-C, and 60 who did not meet criteria for ADHD but were diagnosed with a primary depressive or anxiety disorder or received no diagnosis. Each patient was administered the RAVLT and BVMT-R as part of a comprehensive neuropsychological evaluation. Significant main effects of study group were found, such that patients with ADHD-C demonstrated worse learning and delayed recall of both verbal and visual information than patients with ADHD-I and the non-ADHD group. Patients with ADHD-I performed comparably to the non-ADHD group, apart from visual learning and delayed recall. Notably, more patients in the ADHD groups had possible or probable learning and memory impairment compared to the non-ADHD group. Findings were consistent with previous research indicating that those with ADHD exhibit poorer verbal and visual learning and delayed recall than those without ADHD.
PMID: 36697387
ISSN: 2327-9109
CID: 5592762
