Faculty Bibliography

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 1^st dose, 2 after 2^nd 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.
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Neuroimaging studies have demonstrated aberrant structure and function of the "cognitive-affective cerebellum" in major depressive disorder (MDD), although the specific role of the cerebello-cerebral circuitry in this population remains largely uninvestigated. The objective of this study was to delineate the role of cerebellar functional networks in depression. A total of 308 unmedicated participants completed resting-state functional magnetic resonance imaging scans, of which 247 (148 MDD; 99 healthy controls, HC) were suitable for this study. Seed-based resting-state functional connectivity (RsFc) analysis was performed using three cerebellar regions of interest (ROIs): ROI₁ corresponded to default mode network (DMN)/inattentive processing; ROI₂ corresponded to attentional networks, including frontoparietal, dorsal attention, and ventral attention; ROI₃ corresponded to motor processing. These ROIs were delineated based on prior functional gradient analyses of the cerebellum. A general linear model was used to perform within-group and between-group comparisons. In comparison to HC, participants with MDD displayed increased RsFc within the cerebello-cerebral DMN (ROI₁) and significantly elevated RsFc between the cerebellar ROI₁ and bilateral angular gyrus at a voxel threshold (p < 0.001, two-tailed) and at a cluster level (p < 0.05, FDR-corrected). Group differences were non-significant for ROI₂ and ROI₃. These results contribute to the development of a systems neuroscience approach to the diagnosis and treatment of MDD. Specifically, our findings confirm previously reported associations between MDD, DMN, and cerebellum, and highlight the promising role of these functional and anatomical locations for the development of novel imaging-based biomarkers and targets for neuromodulation therapies. ClinicalTrials.gov TRN: NCT01655706; Date of Registration: August 2nd, 2012.

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.

Rationale: Adverse reactions following COVID-19 vaccination are common. We sought to characterize the most common cutaneous manifestations following COVID-19 vaccine administration and identify potential predictive factors.
Method(s): A retrospective chart review was conducted for patients seen in the allergy clinic between December 2020 and May 2021 for COVID-19 vaccine counseling. Details of reactions to either mRNA COVID-19 vaccine were noted. Cutaneous findings were defined as any local reaction including pain, redness or swelling, or generalized rash.
Result(s): Twenty-four patients out of 115 patients (20.9%) had any type of cutaneous reaction after vaccination. Most were female (n=21, 87.5%). Seven of these 24 patients had a local reaction alone. Two patients had immediate onset of generalized pruritus and rash (1 of these patients had symptom resolution by the next morning, the other resolved 8 days post-vaccination). Four patients (16.7%) had a delayed (>6 hours after vaccination) generalized pruritic rash, three of which resolved within 2 weeks and one resolved after 6 weeks. Four patients with a history of chronic urticaria (CU) had a flare of urticaria following vaccination beginning 1-2 days later. One additional patient with CU had delayed pruritus only. One patient developed urticaria 1 day after receiving vaccination with persistence of urticaria beyond 6 weeks.
Conclusion(s): Cutaneous ARs were common (20%) following COVID-19 vaccination. Most rashes were delayed and resolved within 2 weeks with no additional sequelae. In this cohort, patients with a history of CU were seen to have flares of symptoms following vaccination. Cutaneous reactions were more commonly seen in women.
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Type 1 diabetes (T1D) may affect the peripheral nervous system and alter the expression of proteins contributing to inflammation and cellular cytoskeleton dysfunction, in most cases leading to the development of diabetic length-dependent neuropathy (DLDN). In the present study, we performed immunohistochemistry (IHC) to probe the expression of the receptor for advanced glycation end products (RAGE); its key ligands, high-mobility group box 1 (HMGB1), S100 calcium-binding protein B (S100B), and carboxymethyl-lysine (CML - advanced glycation end products (AGE)); and its cytoplasmic tail-binding partner, diaphanous related formin 1 (DIAPH1) and associated molecules, beta-actin (ACTB) and profilin 1 (PFN1) proteins in sciatic nerves harvested from seven-month old FVB/OVE26 mice with genetically-mediated T1D. We found that the amount of RAGE, HMGB1, and S100B proteins was elevated in diabetic vs the non-diabetic groups, while the amount of DIAPH1, ACTB, as well as PFN1 proteins did not differ between these groups. Moreover, our data revealed linear dependence between RAGE and HMGB1 proteins. Interaction criss-cross of selected sets of proteins in the sciatic nerve revealed that there were connected in a singular network. Our results indicate that T1D may alter expression patterns of RAGE axis proteins and thus contribute to DLDN.

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.

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.