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Testing the Validity and Reliability of a Standardized Virtual Examination for Concussion

Jack, Alani I; Digney, Helena T; Bell, Carter A; Grossman, Scott N; McPherson, Jacob I; Saleem, Ghazala T; Haider, Mohammad N; Leddy, John J; Willer, Barry S; Balcer, Laura J; Galetta, Steven L; Busis, Neil A; Torres, Daniel M
BACKGROUND AND OBJECTIVES/UNASSIGNED:We determined inter-modality (in-person vs telemedicine examination) and inter-rater agreement for telemedicine assessments (2 different examiners) using the Telemedicine Buffalo Concussion Physical Examination (Tele-BCPE), a standardized concussion examination designed for remote use. METHODS/UNASSIGNED:Patients referred for an initial evaluation for concussion were invited to participate. Participants had a brief initial assessment by the treating neurologist. After a patient granted informed consent to participate in the study, the treating neurologist obtained a concussion-related history before leaving the examination room. Using the Tele-BCPE, 2 virtual examinations in no specific sequence were then performed from nearby rooms by the treating neurologist and another neurologist. After the 2 telemedicine examinations, the treating physician returned to the examination room to perform the in-person examination. Intraclass correlation coefficients (ICC) determined inter-modality validity (in-person vs remote examination by the same examiner) and inter-rater reliability (between remote examinations done by 2 examiners) of overall scores of the Tele-BCPE within the comparison datasets. Cohen's kappa, κ, measured levels of agreement of dichotomous ratings (abnormality present vs absent) on individual components of the Tele-BCPE to determine inter-modality and inter-rater agreement. RESULTS/UNASSIGNED:< 0.001]) were reliable (ICC >0.70). There was at least substantial inter-modality agreement (κ ≥ 0.61) for 25 of 29 examination elements. For inter-rater agreement (2 telemedicine examinations), there was at least substantial agreement for 8 of 29 examination elements. DISCUSSION/UNASSIGNED:Our study demonstrates that the Tele-BCPE yielded consistent clinical results, whether conducted in-person or virtually by the same examiner, or when performed virtually by 2 different examiners. The Tele-BCPE is a valid indicator of neurologic examination findings as determined by an in-person concussion assessment. The Tele-BCPE may also be performed with excellent levels of reliability by neurologists with different training and backgrounds in the virtual setting. These findings suggest that a combination of in-person and telemedicine modalities, or involvement of 2 telemedicine examiners for the same patient, can provide consistent concussion assessments across the continuum of care.
PMID: 38895642
ISSN: 2163-0402
CID: 5672092

Testing the Validity and Reliability of a Standardized Virtual Examination for Concussion

Jack, Alani I; Digney, Helena T; Bell, Carter A; Grossman, Scott N; McPherson, Jacob I; Saleem, Ghazala T; Haider, Mohammad N; Leddy, John J; Willer, Barry S; Balcer, Laura J; Galetta, Steven L; Busis, Neil A; Torres, Daniel M
ISSN: 2163-0402
CID: 5670082

Myelin Oligodendrocyte Glycoprotein Antibody Disease Optic Neuritis: A Structure-Function Paradox?

Ross, Ruby; Kenney, Rachel; Balcer, Laura J; Galetta, Steven L; Krupp, Lauren; O'Neill, Kimberly A; Grossman, Scott N
BACKGROUND:Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a demyelinating disorder that most commonly presents with optic neuritis (ON) and affects children more often than adults. We report 8 pediatric patients with MOG-associated ON and characterize focal optical coherence tomography (OCT) abnormalities over time that help distinguish this condition from the trajectories of other demyelinating disorders. These OCT findings are examined in the context of longitudinal visual function testing. METHODS:This is a retrospective case series of 8 pediatric patients with MOG-associated ON who were referred for neuro-ophthalmic evaluation. Longitudinal data for demographics, clinical history, physical examination, and OCT obtained in the course of clinical evaluations were collected through retrospective medical record review. RESULTS:Patients demonstrated acute peripapillary retinal nerve fiber layer (RNFL) thickening in one or both eyes, consistent with optic disc swelling. This was followed by steady patterns of average RNFL thinning, with 9 of 16 eyes reaching significantly low RNFL thickness using OCT platform reference databases (P < 0.01), accompanied by paradoxical recovery of high-contrast visual acuity (HCVA) in every patient. There was no correlation between HCVA and any OCT measures, although contrast sensitivity (CS) was associated with global thickness, PMB thickness, and nasal/temporal (N/T) ratio, and color vision was associated with PMB thickness. There was a lower global and papillomacular bundle (PMB) thickness (P < 0.01) in clinically affected eyes compared with unaffected eyes. There was also a significantly higher N:T ratio in clinically affected eyes compared with unaffected eyes in the acute MOG-ON setting (P = 0.03), but not in the long-term setting. CONCLUSIONS:MOG shows a pattern of prominent retinal atrophy, as demonstrated by global RNFL thinning, with remarkable preservation of HCVA but remaining deficits in CS and color vision. These tests may be better clinical markers of vision changes secondary to MOG-ON. Of the OCT parameters measured, PMB thickness demonstrated the most consistent correlation between structural and functional measures. Thus, it may be a more sensitive marker of clinically significant retinal atrophy in MOG-ON. The N:T ratio in acute clinically affected MOG-ON eyes in our study was higher than the N:T ratio of neuromyelitis optica (NMO)-ON eyes and similar to the N:T ratio in multiple sclerosis (MS)-ON eyes as presented in the prior literature. Therefore, MOG may share a more similar pathophysiology to MS compared with NMO.
PMID: 38526582
ISSN: 1536-5166
CID: 5644452

Multiple Cranial Nerve Palsies as the Presenting Sign of GCA

Merati, Melody; Radomski, Shana; Below, Alexandra; Lambert-Cheatham, Nathan; Keating, Ryan; Chang, Howard; Kaufman, David
PMID: 36892944
ISSN: 1536-5166
CID: 5456872

Association of Loneliness with Functional Connectivity MRI, Amyloid-β PET, and Tau PET Neuroimaging Markers of Vulnerability for Alzheimer's Disease

Zhao, Amanda; Balcer, Laura J; Himali, Jayandra J; O'Donnell, Adrienne; Rahimpour, Yashar; DeCarli, Charles; Gonzales, Mitzi M; Aparicio, Hugo J; Ramos-Cejudo, Jaime; Kenney, Rachel; Beiser, Alexa; Seshadri, Sudha; Salinas, Joel
BACKGROUND/UNASSIGNED:Loneliness has been declared an "epidemic" associated with negative physical, mental, and cognitive health outcomes such as increased dementia risk. Less is known about the relationship between loneliness and advanced neuroimaging correlates of Alzheimer's disease (AD). OBJECTIVE/UNASSIGNED:To assess whether loneliness was associated with advanced neuroimaging markers of AD using neuroimaging data from Framingham Heart Study (FHS) participants without dementia. METHODS/UNASSIGNED:In this cross-sectional observational analysis, we used functional connectivity MRI (fcMRI), amyloid-β (Aβ) PET, and tau PET imaging data collected between 2016 and 2019 on eligible FHS cohort participants. Loneliness was defined as feeling lonely at least one day in the past week. The primary fcMRI marker was Default Mode Network intra-network connectivity. The primary PET imaging markers were Aβ deposition in precuneal and FLR (frontal, lateral parietal and lateral temporal, retrosplenial) regions, and tau deposition in the amygdala, entorhinal, and rhinal regions. RESULTS/UNASSIGNED:Of 381 participants (mean age 58 [SD 10]) who met inclusion criteria for fcMRI analysis, 5% were classified as lonely (17/381). No association was observed between loneliness status and network changes. Of 424 participants (mean age 58 [SD = 10]) meeting inclusion criteria for PET analyses, 5% (21/424) were lonely; no associations were observed between loneliness and either Aβ or tau deposition in primary regions of interest. CONCLUSIONS/UNASSIGNED:In this cross-sectional study, there were no observable associations between loneliness and select fcMRI, Aβ PET, and tau PET neuroimaging markers of AD risk. These findings merit further investigation in prospective studies of community-based cohorts.
PMID: 38820017
ISSN: 1875-8908
CID: 5663972

Navigating the U.S. regulatory landscape for neurologic digital health technologies

Busis, Neil A; Marolia, Dilshad; Montgomery, Robert; Balcer, Laura J; Galetta, Steven L; Grossman, Scott N
Digital health technologies (DHTs) can transform neurological assessments, improving quality and continuity of care. In the United States, the Food & Drug Administration (FDA) oversees the safety and efficacy of these technologies, employing a detailed regulatory process that classifies devices based on risk and requires rigorous review and post-market surveillance. Following FDA approval, DHTs enter the Current Procedural Terminology, Relative Value Scale Update Committee, and Centers for Medicare & Medicaid Services coding and valuation processes leading to coverage and payment decisions. DHT adoption is challenged by rapid technologic advancements, an inconsistent evidence base, marketing discrepancies, ambiguous coding guidance, and variable health insurance coverage. Regulators, policymakers, and payers will need to develop better methods to evaluate these promising technologies and guide their deployment. This includes striking a balance between patient safety and clinical effectiveness versus promotion of innovation, especially as DHTs increasingly incorporate artificial intelligence. Data validity, cybersecurity, risk management, societal, and ethical responsibilities should be addressed. Regulatory advances can support adoption of these promising tools by ensuring DHTs are safe, effective, accessible, and equitable.
PMID: 38609447
ISSN: 2398-6352
CID: 5646182

Brain morphometry in former American football players: Findings from the DIAGNOSE CTE research project

Arciniega, Hector; Baucom, Zachary H; Tuz-Zahra, Fatima; Tripodis, Yorghos; John, Omar; Carrington, Holly; Kim, Nicholas; Knyazhanskaya, Evdokiya E; Jung, Leonard B; Breedlove, Katherine; Wiegand, Tim L T; Daneshvar, Daniel H; Rushmore, R Jarrett; Billah, Tashrif; Pasternak, Ofer; Coleman, Michael J; Adler, Charles H; Bernick, Charles; Balcer, Laura J; Alosco, Michael L; Koerte, Inga K; Lin, Alexander P; Cummings, Jeffrey L; Reiman, Eric M; Stern, Robert A; Shenton, Martha E; Bouix, Sylvain
Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which currently can be diagnosed only at postmortem. American football players are at higher risk of developing CTE given their exposure to RHIs. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at postmortem in living individuals using structural magnetic resonance imaging (MRI). MRI brain morphometry was evaluated in 170 male former American football players ages 45-74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 58 age range 45-74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each Traumatic Encephalopathy Syndrome (TES) diagnosis core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula temporal pole and superior frontal gyrus. Post-hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe age-by-group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggest that MRI morphometrics detects abnormalities in individuals with a history of RHI exposure that resemble the anatomic distribution of pathological findings from postmortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggests that brain morphometry must be complemented by other types of measures to characterize individuals with RHIs.
PMID: 38533783
ISSN: 1460-2156
CID: 5644862

Subacute Vision Loss in a Patient With HIV

Park, George T; Gold, Doria M; Modi, Yasha; Rucker, Janet C
PMID: 37995149
ISSN: 1536-5166
CID: 5608722

Treatment of Periodic Alternating Nystagmus as a Consequence of Ataxia-Telangiectasia

Jauregui, Ruben; Bhagat, Dhristie; Garcia, Mekka R; Miller, Claire; Grossman, Scott N
PMID: 36730924
ISSN: 1536-5166
CID: 5420452

Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project

Su, Yi; Protas, Hillary; Luo, Ji; Chen, Kewei; Alosco, Michael L; Adler, Charles H; Balcer, Laura J; Bernick, Charles; Au, Rhoda; Banks, Sarah J; Barr, William B; Coleman, Michael J; Dodick, David W; Katz, Douglas I; Marek, Kenneth L; McClean, Michael D; McKee, Ann C; Mez, Jesse; Daneshvar, Daniel H; Palmisano, Joseph N; Peskind, Elaine R; Turner, Robert W; Wethe, Jennifer V; Rabinovici, Gil; Johnson, Keith; Tripodis, Yorghos; Cummings, Jeffrey L; Shenton, Martha E; Stern, Robert A; Reiman, Eric M; ,
INTRODUCTION/BACKGROUND:Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project. METHOD/METHODS:We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same-age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES). RESULTS:Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p < 0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups. DISCUSSION/CONCLUSIONS:Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.
PMID: 38134231
ISSN: 1552-5279
CID: 5611852