Searched for: person:meratm01 or cp209 or nb2021 or dg1249 or wolinr01 or balcel01 or ruckej02 or galets01 or grosss15
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Teaching Video NeuroImage: Globe Retraction in Duane Syndrome
Jauregui, Ruben; Grossman, Scott N
PMID: 39889267
ISSN: 1526-632x
CID: 5781292
Advancing Optical Coherence Tomography Diagnostic Capabilities: Machine Learning Approaches to Detect Autoimmune Inflammatory Diseases
Kenney, Rachel C; Flagiello, Thomas A; D' Cunha, Anitha; Alva, Suhan; Grossman, Scott N; Oertel, Frederike C; Paul, Friedemann; Schilling, Kurt G; Balcer, Laura J; Galetta, Steven L; Pandit, Lekha
BACKGROUND:In many parts of the world including India, the prevalence of autoimmune inflammatory diseases such as neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and multiple sclerosis (MS) is rising. A diagnosis is often delayed due to insufficient diagnostic tools. Machine learning (ML) models have accurately differentiated eyes of patients with MS from those of healthy controls (HCs) using optical coherence tomography (OCT)-based retinal images. Examining OCT characteristics may allow for early differentiation of these conditions. The objective of this study was to determine feasibility of ML analyses to distinguish between patients with different autoimmune inflammatory diseases, other ocular diseases, and HCs based on OCT measurements of the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layers (INLs). METHODS:Eyes of people with MS (n = 99 patients), NMOSD (n = 40), MOGAD (n = 74), other ocular diseases (OTHER, n = 16), and HCs (n = 54) from the Mangalore Demyelinating Disease Registry were included. Support vector machine (SVM) classification models incorporating age, pRNFL, GCIPL, and INL were performed. Data were split into training (70%) and testing (30%) data and accounted for within-patient correlations. Cross-validation was used in training to choose the best parameters for the SVM model. Accuracy and area under receiver operating characteristic curves (AUROCs) were used to assess model performance. RESULTS:The SVM models distinguished between eyes of patients with each condition (i.e., MOGAD vs NMOSD, NMOSD vs HC, MS vs OTHER, etc) with strong discriminatory power demonstrated from the AUROCs for these comparisons ranging from 0.81 to 1.00. These models also performed with moderate to high accuracy, ranging from 0.66 to 0.81, with the exception of the MS vs NMOSD comparison, which had an accuracy of 0.53. CONCLUSIONS:ML models are useful for distinguishing between autoimmune inflammatory diseases and for distinguishing these from HCs and other ocular diseases based on OCT measures. This study lays the groundwork for future deep learning studies that use analyses of raw OCT images for identifying eyes of patients with such disorders and other etiologies of optic neuropathy.
PMID: 39910704
ISSN: 1536-5166
CID: 5784172
Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers
Altaras, Caroline; Ly, Monica T; Schultz, Olivia; Barr, William B; Banks, Sarah J; Wethe, Jennifer V; Tripodis, Yorghos; Adler, Charles H; Balcer, Laura J; Bernick, Charles; Zetterberg, Henrik; Blennow, Kaj; Ashton, Nicholas; Peskind, Elaine; Cantu, Robert C; Coleman, Michael J; Lin, Alexander P; Koerte, Inga K; Bouix, Sylvain; Daneshvar, Daniel; Dodick, David W; Geda, Yonas E; Katz, Douglas L; Weller, Jason L; Mez, Jesse; Palmisano, Joseph N; Martin, Brett; Cummings, Jeffrey L; Reiman, Eric M; Shenton, Martha E; Stern, Robert A; Alosco, Michael L
PMID: 39865747
ISSN: 1744-4144
CID: 5780502
Qualitative Exploration of the "Guilt Gap" Among Physician-Faculty with Caregiving Responsibilities
Takayesu, Jamie; Szczygiel, Lauren; Jones, Rochelle D; Perry, Lydia; Balcer, Laura; Daumit, Gail; Drake, Wonder; Gatcombe, Heather; Mangurian, Christina; Marshall, Bess; Regensteiner, Judith; Jagsi, Reshma
PMID: 39258741
ISSN: 1931-843x
CID: 5690342
A Tribute to Norman J. Schatz by Nancy J. Newman and Steven L. Galetta
Newman, Nancy J; Galetta, Steven L
PMID: 39805083
ISSN: 1536-5166
CID: 5776382
Spastic Paraplegia Type 7-Associated Optic Neuropathy: A Case Series
Bell, Carter A; Ko, Melissa W; Mackay, Devin D; Bursztyn, Lulu L C D; Grossman, Scott N
BACKGROUND:Hereditary optic neuropathies comprise a group of clinically and genetically heterogeneous disorders. Optic neuropathy has been previously reported in families with spastic paraplegia type 7 (SPG7) gene mutations. However, the typical time course and clinical presentation of SPG7-associated optic neuropathy is poorly understood. We report a series of 5 patients harboring pathogenic SPG7 mutations who originally presented to a neuro-ophthalmology clinic with symptoms of optic neuropathy. METHODS:Retrospective case series of 5 patients with pathogenic SPG7 mutations and optic atrophy from 3 neuro-ophthalmology clinics. Demographic, clinical, diagnostic, and treatment data were collected and reported by the clinician authors. RESULTS:Five patients ranging in age from 8 to 48 years were evaluated in the neuro-ophthalmology clinic. Although there were variable clinical presentations for each subject, all noted progressive vision loss, typically bilateral, and several also had previous diagnoses of peripheral neuropathy (e.g., Guillain-Barré Syndrome). Patients underwent neuro-ophthalmic examinations and testing with visual fields and optic coherence tomography of the retinal nerve fiber layer. Genetic testing revealed pathogenic variants in the SPG7 gene. CONCLUSIONS:Five patients presented to the neuro-ophthalmology clinic with progressive vision loss and were diagnosed with optic atrophy. Although each patient harbored an SPG7 mutation, this cohort was phenotypically and genotypically heterogeneous. Three patients carried the Ala510Val variant. The patients demonstrated varying degrees of visual acuity and visual field loss, although evaluations were completed during different stages of disease progression. Four patients had a previous diagnosis of peripheral neuropathy. This raises the prospect that a single pathogenic variant of SPG7 may be associated with peripheral neuropathy in addition to optic neuropathy. These results support the consideration of SPG7 testing in patients with high suspicion for genetic optic neuropathy, as manifested by symmetric papillomacular bundle damage without clear etiology on initial workup. Applied judiciously, genetic testing, including for SPG7, may help clarify the cause of unexplained progressive optic neuropathies.
PMID: 37983191
ISSN: 1536-5166
CID: 5608232
A Tribute to Norman J. Schatz by Nancy J. Newman and Steven L. Galetta
Newman, Nancy J; Galetta, Steven L
PMID: 39805083
ISSN: 1536-5166
CID: 5776392
RENEWED: A follow-up study of the opicinumab phase 2 RENEW study in participants with acute optic neuritis
Aktas, Orhan; Ziemssen, Focke; Ziemssen, Tjalf; Klistorner, Alexander; Butzkueven, Helmut; Izquierdo, Guillermo; Leocani, Letizia; Balcer, Laura J; Galetta, Steven L; Castrillo-Viguera, Carmen; Bradley, Daniel P; Naylor, Maria L; Belachew, Shibeshih; Franchimont, Nathalie; Zhu, Bing; Cheng, Wenting; ,
BACKGROUND:The randomized, phase 2 RENEW trial (NCT01721161) evaluated efficacy/safety of opicinumab (anti-LINGO-1) versus placebo in patients with first-episode unilateral acute optic neuritis (AON). Although no significant differences in the latency recovery of visual evoked potential (VEP) were observed between opicinumab and placebo groups in the intention to treat (ITT) population, the prespecified per-protocol (PP) population showed better recovery with opicinumab than with placebo. RENEWED (NCT02657915) was a one-visit, follow-up study 2 years after the last RENEW study visit (Week 32) designed to assess the long-term electrophysiological and clinical outcomes for participants previously enrolled and having received study treatment in RENEW. METHODS:In the original study (RENEW), participants (aged 18-55 years) with a first unilateral AON episode were enrolled ≤28 days from first symptom onset and after treatment with methylprednisolone 1 g/day intravenously for 3-5 days; these participants were randomized to receive opicinumab 100 mg/kg or placebo intravenously once every 4 weeks from baseline to Week 20, assessed up to Week 32. Participants who received ≥1 dose of opicinumab 100 mg/kg or placebo in RENEW were eligible for the RENEWED follow-up study. Participants enrolled in RENEWED at 2 years (with an additional up to 12-month window) after the last RENEW study visit (Week 32) in both ITT and PP populations. The primary endpoint was change in full-field VEP (FF-VEP) latency of the affected eye at RENEWED study visit versus baseline of the fellow eye in RENEW, comparing between participants who received opicinumab and placebo in RENEW. Clinical progression and severity of multiple sclerosis (MS) were assessed. A substudy evaluated latency recovery using multifocal VEP (mfVEP) as an exploratory endpoint. RESULTS:Of 82 RENEW participants, 52 (63.4 %; opicinumab n = 28, placebo n = 24) enrolled in and completed RENEWED. The adjusted mean (95 % CI) difference in FF-VEP latency delay between opicinumab and placebo groups was -6.0 (-14.6, 2.6) msec (p = 0.165) for the PP population and -4.5 (-12.6, 3.7) msec (p = 0.274) for the ITT population at the RENEWED study visit. Nominally significant improvement on mfVEP latency in the opicinumab group versus placebo was observed in participants of the mfVEP substudy (p = 0.009). In participants from the PP population without clinically definite MS (CDMS) at RENEW baseline,12 (55 %) in the opicinumab group and 12 (67 %) in the placebo group developed CDMS from enrollment in the RENEW study up to RENEWED Day 1; the estimated proportion of participants with CDMS at 2 years after the last study visit assessment in RENEW was lower when treated with opicinumab (0.50) than when treated with placebo (0.61) (hazard ratio p-value = 0.23). No benefit on visual acuity or other neurological functions was observed in the opicinumab group vs placebo in RENEWED. CONCLUSION/CONCLUSIONS:The numerically increased VEP latency recovery with opicinumab treatment in RENEWED was consistent with those observed in the parent study RENEW. However, the VEP latency and clinical data in RENEWED should be interpreted with caution, given the nature of the follow-up study, the small sample size and the limitation in study design.
PMID: 39662163
ISSN: 2211-0356
CID: 5762722
Examination of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in former elite American football players
Miner, Annalise E; Groh, Jenna R; Tripodis, Yorghos; Adler, Charles H; Balcer, Laura J; Bernick, Charles; Zetterberg, Henrik; Blennow, Kaj; Peskind, Elaine; Ashton, Nicholas J; Gaudet, Charles E; Martin, Brett; Palmisano, Joseph N; Banks, Sarah J; Barr, William B; Wethe, Jennifer V; Cantu, Robert C; Dodick, David W; Katz, Douglas I; Mez, Jesse; van Amerongen, Suzan; Cummings, Jeffrey L; Shenton, Martha E; Reiman, Eric M; Stern, Robert A; Alosco, Michael L; ,
INTRODUCTION/BACKGROUND:Blood-based biomarkers offer a promising approach for the detection of neuropathologies from repetitive head impacts (RHI). We evaluated plasma biomarkers of amyloid, tau, neurodegeneration, and inflammation in former football players. METHODS:The sample included 180 former football players and 60 asymptomatic, unexposed male participants (aged 45-74). Plasma assays were conducted for beta-amyloid (Aβ) 40, Aβ42, hyper-phosphorylated tau (p-tau) 181+231, total tau (t-tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), interleukin-6 (IL-6), Aβ42/p-tau181 and Aβ42/Aβ40 ratios. We evaluated their ability to differentiate the groups and associations with RHI proxies and traumatic encephalopathy syndrome (TES). RESULTS:= 0.008). DISCUSSION/CONCLUSIONS:Plasma p-tau181 and p-tau231, GFAP, and NfL may offer some usefulness for the characterization of RHI-related neuropathologies. HIGHLIGHTS/CONCLUSIONS:Former football players had higher plasma p-tau181 and p-tau231 and lower Aβ42/ptau-181 compared to asymptomatic, unexposed men. Younger age of first exposure was associated with increased plasma NfL and GFAP in older but not younger participants. Plasma GFAP was higher in participants with TES-CTE possible/probable compared to TES-CTE no/suggestive.
PMCID:11567811
PMID: 39351900
ISSN: 1552-5279
CID: 5751932
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