Relevance of ACE Scores in Teens with Depression and Anxiety: A Maui Pilot Study.

In the aftermath of the Covid pandemic and the notable rise of teen depression and anxiety (DA), there is an urgent need to focus on youth mental health. Another important variable to consider is the presence of adverse childhood experiences (ACE), which can be associated with chronic mental and physical health conditions. This pilot study explores how ACEs relate to DA for adolescents in Maui, Hawai'i. The cohort was 75 patients seen at a Kaiser Pediatric Clinic in the spring of 2022. Data was collected from standard questionnaires and the Pediatric ACEs and Life-Events Screener (PEARLS). There were significant associations between DA and a high ACE score (4+), as well as female sex. A high ACE score can alert providers to initiate a trauma informed dialogue with patients. The effects of trauma are not often discussed at routine visits. Mental health care needs and community support can also be addressed as needed. The PEARLS questionnaire is a standard tool to help clinicians be more trauma-informed. This study explores its relevance at routine adolescent visits.

Recent advances in neuro-ophthalmology.

This review article represents a collaborative effort across continents, bringing together the latest developments in neuro-ophthalmology with a focus on innovative diagnostic and therapeutic modalities that are shaping the future of the field. Among the most significant advancements is the rise of optical coherence tomography (OCT), now recognized as an indispensable tool in neuro-ophthalmological research, providing unparalleled insights into optic nerve and central nervous system pathologies. Gene therapy, particularly for conditions such as Leber's hereditary optic neuropathy, marks a new frontier in personalized medicine, offering hope for previously untreatable conditions. The article also examines the transformative role of telemedicine and artificial intelligence (AI) in clinical practice, which are revolutionizing patient care and enhancing diagnostic precision. Furthermore, it highlights the impact of novel serological biomarkers on the understanding and management of immune-mediated optic neuritis, and discusses the introduction of new therapeutic agents like Tocilizumab and Teprotumumab, which are redefining treatment paradigms. Collectively, these advancements reflect the profound influence of modern medicine on neuro-ophthalmology, paving the way for improved patient outcomes and fostering new avenues for research and clinical practice.

Outcomes of Hyperbaric Oxygen Treatment for Central Retinal Artery Occlusion: A Single Center Experience.

PURPOSE: To describe the outcomes of hyperbaric oxygen therapy (HBOT) for patients with central retinal artery occlusion (CRAO) at a single tertiary care center. DESIGN: Retrospective clinical cohort study. METHODS: Medical records of all patients diagnosed with CRAO who received HBOT at Mayo Clinic in Rochester, Minnesota from 1/1/2009 to 12/31/2020 were reviewed to confirm diagnosis, time from onset to presentation, exam findings, treatments, and follow-up data. Main outcome measures included final visual acuity (VA) and number of lines of improvement. RESULTS: There were 41 patients diagnosed with CRAO who received HBOT during the 12 year study period. Median time from symptom onset to HBOT treatment was 9.5 hours (interquartile range [IQR] 6.5, 14.0 hours), and patients received a median of 4 HBOT sessions (IQR 2.5, 6.0 sessions). There were 20 patients who received HBOT within 9 hours, 14 (70%) of which had clinically meaningful improvement in VA of ≥0.3 logMAR. In comparison, of the 21 patients treated after 9 hours, 6 (28.6%) had VA improvement of ≥0.3 logMAR (p=0.008). For all patients, the median logMAR VA at presentation was 2.00 (IQR 1.70, 2.30) and the median logMAR VA at follow-up was 1.94 (IQR 1.00, 2.00) (p<0.001), with median lines of improvement of 3.0 (IQR 0.0, 7.0). For patients treated within 9 hours, the median logMAR VA at presentation was 2.00 (IQR 1.93, 2.30) and the median logMAR VA at follow-up was 1.70 (IQR 0.54, 2.00). Patients treated within 9 hours had statistically significant greater median lines of VA improvement than cases that were treated after >9 hours from symptom onset at 5.9 (IQR 3.0, 10.0) and 0.0 (IQR 0.0, 3.0), respectively (p<0.001). There was no difference in VA recovery associated with specific retinal exam findings such as cherry-red spot (p=0.22) and cilioretinal artery perfusion (p=0.36) compared to patients without those findings. CONCLUSION: There was a statistically significant improvement in VA after HBOT treatment in CRAO patients among patients that received early HBOT, with patients receiving the most benefit when receiving treatment within 9 hours. Randomized control trials in patients with CRAO are required to confirm the efficacy of HBOT.

Dried blood spot improves global access to aquaporin-4-IgG testing for neuromyelitis optica.

OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of dried blood spot (DBS) compared with conventional serum Aquaporin-4-IgG (AQP4-IgG) testing. METHODS: Prospective multicenter diagnostic study was conducted between April 2018 and October 2023 across medical centers in the United States, Uganda, and the Republic of Guinea. Neuromyelitis optica spectrum disorder (NMOSD) patients and controls collected blood on filter paper cards along with concurrent serum samples. These samples underwent analysis using flow cytometric live-cell-based assays (CBA) and enzyme-linked immunosorbent assay (ELISA) to determine AQP4 serostatus. The accuracy of AQP4-IgG detection between DBS and serum (gold standard) was compared. RESULTS: Among 150 participants (47 cases, 103 controls), there was a strong correlation between DBS and serum samples (Spearman's correlation coefficient of 0.82). The AUC was 0.97 (95% CI: 0.92-0.99). AQP4-IgG detection through DBS showed 87.0% sensitivity (95% CI: 0.74-0.95) and 100% specificity (95% CI: 0.96-1.00) using CBA, and 65.2% sensitivity (95% CI: 0.43-0.84) and 95.2% specificity (95% CI: 0.76-0.99) using ELISA. Serum ELISA demonstrated 69.6% sensitivity (95% CI: 0.47-0.87) and 98.4% specificity (95% CI: 0.91-0.99). The stability of DBS in detecting AQP4-IgG persisted over 24 months for most cases. INTERPRETATION: The DBS represents a viable alternative for detecting AQP4-IgG in resource-limited settings to diagnose NMOSD, offering high sensitivity and specificity comparable to serum testing. Moreover, DBS has low shipping costs, is easy to administer, and is suitable for point-of-care testing.

Etiologies and Outcomes of Granulomatosis With Polyangiitis-Associated Optic Neuropathy: A Case Series and Review of the Literature.

BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is a rare autoimmune disease characterized by inflammation of small- to medium-sized blood vessels (vasculitis). We described the 3 causes of GPA-associated optic neuropathy (compressive, inflammatory, or ischemic) and analyzed initial and final visual acuities (VAs) in each group, which could potentially help prognosticate visual outcomes depending on the etiology of optic neuropathy. METHODS: This was a retrospective chart review of patients who were diagnosed with GPA-associated optic neuropathy and were seen in the Department of Ophthalmology at Mayo Clinic in Rochester, Minnesota. Only patients who met the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology GPA classification criteria were included. RESULTS: A total of 12 patients with GPA-associated optic neuropathy were identified. The etiology of the optic neuropathy was compressive in 6 patients, inflammatory in 4 patients, and ischemic in 3 patients. One patient had compressive optic neuropathy initially, then presented with GPA-related optic neuritis years later. Four patients in the compressive optic neuropathy group had orbital masses requiring orbitotomy for debulking, and the remaining 2 patients had compression from pachymeningitis. Average logarithm of the minimum angle of resolution (logMAR) VA at optic neuropathy onset was 1.50, 1.50, and 0.67 (Snellen equivalent 20/600, 20/600, and 20/100, respectively). At the last follow-up, average logMAR VA was 0.91, 1.73, and 1.10 (Snellen equivalent 20/160, 20/1,000, and 20/250, respectively) for each group. CONCLUSION: Visual outcomes were variable, with compressive and inflammatory optic neuropathies showing improvement in 4 eyes and worsening in 3 eyes in total. Patients with ischemic optic neuropathy from GPA were either stable or worsened over the course of the disease.

Optical coherence tomography angiography measurements in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease: A systematic review and meta-analysis.

PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are immune-mediated disorders that can often manifest with optic neuritis (ON) among other symptoms. Optical coherence tomography angiography (OCTA) is an emerging diagnostic method that can quantify retinal capillary blood flow and vessel density (VD), which have been shown to be affected in NMOSD and MOGAD. Hence, we aimed to systematically review the studies addressing retinal microvasculature using OCTA in these diseases. DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, and Web of Sciences were systematically searched to identify articles addressing OCTA measurements in patients with NMOSD or MOGAD. Following the data extraction, a meta-analysis was performed on the study population and OCTA types amongst at least two homogenous studies. RESULTS: Twenty-two studies on NMOSD, MOGAD, or both were included. Parafoveal superficial retinal capillary plexus (SRCP) VD and radial peripapillary capillary (RPC) VD were diminished in NMOSD ON+ and NMOSD ON- groups compared to healthy controls (HCs). In addition, both the SRCP VD and RPC VD were significantly reduced in NMOSD ON+ compared to NMOSD ON-. However, meta-analysis for deep retinal capillary plexus (DRCP) did not show a significant difference between NMOSD patients and HCs, or among ON+ and ON- patients. Furthermore, there was no significant difference in foveal avascular zone (FAZ) area size between NMOSD patients and HCs. Regarding MOGAD, the meta-analysis showed decreased parafoveal SRCP VD and RPC VD in MOGAD ON+ patients compared to HCs. Comparing NMOSD ON+ and MOGAD ON+, a meta-analysis was conducted for RPC VD, which showed no significant difference between the two groups. CONCLUSIONS: This systematic review and meta-analysis confirmed reduced VD in the macular and peripapillary areas in NMOSD and MOGAD eyes, particularly in the parafoveal SRCP and RPC, which is further impacted by prior ON.

Intracranial Pressure Elevation and MOGAD.

This cross-sectional study examines the frequency of increased intracranial pressure and its association with myelin oligodendrocyte glycoprotein antibody-associated disease in patients of various ages.

Access to Dermatological Appointments Based on Insurance Types in Hawai'i.

Although there is evidence that Medicaid beneficiaries in the continental United States experience barriers to accessing dermatological care, limited data exists on whether these same barriers exist in Hawai'i. Using a secret shopper study design, a total of 46 dermatology offices were contacted, 41 (89%) of which were accepting new patients. Thirty (73%) offices were located on O'ahu, and the remaining 11 (27%) were distributed among the neighboring islands (Hawai'i Island, Kaua'i, Maui). Overall, the acceptance rate for Medicaid (n=14) was 34%, which was significantly lower (P<.0001) than private insurance (n=39 (95%)) and Medicare (n=38 (93%)). The acceptance rate for patients with Medicaid insurance was lower for O'ahu offices (27%) than for neighboring islands' offices (55%), but the difference was not statistically significant (P=.095). Differences in average wait times were not statistically significant among insurance types or between O'ahu and neighboring islands. Overall, these results suggest that Medicaid recipients compared to those with private insurance or Medicare might experience difficulty in accessing dermatological care in Hawai'i.

Application of the international criteria for optic neuritis in the Acute Optic Neuritis Network.

OBJECTIVE: The first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON). METHODS: We included 160 patients with a first-ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present. RESULTS: According to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody-associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%). INTERPRETATION: According to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON.

Radiologic Predictors of Visual Outcome in Myelin Oligodendrocyte Glycoprotein-Related Optic Neuritis.

PURPOSE: This study aimed to determine whether magnetic resonance imaging (MRI) biomarkers are associated with visual prognosis in myelin oligodendrocyte protein (MOG)-associated optic neuritis (ON). DESIGN: Cross-sectional analysis. PARTICIPANTS: Patients meeting 2023 international diagnostic criteria for MOG antibody-associated disease who were seen for first episodes of MOG-associated ON at 3 tertiary neuro-ophthalmology practices between January 2017 and July 2023 were enrolled. Patients who received < 3 months of neuro-ophthalmic follow-up and did not demonstrate visual recovery (visual acuity [VA] ≥ 20/20 and visual field mean deviation [VFMD] > -5.0 dB) during this time were excluded. METHODS: Patients underwent contrast-enhanced, fat-suppressed MRI of the brain and orbits within 1 month of symptom onset. MAIN OUTCOME MEASURES: The associations between radiologic biomarkers and poor VA outcome (< 20/40), incomplete VA recovery (< 20/20), and poor VFMD outcome (VFMD < -5.0 dB) were assessed using multivariable logistic regression adjusting for time from symptom onset to treatment and nadir VA or VFMD. Radiologic biomarkers included length of optic nerve enhancement (> 25% vs. < 25%; > 50% vs. < 50%; and > 75% vs. < 75%); degree of orbital, canalicular, and intracranial or chiasmal optic nerve enhancement (mild vs. moderate to severe compared with the lacrimal gland); and absence versus presence of optic nerve sheath enhancement on baseline T1-weighted MRI. RESULTS: A total of 129 eyes of 92 patients (median age, 37.0 years [interquartile range, 20.8-51.3 years]; 65.2% female) were included. Poor VA outcome was seen in 6.2% of patients, incomplete VA recovery was seen in 19.4% of patients, and poor VFMD outcome was seen in 16.9% of patients. Compared with eyes with moderate to severe enhancement, eyes with mild orbital optic nerve enhancement were more likely to have poor VA outcome (odds ratio [OR], 8.57; 95% confidence interval [CI], 1.85-51.14; P = 0.009), incomplete VA recovery (OR, 7.31, 95% CI, 2.42-25.47; P = 0.001), and poor VFMD outcome (adjusting for time to treatment: OR, 6.81; 95% CI, 1.85-28.98; P = 0.005; adjusting for nadir VFMD: OR, 11.65; 95% CI, 1.60-240.09; P = 0.04). Lack of optic nerve sheath enhancement additionally was associated with incomplete VA recovery (OR, 3.86; 95% CI, 1.19-12.85; P = 0.02) compared with the presence of enhancement. These associations remained consistent in subgroup logistic regression analysis of MRIs performed before initiation of treatment but were not seen in pairwise analysis of MRIs performed after treatment. CONCLUSIONS: In eyes with first MOG-associated ON episodes, milder enhancement in the orbital optic nerve was associated with poorer VA and visual field recovery. Prospective and mechanistic studies are needed to confirm the prognostic usefulness of MRI in MOG-associated ON. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Optical Coherence Tomography Angiography Retinal Imaging Associations With Burden of Small Vessel Disease and Amyloid Positivity in the Brain.

BACKGROUND: Alzheimer disease (AD) and other dementias are associated with vascular changes and amyloid deposition, which may be reflected as density changes in the retinal capillaries. These changes may can be directly visualized and quantified with optical coherence tomography angiography (OCTA), making OCTA a potential noninvasive preclinical biomarker of small vessel disease and amyloid positivity. Our objective was to investigate the feasibility of retinal imaging metrics as noninvasive biomarkers of small vessel disease and amyloid positivity in the brain. METHODS: We investigated associations between OCTA and neuroimaging and cognitive metrics in 41 participants without dementia from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center. OCTA metrics included superficial, deep, and full retina capillary density of the fovea, parafovea, and macula as well as the area of the foveal avascular zone (FAZ). Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds (CMB), lacunar infarcts, and amyloid positivity as evidenced on positron emission tomography (PET), whereas cognitive metrics included mini-mental status examination (MMSE) score. We performed generalized estimating equations to account for measurements in each eye while controlling for age and sex to estimate associations between OCTA metrics and neuroimaging and cognitive scores. RESULTS: Associations between OCTA and neuroimaging metrics were restricted to the fovea. OCTA showed decreased capillary density with high burden of WMH in both the superficial (P = 0.003), deep (P = 0.004), and full retina (P = 0.01) in the fovea but not the parafovea or whole macula. Similarly, participants with amyloid PET positivity had significantly decreased capillary density in the superficial fovea (P = 0.027) and deep fovea (P = 0.03) but higher density in the superficial parafovea (P = 0.038). Participants with amyloid PET positivity also had a significantly larger FAZ (P = 0.031), whereas in those with high WMH burden the difference did not reach statistical significance (P = 0.075). There was also a positive association between MMSE and capillary density of the full retina within the fovea (P = 0.037) and in the superficial parafovea (P = 0.046). No associations were found between OCTA metrics and presence of CMB or presence of lacunar infarcts. CONCLUSION: The associations of lower foveal capillary density with cerebral WMH and amyloid positivity suggest that further research is warranted to evaluate for shared mechanisms of disease between small vessel disease and AD pathologies.

Effect of the COVID-19 Pandemic on Medical Student Performance and Evaluation Scores.

In March 2020, the University of Hawaii John A. Burns School of Medicine suspended in person clinical teaching due to the SARS-CoV-2 (COVID) pandemic. During this period, virtual cases, telehealth participation, and online cases were incorporated into medical education. We have examined the effects of educational outcomes of third and fourth year students throughout clerkship performance, national standardized test scores, and our local fourth year OSCE examination. We found that USMLE step 2 scores were higher in the COVID-affected group. Patient logs in the COVID-affected group were lower for internal medicine, family medicine, OBGYN, and psychiatry clerkships. Clerkship performance grades in the COVID-affected group were lower for OBGYN and higher for surgery and psychiatry, but not different in other clerkships. USNBME subject specific examination scores in the COVID-affected group were higher for internal medicine, surgery, family medicine and psychiatry, but not different in all other specialties. For the fourth year OSCE, students in the COVID-affected group performed better on note taking and worse on physical examination. Future investigations will be needed to explore how our COVID-affected medical students perform in residency and beyond.

Optic Disc Cupping in Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, and Multiple Sclerosis and Its Relationship With Optical Coherence Tomography Parameters: A Multicenter Study.

BACKGROUND: Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning. METHODS: This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC. RESULTS: Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD (P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group (P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant (P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = -0.60 and R = -0.64, respectively), inversely moderate in patients with MOGAD (R = -0.34 and R = -0.40, respectively), and weak in patients with NMOSD (R = -0.03 and R = -0.17, respectively). CONCLUSIONS: Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD.

Self-performed Rh typing: a cross-sectional study.

OBJECTIVE: To evaluate whether patients are capable and willing to self-administer and interpret an EldonCard test to determine their Rh status. METHODS: This was a cross-sectional study in Honolulu, HI, USA of pregnancy-capable people aged 14-50 years who did not know their blood type and had never used an EldonCard. Participants independently completed EldonCard testing, determined their Rh type and answered a survey on feasibility and acceptability. Separately, a blinded clinician recorded their interpretation of the participant's EldonCard. When available, we obtained blood type from the electronic health record (EHR). We measured Rh type agreement between participant, clinician and EHR, as well as participant comfort and acceptability of testing. RESULTS: Of the 330 total participants, 288 (87.3%) completed testing. Patients and clinicians had 94.0% agreement in their interpretation of the EldonCard for Rh status. Patient interpretation had 83.5% agreement with EHR while clinician and EHR had 92.3% agreement. Sensitivity of EldonCard interpretation by patient and clinician was 100%. Specificity was 83.2% for patients and 92.2% for clinicians. Two patients (of 117) had Rh-negative blood type in the EHR. The vast majority of participants found the EldonCard testing easy (94.4%) and felt comfortable doing the testing (93.7%). Participants with lower education levels felt less confident (p=0.003) and less comfortable with testing (p=0.038); however, their ability to interpret results was similar to others (p=0.051). CONCLUSIONS: Patient-performed Rh typing via the EldonCard is an effective and acceptable option for patients, and could be used as a primary screening test for Rh status.

Frequency of Asymptomatic Optic Nerve Enhancement in 203 Patients With MOG Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI has not been explored in patients with MOGAD. An improved understanding of this would guide clinical practice and assessment of treatment efficacy. We aimed to determine the frequency of asymptomatic optic nerve enhancement in MOGAD. METHODS: This was a retrospective review of patients evaluated at Mayo Clinic with MOGAD between January 1, 2000, and August 1, 2021 (median follow-up 1.6 [range 1-19] years). MRI studies were reviewed by masked neuroradiologists. Scans performed within 30 days of ON attack were classified as attack scans. Images obtained for routine surveillance, before ON attack, or at the time of non-ON attack were classified as interattack scans. RESULTS: Five hundred sixty-six MRIs (203 unique patients, 53% female) were included. Interattack MRIs represented 341 (60%) of the scans (median 36 days post-ON [range -1,032 to 6,001]). Of the interattack scans, 43 of 341 (13%), 30 unique patients, showed optic nerve enhancement. The enhancement was located at prior sites of ON in 35 of 43 (81%). Among the 8 patients with enhancement in new optic nerve areas, 6 had acute disseminated encephalomyelitis without an eye examination at the time of the MRI and 2 had preceding ON without imaging. Long-term visual outcomes showed no significant difference between those with and without asymptomatic enhancement, with improved visual acuity in most patients. DISCUSSION: Asymptomatic optic nerve enhancement occurred in 13% of interattack MRIs, the majority in patients with prior ON and occurring at prior sites of optic nerve enhancement. New asymptomatic optic nerve enhancement in areas without prior ON was rare. These findings are important for understanding the natural history of MOGAD, the interpretation of symptoms or response to treatment, and the adjudication of attacks in clinical trials.

Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). METHODS: This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis. RESULTS: Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]). DISCUSSION: Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.

MOG Antibody-Associated Disease in the Setting of Metastatic Melanoma Complicated by Immune Checkpoint Inhibitor Use.

OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disease rarely associated with malignancy. We report the clinical, MRI, immunopathology, and treatment response in a person with MOGAD and melanoma. METHODS: This is a case report of a person with a multidisciplinary evaluation at a tertiary referral center. RESULTS: A 52-year-old man presented with progressive encephalomyelitis that led to identification of metastatic melanoma. Investigations revealed positive MOG-IgG at high titers in serum (1:1,000; normal, <1:20) and CSF (1:4,096; normal, <1:2). MRI demonstrated multifocal T2 lesions with enhancement in the brain and spine. Brain biopsy showed demyelination and inflammation. MOG immunostaining was not present in the tumor tissue. He initially improved with methylprednisolone, plasmapheresis, prolonged oral steroid taper, and cancer-directed treatment with BRAF and MEK 1/2 inhibitors, but then developed bilateral optic neuritis. IV immunoglobulin (IVIG) was initiated. Five months later, he developed metastases and immune checkpoint inhibitor (ICI) treatment was started, which precipitated optic neuritis and myelitis despite IVIG and prednisone. Tocilizumab, an interleukin-6 receptor blocker, was started with excellent and sustained clinical and radiologic response. DISCUSSION: This case revealed a presentation of MOGAD concurrent with melanoma without tumor MOG immunostaining. We highlight tocilizumab as a dual-purpose treatment of MOGAD and the neurologic immune-related adverse effect of ICI.