Myelin oligodendrocyte glycoprotein antibody-associated disease in children: Are there MRI predictors of relapse?

BACKGROUND AND PURPOSE: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is increasingly recognized in children. Some children have isolated disease while others relapse. The study evaluates clinical, demographic and imaging features children with positive anti-MOG antibodies comparing to previously reported findings and correlate patterns on MR imaging with a relapsing course in MOGAD. MATERIAL AND METHODS: All pediatrics patients with serum anti-MOG antibodies were reviewed. Demographic, clinical, and imaging data were evaluated. Patients with a relapsing course were compared to those with a single event. We assessed initial MR images of the brain, orbits and spine obtained at the onset of clinical symptoms, whether performed at our institution or elsewhere. RESULTS: Thirty patients were included, fourteen with a single event and sixteen with more than one clinical event. The mean age was 8.1 years, with a mean follow-up of 58 months (range of 0.67 to 238 months). The relapsing patients had a mean of 3.5 relapses (range 2-12). 55% of patients had long segment optic nerve lesions, 53% of patients had cortical or peripheral white matter lesions, and 46% of patients had thalamic lesions. 43% of patients had spinal cord lesions, with 39% involving the central cord and 26% with long segment involvement. The imaging features between the groups were not statistically significant. CONCLUSION: There were no distinguishing features in relapsing versus non-relapsing patients. In the absence of any predictive characteristics for future relapse, patients should have regular clinical and imaging follow up.

Lifetime personal cigarette smoking and risk of young-onset breast cancer by subtype among non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). METHODS: Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. RESULTS: YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP. CONCLUSION: Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.

Theory, methods, and operational results of the Young Women's Health History Study: a study of young-onset breast cancer incidence in Black and White women.

PURPOSE: The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and persistent racial and socioeconomic inequities. We conducted a population-based case-control study of BC among young Black and White women and here discuss the theory that informed our study, exposures collected, study methods, and operational results. METHODS: Cases were non-Hispanic Black (NHB) and White (NHW) women age 20-49 years with invasive BC in metropolitan Detroit and Los Angeles County SEER registries 2010-2015. Controls were identified through area-based sampling from the U.S. census and frequency matched to cases on study site, race, and age. An eco-social theory of health informed life-course exposures collected from in-person interviews, including socioeconomic, reproductive, and energy balance factors. Measured anthropometry, blood (or saliva), and among cases SEER tumor characteristics and tumor tissue (from a subset of cases) were also collected. RESULTS: Of 5,309 identified potentially eligible cases, 2,720 sampled participants were screened and 1,812 completed interviews (682 NHB, 1140 NHW; response rate (RR): 60%). Of 24,612 sampled control households 18,612 were rostered, 2,716 participants were sampled and screened, and 1,381 completed interviews (665 NHB, 716 NHW; RR: 53%). Ninety-nine% of participants completed the main interview, 82% provided blood or saliva (75% blood only), and SEER tumor characteristics (including ER, PR and HER2 status) were obtained from 96% of cases. CONCLUSIONS: Results from the successfully established YWHHS should expand our understanding of young-onset BC etiology overall and by tumor type and identify sources of racial and socioeconomic inequities in BC.

Teenager With Recurrent Ataxia, Ophthalmoplegia, and Encephalopathy Associated With Demyelination: From the National Multiple Sclerosis Society Case Conference Proceedings

A 15-year-old adolescent boy developed subacute ataxia, encephalopathy, ophthalmoplegia, and dysarthria following a sore throat. An MRI examination revealed multifocal enhancing and nonenhancing supratentorial white matter and symmetric brainstem lesions. After 2 additional presentations with worsening symptoms and lesion accumulation, he was ultimately successfully treated with rituximab for his condition.

Rehabilitation Outcomes in Children With Acute Flaccid Myelitis From 2014 to 2019: A Multicenter Retrospective Review.

BACKGROUND: Acute flaccid myelitis (AFM) is a childhood illness characterized by sudden-onset weakness impairing function. The primary goal was to compare the motor recovery patterns of patients with AFM who were discharged home or to inpatient rehabilitation. Secondary analyses focused on recovery of respiratory status, nutritional status, and neurogenic bowel and bladder in both cohorts. METHODS: Eleven tertiary care centers in the United States performed a retrospective chart review of children with AFM between January 1, 2014, and October 1, 2019. Data included demographics, treatments, and outcomes on admission, discharge, and follow-up visits. RESULTS: Medical records of 109 children met inclusion criteria; 67 children required inpatient rehabilitation, whereas 42 children were discharged directly home. The median age was 5 years (range 4 months to 17 years), and the median time observed was 417 days (interquartile range = 645 days). Distal upper extremities recovered better than the proximal upper extremities. At acute presentation, children who needed inpatient rehabilitation had significantly higher rates of respiratory support (P < 0.001), nutritional support (P < 0.001), and neurogenic bowel (P = 0.004) and bladder (P = 0.002). At follow-up, those who attended inpatient rehabilitation continued to have higher rates of respiratory support (28% vs 12%, P = 0.043); however, the nutritional status and bowel/bladder function were no longer statistically different. CONCLUSIONS: All children made improvements in strength. Proximal muscles remained weaker than distal muscles in the upper extremities. Children who qualified for inpatient rehabilitation had ongoing respiratory needs at follow-up; however, recovery of nutritional status and bowel/bladder were similar.

Pediatric N-Methyl-d-Aspartate (NMDA) Receptor Encephalitis, With and Without Herpes Encephalitis.

OBJECTIVE: To compare clinical, diagnostic, management, and outcome factors in children with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and a history of herpes simplex encephalitis (HSE) to children with NMDAR encephalitis without a history of HSE. METHODS: All patients with anti-NMDAR antibodies in cerebrospinal fluid treated at our institution between 2012 and 2019 were identified and divided into those with a history of HSE (HSE+NMDAR group) and those without a history of HSE (NMDAR-only group). Demographic data, clinical characteristics, immunotherapy, and outcome data were collected on all patients and compared between the 2 groups. RESULTS: Seventeen patients were identified with anti-NMDAR antibodies in cerebrospinal fluid, 6 of whom had a history of HSE. Mean age in the HSE+NMDAR cohort was significantly younger in the HSE+NMDAR cohort, as 5 of the 6 patients were infants. Of HSE+NMDAR patients, 50% had behavioral symptoms, 67% had movement disorders, and 100% had seizures at disease nadir. In the NMDAR-only group, 100% had behavioral symptoms, 73% had movement disorders, and 73% had seizures at nadir. HSE+NMDAR patients received a median of 1 immunotherapy, compared to a median of 4.5 immunotherapies in the NMDAR-only group. CONCLUSION: Behavioral symptoms were more common in NMDAR-only patients, whereas seizures were more common in HSE+NMDAR patients. Both groups had significant disability at disease nadir, with more improvement in disability over time in the NMDAR-only group. HSE+NMDAR patients received fewer immunotherapies than NMDAR-only patients. Outcomes of infants with HSE appear to primarily reflect sequelae from HSE.

An assessment of prevalence and expenditure associated with discharge brain MRI in preterm infants.

To assess national expenditure associated with preterm-infant brain MRI and potential impact of reduction per Choosing Wisely campaign 2015 recommendation to "avoid routine screening term-equivalent or discharge brain MRIs in preterm-infants". Cross-sectional U.S. trend data from the Agency for Healthcare Research and Quality (AHRQ), Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) database (2006, 2009, 2012, 2016) was used to estimate overall national expenditure associated with brain MRI among infants with gestational age (GA) ≤36 weeks, and also when classified as 'not indicated' (NI-MRI) i.e., equivalent to routine use without clinical indications and regarded as low-value service (LVS). Associated cost was determined by querying CMS-database for physician-fee-schedules to find the highest global procedure-cost per cycle, then adjusting for inflation. Sensitivity-analyses were conducted to account for additional clinical charges associated with NI-MRI. 3,768 (0.26%) of 1,472,236 preterm-infants had brain MRI across all cycles (inflation-adjusted total $3,690,088). Overall proportion of brain MRIs increased across 2006-2012 from 0.25%-0.33% but decreased in 2016 to 0.16% (P<0.001). Inflation-adjusted overall expenditure by cycle was: 2006, $1,299,130 (95% CI: $987,505, $1,610,755); 2009, $1,194,208 (95% CI: $873,487, $1,516,154); 2012, $931,836 (95% CI: $666,114, $1,197,156); and 2016, $264,648 (95% CI: $172,061, $357,280). Prevalence for NI-MRI in 2006, 2009, 2012 and 2016 was 86% (n = 809), 88% (n = 940), 89% (n = 1028) and 50% (n = 299), respectively; and 70% were in infants 35-36 weeks GA. NI-MRI prevalence was not different over time by payer-type (Medicaid, private), sex or race/ethnicity (white, black, Hispanic); larger hospital size was significantly associated across 2006-2012 but this declined for all sizes in 2016, with most decline in larger hospitals (P for interaction <0.05). NI-MRI expenditure sensitivity-analysis with addition of cycle median total-admission-charge to inflation-adjusted CMS-fee was $1,190,919/$518,343, for 2012/2016 cycles respectively. National MRI prevalence in preterm infants (both overall and LVS) and associated expenditure decreased substantially post recommendation; however, annual savings are modest and unlikely to be >$1.2 million.

Comparison of children with acute flaccid myeltis before and after 2014.

OBJECTIVE: To observe whether cases of acute flaccid myelitis (AFM) before and since August 1, 2014, had important differences and to further characterize patients with AFM regarding clinical, laboratory, imaging, and treatment findings. METHODS: All pediatric patients with AFM at our institution were reviewed. Demographic, clinical, and diagnostic data were collected through medical record review. Patients with onset before August 1, 2014, and after that date were compared and when applicable compared with Centers for Disease Control and Prevention data. RESULTS: Sixteen patients were included, 6 in the pre-2014 and 10 in the post-2014 group. The mean age in the pre-2014 group was 7.4 years and in the post-2014 group was 6.4 years. Initial symptoms were similar in both groups, as were functional and motor abilities at disease nadir and the most recent follow-up. Post-2014 patients had a higher mean CSF white blood cell count (57) and neutrophil count (30%) compared with pre-2014 patients (3.2 and 0.5%, respectively). Eighty percent of post-2014 patients had positive enterovirus/rhinovirus testing, with 57% of specimens positive for enterovirus D68 (EV-D68). On acute imaging, a triad of brainstem, cervical cord gray matter involvement, and ventral nerve root/cauda equina (CE) thickening/enhancement was found in 5 patients. CONCLUSION: The groups had more similarities than differences but with a more inflammatory picture in the post-2014 patients. The constellation of cervical cord gray matter, brainstem, and nerve root/CE thickening should raise suspicion for AFM in the appropriate clinical setting. Most post-2014 patients had associated enterovirus infections, and over half tested for EV-D68 were positive. There was minimal clinical improvement in both groups despite various immunotherapies.