The MOG antibody non-P42 epitope is predictive of a relapsing course in MOG antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) IgG seropositivity is a prerequisite for MOG antibody-associated disease (MOGAD) diagnosis. While a significant proportion of patients experience a relapsing disease, there is currently no biomarker predictive of disease course. We aim to determine whether MOG-IgG epitopes can predict a relapsing course in MOGAD patients. METHODS: MOG-IgG-seropositive confirmed adult MOGAD patients were included (n=202). Serum MOG-IgG and epitope binding were determined by validated flow cytometry live cell-based assays. Associations between epitopes, disease course, clinical phenotype, Expanded Disability Status Scale and Visual Functional System Score at onset and last review were evaluated. RESULTS: Of 202 MOGAD patients, 150 (74%) patients had MOG-IgG that recognised the immunodominant proline42 (P42) epitope and 115 (57%) recognised histidine103/serine104 (H103/S104). Fifty-two (26%) patients had non-P42 MOG-IgG and showed an increased risk of a relapsing course (HR 1.7; 95% CI 1.15 to 2.60, p=0.009). Relapse-freedom was shorter in patients with non-P42 MOG-IgG (p=0.0079). Non-P42 MOG-IgG epitope status remained unchanged from onset throughout the disease course and was a strong predictor of a relapsing course in patients with unilateral optic neuritis (HR 2.7, 95% CI 1.06 to 6.98, p=0.038), with high specificity (95%, 95% CI 77% to 100%) and positive predictive value (85%, 95% CI 45% to 98%). CONCLUSIONS: Non-P42 MOG-IgG predicts a relapsing course in a significant subgroup of MOGAD patients. Patients with unilateral optic neuritis, the most frequent MOGAD phenotype, can reliably be tested at onset, regardless of age and sex. Early detection and specialised management in these patients could minimise disability and improve long-term outcomes.

Primary leptomeningeal melanoma: the prognostic significance of its genetic signature and embryological origin.

Primary leptomeningeal melanomas are rare, comprising less than one percent of all brain tumours. They are aggressive and radioresistant tumours, with a poor prognosis. The mainstay of treatment is complete surgical resection and chemotherapy with limited success. Distinguishing a primary leptomeningeal melanoma from the more common metastatic disease can be difficult, and often requires the use of ancillary molecular testing. Primary central nervous system melanomas, including uveal melanomas, frequently exhibit mutations in GNAQ and GNA11, rare in the cutaneous and mucosal counterparts.A case of a primary leptomeningeal melanoma of the cerebellopontine angle is described. Molecular studies identified a GNA11 p.Q209L and a KIT p.M541L missense variant, with losses of chromosomes 1p and 3p demonstrated with cytogenetic studies. Complete surgical resection was not possible and leptomeningeal metastatic disease rapidly ensued despite immunotherapy. Further understanding of the molecular signature may translate to improved diagnosis, prognostication and development of targeted therapies.

Voice abnormalities at school age in children born extremely preterm.

BACKGROUND AND OBJECTIVES: Voice abnormality is a frequent finding in school age children born at <25 weeks' gestation in Western Australia. The objective of this study was to determine the frequency of voice abnormality, voice-related quality of life, and demographic and intubation factors in this population. METHODS: Survivors <25 weeks' gestational age in Western Australia born from 1996 to 2004 were included. Voice assessments (auditory perceptual assessment scale and Pediatric Voice Handicap Index) were carried out by speech pathologists. Intubation history was obtained by retrospective chart review. RESULTS: Of 251 NICU admissions, 154 (61%) survived. Exclusions were based on severe disability (11) or distant residence (13). Of 70 assessed, 67 completed assessments, 4 (6%) were in the normal range and 39 (58%) showed moderate-severe hoarseness. Simultaneous modeling of demographic and intubation characteristics showed an increased odds of moderate-severe voice disorder for children who had more than 5 intubations (odds ratio 6.96, 95% confidence interval 2.07-23.40, P = .002) and for girls relative to boys (odds ratio 3.46, 95% confidence interval 1.12-10.62, P = .030). Tube size and duration of intubation were not significant in the multivariable model. Median scores of parent-reported voice quality of life on the Pediatric Voice Handicap Index were markedly different for preterm (22) and term (3) groups, P < .001. CONCLUSIONS: Voice disorders in this population were much more frequent than expected. Further studies are required to assess voice across a broader range of gestational ages, and to investigate voice-protective strategies in infants requiring multiple episodes of intubation.

Objective assessment of pediatric voice disorders with the acoustic voice quality index.

OBJECTIVES/HYPOTHESIS: Instrumental measures of voice allow practitioners to assess the severity of voice disorders and objectively measure treatment outcomes. Instrumental measures should be calculated on both sustained vowel and connected speech samples to ensure ecological validity. However, there is a lack of appropriate, validated acoustic measurements for use in the pediatric population. The Acoustic Voice Quality Index (AVQI) is a multivariate acoustic measure of dysphonia that has been found to be reliable, valid, and have diagnostic accuracy and response to change in an adult population. This study aimed to evaluate the AVQI in a pediatric population. STUDY DESIGN: This study was a prospective observational study of a sample of dysphonic and normophonic children. METHODS: Sixty-seven preterm participants (born at less than 25 weeks gestation) aged between 6 and 15 years were recruited. Participants were excluded because of either inability to comply with task requirements or other speech-related factors that affected acoustic measurement. Forty normophonic term-born participants aged between 5 and 15 years were also recruited. AVQI analysis was conducted on a prolonged vowel sample and a sample of continuous speech. RESULTS: The AVQI was found to have diagnostic accuracy and specificity in this population of children with and without dysphonia. It was moderately correlated with ratings of severity on the GRBAS (overall grade of hoarseness (G), roughness (R), breathiness (B), aesthenicity (A), and strain (S)), a subjective rating scale. The threshold for pathology of this sample of 3.46 showed strong sensitivity, specificity, and accuracy, with good-to-excellent likelihood ratios. CONCLUSIONS: This study found that the AVQI has diagnostic accuracy in a pediatric population, suggesting that it is an appropriate assessment tool to determine the presence and severity of pediatric voice disorders.