Central vein sign: A diagnostic biomarker in multiple sclerosis (CAVS-MS) study protocol for a prospective multicenter trial.

The specificity and implementation of current MRI-based diagnostic criteria for multiple sclerosis (MS) are imperfect. Approximately 1 in 5 of individuals diagnosed with MS are eventually determined not to have the disease, with overreliance on MRI findings a major cause of MS misdiagnosis. The central vein sign (CVS), a proposed MRI biomarker for MS lesions, has been extensively studied in numerous cross sectional studies and may increase diagnostic specificity for MS. CVS has desirable analytical, measurement, and scalability properties. "Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS)" is an NIH-supported, 2-year, prospective, international, multicenter study conducted by the North American Imaging in MS Cooperative (NAIMS) to evaluate CVS as a diagnostic biomarker for immediate translation into clinical care. Study objectives include determining the concordance of CVS and McDonald Criteria to diagnose MS, the sensitivity of CVS to detect MS in those with typical presentations, and the specificity of CVS among those with atypical presentations. The study will recruit a total of 400 participants (200 with typical and 200 with atypical presentations) across 11 sites. T2*-weighted, high-isotropic-resolution, segmented echo-planar MRI will be acquired at baseline and 24 months on 3-tesla scanners, and FLAIR* images (combination of FLAIR and T2*) will be generated for evaluating CVS. Data will be processed on a cloud-based platform that contains clinical and CVS rating modules. Imaging quality control will be conducted by automated methods and neuroradiologist review. CVS will be determined by Select6* and Select3* lesion methods following published criteria at each site and by central readers, including neurologists and neuroradiologists. Automated CVS detection and algorithms for incorporation of CVS into McDonald Criteria will be tested. Diagnosis will be adjudicated by three neurologists who served on the 2017 International Panel on the Diagnosis of MS. The CAVS-MS study aims to definitively establish CVS as a diagnostic biomarker that can be applied broadly to individuals presenting for evaluation of the diagnosis of MS.

Acute disseminated encephalomyelitis in China, Singapore and Japan: a comparison with the USA.

BACKGROUND AND PURPOSE: Ethnicity-related differences in the incidence of acute disseminated encephalomyelitis (ADEM) and other demyelinating diseases including multiple sclerosis and neuromyelitis optica spectrum disorders have been reported. Little is reported on the influence of ethnicity and geographical location in ADEM. METHODS: Medical records of patients who presented with ADEM (ICD-9 323.61 and 323.81) at large referral hospitals in China, Singapore and Japan (years 1992-2015) were retrospectively reviewed and data were collected in a centralized database. Presenting features and outcomes of ADEM were compared between this multi-country Asian cohort and a uniformly collected US cohort using risk differences and risk ratios. Both cohorts were standardized to a 35% pediatric population to facilitate the comparison. RESULTS: There were 83 Asian patients (48 male, 16 pediatric) followed for a median of 2 (25th-75th percentile 1-10) months. Asian patients exhibited a 26% higher prevalence of spinal cord involvement on magnetic resonance imaging [95% confidence interval (CI) 0-52%; P = 0.05; 63% vs. 37%], a 39% lower prevalence of preceding events (95% CI 12-65%; P < 0.01; 33% vs. 72%) and a 23% lower prevalence of corpus callosum involvement (95% CI 7-39%; P < 0.01; 8% vs. 31%). No difference was observed between the two cohorts in the probability of relapse over the first year after disease onset. CONCLUSIONS: It is hypothesized that the high proportion of Asian patients with spinal cord lesions relates to genetic vulnerability or the higher incidence of neuromyelitis optica spectrum disorders in Asia or could be a spurious association. ADEM presentations most probably vary across geographical settings or ethnicities.

Elevation of serum luteinizing hormone levels during hydrocortisone treatment in infant girls with 21-hydroxylase deficiency.

During the first months of postnatal life serum luteinizing hormone (LH) levels in girls are lower than in boys. The mechanism of this sex difference is not known. In order to study the possible influence of high levels of androgens and other adrenal steroids on serum gonadotropins during the first months of life, nine girls with salt-losing congenital adrenal hyperplasia (CAH), mean +/- SD age 17.1 +/- 7.52 days at diagnosis, were studied before and during oral hydrocortisone replacement therapy for 45.7 +/- 29.8 days. A control group of 16 girls (C1) and 15 boys (C2), mean ages 41.7 +/- 33.6 and 59.3 +/- 43.3 days, respectively, was also studied. Serum LH and follicle stimulating hormone (FSH) were determined by enzymoimmunoassay in the presence of one monoclonal and one polyclonal antibody. In treated girls with CAH, mean +/- SD LH (3.49 +/- 4.82 IU 1-1) was significantly higher than in C1, (0.47 +/- 0.38) p < 0.02, and similar to C2 (2.52 +/- 1.74), while mean +/- SD serum FSH (3.72 +/- 1.78 IU l-1) was not different from C1 (6.57 +/- 5.23). The mean +/- SD serum FSH/ serum LH ratio (2.53 +/- 1.44) was lower than in C1 (14.9 +/- 13.6) and similar to C2 (1.60 +/- 1.69). These data suggest that high levels of foetal and/or perinatal adrenal steroids, probably androgens, might modulate gonadotropin secretion after the neonatal period. The fact that, after adrenal steroid suppression, serum LH and the serum FSH/serum LH ratio in these infant girls with CAH were similar to that of control boys suggests that foetal or perinatal androgenic steroids have an effect on the control of LH secretion that persists after androgen withdrawal.

Serum concentrations of follicle stimulating hormone and luteinizing hormone in normal girls and boys during prepuberty and at early puberty.

Serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) morning levels were determined in 327 normal prepubertal and early pubertal children of both sexes, utilizing a highly sensitive and specific microparticle enzyme immunoassay. Female (F) and male (M) prepubertal (Tanner's stage I) subjects were divided into 4 age groups: less than 3 months (F1, M1), 3 to 12 months (F2, M2) 12 to 24 months (F3, M3) and older than 24 months (F4 and M4). F pubertal subjects were classified in Tanner's stage breast II (F5) and III F6), while M pubertal subjects belonged to Tanner's stage genitalia II (M5). Serum LH levels were relatively low in prepubertal girls and showed a significant increment in group F6. By contrast, serum LH levels were relatively high in M1 and M2, decreased to levels similar to F in M3 and M4, and increased again at puberty in M5. Serum FSH levels were relatively high in girls of all prepubertal groups, even though they decrease significantly in M4. An increase was detected in pubertal group M6. All M prepubertal groups had significantly lower FSH levels than F prepubertal groups. The high serum LH of boys during the first year of life is probably a consequence of an activation of the hypothalamic GnRH pulse generator that is not apparent in girls. On the other hand, the high serum FSH of prepubertal girls is probably a consequence of a weak restraint influence of the prepubertal ovary on pituitary FSH secretion. This sexual dimorphism in gonadotropin secretion regulates, in a sex-specific fashion, prepubertal gonadal function in the two sexes.