Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years.

OBJECTIVE: To compare relapse rates in pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (AOMS) over the first 6-years of disease. METHODS: Patients with relapsing-remitting disease onset were identified from the Partners Pediatric MS Center, Massachusetts General Hospital and Partners MS Center, Brigham and Women's Hospital. 84 POMS and 258 AOMS patients were included. Annualized relapse rates (ARR) for each individual year from year 1 to year 6, after first attack were compared using Poisson regression, as was expanded disability status scale (EDSS) score at the visit closest to each year interval. RESULTS: ARR was significantly higher in POMS compared to AOMS at individual years (except year 4), and was not significantly affected by adjustment for gender, race and proportion of time on treatment. Despite a 2.30 times higher relapse rate over 6-years, EDSS between groups did not differ. ARR in years 1-5 did not impact year 5 disability measured by EDSS in POMS. CONCLUSIONS: Our findings demonstrate that higher ARR in POMS relative to AOMS is sustained over 6-years, suggesting a more inflammatory nature and potential disconnect between relapses and disability measured by EDSS early in POMS. This data may be useful when designing clinical trials for POMS.

Demographic and clinical characteristics of malignant multiple sclerosis.

OBJECTIVE: Multiple sclerosis (MS) that causes patients to require assistance for ambulation (Expanded Disability Status Scale [EDSS] ≥6) within 5 years from symptom onset is generally termed malignant. Malignant status can be transient (TM) or sustained until year 5 (SM). We studied the incidence, predictors, and demographic and clinical characteristics of malignant MS. METHODS: Patients with symptom onset in 2002-2005 and 5-year follow-up were selected from the Partners Multiple Sclerosis Center database. Patients with TM were further grouped into TM and SM. The mechanism of reaching EDSS 6 (relapse- vs progression-related) was determined. RESULTS: A total of 487 patients were included (17 TM, 42 SM). The incidence proportion of ever malignant (EM=SM+TM) was estimated as 12.11% and SM as 8.62%. Patients with older age at onset, male gender, and positive smoking history were more likely to become SM. Compared to nonmalignant patients, the proportion of progressive-onset MS in the SM group was significantly higher, but not different in TM. Within relapsing-onset patients, most of TM, and a smaller proportion of the SM group had a relapse-related as opposed to progression-related mechanism. The final model predictors for EM vs nonmalignant were older age at onset, motor symptoms at onset, and progressive disease onset. Within the malignant patients, predictors of TM vs SM were younger age and brainstem symptoms at onset. CONCLUSIONS: Over 10% of patients with MS experience a malignant course as defined above. Some demographic and clinical factors are found to predict a malignant outcome. MS in patients who reach a high EDSS based on disease progression is more likely to remain malignant.

Role of the nitric oxide pathway and the endocannabinoid system in neurogenic relaxation of corpus cavernosum from biliary cirrhotic rats.

BACKGROUND AND PURPOSE: Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model. EXPERIMENTAL APPROACH: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation. KEY RESULTS: The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB(1) antagonist) or capsazepine (vanilloid VR(1) antagonist), but not AM630 (CB(2) antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups. CONCLUSIONS AND IMPLICATIONS: Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB(1) and vanilloid VR(1) receptors.