Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

beta-trace Protein (Prostaglandin D Synthase) - ein stabiles und signifikantes Protein in Perilymphe

Objective: Beta-trace protein (beta-TP) has been analysed in human cerebrospinal fluid (CSF) and other body fluids. Beta-trace protein is a very sensitive and specific clinical marker and can confirm reliably the presence of CSF in patients with a suspected CSF leakage.Design: Perilymph specimens from the scala vestibuli (n=10) and from the lateral semicircular canal (n=4) were taken from patients undergoing stapedotomy or surgery for acoustic neuroma. During post-mortem examinations perilymph specimens from the scala vestibuli (n=70), the scala tympani (n=11), endolymph specimens (n=21) and CSF specimens (n=17) were obtained. All specimens were analyzed by a one-dimensional immunoelectrophoresis using a polyclonal, monospecific antibody. Results: Specimens from live surgery showed a mean concentration of 51.5 ± 48.9 mg/l beta-TP in scala vestibuli perilymph. Specimens from post-mortem examinations revealed a mean concentration of 49.1 ± 17.7 mg/l in CSF, 71.9 ± 29.3 mg/l in perilymph and 68.0 ± 21.7 mg/l in endolymph. There was no evidence of a circadian alteration of beta-TP in CSF or inner ear fluids.Conclusions: Our results demonstrated clearly that beta-TP is contained in human perilymph and endolymph. This is the first published data that point out the aptitude of the beta-TP-test in verifying traces of perilymph, a valuable diagnostic tool for the existence of perilymphatic leaks.Ziel: Beta-trace Protein (beta-TP) wurde in der menschlichen Hirnflüssigkeit (Liquor) und in anderen Körperflüssigkeiten nachgewiesen. Beta-trace Protein ist ein sehr sensitiver und spezifischer klinischer Marker und kann die Anwesenheit von Liquor cerebrospinalis in Patienten mit dem Verdacht auf ein Liquorleck sicher nachweisen.Methodik: Perilymph-Probenfrom aus der Scala vestibuli (n=10) und vom lateralen Bogengang (n=4) wurden Patienten abgenommen, die stapedotomiert oder wegen eines Akustikusneurinoms labyrinthektomiert wurden. Auch wurden post mortem humane Perilymph-Probenfrom aus der Scala vestibuli (n=70), der Scala tympani (n=11), Endolymphe (n=21) und Liquorproben (n=17) entnommen. Alle Proben wurden mit einer eindimensionalen Immunoelektrophorese und einem polyclonalen, monospezifischen Antikörper untersucht.Ergebnisse: Die Proben, die während der chirurgischen Eingriffe gewonnen wurden, wiesen eine mittlere Konzentration von 51,5 ± 48,9 mg/l beta-TP in der Perilymphe der Scala vestibuli auf. Proben, die post mortem gewonnen wurden, wiesen eine mittlere Konzentration von 49,1 ± 17,7 mg/l im Liquor, 71,9 ± 29,3 mg/l in der Perilymphe und 68,0 ± 21,7 mg/l in der Endolymphe auf. Ein Hinweis auf einen zirkadianen Rhythmus wurde weder im Liquor noch in der Perilymphe gefunden.Schlussfolgerung:. Unsere Ergebnisse weisen nach, dass beta-TP ohne Ausnahme in der menschlichen Perilymphe und Endolymphe in hoher Konzentration vorkommt. Dies sind die ersten veröffentlichten Daten, die zeigen, dass der beta-TP-Test geeignet ist, auch Spuren von Perilymphe nachzuweisen. Damit steht erstmals ein klinischer Test zum sicheren Nachweis von Perilymphfisteln zur Verfügung

Low interferon gamma producers are better treatment responders. A two years follow-up of interferon beta treated multiple sclerosis patients

As response to interferon beta (IFNB) treatment a 50% reduction of the mean relapse rate compared to pretreatment values has been reported. However, individual responses vary considerably, ranging from no reduction in exacerbation frequency to complete suppression of relapses for at least two years. At the moment valid predictors for IFNB response are lacking. Here we present a prospective evaluation of 33 patients with primary relapsing multiple sclerosis, who were followed for two years of IFNB treatment. A low interferon gamma (IFG) production before treatment predicted a two-year term without exacerbations in 68.8% of cases correctly, whereas a high pretreatment IFG production implied the risk of at least one relapse in the first two years in 70.6%. These preliminary results encourage further evaluation of IFG as predictor of an IFNB treatment response

Low interleukin-10 production is associated with higher disability and MRI lesion load in secondary progressive multiple sclerosis.

Item does not contain fulltextAbnormalities in T-cell-derived cytokine production are a well-known phenomenon in multiple sclerosis (MS). An association between disability and the production of interferon gamma has been demonstrated recently. The present study investigated associations between disability, cytokine production in stimulated blood lymphocytes and magnetic resonance imaging data in 37 patients with the secondary progressive course in the stable phase of the disease. Patients with high interleukin-10 (IL-10) production had significantly lower disability scores (p=0.009) and lower T2 lesion load (p=0.03). Interleukin-10 might not only play a role in the pathological process of multiple sclerosis but has an impact on disease outcome as well

The phenotypic spectrum of PCDH12 associated disorders - Five new cases and review of the literature

PCDH12 is a member of the non-clustered protocadherin family of calcium-dependent cell adhesion proteins, which are involved in the regulation of brain development and endothelial adhesion. To date, only 15 families have been reported with PCDH12 associated disease. The main features previously associated with PCDH12 deficiency are developmental delay, movement disorder, epilepsy, microcephaly, visual impairment, midbrain malformations, and intracranial calcifications. Here, we report novel clinical features such as onset of epilepsy after infancy, episodes of transient developmental regression, and dysplasia of the medulla oblongata associated with three different novel truncating PCDH12 mutations in five cases (three children, two adults) from three unrelated families. Interestingly, our data suggests a clinical overlap with interferonopathies, and we show an elevated interferon score in two pediatric patients. This case series expands the genetic and phenotypic spectrum of PCDH12 associated diseases and highlights the broad clinical variability. © 2021 European Paediatric Neurology Societ