X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Guía para el uso de inmunoglobulina endovenosa en síndrome de Guillan-Barre y neuropatías desmielinizantes crónicas

Fil: Amores, M.. Sociedad Neurológica Argentina; ArgentinaFil: Bertotti, A.. Sociedad Neurológica Argentina; ArgentinaFil: Cueto, A.. Sociedad Neurológica Argentina; ArgentinaFil: Di Egidio, M.. Sociedad Neurológica Argentina; ArgentinaFil: Doumic, J.. Sociedad Neurológica Argentina; ArgentinaFil: Dubrovsky, Alberto. Sociedad Neurológica Argentina; ArgentinaFil: Figueredo, A.. Sociedad Neurológica Argentina; ArgentinaFil: Fulgenzi, E.. Sociedad Neurológica Argentina; ArgentinaFil: Lautre, A.. Sociedad Neurológica Argentina; ArgentinaFil: Losavio, Adriana Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Martinez Alvarez, M.. Sociedad Neurológica Argentina; ArgentinaFil: Mazia, C.. Sociedad Neurológica Argentina; ArgentinaFil: Nacul, R.. Sociedad Neurológica Argentina; ArgentinaFil: Pardal, A.. Sociedad Neurológica Argentina; ArgentinaFil: Pirra, L.. Sociedad Neurológica Argentina; ArgentinaFil: Politei, J.. Sociedad Neurológica Argentina; ArgentinaFil: Reisin, R.. Sociedad Neurológica Argentina; ArgentinaFil: Rey, R.. Sociedad Neurológica Argentina; ArgentinaFil: Rodriguez, G.. Sociedad Neurológica Argentina; ArgentinaFil: Rugiero, M.. Sociedad Neurológica Argentina; ArgentinaFil: Tarulla, A.. Sociedad Neurológica Argentina; ArgentinaFil: Yorio, Alberto. Sociedad Neurológica Argentina; Argentin

Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial

Background: Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. Methods: 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740. Findings: During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33·5%, 95% CI 15·4-51·7; p=0·0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10·9 kPa, 4·6-17·2; p=0·0008) and the non-dominant hand (8·6 kPa, 2·6-14·6; p=0·005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0·011). The incidence of serious adverse events per infusion was 0·8% (9/1096) with IGIV-C versus 1·9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension. Interpretation: This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP

Electrophysiology in chronic inflammatory demyelinating polyneuropathy with IGIV.

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) received immune globulin intravenous, 10% caprylate/chromatography purified (IGIV-C, Gamunex; n=59) or placebo (n=58) every 3 weeks for up to 24 weeks (first period) in a randomized, double-blind, parallel-group, response-conditional, crossover study. Motor and sensory nerves were assessed at baseline and endpoint/week 24. A nonsignificant trend toward improvement in the proximal amplitude of the most severely affected motor nerve was observed with IGIV-C (0.69+/-1.86 mV) versus placebo (0.47+/-2.29 mV), and a greater improvement of 1.08+/-2.15 mV with IGIV-C versus 0.46+/-2.03 mV with placebo (P=0.089) was observed with exclusion of data from Erb's point stimulation. Greater improvements from baseline favoring IGIV-C were observed for 127/142 electrophysiologic parameters. The averaged motor amplitudes from all motor nerves significantly improved with IGIV-C versus placebo [treatment difference, 0.62 mV; 95% confidence interval (CI), 0.05, 1.20; P=0.035], and conduction block decreased significantly (treatment difference, -5.54%; 95% CI, -10.43, -0.64; P=0.027), particularly in the lower limbs. Overall, the data suggest that IGIV-C improves electrophysiologic parameters in CIDP