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Background and Purpose: Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD., Methods: A meta-analysis of an N-of-1 prospective, randomized, double-blind, multicenter DBS study was conducted at two French WD reference centers. Main inclusion criteria were patients with WD, stabilized for at least 6 months with significant disability due to dystonia despite optimized medical treatment. The subthalamic nucleus (STN) was targeted for bradykinetic patients with tonic dystonia, and the internal globus pallidus (GPi) was chosen for patients with hyperkinetic dystonia. Each patient underwent two periods of DBS "on" and two periods of DBS "off," each lasting 4 months. The order of stimulation conditions was randomized. The primary outcome was the change in the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores after each 4-month period. Secondary outcomes were changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores and Unified Wilson's Disease Rating Scale (UWDRS) scores., Results: Between 12 May 2016 and 7 October 2022, three patients were included. Two patients received bilateral GPi DBS, and one received bilateral STN DBS. There was no change of COPM-P (p = 0.956), BFMDRS, and UWDRS scores. No serious adverse events were reported., Conclusions: STN or GPi DBS are ineffective on dystonia related to WD., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: To describe utilization of health services for, and case fatality from, abortion in Mexico., Method: A historical cohort study using a census of state-level aggregate hospital discharge and primary care clinic data across Mexico's 32 states from January 2000 to December 2016. Abortive events and changes over time in utilization per 1000 women aged 15-44 years, and case fatality per 100 000 abortion-related events were described by year, health sector, and state. Associations of location (Mexico City vs 31 other states) and time (Mexico City implemented legal abortion services in 2007) with outcomes were tested by linear regression, controlling for secular trends., Results: The national abortion utilization rate was 6.7 per 1000 women in 2000, peaked at 7.9 in 2011, and plateaued to 7.0 in 2016. In Mexico City, utilization peaked at 16.7 in 2014 and then plateaued. Nationwide, the case-fatality rate declined over time from 53.7 deaths per 100 000 events in 2000 to 33.0 in 2016. Case fatality declined more rapidly in Mexico City than in the other 31 states to 12.3 in 2015., Conclusion: Case fatality from abortive events has decreased across Mexico. Where abortion became legal, utilization increased sharply but plateaued afterward., (© 2019 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Lysosomal storage diseases (LSDs) are inborn errors of metabolism resulting from 50 different inherited disorders. The increasing availability of treatments and the importance of early intervention have stimulated newborn screening (NBS) to diagnose LSDs and permit early intervention to prevent irreversible impairment or severe disability. We present our experience screening newborns in North East Italy to identify neonates with Mucopolysaccharidosis type I (MPS I) and Pompe, Fabry, and Gaucher diseases., Methods: Activities of acid β-glucocerebrosidase (ABG; Gaucher), acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), and acid α-L-iduronidase (IDUA; MPS-I) in dried blood spots (DBS) from all newborns during a 17-month period were determined by multiplexed tandem mass spectrometry (MS/MS) using the NeoLSD ® assay system. Enzymatic activity cutoff values were determined from 3500 anonymous newborn DBS. In the screening study, samples were retested if the value was below cutoff and a second spot was requested, with referral for confirmatory testing and medical evaluation if a low value was obtained., Results: From September 2015 to January 2017, 44,411 newborns were screened for the four LSDs. We recalled 40 neonates (0.09%) for collection of a second DBS. Low activity was confirmed in 20, who had confirmatory testing. Ten of 20 had pathogenic mutations: two Pompe, two Gaucher, five Fabry, and one MPS-I. The incidences of Pompe and Gaucher diseases were similar (1/22,205), with Fabry disease the most frequent (1/8882) and MPS-I the rarest (1/44411). The combined incidence of the four disorders was 1/4411 births., Conclusions: Simultaneously determining multiple enzyme activities by MS/MS, with a focus on specific biochemical markers, successfully detected newborns with LSDs. The high incidence of these disorders supports this screening program.

Introduction: Niemann-Pick type C disease is a rare disorder caused by impaired intracellular lipid transport due to mutations in either the NPC1 or the NPC2 gene. Ninety-five % of NPC patients show mutations in the NPC1 gene. A much smaller number of patients suffer from NPC2 disease and present respiratory failure as one of the most frequent symptoms. Several plasma oxysterols are highly elevated in NPC1 and can be used as a biomarker in the diagnosis of NPC1., Methods: Plasma cholestane-3β,5α,6β-triol was evaluated as biomarker for NPC2 by GC/MS and LC-MS/MS analysis. The diagnosis was confirmed by Sanger sequencing and filipin staining., Results: We report three NPC2 patients with typical respiratory problems and a detailed description of the nature of the lung disease in one of them. All patients had elevated levels of plasma cholestane-3β,5α,6β-triol. In two of these patients, the positive oxysterol result led to a rapid diagnosis of NPC2 by genetic analysis. The phenotype of the third patient has been described previously. In this patient a cholestane-3β,5α,6β-triol concentration markedly above the reference range was found., Conclusions: Measurement of plasma cholestane-3β,5α,6β-triol enables to discriminate between controls and NPC1 and NPC2 patients, making it a valuable biomarker for the rapid diagnosis not only for NPC1 but also for NPC2 disease.The measurement of oxysterols should be well kept in mind in the differential diagnosis of lysosomal diseases, as the elevation of oxysterols in plasma may speed up the diagnosis of NPC1 and NPC2.

To document the relative contribution of abortion-related deaths to overall maternal deaths in Mexico, official mortality data were analyzed according to International Classification of Diseases (ICD) codes. During 1990-2008, among 24 805 maternal deaths, 1786 (7.2%) were abortion related. Of these, 13.2% occurred in adolescents and 65% in uninsured women; 60% were probably associated with unsafely induced procedures. The study calculated the number of abortion-related deaths per 100,000 abortion-related hospitalizations, expressed as a modified abortion case-fatality rate. During 2000-2008, this rate was 48 at the national level, with wide variations among states: from 140 deaths in Guerrero to 8 in Baja California Sur per 100,000 abortion hospitalizations. Unsafe abortion continues to represent a significant proportion of all maternal deaths in Mexico., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)