Safety and efficacy of rivastigmine in adolescents with Down syndrome: long-term follow-up.

Following the completion of a 20-week, open-label study of the safety and efficacy of liquid rivastigmine for adolescents with Down syndrome, 5 of the 10 adolescents in the clinical trial continued long-term rivastigmine therapy and 5 did not. After an average period of 38 months, all 10 subjects returned for a follow-up assessment to determine the safety and efficacy of long-term rivastigmine use. Rivastigmine was well tolerated and overall health appeared to be unaffected by long-term rivastigmine use. Performance change on cognitive and language measures administered at the termination of the open-label clinical trial was compared between the two groups. No between-group difference in median performance change across the long-term period was found, suggesting that the long-term use of rivastigmine does not improve cognitive and language performance. However, two subjects demonstrated remarkable improvement in adaptive function over the long-term period. Both subjects had received long-term rivastigmine therapy. The discussion addresses the challenge of assessing cognitive change in clinical trials using adolescents with Down syndrome as subjects and the use of group versus individual data to evaluate the relevance of medication effects

Postmortem Findings and Clinical Correlates in Individuals with Infantile-Onset Pompe Disease

Pompe disease (OMIM 232300), a glycogen storage disorder caused by deficiency in the lysosomal enzyme acid alpha-glucosidase (EC 3.2.1.20), results in weakness and cardiomyopathy in infants affected with the classic form. Although the primary disease manifestations are due to glycogen accumulation in skeletal and cardiac muscle, glycogen also accumulates in a variety of additional tissues. To improve our understanding of disease pathogenesis in long-term survivors, we reviewed postmortem results for three infants with the classic form of Pompe disease. We have observed a number of new complications in long-term survivors of infantile-onset Pompe disease, and we focused this postmortem study on pathological correlates. Findings in survivors include cardiac arrhythmias, which may be related to glycogen accumulation in cardiac conduction tissue; urinary incontinence, likely due to glycogen accumulation in smooth muscle; and refractory errors, possibly related to accumulation in ocular structures. These observations provide potential pathophysiologic correlates for complications in long-term survivors of infantile Pompe disease

Swiss national guideline for reimbursement of enzyme replacement therapy in late-onset Pompe disease

Glycogen storage disease type II is a rare multi-systemic disorder characterised by an intracellular accumulation of glycogen due a mutation in the acid alpha glucosidase (GAA) gene. The level of residual enzyme activity, the genotype and other yet unknown factors account for the broad variation of the clinical phenotype. The classical infantile form is characterised by severe muscle hypotonia and cardiomyopathy leading to early death. The late-onset form presents as a limb girdle myopathy with or without pulmonary dysfunction. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) in infants is life saving. In contrast, therapeutic efficacy of rhGAA in the late-onset form is modest. High expenses of rhGAA, on-going infusions and poor pharmacokinetic efficacy raised a discussion of the cost effectiveness of ERT in late-onset Pompe disease in Switzerland. This discussion was triggered by a Swiss federal court ruling which confirmed the reluctance of a health care insurer not to reimburse treatment costs in a 67-year-old female suffering from Pompe disease. As a consequence of this judgement ERT was stopped by all insurance companies in late-onset Pompe patients in Switzerland regardless of their clinical condition. Subsequent negotiations lead to the release of a national guideline of the management of late-onset Pompe disease. Initiation and limitation of ERT is outlined in a national Pompe registry. Reimbursement criteria are defined and individual efficacy of ERT with rhGAA is continuously monitored