Lancet neurology
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Observational Study
Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study.
Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome. ⋯ European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences.
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Duchenne muscular dystrophy is an X-linked disease caused by the absence of functional dystrophin in the muscle cells. Major advances have led to the development of gene therapies, tools that induce exon skipping, and other therapeutic approaches, including treatments targeting molecular pathways downstream of the absence of functional dystrophin. However, glucocorticoids remain the only treatment unequivocally shown to slow disease progression, despite the adverse effects associated with their long-term use. ⋯ Several compounds with promising results in early-phase clinical trials have not met their efficacy endpoints in late-phase trials, but the clinical development of many other compounds is ongoing. The current landscape is complicated by the number of compounds in various stages of development, their various mechanisms of action, and their genotype-specific applicability. The difficulties of clinical development that arise from both the rarity and variability of Duchenne muscular dystrophy might be overcome in the future by use of sensitive biomarkers, natural history data, and ameliorated trial designs.
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Tuberous sclerosis complex is a rare genetic disease associated with mutations in the TSC1 or TSC2 genes, which cause overactivation of the mTOR complex. In the past 5 years, understanding has increased of the cellular consequences of TSC1 and TSC2 genetic variants and the mTORC1 overactivation in neurons and glial cells and their contribution to network dysfunction. Infants and young children (aged 1-5 years) with tuberous sclerosis complex might now benefit from early assessment of gene variant status and mosaicism. ⋯ Vigabatrin has been used successfully as a treatment in infants with tuberous sclerosis complex who showed abnormalities on EEG before seizure onset. The scope for mitigation of tuberous sclerosis complex-associated symptoms has expanded, including the use of mTOR inhibitors such as sirolimus and everolimus. Close cooperation between clinical and basic neuroscientists has provided new opportunities for future advances.