Authors: Liesbeth De Waele, Lieven Lagae, Djalila Mekahli
Pediatr Nephrol; DOI 10.1007/s00467-014-3027-9
Renal lesions represent the second most significant cause of morbidity and mortality in patients with tuberous sclerosis complex (TSC). Recent advances in the understanding of the pathophysiology of TSC have led to the exploration of new potential therapeutic targets. Clinical trials with mammalian
target of rapamycin (mTOR) inhibitors have demonstrated promising results for several indications, such as renal angiomyolipoma, subependymal giant cell astrocytoma, lymphangioleiomyomatosis and facial angiofibromas. Currently, there is a scarcity of natural history data and randomized, placebo-controlled clinical trials on TSC. Recently, however, recommendations for the diagnostic criteria, surveillance,
and management of TSC patients have been updated. This review focuses on these novel recommendations and highlights the need for multidisciplinary follow-up of this multi-systemic disease.
Authors: Eleonora Aronica, Peter B. Crino
Neurotherapeutics. 2014 Apr;11(2):251-68. doi: 10.1007/s13311-013-0251-0.
Structural abnormalities of the brain are increasing-ly recognized in patients with neurodevelopmental delay andintractable focal epilepsies. The access to clinically well-characterized neurosurgical material has provided a uniqueopportunity to better define the neuropathological, neuro-chemical, and molecular features of epilepsy-associated focaldevelopmental lesions. These studies help to further under-stand the epileptogenic mechanisms of these lesions.Neuropathological evaluation of surgical specimens from pa-tients with epilepsy-associated developmental lesions revealstwo major pathologies: focal cortical dysplasia and low-gradedevelopmental tumors (glioneuronal tumors). In the last fewyears there have been major advances in the recognition of awide spectrum of developmental lesions associated with aintractable epilepsy, including cortical tubers in patients withtuberous sclerosis complex and hemimegalencephaly. As anincreasing number of entities are identified, the developmentof a unified and comprehensive classification represents agreat challenge and requires continuous updates. The presentarticle reviews current knowledge of molecular pathogenesisand the pathophysiological mechanisms of epileptogenesis inthis group of developmental disorders. Both emerging neuro-pathological and basic science evidence will be analyzed,highlighting the involvement of different, but often converg-ing, pathogenetic and epileptogenic mechanisms, which maycreate the basis for new therapeutic strategies in thesedisorders.
Authors: Nataša Jovanov Milošević1, 2, Miloš Judaš1, Eleonora Aronica3,4, Ivica Kostovic1
Prog Brain Res. 2014;214:159-78. doi: 10.1016/B978-0-444-63486-3.00007-4.
The neural extracellular matrix (ECM) provides a supportive framework to differentiating cells and their processes, and regulates morphogenetic events by spatially and temporally relevant localization of signaling molecules and by direct signaling via receptor and/or co-receptor-mediated action. Embryonic and fetal human brain contains large amount and diversity of extracellular matrix components, which is especially prominent in the transient subplate zone, in the crossroads of axonal pathways, at the developing cortex-white matter interface and in the marginal zone. Perinatal and postnatal reorganization of these tissue compartments extends into the second year of life. Developmental changes in the amount and composition of the extracellular matrix (as well as changes in fibre architectonics) are significant for plastic responses to damage as well as for changes in magnetic resonance imaging (MRI) signal intensity of the fetal and early postnatal human brain.
In this chapter we discuss the expression pattern of major components of the fetal ECM of the human brain and the role they play during laminar and connectivity development in healthy brain as well as in the neurodevelopmental disorders. The aim of the chapter is to elucidate ECM-related developmental events as potential models of successful functional recovery after injury and to explore its relevance for diagnostic and therapeutic approaches.
Authors: Sadowski K. , Józwiak S.
Journal of Epileptology, 2014; 22(2):89-98
Manuscript ID: 892079
- Introduction. Epilepsy that is associated with neurocutaneous disorders seriously deteriorates quality of life and cognitive outcome of affected children. Recent advances in epilepsy pathophysiology raise hopes for better treatment results in this difficult group of patients.
- Aim. The aim of this review is to present recent treatment recommendations as well as current research progress in the most frequent neurocutaneous disorders.
- Material and methods. We analyzed PubMed database to select the most prominent and recent (up to 2014 year) publications on the treatment and mechanisms of epilepsy in selected neurocutaneous disorders. We aimed to emphasize evidence-based medicine recommendations as well as basic experimental studies dealing with molecular mechanisms of epileptogenesis.
- Discussion and conclusions. Recent advances in disease-modifying treatment options such as mTOR inhibitors in patients with tuberous sclerosis complex open up new perspectives for neurologists. Traditional resective surgery has still a major role as a treatment of choice in carefully selected cases.
Pediatric Neurology 51 (2014), pp. 758-759