Oligodencrocytes (OLs) are the main glial cells of the central nervous system involved in myelination of axons. In multiple sclerosis (MS), there is an imbalance between demyelination and remyelination processes, the last one performed by oligodendrocyte progenitor cells (OPCs) and OLs, resulting into a permanent demyelination, axonal damage and neuronal loss. In MS lesions, astrocytes and microglias play an important part in permeabilization of blood-brain barrier and initiation of OPCs proliferation. Migration and differentiation of OPCs are influenced by various factors and the process is finalized by insufficient acummulation of OLs into the MS lesion. In relation to all these processes, the author will discuss the potential targets for remyelination strategies.
12 May 2024 in Journal of the Neurological Sciences
Cerebral cavernous malformations (CCMs) are abnormally packed blood vessels lined with endothelial cells, that do not exhibit intervening tight junctions, lack muscular and elastic layers and are usually surrounded by hemosiderin and gliosis. CCMs may be sporadic or familial autosomal dominant (FCCMs) caused by loss of function mutations in CCM1 (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10) genes. In the FCCMs, patients have multiple CCMs, different family members are affected, and developmental venous anomalies are absent. CCMs may be asymptomatic or may manifest with focal neurological deficits with or without associated hemorrhage andseizures. Recent studies identify a digenic "triple-hit" mechanism involving the aquisition of three distinct genetic mutations that culminate in phosphatidylinositol-3-kinase (PIK3CA) gain of function, as the basis for rapidly growing and clinically symptomatic CCMs. The pathophysiology of CCMs involves signaling aberrations in the neurovascular unit, including proliferative dysangiogenesis, blood-brain barrier hyperpermeability, inflammation and immune mediated processes, anticoagulant vascular domain, and gut microbiome-driven mechanisms. Clinical trials are investigating potential therapies, magnetic resonance imaging and plasma biomarkers for hemorrhage and CCMs-related epilepsy, as well as different techniques of neuronavigation and neurosonology to guide surgery in order to minimize post-operatory morbidity and mortality. This review addresses the recent data about the natural history, genetics, neuroimaging and therapeutic approaches for CCMs.
Hematopoietic cell transplantation (HCT) is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen (HLA)-matched donor (allogeneic) or from the patient (autologous). Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease (GvHD). Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, GvHD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT: (1) early complications (in the first month) - related to harvesting of stem cells, during conditioning (drug toxicity, posterior reversible encephalopathy syndrome), related to pancytopenia, (2) intermediate phase complications (second to sixth month) - central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus, (3) late phase complications (after sixth month) - neurological complications of GvHD, second neoplasms and relapses of the original disease.
1 May 2015 in Journal of the Neurological Sciences
The aim of the COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel (COSMOS) was to assess the use of levodopa/carbidopa intestinal gel (LCIG) as monotherapy in patients with advanced Parkinson’s disease (APD) in routine clinical practice. COSMOS was an international observational study with one cross-sectional visit and retrospective data collection. In Romania, 95 adult patients with APD on LCIG treatment for at least 12 months were enrolled and stratified according to their LCIG therapy after 12 months: monotherapy (without any add-on PD medication), monotherapy with night PD medication and LCIG + add-on medication. Compared to the moment of LCIG initiation, the percentage of patients on monotherapy increased at three months after LCIG initiation and remained constant up to 12 months, when 30.5% of the patients were on LCIG monotherapy and 11.6% were on monotherapy with night medication. “Off” time and “On” time with dyskinesia decreased from LCIG initiation to patient visit in all groups. LCIG monotherapy with or without night medication may provide a simplified treatment option for selected APD patients, with long-term efficacy similar to that of LCIG plus add-on medication.