Refractory Epilepsy Associated With Microglial Activation
ABSTRACT Experimental and clinical studies support a pathogenic role of microglial activation and proliferation (MAP) in epileptogenesis.
From a consecutive series of 319 surgically treated epilepsy cases, we retrospectively reviewed the histopathological sections of 92 cases to define the prevalence and severity of MAP after excluding the other 227 because of coexisting disorders that might contribute to MAP. Severity of MAP was compared with underlying abnormalities. We assessed the response to intravenous immunoglobulin and plasmapheresis in one patient with severe MAP who had failed multiple antiepileptic drugs and epilepsy surgery.
MAP was detected with routine (hematoxylin and eosin) stain in 46 of 92 cases (50%). MAP was mild in 32 cases (69.6%), moderate in 12 (26.1%), and severe in 2 (4.3%). The prevalence and severity of MAP were independent of underlying abnormalities. Immunomodulatory therapy was followed by a greater than 90% reduction in seizure activity in the treated patient.
MAP is prevalent in resected human epilepsy tissue. Failure to down-regulate MAP contributes to chronic neuronal hyperexcitability. We hypothesize that MAP initiates a cycle of inflammation-induced seizures and seizure-induced inflammation. Microglia-driven epilepsy may be a primary pathogenic process in a small number of cases, as suggested by the pathology and therapeutic response in our patient, but may contribute to epileptogenesis in many more.
SourceAvailable from: Waldemar Brola[Show abstract] [Hide abstract]
ABSTRACT: Introduction: Epilepsy is one of the most common neurological illnesses occurring in children. In approximately 20–30% of cases it is drug-resistant. Aim of the research: To assess the already-known risk factors, analyse the rarely described ones, and find new causes of epilepsy drug resistance in children, taking into account the level of impact of each factor. Material and methods: The study comprised 152 of all 383 children hospitalised in 2012 at the Neurology Department of the Polish Mother's Memorial Hospital in Lodz due to epilepsy. Based on medical documentation, neurological examination, and our own questionnaire, we divided patients into two groups: drug-resistant epilepsy or drug-sensitive epilepsy. We com-pared the type, level of influence, and prevalence of different factors. For statistical analysis, the χ 2 test was used. Statistical significance was set at p < 0.05. Results: Drug-resistant epilepsy was found in 64 patients (42.1%), and drug-sensitive epilepsy was found in 88 patients (57.9%). Factors that were most probable to cause drug resistance included: high prevalence of seizures (Cramer's V = 0.66), type of epileptic syndrome (V = 0.62), psychomotor developmental delay (V = 0.62), and occurrence of status epilepticus (V = 0.6). Factors such as infections of CNS in early childhood, repeated severe infections of airways in childhood, and mother's infectious diseases with high fever during pregnancy were rare or non occurring (Cramer's V = 0.41, 0.32, and 0.31, respectively). Conclusions: The study confirmed the previously known causes of drug resistance and indicated the significance of under-estimated inflammatory and infectious factors involving pyrexia, in children and also in mothers during pregnancy.01/2014; 30(3):141-147. DOI:10.5114/ms.2014.45418
[Show abstract] [Hide abstract]
ABSTRACT: The factors underlying epilepsy are multifaceted, but recent research suggests that the brain's neural circuits, which play a key role in controlling the balance between epileptic and antiepileptic factors, may lie at the heart of epilepsy. This article provides a comprehensive review of the neural mechanisms and potential treatment of intractable epilepsy from neural inflammatory responses, melanocortin circuits in brain and pedunculopontine tegmental nucleus. Further studies should be undertaken to elucidate the nature of neural circuits so that we may more effectively apply these new preventive and symptomatic therapies to the patient suffering from medically refractory seizures and its complications.American Journal of Translational Research 01/2014; 6(6):625-30. · 3.23 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells (ECs) together with neurons and glial cells, including microglia, forms the neurovascular unit (NVU). The crosstalk between these cells guarantees a proper environment for brain function. In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function. On the other hand, the endothelium can regulate the state of microglial activation. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders.Frontiers in Cellular Neuroscience 11/2014; 8:362. DOI:10.3389/fncel.2014.00362 · 4.18 Impact Factor