title: Refractory epilepsy associated with microglial activation.
abstract: BACKGROUND
  Experimental and clinical studies support a pathogenic role of microglial activation and proliferation (MAP) in epileptogenesis.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurology, NYU Comprehensive Epilepsy Center, USA. mna1024231@aol.com
authors: Souhel
authors: S
authors: Najjar
authors: Daniel
authors: D
authors: Pearlman
authors: Douglas C
authors: DC
authors: Miller
authors: Orrin
authors: O
authors: Devinsky
mesh_terms: D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D004827:Epilepsy / Q000209:etiology / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000209:etiology; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins; D004247:DNA; D007453:Iodide Peroxidase