title: [Sleepiness:a frequent adverse reaction of antiepileptic drugs in patients with epilepsy after encephalitis/encephalopathy].
abstract: OBJECTIVE
  Patients with epilepsy after encephalitis/encephalopathy (EAE) are often on polytherapy with anti-epileptic drugs (AEDs), and are at risk of adverse reactions. We examined the adverse effects of AEDs, especially sleepiness, in these patients.
  
  
  METHODS
  In this retrospective study, the medical records of 66 patients who were diagnosed with EAE in our hospital were reviewed and the clinical characteristics were analyzed. Immunological biomarkers including cytokines, chemokines, granzyme B, soluble tumor necrosis factor receptor 1, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were also investigated.
  
  
  RESULTS
  The mean onset age of acute encephalitis was 9 years and 1 month and the mean interval from onset of acute encephalitis to onset of epilepsy was 6.4 months. Sleepiness induced by AEDs was observed in 26 of 66 patients (39.3%). The incidence of sleepiness was high in patients treated with clorazepate (75%), lamotrigine (66.7%), and ethosuximide (40%). Comparing the AEDs used by more than 20 patients, the incidence of sleepiness was high for clonazepam (30.4%) and phenytoin (25.8%). IgG, protein, and albumin levels in cerebrospinal fluid were significantly higher in patients affected by sleepiness than in those not affected. IL-8 in cerebrospinal fluid was significantly higher in the group with sleepiness compared to that without. Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels were not different between the two groups.
  
  
  CONCLUSIONS
  Long-lasting blood-brain barrier dysfunction and proliferation of immature vessels induced by IL-8 may contribute to the occurrence of sleepiness as an adverse effect of AEDs in patients with EAE. We recommend to assess for blood-brain barrier dysfunction when choosing AEDs for treating patients with intractable EAE.
authors.affiliation: Department of Pediatrics and Psychiatry, National Epilepsy Center Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka. yukimoga@mch.pref.osaka.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Mogami
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fukuyama
authors.forename: Rumiko
authors.initials: R
authors.lastname: Takayama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ohtani
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.forename: Hideo
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000188:drug therapy*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012890:Sleep / Q000502:physiology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants