Abstracts

Rationale: Ohtahara syndrome (OS), early myoclonic encephalopathy (EME), migrating partial seizures in infancy (MPSI), and Dravet syndrome (DS) are the severe early infantile epileptic encephalopathies (SEIEE). Seizures (Sz) do not respond to conventional antiepileptic drugs (AEDs) and it is very difficult to achieve Sz freedom. Bromide has very unique mechanism of action, hyperpolarization of postsynaptic membranes, which is not seen in other AEDs. We have experienced excellent efficacy of bromide for some SEIEE cases, and proceeded to ascertain the efficacy of bromide for SEIEE.Methods: Potassium bromide (KBr) was added on or switched to SEIEE patients who had not responded to many conventional AEDs. The subjects consisted of 9 cases of OS, 8 cases of EME, 11 cases of MPSI, and 10 cases of DS with onset at 0 day-8 months (mo), and were followed-up for 1-9 years (yr) on KBr. KBr was initiated at 2 mo-8 yr except at 16-25 yr in 3 cases, and its efficacy was finally evaluated at 1.3-13 yr except at 22-31 yr in 3 cases. KBr was started at 20-30mg/kg and increased by 5-10mg every 2 weeks up to 50mg/kg and thereafter by 5mg/kg every 2 weeks up to 70mg/kg to avoid side effects by rapid titration. Sz outcome was evaluated at 3 mo after introduction of KBr (short-term efficacy) and at the last observation (long-term efficacy), and side effects were delineated. Sz outcome was classified into seizure free (SF), Sz reduction by 75-99% (markedly effective: ME), by 50-74% (effective: EF) and by < 50% (Ineffective: IE). In long-term follow-up, epochs with >1 year SF during the follow-up period (SF-epoch) was also counted in patients showing ME, EF or IE. Results: 1) Short-term efficacy: SF/ME/EF/IF was 0/3/6/0 in OS, 2/5/1/0 in EME, 9/2/0/0 in MPSI and 5/6/0/0 in DS. 2) Long-term efficacy: SF/ME/EF/IF/Discontinued was 1/3/3/0/2 in OS, 1/1/0/0/6 in EME, 4/1/2/0/4 in MPSI and 3/5/1/0/2 in DS. KBr was discontinued because of death by mainly respiratory infection or insufficiency in 6 cases in EME, one each in MPSI and DS, ineffectiveness and increased secretion one each in OS, decreased activity, bromoderma and severe acneform eruptions one each in MPSI and bromoderma in one case in DS. 3) SF-epoch was seen in no case in OS, 1 case in EME, 2 cases in MPSI and 4 cases in DS. 4) Overall side effects included decreased activity in 4 cases, severe acneform eruptions in 2 cases, bromoderma in 2 cases, and increased secretion in 1 case, mainly with high dose (>60mg/kg) and long use of KBr. These side effects could be managed by discontinuation or reduction of KBr.Conclusions: Bromide is very effective for SEIEE, particularly for MPSI and DS, and side effects are not severe in SEIEE. Very unique mechanism of action of bromide, hyperpolarization of postsynaptic membranes, seems to suppress seizures in SEIEE which do not respond to conventional AEDs with other mechanisms of action.