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The final step in neutrophil bacterial killing is formation of a toxic halide complex. For this reason, we studied neutrophil function in children receiving bromide anticonvulsant therapy. Whole blood and serum were obtained from 7 patients with seizure disorders treated orally with triple bromide elixir to examine neutrophil function as measured by luminol enhanced chemiluminescence (CL). Serum bromide concentrations [Br-] were determined concomitantly. There was a direct correlation between [Br-] and CL activity of neutrophils (r = 0.87) with peak CL responses significantly higher than controls when [Br-] were in the therapeutic range (10-20 mM). With [Br-] above 25 mM, CL activity was reduced. Serum from patients also enhanced CL of control neutrophils with a similar relationship to measured [Br-]. To confirm that enhanced neutrophil activity was attributable to [Br-] use, [Br-] ranging from 0-50 mM were added to control neutrophils in otherwise normal physiologic conditions and the CL assay was performed. Results expressed as percent of control values were as follows: [Br-] 5 mM, 110%; 10 mM, 158%; 15 mM, 194%; 20 mM, 252%; 25 mM, 136%; 30 mM, 364%; and 50 mM, 205%. These data demonstrate that Br- enhances phagocytic and bactericidal activity of neutrophils and suggest that Br- therapy may augment host defense capabilities.

Bromide is not often prescribed today as antiepileptic therapy. One reason is that serum bromide concentrations are not routinely performed in hospital laboratories, making clinical decisions difficult. Because of bromide ion interference with the electrodes of commonly used automated electrolyte analyzers, factitious "hyperchloremia" (and in some cases, "hyperbicarbonatemia"), are produced. These values, and the resulting calculated anion gap, correlate well with the measured serum bromide concentration. The correlation permits results from routine automated electrolyte analyzers to be used to indirectly determine serum bromide concentration.

Triple bromide elixir was used as an adjunctive antiepileptic drug in 11 children whose seizure disorders were intractable to other antiepileptic therapy. The patients' ages ranged from 2 to 17 years. The seizure disorders treated included photosensitive epilepsy (one case), acquired epileptic aphasia (one case), Lennox-Gastaut syndrome (three cases), and symptomatic localization-related epilepsies (six cases). Two patients' seizures completely stopped with bromide therapy. Four patients had a significant and sustained improvement on bromide therapy, while three more had a transient improvement. In these six patients with complete or significant control, the mean therapeutic dose was 33 mg bromide/kg daily, and the mean therapeutic serum concentration was 14.1 mmol/L (range, 4 to 30.5 mmol/L). The combination of bromide with valproate appeared to be particularly effective in these patients. Toxicity was minimal, and in only one patient was the medication stopped, because of anorexia and weight loss. Given the low cost, long half-life, and minimal toxicity when serum bromide concentrations are followed, bromide therapy should be considered as adjunctive antiepileptic drug therapy for patients whose seizures are intractable to other drugs.