Abstracts

RATIONALE: L-Carnosine is an amino acid dipeptide (histidine and alanine), that may indirectly affect spike and wave discharges by altering GABA bioavailability or affecting copper and zinc influx at the cellular level. MRI spectroscopy has recently demonstrated that brain homocarnosine levels may correlate with seizure control. We hypothesized that if dietary carnosine could be ingested to create homocarnosine in the brain, then spike and wave activity would decrease and seizure control should improve. We gave L-Carnosine to four patients as add-on therapy for intractable spike-wave discharge and documented changes in both clinical (overt seizures) and physiological (EEG) status.
METHODS: Seven children (3 female, 4 male, age range 2-12) met inclusion criteria. All had intractable seizures for at least two years, had failed at least 3 anticonvulsants, had documented, abnormal generalized or secondarily generalized spike-wave, atypical absence, or Lennox [ndash]Gastaut Syndrome. All families signed written consent from an IRB approved protocol. All children were evaluated with a Baseline EEG on the same day they were started on 400 mg b.i.d. of L-Carnosine. Post-treatment EEG was undertaken after 10 weeks of L-carnosine therapy. No other concurrent medications were changed.
RESULTS: After 10 weeks of carnosine therapy at 400 mg p.o. b.i.d., 5 of these 7 children had documented improved EEG findings. Changes included decreased frequency of polyspikes (2 children), improved secondarily generalized spike-wave activity(1 child), and improved background and decreased electrographic slow-spike and wave activity ,(2 children). No significant EEG changes occurred in 2 children. Seizure frequency improved in all 7 patients. Although not evaluated formally, improvement in the domains of global cognition, behavior, and language function was reported in all 7 patients. Those domains were not predicted to react to carnosine, and were elicited spontaneously via blinded therapists and family members who noted gains in areas not typically associated with the GABA-ergic system.
CONCLUSIONS: L-Carnosine may be a useful add-on medication for intractable seizure disorders with encephalopathic EEG changes or generalized epileptiform activity. Although the exact mechanism is unknown, L-Carnosine is believed to bind with GABA to form homo-carnosine, and may also modulate copper and zinc influx into the neurons decreasing the after-discharges of spike-wave discharges. Further investigation of the effects and exact mechanisms of L-Carnosine is warranted.