Abstracts

Epileptic seizure is one of the main features of Menkes disease, an X-linked recessive disorder of copper transport that is typically lethal by age three years. Two prior published series that reported symptomatic Menkes disease patients indicated normal EEG findings in 2/9 (22%) (White et al., 1992), and in 0/12 (0%) (Bahi-Buisson et al., 2006). The current study describes EEG findings in 24 patients prospectively diagnosed with Menkes disease during the asymptomatic neonatal period who received very early copper histidine treatment., From 1992-2006, 24 patients with classical Menkes disease diagnosed as newborns by plasma catechol levels (Kaler et al., 1993) or by genomic DNA-based techniques (Liu et al., 2002) began daily subcutaneous copper histidine injections within 10 days of age, in the absence of neurological symptoms, under a NIH intramural research program clinical protocol. EEGs and subsequent seizure occurrence were monitored., The patients underwent from 1 to 7 (2.7 [plusmn] 1.7) EEGs during follow-up or until death. Mean follow-up time was 22.6 [plusmn] 25.0 months. 14/24 (58%) patients had normal EEGs at a mean age of 22.5[plusmn] 28.4 months. 10/24 patients (42%) had abnormal EEG recordings. Three patients had clinical seizures and received anti-epileptic drugs. Two other patients had events (apnea, jittery movements) suspicious for seizure activity. One patient had a seizure within 48 hrs of DPT vaccination. Abnormal EEG findings included background slowing or disorganization, focal slowing mainly in the posterior head region, focal spike-waves or poly-spikes (with half of cases in the occipital region), and diffuse spike and slow waves. Two patients had several runs of electrographic events with and without clinical seizure symptoms., Compared to cohorts of older Menkes disease patients who did not have the benefit of early diagnosis and very early copper replacement treatment, our findings indicate that neonatal diagnosis and institution of copper replacement therapy improves EEG spectrum and decreases seizure occurrence in this difficult neurogenetic disorder.,