Abstracts

LINCL is a fatal, neurodegenerative, childhood, autosomal recessive lysosomal storage disease resulting from mutations in the CLN2 gene. The present study assesses EEG abnormalities before and 2 wk after therapy., Five subjects (2 female, 3 male, ages 3.5 to 6 yr, median 5.5) underwent direct CNS administration (2x10¹² particle units) of AAV2[sub]CU[/sub]hCLN2 through 6 burr holes. Sixteen channel video-EEG recording was performed for 24 hours: 4 days prior to treatment and 14 days after treatment. Quantitative spike analysis was performed during wakefulness for 1 hr of each video-EEG study by 2 readers unblinded as to treatment status. All subjects had a history of generalized convulsions., The initial EEGs showed generalized moderate to high amplitude spike and wave discharges with maximum amplitude occipitally. The background was characterized by diffuse 3-5 Hz rhythmic activity. Features of normal sleep patterns were generally preserved. No patients had electrographic seizures while on monitoring. This EEG background did not change significantly when assessed 2 wk post-gene therapy. The mean spike frequency over 1 hr in 5 subjects prior to gene therapy was 56.6 [plusmn] 15.5 (SD) and the mean spike frequency 2 wk after gene therapy was 38.8 [plusmn] 16.7 (SD; paired samples t-test p=0.006)., Initial evaluation of the effect of AAV2[sub]CU[/sub]hCLN2 on EEGs as assessed by quantitative spike analysis suggests a decrease of epileptiform discharges 14 days post-vector administration. Longer follow-up for assessment of the impact of gene therapy on clinical seizure occurrence is underway., (Supported by Nathan[apos]s Battle Foundation, Greenwood, Indiana.)