Abstracts

Rationale: Angelman Syndrome (AS) is a genetic neurodevelopmental disorder caused by functional loss of the Ube3a gene. AS patients have intellectual disability, speech deficits, motor dysfunction, and may have epilepsy that can be severe and resistant anti-epileptic drugs. EEG recordings provide a qualitative assessment of epileptiform activity and humans with AS often have stereotyped EEG background abnormalities. Quantification of intrinsic background EEG activity using spectral analysis is proposed as a consistent biomarker and outcome measure in pre-clinical and clinical studies for AS. Spectral analysis of EEG recordings from human AS subjects reveal prominent increases within delta and theta frequency bands in areas important for cognitive function. A small clinical study recently showed significant improvements in communication, cognitive, and fine motor function in AS children treated with minocycline for eight weeks. These studies used qualitative EEG analysis at baseline following minocycline treatment. Methods: EEG records (standard 10-20 system) were analyzed from 17 children aged 5-12 with Angelman syndrome that received minocycline for eight weeks. EEG recordings were taken prior to start of minocycline treatment (T1), at the end of treatment (T2) and 8 weeks after end of treatment (T3). EEG records from 11 neurotypical children aged 5-15 that were not part of the clinical study and did not receive minocycline were also analyzed for comparison. Spectral analysis was conducted on referenced Fp2, T4, O2 and C4 channels using Labchart 8. Spike counts were obtained by spike histogram analysis on an average of 31 min. EEG recordings from AS subjects taken prior to and after minocycline treatment.  Results: Absolute and relative spectral power within the delta and theta bands in AS subjects were significantly higher compared to neurotypical controls (p < 0.05) while higher frequency bands (alpha, beta, gamma) were decreased (p < 0.05). Whereas, relative spectral power in Fp2 channel remained unchanged after minocycline treatment, absolute spectral power was reduced (T1 vs. T3; p < 0.05). Absolute spectral power showed a reduction of delta and theta frequencies after minocycline treatment in frontal and temporal regions. Furthermore, polyspike counts, an indicator of epileptiform activity, were significantly reduced after minocycline treatment (p < 0.01). Conclusions: These studies extend previous findings on the positive effect of minocycline in AS showing that EEG spectral power in AS improves with minocycline therapy, paralleling cognitive improvement. We also have data suggesting that minocycline improves interictal epileptiform activity. Funding: FAST