Abstracts

Rationale: Practitioners often ask-- do focal spikes or sharp waves mean secondary bilateral synchrony symptomatic of a lesion in patients with diffuse spike wave complexes? In the same vein, practitioners wonder about the significance of diffuse well formed spike wave complexes found in routine EEGs of patients without epilepsy? Do these individuals have clinical epilepsy? Methods: To address these questions, we performed EEGs in 211 members belonging to multiplex multigenerational families of four patients with JME (juvenille myoclonic epilepsy). We screened for mulations in myoclonin 1 / EFHC1 in families one and two and performed whole exome sequencing in families 3 and 4. EEGs were 30 minutes in duration and included photic stimulation. Most were obtained in the awake and drowsy state, not all of them had hyperventilation performed. Asymptomatic members with epileptiform EEGs did not have video EEGs. Results: 27 members of family 1 had EEGs. Family 1 was negative for myoclonin 1/EFHC1 mutation. The proband and 2 clinically affected members had 3-4Hz spikewave complexes. 2 other affected members had 4-6Hz PSW and 2 others had irregularly formed diffuse sharp and slow waves with spikes. 3 clinically asymptomatic members had 4-6 Hz polyspike waves while 2 other asymptomatics had irregularly formed 5 Hz spike and multispike waves. 5 clinically asymptomatic members had focal spikes while two had bifrontal spikes. 32 members of family 2 had EEGs. Four symptomatic members with myoclonin1/ EFHC1 mutations had 3-4 Hz spike waves. Seven with mutations were asymptomatic but had 3-6 Hz polyspike waves. Two asymptomatic with mutations had focal T3/T5 or F7 spikes. 33 members of family 3 had EEGs. 5 affected members with myoclonin 3 mutations had 4-6 Hz polyspike wave while 4 asymptomatic individuals with mutations had 4-6 Hz polyspike waves. 119 members of family 4 had EEGs. Family 4 with myoclonin 4 mutations had 11 clinically affected members, five with 4-6 Hz polyspike waves and six with 3Hz spikewaves. Amongst the thirteen asymptomatics with myoclonin 4 mutation, 11 had 3-4 Hz polyspike waves and 2 had temporal spikes. Conclusions: Focal spikes or sharp waves can be the expression of the JME genotype even when the individuals are clinically asymptomatic. Focal spikes or sharp waves in patients with spike wave complexes do not necessarily mean secondary bilateral synchrony. Diffuse 3-4Hz spikewave or 4-6Hz polyspike waves or bifrontal spikes can also be the expression of the JME genotype in clinically asymptomatic family members. Classic JME probands and family members have 4-6Hz polyspike waves, while CAE (childhood absence epilepsy) evolving into JME probands and family members have both 3Hz spike wave and 4-6 Hz polyspike waves. More EEG studies should be performed in families with proven JME mutations.