Authors :
Presenting Author: Hisako Fujiwara, PhD – Cincinnati Children's Hospital Medical Center
Jeffrey Tenney, MD, PhD – Cincinnati Children's Hospital Medical Center
Paul Horn, PhD – Cincinnati Children's Hospital Medical Center
Rationale:
Single unprovoked seizures are common with 1 in 10 people experiencing one in their lifetime. However, there is no effective way to predict who will develop epilepsy. It has been reported that high frequency oscillations (HFOs) associated with somatosensory evoked field (SEF) is prolonged in some patients with epilepsy. Therefore, it is a potential biomarker to identify those patients with a single unprovoked seizure who will develop epilepsy. It has been proposed that somatosensory HFOs represent localized activity of inhibitory interneurons receiving thalamocortical input that regulates the activity of excitatory pyramidal neurons. The aim of this study is to measure somatosensory HFOs in patients with a single unprovoked seizure compared to typically developing peers.
Methods:
Participants with a diagnosis of single unprovoked seizure without any other neurological disease were recruited from New Onset Seizure Clinic at Cincinnati Children's Hospital Medical Center. Age and sex matched typically developing peers were also recruited n. SEFs were obtained with a whole-head 274-channel CTF-MEG system with 4kHz sampling rate. The electrical stimulation consisted of 200 microsecond monophasic rectangular pulses constant current applied to median nerves at the wrist bilaterally. Conventional N20m latencies were measured after 3-300Hz filter applied to the averaged data. HFO durations were measured, after the data was filtered from 400-800Hz, from the first to the last potential amplitude above 3 standard deviations from the averaged background noise and latency interval and from the ascending slope of the conventional N20m component to the ascending slope of the P30m. These were categorized in two segments; early and late HFOs divided by the N20m peak.
Results:
Eleven patients (age range: 6.7-17.8 years, mean: 13.0 years, F/M=5/6) with a single unprovoked seizure were included in this study. Four patients were subsequently diagnosed with epilepsy, (2=idiopathic localized-related epilepsy: bifrontal and left central, 2=epilepsy undetermined as to focal or generalized). Seven had not been diagnosed with epilepsy after one year since the single seizure diagnosis. There were no significant differences in N20m latency and early HFO latency between control, epilepsy and non-epilepsy patients. The latency of late HFOs of the left median nerve were significantly prolonged in patients with epilepsy (5.2 ± 0.7ms, p=0.04) and without epilepsy (5.4 ± 2.2ms, p=0.03) compared to control group (3.7 ± 1.7ms). For the right median nerve, the late HFO latency was significantly prolonged in patients with epilepsy compared to the control (6.6 ± 4.5 vs. 4.6 ± 2.1ms, p=0.045). There were no differences in the early HFOs between groups.
Conclusions:
This prospective study provides preliminary evidence that prolonged late HFOs could be a biomarker of epilepsy diagnosis. The next step is to uncover the cellular mechanisms underlying normal and abnormal somatosensory HFOs mechanisms using computational modeling which could potentially predict medication effects.
Funding: Trustee award at Cincinnati Childrens Hospital Medical Center