Ictal high-frequency oscillations and hyperexcitability in refractory epilepsy Howan Leung a,⇑ , Cannon X.L. Zhu b , Danny T.M. Chan b , Wai S. Poon b , Lin Shi a , Vincent C.T. Mok a , Lawrence K.S. Wong a a Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region b Division of Neurosurgery, Department of Surgery, The Chinese University of Hong Kong, Hong Kong Special Administrative Region article info Article history: Accepted 1 January 2015 Available online xxxx Keywords: High-frequency oscillations Hyperexcitability Refractory epilepsy highlights  High-frequency oscillations captured at the onset of seizure may help determine surgical outcome in patients with refractory epilepsy.  Cortical areas demonstrating hyperexcitability may be associated with ictal high-frequency oscillations.  By examining hyperexcitability and ictal high-frequency oscillations, the decision-making process for surgical resection to treat refractory epilepsy may be improved with values of sensitivity and speci- ficity that are more optimal. abstract Objective: High-frequency oscillations (HFOs, 80–500 Hz) from intracranial electroencephalography (EEG) may represent a biomarker of epileptogenicity for epilepsy. We explored the relationship between ictal HFOs and hyperexcitability with a view to improving surgical outcome. Methods: We evaluated 262 patients with refractory epilepsy. Fifteen patients underwent electrode implantation, and surgical resection was performed in 12 patients using a semi-prospective design. Ictal intracranial EEGs were examined by continuous wavelet transform (CWT). Significant ictal HFOs were denoted by normalized wavelet power above the 50th percentile across all channels. Each patient under- went functional mapping with cortical electrical stimulation. Hyperexcitability was defined as the appearance of afterdischarges or clinical seizures after electrical stimulation (50 Hz, biphasic, pulse width = 0.5 ms, 5 s, 5 mA). Results: Among the group of patients achieving Engel Class I/II outcome at 1+ year, the mean proportion of significant ictal HFOs among resected channels for any given patient was 69% (33.3–100%). The respec- tive figures for conventional frequency ictal patterns (CFIPs), hyperexcitability, and radiological lesion were 68.3% (26.3–100%), 39.6% (0–100%), and 52.8% (0–100%). Statistical significance was only achieved with ictal HFOs when comparing patients with Engel Class I/II outcomes versus III/IV outcomes (12.6% vs. 4.2%, the number of channels as the denominator, p = 0.005). Results: Further analysis from all patients irrespective of the surgical outcome showed that ictal HFOs co-occurred with CFIP (p < 0.001), hyperexcitability (p < 0.001), and radiological lesion (p < 0.001). The combination of ictal HFOs/hyperexcitability improved the sensitivity from 66.7% to 100%, and the specifici- ty from 66.7% to 75% when compared with ictal HFOs or hyperexcitability alone. Conclusions: We confirmed the utility of ictal HFOs in determining surgical outcome. Ictal HFOs are affiliat- ed to cortical hyperexcitability, which may represent a pathological manifestation of epileptogenicity. Significance: Presurgical evaluation of refractory epilepsy may incorporate both ictal HFOs and cortical stimulation in determining epileptogenic foci. Ó 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2015.01.009 1388-2457/Ó 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. ⇑ Corresponding author at: 10/F, Clinical Science Building, Prince of Wales Hospital, Shatin NT, Hong Kong Special Administrative Region. Tel.: +852 2632 1855; fax: +852 2637 3852. E-mail address: howanleung@cuhk.edu.hk (H. Leung). Clinical Neurophysiology xxx (2015) xxx–xxx Contents lists available at ScienceDirect Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph Please cite this article in press as: Leung H et al. Ictal high-frequency oscillations and hyperexcitability in refractory epilepsy. Clin Neurophysiol (2015), http://dx.doi.org/10.1016/j.clinph.2015.01.009