The localizing value of scalp high-frequency oscillations for the epileptogenic zone in infantile epileptic spasms syndrome with structural etiologies_Journal of Epilepsy

Authors：

LIN Chun ¹ , CHEN Yan ¹ , LIU Zhenzhen ¹ , ZHANG Tian ¹ , LI Ying ¹ , ZHU Fengjun ¹ , FENG Guoyun ³ , YANG Xiaofeng ³ ,  CAO Dezhi ^1,2

1. Department of Epilepsy Surgery, Shenzhen Children’s Hospital, Shenzhen 518038, China Department of Neurology, Shenzhen Children’s Hospital, Shenzhen 518038, China Guangzhou National Laboratory, Guangzhou 510220, China;
2. ;
3. ;

Corresponding author：

CAO Dezhi, Email: Caodezhi888@aliyun.com

Keywords：

Infantile epileptic spasms syndrome; High-frequency oscillations; Epilepsy surgery; Prognosis; Electroencephalography

DOI：

10.7507/2096-0247.202508012

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Objective To investigate the value of interictal scalp high-frequency oscillations (HFOs) in localizing the epileptogenic zone (EZ) in children with infantile epileptic spasms syndrome (IESS). Methods A retrospective analysis was conducted on surgical IESS patients treated at the Epilepsy Center of Shenzhen Children’s Hospital from August 2018 to November 2021. Preoperative EEG and clinical data were collected. Based on Engel classification at 2-year follow-up, patients were divided into a seizure-free group (Engel Ia) and a non–seizure-free group (non–Engel Ia). An automated detection system was used to identify ripple events (80–250 Hz), and the H-index (ripples per channel per minute) was calculated in the resection zone (RZ) and non-resection zone (non-RZ). Result 35 children were included (19 seizure-free, 16 non–seizure-free). The H-index in the RZ was significantly higher than in the non-RZ in the seizure-free group [(58.16±43.95) vs. (24.07±22.85), P<0.05]. Using the RZ of the seizure-free group as the gold standard, the area under the ROC curve (AUC) of the H-index for predicting the EZ was 0.83 [95%CI (0.70, 0.96) , P<0.001], with an optimal diagnostic threshold of 21.50 (sensitivity 73.68%, specificity 84.21%). Conclusion The results confirm that the interictal scalp HFO index may serve as a potential biomarker for localizing the EZ in IESS children with structural etiologies.

Citation： LIN Chun, CHEN Yan, LIU Zhenzhen, ZHANG Tian, LI Ying, ZHU Fengjun, FENG Guoyun, YANG Xiaofeng, CAO Dezhi. The localizing value of scalp high-frequency oscillations for the epileptogenic zone in infantile epileptic spasms syndrome with structural etiologies. Journal of Epilepsy, 2025, 11(6): 471-476. doi: 10.7507/2096-0247.202508012 Copy

1.	Pavone P, Polizzi A, Marino S D, et al. West syndrome: a comprehensive review. Neurological Sciences, 2020, 41(12): 3547-3562.
2.	Zuberi S M, Wirrell E, Yozawitz E, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia, 2022, 63(6): 1349-1397.
3.	Tekin Guveli B, Cokar O, Dortcan N, et al. Long-term outcomes in patients with West syndrome: An outpatient clinical study. Seizure, 2015, 25: 68-71.
4.	Riikonen R. Biochemical mechanisms in pathogenesis of infantile epileptic spasm syndrome. Seizure, 2023, 105: 1-9.
5.	Li L, Lin S, Tan Z, et al. Resective epilepsy surgery for west syndrome: the hypsarrhythmic asymmetric scoring scheme is a determining predictor of seizure outcome. Seizure: European Journal of Epilepsy, 2022, 101: 205-210.
6.	Asano E, Chugani D C, Juhásza C, et al. Surgical treatment of West syndrome. Brain and Development, 2001, 23(7): 668-676.
7.	Kwon H E, Kim S H, Kang H C, et al. Epilepsy surgery for pediatric patients with mild malformation of cortical development. Seizure, 2020, 82: 50-55.
8.	Cai L, Zhang K, Zhou W, et al. Consensus on pediatric epilepsy surgery for young children: an investigation by the China Association Against Epilepsy task force on epilepsy surgery. Acta Epileptologica, 2023, 5(1): 20.
9.	Cao X, Ding X, Zhu F, et al. Surgical outcomes of drug-refractory infantile epileptic spasms syndrome and related prognostic factors: a retrospective study. Acta Epileptologica, 2024, 6(1): 36.
10.	Liu Y D, Zhu F J, Chen Y, et al. Preliminary observation on clinical outcome and safety of surgery in early infants (<12 months) with drug-resistant epilepsy. Seizure: European Journal of Epilepsy, 2024, 122: 165-171.
11.	Liu S Y, An N, Yang M H, et al. Surgical treatment for epilepsy in 17 children with tuberous sclerosis-related West syndrome. Epilepsy Research, 2012, 101(1-2): 36-45.
12.	季涛云, 王若凡, 刘庆祝, 等. 局灶起源的药物难治性癫痫性痉挛的手术预后及相关预后因素分析. 中华实用儿科临床杂志, 2021, 36(17): 133-137.
13.	Pindrik J, Hoang N, Smith L, et al. Preoperative evaluation and surgical management of infants and toddlers with drug-resistant epilepsy. Neurosurgical Focus, 2018, 45(3): E3.
14.	Santana C E, Jr J E, Staba R. Drug-resistant epilepsy and the hypothesis of intrinsic severity: What about the high-f requency oscillations? Epilepsia Open, 2022, 7(Suppl 1): 59-67.
15.	Jiang C, Li X, Yan J, et al. Determining the quantitative threshold of high-frequency oscillation distribution to delineate the epileptogenic zone by automated detection. Frontiers in Neurology, 2018, 9: 889.
16.	Jacobs J, Staba R, Asano E, et al. High-frequency oscillations (HFOs) in clinical epilepsy. Progress in Neurobiology, 2012, 98(3): 302-315.
17.	Zijlmans M, Jiruska P, Zelmann R, et al. High-frequency oscillations as a new biomarker in epilepsy. Annals of Neurology, 2012, 71(2): 169-178.
18.	Frauscher B, Bartolomei F, Kobayashi K, et al. High-frequency oscillations: The state of clinical research. Epilepsia, 2017, 58(8): 1316-1329.
19.	Thomschewski A, Hincapié AS, Frauscher B. Localization of the epileptogenic zone using high frequency oscillations. Frontiers in Neurology, 2019, 10: 94.
20.	Gloss D, Nevitt S J, Staba R. The role of high-frequency oscillations in epilepsy surgery planning. Cochrane Database of Systematic Reviews, 2017, 2017(10): 1-34.
21.	Jiruska P, Alvarado‐Rojas C, Schevon CA, et al. Update on the mechanisms and roles of high‐frequency oscillations in seizures and epileptic disorders. Epilepsia, 2017, 58(8): 1330-1339.
22.	Wu J Y, Koh S, Sankar R, et al. Paroxysmal fast activity: an interictal scalp EEG marker of epileptogenesis in children. Epilepsy Research, 2008, 82(1): 99-106.
23.	Wang W, Li H, Yan J, et al. Automatic detection of interictal ripples on scalp EEG to evaluate the effect and prognosis of ACTH therapy in patients with infantile spasms. Epilepsia, 2021, 62(9): 2240-2251.
24.	Ibrahim GM, Fallah A, Snead OC, et al. The use of high frequency oscillations to guide neocortical resections in children with medically-intractable epilepsy: How do we ethically apply surgical innovations to patient care? Seizure, 2012, 21(10): 743-747.
25.	Kobayashi K, Akiyama T, Oka M, et al. A storm of fast (40–150 H z) oscillations during hypsarrhythmia in west syndrome. Annals of Neurology, 2015, 77(1): 58-67.
26.	Kobayashi K, Oka M, Akiyama T, et al. Very Fast Rhythmic Activity on Scalp EEG Associated with Epileptic Spasms. Epilepsia, 2004, 45(5): 488-496.
27.	Iwatani Y, Kagitani-Shimono K, Tominaga K, et al. Ictal highfrequency oscillations on scalp EEG recordings in symptomatic West syndrome. Epilepsy Research, 2012, 102: 60-70.
28.	Nariai H, Beal J, Galanopoulou AS, et al. Scalp EEG Ictal gamma and beta activity during infantile spasms: Evidence of focality. Epilepsia, 2017, 58(5): 882-892.
29.	Kobayashi K, Endoh F, Agari T, et al. Complex observation of scalp fast (40-150 Hz) oscillations in West syndrome and related disorders with structural brain pathology. Epilepsia Open, 2017, 2(2): 260-266.
30.	Nariai H, Hussain S A, Bernardo D, et al. Scalp EEG interictal high frequency oscillations as an objective biomarker of infantile spasms. Clinical Neurophysiology, 2020, 131(11): 2527-2536.
31.	Baba S, Vakorin VA, Doesburg SM, et al. EEG before and after total corpus callosotomy for pharmacoresistant infantile spasms: fast oscillations and slow‐wave connectivity in hypsarrhythmia. Epilepsia, 2019, 60(9): 1849-1860.
32.	Scheffer I E, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology. Epilepsia, 2017, 58(4): 512-521.
33.	Binnie CD, Polkey CE. Commission on neurosurgery of the international league against epilepsy (ILAE) 1993–1997: recommended standards. Epilepsia, 2000, 41(10): 1346-1349.
34.	Karatza P, Cserpan D, Moser K, et al. Scalp high‐frequency oscillation spatial distribution is consistent over consecutive nights, while rates vary with antiseizure medication changes. Epilepsia, 2025, 66(4): 1250-1259.
35.	Liu X, Li Y, Li X, et al. Scalp ripple rates for rapid epilepsy differentiation and seizure activity assessment: applicability and influential factors. Epilepsia, 2023, 64(6): 1541-1553.
36.	Yang Y, Wang W, Wang J, et al. Scalp-HFO indexes are biomarkers for the lateralization and localization of the epileptogenic zone in preoperative assessment. Journal of Neurophysiology, 2021, 126(4): 1148-1158.
37.	杨小枫, 李晓楠, 王玮. 高频脑电信号在癫痫诊疗中的研究与应用. 癫痫与神经电生理学杂志, 2020, 29(3): 129-133.
38.	Cao D, Chen Y, Liao J, et al. Scalp EEG high frequency oscillations as a biomarker of treatment response in epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS). Seizure, 2019, 71: 151-157.
39.	Lüders HO. Textbook of epilepsy surgery. London: Informa Healthcare, 2008: 530-536.
40.	Sakaguchi Y, Kidokoro H, Ogawa C, et al. Longitudinal findings of MRI and PET in west syndrome with subtle focal cortical dysplasia. American Journal of Neuroradiology, 2018, 39(10): 1932-1937.
41.	Bast T. Outcome after epilepsy surgery in children with MRI-negative non-idiopathic focal epilepsies. Epileptic Disorders, 2013, 15(2): 105-11.
42.	Weng J K, Ahn R, Hussain SA. Hypsarrhythmia is associated with widespread, asymmetric cerebral hypermetabolism. Seizure, 2019, 71: 29-34.
43.	Haginoya K, Kon K, Tanaka S, et al. The origin of hypsarrhythmia and tonic spasms in West syndrome: evidence from a case of porencephaly and hydrocephalus with focal hypsarrhythmia. Brain and Development, 1999, 21(2): 129-131.
44.	Shibata T, Kobayashi K. Epileptic high-frequency oscillations in scalp electroencephalography. Acta Med. Okayama, 2018, 72(4): 325-329.

1. Pavone P, Polizzi A, Marino S D, et al. West syndrome: a comprehensive review. Neurological Sciences, 2020, 41(12): 3547-3562.
2. Zuberi S M, Wirrell E, Yozawitz E, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia, 2022, 63(6): 1349-1397.
3. Tekin Guveli B, Cokar O, Dortcan N, et al. Long-term outcomes in patients with West syndrome: An outpatient clinical study. Seizure, 2015, 25: 68-71.
4. Riikonen R. Biochemical mechanisms in pathogenesis of infantile epileptic spasm syndrome. Seizure, 2023, 105: 1-9.
5. Li L, Lin S, Tan Z, et al. Resective epilepsy surgery for west syndrome: the hypsarrhythmic asymmetric scoring scheme is a determining predictor of seizure outcome. Seizure: European Journal of Epilepsy, 2022, 101: 205-210.
6. Asano E, Chugani D C, Juhásza C, et al. Surgical treatment of West syndrome. Brain and Development, 2001, 23(7): 668-676.
7. Kwon H E, Kim S H, Kang H C, et al. Epilepsy surgery for pediatric patients with mild malformation of cortical development. Seizure, 2020, 82: 50-55.
8. Cai L, Zhang K, Zhou W, et al. Consensus on pediatric epilepsy surgery for young children: an investigation by the China Association Against Epilepsy task force on epilepsy surgery. Acta Epileptologica, 2023, 5(1): 20.
9. Cao X, Ding X, Zhu F, et al. Surgical outcomes of drug-refractory infantile epileptic spasms syndrome and related prognostic factors: a retrospective study. Acta Epileptologica, 2024, 6(1): 36.
10. Liu Y D, Zhu F J, Chen Y, et al. Preliminary observation on clinical outcome and safety of surgery in early infants (<12 months) with drug-resistant epilepsy. Seizure: European Journal of Epilepsy, 2024, 122: 165-171.
11. Liu S Y, An N, Yang M H, et al. Surgical treatment for epilepsy in 17 children with tuberous sclerosis-related West syndrome. Epilepsy Research, 2012, 101(1-2): 36-45.
12. 季涛云, 王若凡, 刘庆祝, 等. 局灶起源的药物难治性癫痫性痉挛的手术预后及相关预后因素分析. 中华实用儿科临床杂志, 2021, 36(17): 133-137.
13. Pindrik J, Hoang N, Smith L, et al. Preoperative evaluation and surgical management of infants and toddlers with drug-resistant epilepsy. Neurosurgical Focus, 2018, 45(3): E3.
14. Santana C E, Jr J E, Staba R. Drug-resistant epilepsy and the hypothesis of intrinsic severity: What about the high-f requency oscillations? Epilepsia Open, 2022, 7(Suppl 1): 59-67.
15. Jiang C, Li X, Yan J, et al. Determining the quantitative threshold of high-frequency oscillation distribution to delineate the epileptogenic zone by automated detection. Frontiers in Neurology, 2018, 9: 889.
16. Jacobs J, Staba R, Asano E, et al. High-frequency oscillations (HFOs) in clinical epilepsy. Progress in Neurobiology, 2012, 98(3): 302-315.
17. Zijlmans M, Jiruska P, Zelmann R, et al. High-frequency oscillations as a new biomarker in epilepsy. Annals of Neurology, 2012, 71(2): 169-178.
18. Frauscher B, Bartolomei F, Kobayashi K, et al. High-frequency oscillations: The state of clinical research. Epilepsia, 2017, 58(8): 1316-1329.
19. Thomschewski A, Hincapié AS, Frauscher B. Localization of the epileptogenic zone using high frequency oscillations. Frontiers in Neurology, 2019, 10: 94.
20. Gloss D, Nevitt S J, Staba R. The role of high-frequency oscillations in epilepsy surgery planning. Cochrane Database of Systematic Reviews, 2017, 2017(10): 1-34.
21. Jiruska P, Alvarado‐Rojas C, Schevon CA, et al. Update on the mechanisms and roles of high‐frequency oscillations in seizures and epileptic disorders. Epilepsia, 2017, 58(8): 1330-1339.
22. Wu J Y, Koh S, Sankar R, et al. Paroxysmal fast activity: an interictal scalp EEG marker of epileptogenesis in children. Epilepsy Research, 2008, 82(1): 99-106.
23. Wang W, Li H, Yan J, et al. Automatic detection of interictal ripples on scalp EEG to evaluate the effect and prognosis of ACTH therapy in patients with infantile spasms. Epilepsia, 2021, 62(9): 2240-2251.
24. Ibrahim GM, Fallah A, Snead OC, et al. The use of high frequency oscillations to guide neocortical resections in children with medically-intractable epilepsy: How do we ethically apply surgical innovations to patient care? Seizure, 2012, 21(10): 743-747.
25. Kobayashi K, Akiyama T, Oka M, et al. A storm of fast (40–150 H z) oscillations during hypsarrhythmia in west syndrome. Annals of Neurology, 2015, 77(1): 58-67.
26. Kobayashi K, Oka M, Akiyama T, et al. Very Fast Rhythmic Activity on Scalp EEG Associated with Epileptic Spasms. Epilepsia, 2004, 45(5): 488-496.
27. Iwatani Y, Kagitani-Shimono K, Tominaga K, et al. Ictal highfrequency oscillations on scalp EEG recordings in symptomatic West syndrome. Epilepsy Research, 2012, 102: 60-70.
28. Nariai H, Beal J, Galanopoulou AS, et al. Scalp EEG Ictal gamma and beta activity during infantile spasms: Evidence of focality. Epilepsia, 2017, 58(5): 882-892.
29. Kobayashi K, Endoh F, Agari T, et al. Complex observation of scalp fast (40-150 Hz) oscillations in West syndrome and related disorders with structural brain pathology. Epilepsia Open, 2017, 2(2): 260-266.
30. Nariai H, Hussain S A, Bernardo D, et al. Scalp EEG interictal high frequency oscillations as an objective biomarker of infantile spasms. Clinical Neurophysiology, 2020, 131(11): 2527-2536.
31. Baba S, Vakorin VA, Doesburg SM, et al. EEG before and after total corpus callosotomy for pharmacoresistant infantile spasms: fast oscillations and slow‐wave connectivity in hypsarrhythmia. Epilepsia, 2019, 60(9): 1849-1860.
32. Scheffer I E, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology. Epilepsia, 2017, 58(4): 512-521.
33. Binnie CD, Polkey CE. Commission on neurosurgery of the international league against epilepsy (ILAE) 1993–1997: recommended standards. Epilepsia, 2000, 41(10): 1346-1349.
34. Karatza P, Cserpan D, Moser K, et al. Scalp high‐frequency oscillation spatial distribution is consistent over consecutive nights, while rates vary with antiseizure medication changes. Epilepsia, 2025, 66(4): 1250-1259.
35. Liu X, Li Y, Li X, et al. Scalp ripple rates for rapid epilepsy differentiation and seizure activity assessment: applicability and influential factors. Epilepsia, 2023, 64(6): 1541-1553.
36. Yang Y, Wang W, Wang J, et al. Scalp-HFO indexes are biomarkers for the lateralization and localization of the epileptogenic zone in preoperative assessment. Journal of Neurophysiology, 2021, 126(4): 1148-1158.
37. 杨小枫, 李晓楠, 王玮. 高频脑电信号在癫痫诊疗中的研究与应用. 癫痫与神经电生理学杂志, 2020, 29(3): 129-133.
38. Cao D, Chen Y, Liao J, et al. Scalp EEG high frequency oscillations as a biomarker of treatment response in epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS). Seizure, 2019, 71: 151-157.
39. Lüders HO. Textbook of epilepsy surgery. London: Informa Healthcare, 2008: 530-536.
40. Sakaguchi Y, Kidokoro H, Ogawa C, et al. Longitudinal findings of MRI and PET in west syndrome with subtle focal cortical dysplasia. American Journal of Neuroradiology, 2018, 39(10): 1932-1937.
41. Bast T. Outcome after epilepsy surgery in children with MRI-negative non-idiopathic focal epilepsies. Epileptic Disorders, 2013, 15(2): 105-11.
42. Weng J K, Ahn R, Hussain SA. Hypsarrhythmia is associated with widespread, asymmetric cerebral hypermetabolism. Seizure, 2019, 71: 29-34.
43. Haginoya K, Kon K, Tanaka S, et al. The origin of hypsarrhythmia and tonic spasms in West syndrome: evidence from a case of porencephaly and hydrocephalus with focal hypsarrhythmia. Brain and Development, 1999, 21(2): 129-131.
44. Shibata T, Kobayashi K. Epileptic high-frequency oscillations in scalp electroencephalography. Acta Med. Okayama, 2018, 72(4): 325-329.

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The localizing value of scalp high-frequency oscillations for the epileptogenic zone in infantile epileptic spasms syndrome with structural etiologies

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