Longitudinal study of multimodal quantitative EEG characterization in Kleine-Levin syndrome

doi:10.16352/j.issn.1001-6325.2026.10.1384

Abstract

Abstract: Objective To characterize longitudinal quantitative electroencephalography(qEEG) changes from the symptomatic to recovery phase of Kleine-Levin syndrome (KLS) and examine the temporal relationship between clinical and electrophysiological recovery. Methods Longitudinal changes in brain electrical dynamics during a KLS episode were investigated using quantitative EEG approaches. A 14-year-old boy underwent serial EEG recordings on illness Days 2, 3, 4, 5, 8 and 14. Twelve age-matched healthy participants provided reference distributions. Six-minute artifact-cleaned eyes-closed segments were analyzed by conventional EEG assessment, microstate analysis, power spectral density (PSD), and correlation-based Omega complexity. The six KLS sessions were treated as repeated observations from one individual, with healthy reference-based standardized scores and single-case methods used for exploratory comparison. Results Days 2-5 showed paroxysmal generalized theta-delta slowing, poor preservation of conventional NREM markers, and occasional posterior sharp-and-slow-wave activity. Low-frequency intermittent photic stimulation elicited a self-limited bilateral occipital photoparoxysmal response. Clinical hypersomnia resolved by Day 8, although mild residual slowing remained; the conventional EEG was overall normal by Day 14. Global microstate mean duration decreased from 122.44-139.07 ms on Days 2-5 to 89.47 ms on Day 8 and 80.28 ms on Day 14, while occurrence increased from 7.19-8.17/s to 11.18/s and 12.46/s, respectively. PSD showed marked symptomatic delta predominance with progressive alpha-beta recovery. Omega complexity showed frequency- and region-dependent spatial changes. Conclusions KLS is associated with reversible temporal, spectral and spatial EEG abnormalities. Clinical recovery is preceded complete electrophysiological normalization, supporting quantitative EEG as a candidate tool for tracking disease-state transitions.

Key words: Kleine-Levin syndrome, quantitative EEG, EEG microstate, power spectral density, Omega complexity

CLC Number:

R741

ZHANG Le, HUANG Yan, CHEN Jianhua. Longitudinal study of multimodal quantitative EEG characterization in Kleine-Levin syndrome[J]. Basic & Clinical Medicine, 2026, 46(10): 1384-1391.

References

[1] Billiard M, Jaussent I. Kleine-Levin syndrome. Clinical boarderlands based on a thorough analysis of 475 case reports[J]. Sleep Med, 2024, 121: 135-143. doi:10.1016/j.sleep.2024.06.003.
[2] Benbir G, Delil S, Karadeniz D, et al. Misdiagnosis of menstruation-related recurrent hypersomnia as epilepsy in a patient with generalized epileptic discharges[J]. J Pediatr Neurosci, 2015, 10: 28-30. doi:10.4103/1817-1745.154325.
[3] Papacostas SS. Photosensitivity during the hypersomnic phase in a patient with Kleine-Levin syndrome[J]. J Child Neurol, 2003, 18: 432-433. doi:10.1177/08830738030180061701.
[4] Arnulf I, Dodet P, Leu-Semenescu S, et al. Idiopathic hypersomnia and Kleine-Levin syndrome[J]. Rev Neurol (Paris), 2023, 179: 741-754. doi:10.1016/j.neurol.2023.08.010.
[5] Dominguez D, Rudock R, Tomko S, et al. Apparent resolution of hypersomnia episodes in two patients with Kleine-Levin syndrome following treatment with the melatonin receptor agonist ramelteon[J]. J Clin Sleep Med, 2024, 20: 657-662. doi:10.5664/jcsm.10968.
[6] Lv YF, Dong XS, Sun TT, et al. Acute effects of different physical activity on executive function and regulation role of beta oscillation in sedentary youth frontal region[J]. Sci Rep, 2024, 14: 30939. doi:10.1038/s41598-024-81538-0.
[7] Arnulf I, Rico TJ, Mignot E. Diagnosis, disease course, and management of patients with Kleine-Levin syndrome[J]. Lancet Neurol, 2012, 11: 918-928. doi:10.1016/S1474-4422(12)70187-4.
[8] Wang JY, Han F, Dong XS, et al. Cerebrospinal fluid orexin A levels and autonomic function in Kleine-Levin syndrome[J]. Sleep, 2016, 39: 855-860. doi:10.5665/sleep.5642.
[9] Malhotra S, Kumar Das M, Gupta N, et al. A clinical study of Kleine-Levin syndrome with evidence for hypothalamic-pituitary axis dysfunction[J]. Biol Psychiatry, 1997, 42: 299-301. doi:10.1016/s0006-3223(97)00252-7.
[10] Alsalman OA, Li WX, Figueiro MG. Microstate dynamics alterations in response to 40 Hz rhythmic light intervention in mild cognitive impairment[J]. Brain Topogr, 2025, 39: 9. doi:10.1007/s10548-025-01159-2.

[1]	ZHANG Kexin, XIAO Fangyan, LI Wenhua, HUANG Wei, LIU Yanyong, YANG Nan. Murine pancreatic cancer cell line Pan02-derived exosomes effectively improve motor dysfunction in mouse models of Parkinson's disease [J]. Basic & Clinical Medicine, 2026, 46(7): 957-964.
[2]	WANG Yonghao. Research progress in exosomes for the diagnosis and treatment of post-stroke cognitive impairment [J]. Basic & Clinical Medicine, 2026, 46(6): 861-865.
[3]	LI Nan, ZHANG Guitao, WANG Bin, FENG Yao, LI Shujuan, ZHOU Yinghua. Correlation between inflammatory response-related indicators and poor outcomes of in-hospital patients with symptomatic stroke [J]. Basic & Clinical Medicine, 2025, 45(8): 1083-1087.
[4]	XIAO Fangyan, LI Wenhua, YANG Nan, HUANG Wei, LIU Yanyong. Aβ_25-35-based recombinant gene vaccine effectively improves cognitive dysfunction in Alzheimer′s disease mouse models [J]. Basic & Clinical Medicine, 2025, 45(7): 897-904.
[5]	SHEN Luxi, XU Xuejing, YE Yifan, CHEN Zhuo, CHEN Lan, SHEN Yuqi, LI Hongzhi. Transduction of yeast NDI1 gene reduces the damages demonstrated by a rotenone-induced differentiated Parkinson's disease cell model [J]. Basic & Clinical Medicine, 2023, 43(10): 1491-1497.
[6]	CHEN Xiaokun, BAO Xinjie, GAO Jun, LI Yongning. An update on the mechanism of neural stem cell transplantation in the treatment of Alzheimer’s disease [J]. Basic & Clinical Medicine, 2023, 43(7): 1148-1151.
[7]	YUE Jingjing, WU Chao, GAO Ge, LU Lingling. Alpha-synuclein /A53T mutant damages the mitochondria associated membrane and results in mitochondrial structural abnormalities and autophagy of neuroblastoma cell line SH-SY5Y [J]. Basic & Clinical Medicine, 2023, 43(2): 219-224.
[8]	LIU Liyang, LIU Qing, LIU Yaping, ZHANG Xue. Progress in the study of mitochondrial dysfunction in pathogenesis of amyotrophic lateral sclerosis [J]. Basic & Clinical Medicine, 2023, 43(2): 332-335.
[9]	WANG Yuan-zhuo, ZHENG Qing-yue, ZHANG Han-lin, QIU Wen-ying, WANG Tao, MA Chao. Function of the microglia in neuroinflammation of Alzheimer's disease:a brief review [J]. Basic & Clinical Medicine, 2022, 42(8): 1310-1313.
[10]	XU Juan, LI Ye. Research progress on the role of ferroptosis in Alzheimer's disease [J]. Basic & Clinical Medicine, 2022, 42(7): 1129-1133.
[11]	LIU Yan-li, MA Ya-jun, PAN Yan, ZHAO Rui-xue, ZHAO Tun, JIANG Xiao-yan, LI Shu-juan. Timed Up and Go test is associated with cognitive impairment in elders from East China [J]. Basic & Clinical Medicine, 2022, 42(7): 1042-1046.
[12]	LIU Yan-li, ZHAO Rui-xue, PAN Yan, MA Ya-jun, ZHAO Tun, JIANG Xiao-yan, LI Shu-juan. Depressive symptoms increase the risk of falls in elderly Chinese [J]. Basic & Clinical Medicine, 2022, 42(6): 945-949.
[13]	YUAN Jing-lin, MA Ya-jun, LI Xiao-dong, JIANG Xiao-yan, WANG Xiao-feng, LI Shu-juan, ZHOU Xiao-mei. Cognitive frailty increases the risk of falls of elderly in five years [J]. Basic & Clinical Medicine, 2022, 42(2): 201-207.
[14]	YUAN Jing-lin, ZHAO Rui-xue, LI Xiao-dong, JIANG Xiao-yan, WANG Xiao-feng, ZHOU Xiao-mei, LI Shu-juan. Motoric cognitive risk syndrome increases the risk of hospitalization in the elderly [J]. Basic & Clinical Medicine, 2021, 41(8): 1169-1173.
[15]	ZHAO Rui-xue, MA Ya-jun, LIU Hui, LI Xiao-dong, WANG Xiao-feng, JIANG Xiao-yan, LI Shu-juan. Progress in the diagnosis and treatment of cognitive frailty [J]. Basic & Clinical Medicine, 2021, 41(6): 895-898.