Characteristics of neuropsychological, sleep structure and distribution of HLA-DQB1 genotype of narcolepsy type 1

doi:10.3969/j.issn.1672-6731.2023.08.012

Abstract

Abstract:

Objective: To analyse the neuropsychological characteristics, sleep structure and HLA-DQB1 gene distribution of narcolepsy type 1 (NT1) patients. Methods: A total of 35 patients with NT1 admitted to Tianjin Medical University General Hospital, from August 2018 to November 2022 were included, all of whom underwent neuropsychological tests, noctural polysomnography (nPSG) monitoring, Multiple Sleep Latency Test (MSLT), narcolepsy evaluation and HLA-DQB1 gene detection. Results: Neuropsychological tests showed the scores of Montreal Cognitive Assessment (MoCA; t=3.159, P=0.004) and the correct number of immediate recall of the first (t=3.028, P=0.004) and the second (t=2.054, P=0.044) of Hopkins Verbal Learning Test-Revised (HVLT-R) were lower of the NT1 group than those of the control group. Trail Making Test (TMT)-B completion time (t=-2.126, P=0.019), Hamilton Anxiety Scale (HAMA) score (Z=-5.109, P=0.000), Hamilton Depression Scale-17 (HAMD-17) score (Z=-3.204, P=0.001), Epworth Sleepiness Scale (ESS) socre (t=-13.609, P=0.000) and Pittsburgh Sleep Quality Index (PSQI) score (Z=-3.004, P=0.003) were higher of the NT1 group than those of the control group. nPSG showed the total recording time (Z=-4.491, P=0.000), the proportion of non-rapid eye movement (NREM) 3 (Z=-2.647, P=0.008), the proportion of rapid eye movement (REM; t=2.908, P=0.005) and periodic limb movements of sleep index (PLMSI; Z=-3.501, P=0.000) were higher of the NT1 group than those of the control group. Sleep efficiency (t=-2.489, P=0.016), sleep latency (Z=-4.112, P=0.000), REM sleep latency (Z=-4.318, P=0.000) and the proportion of NREM2 (t=-5.224, P=0.000) were lower of the NT1 group than those of the control group. The clinical features of NT1 patients were excessive daytime sleepiness (97.14%, 34/35), cataplexy (97.14%, 34/35), other sleep disturbances (88.57%, 31/35), sleep hallucination (82.86%, 29/35), and sleep paralysis (68.57%, 24/35). And 34 cases (97.14%) carried the allele HLA-DQB1*0602. Conclusions: Patients with NT1 have cognitive decline, mood change and sleep structure disorder, and the carrying rate of HLA-DQB1*0602 is high.

Key words: Narcolepsy, Neuropsychological tests, Polysomnography, HLA-DQ antigens

摘要：

目的: 探讨发作性睡病1型（NT1）患者神经心理学、睡眠结构以及HLA-DQB1基因型特征。方法: 共纳入2018年8月至2022年11月天津医科大学总医院收治的35例NT1患者，均进行神经心理学测验、夜间多导睡眠图监测、多次睡眠潜伏期试验、发作性睡病评价和HLA-DQB1基因检测。结果: 神经心理学测验，NT1患者蒙特利尔认知评价量表评分（t=3.159，P=0.004）、霍普金斯词语学习测验修订版第1次（t=3.028，P=0.004）和第2次（t=2.054，P=0.044）即刻回忆正确个数低于对照者，连线测验-B完成时间（t=-2.126，P=0.019）、汉密尔顿焦虑量表评分（Z=-5.109，P=0.000）、汉密尔顿抑郁量表 17项评分（Z=-3.204，P=0.001）、Epworth嗜睡量表评分（t=-13.609，P=0.000）、匹兹堡睡眠质量指数评分（Z=-3.004，P=0.003）高于对照者。多导睡眠图监测，NT1患者总记录时间（Z=-4.491，P=0.000）、非快速眼动睡眠期（NREM）3期占比（Z=-2.647，P=0.008）、快速眼动睡眠期占比（t=2.908，P=0.005）、睡眠周期性肢体运动指数（Z=-3.501，P=0.000）高于对照者，睡眠效率（t=-2.489，P=0.016）、睡眠潜伏期（Z=-4.112，P=0.000）、快速眼动睡眠潜伏期（Z=-4.318，P=0.000）、NREM 2期占比（t=-5.224，P=0.000）低于对照者。NT1患者临床表现为日间过度思睡占97.14%（34/35）、猝倒发作占97.14%（34/35）、其他夜间睡眠紊乱占88.57%（31/35）、入睡前幻觉占82.86%（29/35）、睡眠瘫痪占68.57%（24/35）；34例（97.14%）携带等位基因HLA-DQB1*0602。结论: NT1患者存在认知功能减退、情绪异常和睡眠结构紊乱，且HLA-DQB1*0602携带率较高。

关键词: 发作性睡病, 神经心理学测验, 多道睡眠描记术, HLA-DQ抗原

Ya-qin HUANG, Lin XU, Zhu AI, Lin-lin WANG, Rong XUE. Characteristics of neuropsychological, sleep structure and distribution of HLA-DQB1 genotype of narcolepsy type 1[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2023, 23(8): 730-737.

黄雅琴, 徐琳, 艾竹, 王林林, 薛蓉. 发作性睡病1型患者神经心理学、睡眠结构及HLA-DQB1基因型分布特征[J]. 中国现代神经疾病杂志, 2023, 23(8): 730-737.

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观察指标	对照组（n=33）	NT1组（n=35）	统计量值	P值
性别[例（%）]			0.025	0.876
男性	23（69.70）	25（71.43）
女性	10（30.30）	10（28.57）
年龄（${\bar x}$±s，岁）	29.00±11.85	29.80±12.19	-0.274	0.785
BMI [M（P₂₅，P₇₅），kg/m²]	22.49 （20.31，24.63）	30.75 （26.84，33.91）	-4.632	0.000
受教育程度 [M（P₂₅，P₇₅），年]	16.00 （12.00，16.00）	16.00 （9.00，16.00）	-0.731	0.461
高血压[例（%）]	2（6.06）	1（2.86）	—	0.608
吸烟[例（%）]	2（6.06）	2（5.71）	—	1.000
饮酒[例（%）]	3（9.09）	3（8.57）	—	1.000

观察指标	对照组（n=33）	NT1组（n=35）	统计量值	P值
性别[例（%）]			0.025	0.876
男性	23（69.70）	25（71.43）
女性	10（30.30）	10（28.57）
年龄（${\bar x}$±s，岁）	29.00±11.85	29.80±12.19	-0.274	0.785
BMI [M（P₂₅，P₇₅），kg/m²]	22.49 （20.31，24.63）	30.75 （26.84，33.91）	-4.632	0.000
受教育程度 [M（P₂₅，P₇₅），年]	16.00 （12.00，16.00）	16.00 （9.00，16.00）	-0.731	0.461
高血压[例（%）]	2（6.06）	1（2.86）	—	0.608
吸烟[例（%）]	2（6.06）	2（5.71）	—	1.000
饮酒[例（%）]	3（9.09）	3（8.57）	—	1.000

观察指标	对照组（n=33）	NT1组（n=35）	t或Z值	P值
MoCA （${\bar x}$±s，评分）	29.61±0.79	27.29±3.82	3.159	0.004
TMT-A完成时间（${\bar x}$±s，s）	23.90±8.52	26.27±9.02	-1.079	0.285
TMT-B完成时间（${\bar x}$±s，s）	40.35±11.56	50.58±21.19	-2.126	0.019
HVLT-R正确个数（${\bar x}$±s，个）
第1次即刻回忆	7.44±2.58	5.73±1.94	3.028	0.004
第2次即刻回忆	8.59±2.35	7.42±2.24	2.054	0.044
第3次即刻回忆	9.69±2.31	8.97±2.24	1.272	0.208
延迟回忆	8.63±1.76	7.55±2.40	1.820	0.075
HAMA [M（P₂₅，P₇₅），评分]	1.00 （0.00，3.00）	9.00 （5.25，12.00）	-5.109	0.000
HAMD-17 [M（P₂₅，P₇₅），评分]	1.00 （0.00，2.00）	3.00 （1.00，7.00）	-3.204	0.001
ESS（${\bar x}$±s，评分）	5.61±2.68	17.31±4.21	-13.609	0.000
PSQI [M（P₂₅，P₇₅），评分]	2.00 （1.00，3.75）	7.00 （2.25，8.75）	-3.004	0.003

观察指标	对照组（n=33）	NT1组（n=35）	t或Z值	P值
MoCA （${\bar x}$±s，评分）	29.61±0.79	27.29±3.82	3.159	0.004
TMT-A完成时间（${\bar x}$±s，s）	23.90±8.52	26.27±9.02	-1.079	0.285
TMT-B完成时间（${\bar x}$±s，s）	40.35±11.56	50.58±21.19	-2.126	0.019
HVLT-R正确个数（${\bar x}$±s，个）
第1次即刻回忆	7.44±2.58	5.73±1.94	3.028	0.004
第2次即刻回忆	8.59±2.35	7.42±2.24	2.054	0.044
第3次即刻回忆	9.69±2.31	8.97±2.24	1.272	0.208
延迟回忆	8.63±1.76	7.55±2.40	1.820	0.075
HAMA [M（P₂₅，P₇₅），评分]	1.00 （0.00，3.00）	9.00 （5.25，12.00）	-5.109	0.000
HAMD-17 [M（P₂₅，P₇₅），评分]	1.00 （0.00，2.00）	3.00 （1.00，7.00）	-3.204	0.001
ESS（${\bar x}$±s，评分）	5.61±2.68	17.31±4.21	-13.609	0.000
PSQI [M（P₂₅，P₇₅），评分]	2.00 （1.00，3.75）	7.00 （2.25，8.75）	-3.004	0.003

观察指标	对照组（n=29）	NT1组（n=35）	Z或t值	P值
总记录时间 [M（P₂₅，P₇₅），min]	512.48 （470.08，542.82）	548.50 （518.25，605.50）	-4.491	0.000
TST [M（P₂₅，P₇₅），min]	401.50 （366.25，417.38）	428.25 （362.38，476.38）	1.793	0.078
SE（${\bar x}$±s，%）	88.32±5.97	73.50±12.91	-2.489	0.016
SL [M（P₂₅，P₇₅），min]	11.00 （4.38，15.63）	1.50 （1.00，4.50）	-4.112	0.000
RSL [M（P₂₅，P₇₅），min]	114.00 （90.25，172.75）	3.00 （1.88，70.25）	-4.318	0.000
NREM 1期占比 [M（P₂₅，P₇₅），%]	10.50 （7.00，17.75）	15.00 （9.75，24.00）	-1.845	0.065
NREM 2期占比 [M（P₂₅，P₇₅），%]	59.58±8.10	45.79±12.36	-5.224	0.000
NREM 3期占比 [M（P₂₅，P₇₅），%]	13.00 （4.00，16.00）	18.00 （10.00，20.00）	-2.647	0.008
REM占比（${\bar x}$±s，%）	12.92±5.55	22.79±9.56	2.908	0.005
PLMSI [M（P₂₅，P₇₅），次/h]	0.00 （0.00，1.65）	3.30 （1.70，8.10）	-3.501	0.000
平均SaO₂ [M（P₂₅，P₇₅），%]	95.00 （94.00，96.50）	96.00 （94.00，97.00）	-0.707	0.480
最低SaO₂ [M（P₂₅，P₇₅），%]	88.00 （86.00，93.50）	81.00 （88.00，94.00）	-0.603	0.547

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