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Chinese Journal of Alzheimer's Disease and Related Disorders

Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders      Editor in chief: Jun WANG

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Chinese Journal of Alzheimer's Disease and Related Disorders >

2021 , Vol. 4 >Issue 2: 127 - 130

DOI: https://doi.org/10.3969/j.issn.2096-5516.2021.02.008

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Quantitative electroencephalogram in Parkinson's disease with white matter lesions

  • YU Yue-hua , 1 ,
  • ZHAO De-hao 2 ,
  • DING Ping 2 ,
  • ZHANG Li 2 ,
  • WEI Wen-shi , 2
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  • 1 Department of Neurology, Qingpu Branch, Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, China
  • 2 Department of Neurology, East China Hospital Affiliated to Fudan University; Cognitive impairment center of East China Hospital Affiliated to Fudan University, Shanghai 200040, China.

Received date: 2021-01-14

  Revised date: 2021-03-08

  Online published: 2021-06-25

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Abstract

Objective: To analyze the relationship between the degree of cerebral white matter lesions and quantitative EEG in patients with Parkinson's disease. Methods: According to Fazekas classification, 31 PD patients with WML were divided into mild WML group and moderate severe WML group. The cognitive function and quantitative EEG indexes were compared between the two groups, and the correlation between the severity of white matter lesions and EEG changes was analyzed. Results: Compared with the mild WML the group, the overall cognitive level (MoCA) of patients in the moderate to serve WML group decreased (P=0.013);Analysis of QEEG data between the two groups found that the moderate to serve WML group had a lower relative alpha band powers than the mild WML group in C3 (left central area), P3(Left parietal region) and T5(left posterior temporal) (P <0.05 ); The relative theta band powers was increased in P3 (Left parietal region), T4 (right middle temporal) and O1 (left occipital region) (P <0.05); and the ratio of (α + β / θ + δ) was reduced in F7 (left front temporal) (P <0.05). For the analysis of the correlation between WML severity, clinical characteristics and QEEG activity in PD patients, the PD patients age, motor symptom severity, vascular risk factors and statistically significant QEEG indicators into the Logistic regression analysis model, the results showed that the decrease of the relative alpha band powers in T5 (left posterior temporal) and hypertension are associated with WML severity in PD (P <0.05). Conclusion: Decrease of a band relative energy of T5 (left posterior temporal) has certain clinical value in the identification of PD patients with moderate severe WML.

Key words： Parkinson's disease; leukoencephalopathy; cognitive function; Quantitative electroencephalogram

Cite this article

YU Yue-hua , ZHAO De-hao , DING Ping , ZHANG Li , WEI Wen-shi . Quantitative electroencephalogram in Parkinson's disease with white matter lesions[J]. Chinese Journal of Alzheimer's Disease and Related Disorders, 2021 , 4(2) : 127 -130 . DOI: 10.3969/j.issn.2096-5516.2021.02.008

认知功能障碍是帕金森病(Parkinson's disease, PD)患者常见的非运动症状之一。近年来的研究发现,脑白质病变(white matter lesions, WML)是PD认知功能障碍的重要危险因素,约30%的PD患者合并WML,且WML越严重的PD患者认知功能越差[1⇓~3]。WML可能通过加重已受损的神经元间功能连接影响PD患者的认知功能[4]。但目前以脑电活动形式反映PD不同程度WML的研究极少,因此本研究通过观察不同程度WML的PD患者定量脑电图特点,寻找用于早期识别PD患者的相关脑电图指标,进而探索WML对于PD患者认知功能影响的可能病理机制。

1 资料与方法

1.1 一般资料

纳入2018年6月~2019年7月复旦大学附属华东医院门诊的31例PD合并WML患者,年龄60~86岁,平均年龄(70.58±3.54)岁,其中男性18例、女性13例。纳入标准：(1)符合2015年MDS(Movement Disorder Society,国际运动障碍学会)修订的PD诊断标准[5];(2)符合WML诊断标准[6];(3)能够配合完成头颅磁共振成像（magnetic resonance imaging, MRI）和脑电图。排除标准：(1)脑外伤、脑血管病、脑部肿瘤史或合并其他脏器严重功能障碍者;(2)继发性帕金森综合征及帕金森叠加综合征;(3)精神病史者。所有入组患者或家属均签署知情同意书。

1.2 研究方法

1.2.1 临床信息采集

收集所有入组患者的年龄、性别、起病年龄、血管危险因素（高血压、糖尿病、心脏病、高脂血症和吸烟）、服药情况、文化水平以及家族史等基线资料。

1.2.2 神经心理学测试

认知功能评估使用蒙特利尔认知评估量表(Montreal Cognitive Assessment, MoCA),其中MoCA量表包括视空间功能,执行功能,命名,注意力,语言,抽象,延迟回忆,定向功能;MoCA量表以26分为界（受教育年限<12年者加1分）,<26分为认知功能障碍,>26分为认知功能正常。

1.2.3 神经影像学检查

采用3.0T MRI（德国Siemens）进行头颅扫描,包括T1加权像(weighted image, WI)、T2WI、液体衰减反转恢复(fluid attented inversion recovery, FLAIR)轴位和 T1WI矢状位。由2名有经验的神经内科医师（副主任医师）根据WML诊断标准[6]及Fazekas评分[7]进行WML严重程度评估。

1.2.4 脑电图信息采集

在PD患者开期,完成清醒、安静、闭目状态时的脑电信息采集。脑电监测系统为上海诺诚公司的NCERP-P,版本为1.0.2.0,灵敏度7µV/mm,低频滤波0.5HZ,高频滤波70HZ,陷波滤波50HZ。根据国际10-20系统标准放置电极,以双侧耳极为参考电极。电极置于F3、F4（双侧额区）,P3、P4（双侧顶区）,O1、O2（双侧枕区）,F7、F8（双侧前颞）,T3、T4（双侧中颞）,T5、T6（双侧后颞）,C3、C4（双侧中央区）以及FP1、FP2（双侧额极）。由3名有经验的神经电生理医师采集5 min无伪迹的脑电信息,通过傅里叶转换获取各脑区的定量脑电指标,包括α(8-13HZ)、β(13-30HZ)、θ(4-8HZ)、δ(0.5-4HZ)频带相对能量值及频带快慢比值(α+β/δ+θ)。

1.3 统计学方法

应用SPSS25.0统计软件进行数据分析。计数资料用例(%)进行描述,组间比较使用卡方检验;正态分布的计量资料用均数±标准差($\bar{x}±s$)表示,组间比较使用t检验;非正态分布的计量资料用中位数和四分位数间距表示,组间比较使用非参数检验。Logistic回归分析探索不同程度WML与定量脑电图指标之间的相关性,P<0.05为差异有统计学意义。

2 结果

2.1 PD合并WML的临床特点

31例PD合并WML患者,轻度WML组17例、中重度WML组14例。与轻度WML组比较,中重度WML组患者年龄更大(P=0.028)、合并高血压更多(P<0.0001)、MoCA评分(P=0.013)、延迟回忆评分(P=0.003)和定向评分(P=0.048)更低。见表1。
表1 WML的危险因素分析

Tab.1 Analysis of risk factors of white matter lesions

项目 轻度WML组(n=17) 中重度WML组(n=14) P
年龄（岁） 67.9±6.1 73.8±8.0 0.028
性别[例（%）]
男性 9(52.9) 8(57.1) 0.551
女性 8 (47.1) 6(42.9)
血管危险因素[例（%）]
高血压 2(11.76) 11(78.57) 0.000
糖尿病 2(11.76) 2(14.28) 0.676
心脏病 0(0) 1(7.14) 0.452
高脂血症 3(17.64) 2(14.28) 0.597
吸烟 1(5.88) 1(7.14) 0.708
MoCA（分） 26(26,27) 23.50(21.25,25.75) 0.013
视空间 4(3,4) 4(3,4) 0.664
执行 0(0,1) 0(0,1) 0.760
命名 3(3,3) 3(3,3) 0.113
注意 6(5,6) 5.00(4.25,6.00) 0.375
语言 3(3,3) 3(2,3) 0.118
抽象 2(1,2) 1(1,2) 0.162
延迟回忆 3(3,4) 2.00(1.00,2.75) 0.003
定向 6(6,6) 6(6,6) 0.048

2.2 PD合并WML的定量脑电图

2.2.1 频带相对能量值

与轻度WML组比较,中重度WML组C3、P3及T5的α频带相对能量值降低,差异有统计学意义（均P<0.05）;P3、O1及T4的θ频带相对能量值升高,差异有统计学意义（均P<0.05）。中重度WML组定量脑电图表现为广泛的快波频带相对能量值降低,慢波频带相对能量值升高。见表2。
表2 2组频带相对能量值比较

Tab.2 Comparison of relative energy values of two groups of frequency bands

项目 轻度WML组
(n=17)		 中重度WML组
(n=14)		 P
FP1
α 48.42±15.06 39.15±18.80 0.138
β 18.03±13.46 14.31±9.47 0.391
θ 17.80(14.00, 19.80) 19.30(15.35, 29.45) 0.405
δ 14.65±5.58 20.76±10.97 0.054
FP2
α 46.75±16.22 38.31±16.28 0.160
β 10.40(8.70, 18.70) 13.30(8.25, 20.00) 0.953
θ 16.60(11.80, 24.20) 22.55(15.45, 34.23) 0.382
δ 17.62±8.05 21.98±10.40 0.199
F3
α 51.06±16.20 39.26±18.28 0.067
β 18.32±12.41 17.45±11.74 0.844
θ 17.60(12.7, 19.7) 19.45(12.05, 26.65) 0.512
δ 12.00(10.50, 14.20) 14.65(11.50, 26.23) 0.112
F4
α 51.54±16.32 41.1±16.94 0.092
β 11.20(9.30, 26.30) 13.05(9.57, 22.75) 0.827
θ 16.80(12.40, 20.50) 20.55(12.15, 34.20) 0.450
δ 11.00(9.30, 16.20) 14.85(12.83, 24.35) 0.142
C3
α 50.15±14.87 36.09±16.86 0.020
β 20.78±12.44 22.76±12.16 0.659
θ 16.01±6.52 23.01±16.58 0.120
δ 9.70(7.60, 15.60) 19.75(10.58, 21.08) 0.091
C4
α 49.61±14.68 40.23±15.28 0.093
β 15.10(9.50, 26.80) 12.95(10.43, 25.60) 0.937
θ 17.89±9.41 24.69±17.53 0.179
δ 13.19±6.10 16.92±8.67 0.171
P3
α 50.10±15.49 37.94±15.62 0.039
β 18.89±12.48 20.48±10.98 0.712
θ 15.04±6.78 23.16±13.94 0.042
δ 11.70(8.10, 19.80) 16.00(9.18, 23.53) 0.463
P4
α 48.39±16.05 40.91±18.50 0.238
β 16.50(8.80, 28.10) 12.95(8.00, 19.35) 0.250
θ 12.30(8.70, 18.90) 14.00(9.05, 34.98) 0.451
δ 12.50(7.70, 23.80) 18.50(14.68, 24.30) 0.266
O1
α 55.16±18.86 45.31±23.27 0.203
β 17.81±14.62 16.82±12.19 0.841
θ 12.74±6.71 21.64±13.84 0.026
δ 11.60(7.30, 18.10) 13.50(7.85, 23.28) 0.525
O2
α 57.29±20.04 47.90±23.25 0.237
β 11.20(6.40, 20.60) 9.25(6.00, 16.73) 0.382
θ 12.00(7.40, 15.40) 16.45(10.95, 29.88) 0.131
δ 12.95±8.57 16.32±12.19 0.374
F7
α 45.08±14.95 35.04±15.43 0.077
β 16.65±9.67 14.30±8.84 0.489
θ 16.40(11.70, 22.00) 17.25(11.58, 29.23) 0.475
δ 15.60(12.10, 27.00) 23.50(19.30, 29.45) 0.226
F8
α 43.66±14.30 34.46±15.77 0.099
β 17.44±11.68 16.01±8.26 0.703
项目 轻度WML组
(n=17)		 中重度WML组
(n=14)		 P
θ 15.00(13.00, 18.20) 19.00(10.18, 40.23) 0.405
δ 22.35±10.00 23.35±10.69 0.790
T3
α 40.21±14.54 32.55±12.90 0.136
β 21.24±12.02 25.21±16.02 0.437
θ 16.40(12.00, 20.20) 15.40(10.30, 33.20) 0.905
δ 18.00(15.40, 22.00) 15.05(13.98, 18.38) 0.183
T4
α 41.40(23.90, 47.20) 22.25(18.80, 37.95) 0.074
β 25.15±12.49 28.09±18.83 0.607
θ 14.74±6.24 24.66±18.32 0.045
δ 22.39±11.62 18.30±9.81 0.304
T5
α 57.20(45.70, 61.10) 37.65(27.68, 44.90) 0.024
β 18.97±12.01 21.58±12.25 0.556
θ 14.96±6.30 19.43±8.70 0.109
δ 12.90(7.70, 14.80) 14.85(11.58, 29.90) 0.159
T6
α 45.05±16.80 41.96±20.89 0.651
β 11.70(11.10, 31.40) 14.20(9.85, 25.98) 0.905
θ 15.46±7.44 19.57±13.24 0.284
δ 19.32±11.16 19.32±12.30 0.999

2.2.2 频带快慢比比值

中重度WML组患者F7快慢比比值降低（P=0.045）。见表3。
表3 2组频带快慢比比值比较

Tab.3 Comparison of the ratio of frequency band speed and slowness of two groups

项目 轻度WML组
(n=17)		 中重度WML组
(n=14)		 P
FP1比值 2.27±0.94 1.67±1.35 0.154
FP2比值 1.98±0.93 1.45±0.98 0.132
F3比值 2.64±1.29 1.84±1.42 0.111
F4比值 2.57±1.24 1.77±1.10 0.069
C3比值 2.93±1.57 2.06±1.54 0.130
C4比值 2.51(2.16, 3.26) 2.01(1.02, 2.79) 0.284
P3比值 2.20(1.62, 3.95) 1.78(0.76, 2.33) 0.321
P4比值 2.78±1.44 2.02±1.72 0.189
O1比值 3.04(2.21, 4.92) 2.40(0.79, 3.43) 0.250
O2比值 3.22(2.33, 3.98) 2.02(0.66, 3.77) 0.159
F7比值 1.94±1.05 1.23±0.77 0.045
F8比值 1.75±0.67 1.35±1.03 0.201
T3比值 1.85±0.80 2.16±1.75 0.514
T4比值 1.80(1.36, 2.24) 1.44(0.71, 2.14) 0.302
T5比值 2.71±1.48 2.04±1.43 0.217
T6比值 2.10(1.36, 2.66) 1.75(0.95, 2.88) 0.721

2.3 Logistic回归分析

Logistic回归分析结果显示,高血压和T5 α频带相对能量值降低与中重度WML相关。见表4。
表4 WML的Logistic回归分析

Tab.4 logistic regression analysis of white matter lesions

变量 β OR(95%CI) P
高血压 3.680 39.51(3.07~508.08) 0.005
T5 α -0.089 0.915(0.841~0.995) 0.038

3 讨论

Kandiah等[2]研究报道,PD患者的记忆功能、执行功能及语言功能与WML的严重程度相关。国内有报道[8],在PD患者中,重度WML与记忆功能相关。Koshimori等[3]研究报道,PD合并WML的患者出现整体认知功能下降。本研究发现,PD合并中重度脑白质病变的患者整体认知水平下降,尤其表现为记忆功能受损,与既往报道一致,可能病理机制为WML破坏皮层胆碱能纤维与边缘系统的联系。
有研究报道[9],WMH患者常规脑电图上表现为慢波比例明显升高,可能机制为：神经纤维束的髓鞘及轴突受损等病理改变,导致脑内电网络异常（包括神经元间功能发生失联;突触兴奋传导及电活动减弱）[10],从而出现慢波发放或增多的异常表现[11];脑内皮质间或皮质-皮质下的信号传导通路受损可能导致认知功能障碍[10]。而目前对PD患者WMH的脑电研究极少,本研究进行了相关探索。
本研究发现：PD中重度WML组较轻度WML组,脑电图上C3,P3,T5 α频带相对能量值降低（具有统计学差异,P<0.05）;P3,O1,T4θ频带相对能量值升高（具有统计学差异,P<0.05）。脑电图上α频带能量值降低的可能机制包括：大脑皮层间及皮层-丘脑的神经元/突触受损,及基底节与皮层间胆碱能的损害;脑电图上的θ频带电活动增加可能与Meynert基底核的胆碱能损伤相关[12]。在PD中重度WML的患者中,脑电图上出现以上频带能量值的变化,可能与WML本身的病理损害导致皮层间及皮层-丘脑间发生失联,及WML破坏PD患者已受损的胆碱能纤维有关;以上假设可能需要通过联合脑内功能性连接的影像学来进一步证实。
经过Logistic逐步回归分析发现,在PD患者的QEEG上,T5 α频带相对能量值降低与PD患者WML的严重程度相关。有学者曾报道[2,3],PD认知功能障碍患者的WML易出现在与认知功能相关的额颞叶的皮质下区域,并导致与上述脑区相关的记忆功能、执行功能下降。其中,PD患者的颞区尤其是海马萎缩与认知功能障碍相关,而WML可能早于甚至促进皮质萎缩[13],且脑内WML可能以额颞叶皮质下区域为核心,逐渐向顶枕叶区进展[14],因此识别颞区的WML对于早期识别PD认知功能障碍患者具有重要意义。
本研究探索了QEEG与PD患者WML之间的关系,分析各脑区不同频带能量值的特点,以期探索WML影响PD认知功能障碍的可能机制。但本研究存在不足之处,对于研究结果可能有一定影响。未来研究中,拟进一步扩大样本量,比较PD无脑白质病变组,PD轻度、中度、重度脑白质病变组患者的定量脑电特点,进而分析QEEG的定量脑电指标与PD患者WML间的相关性。

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