帕金森病非运动症状刘卫国课件

帕金森病非运动症状帕金森病非运动症状 (non-motor symptoms in PD) 刘 卫 国 博 士 南京医科大学附属脑科医院 非运动性症状的组成和分类 n神经 精神症状 抑郁、焦虑、冷漠 缺乏快感、注意力缺陷 幻觉、错觉 痴呆 强迫行为 n睡眠障碍不宁腿综合征(RLs) 周期性肢体运动(PLM) 快速眼动(REM)睡眠及非快速眼动 睡眠行为障碍 白日嗜睡、失眠 n自主神经 系统症状 膀胱功能障碍(尿频、尿急、夜尿) 潮热多汗 体位性低血压及其引起的跌倒 性功能障碍(性欲亢进、阳痿、性 激素分泌不足) n胃肠道 症状 吞咽困难、食管反流 恶心、呕吐 便秘、大便失禁 n其他症 状 疼痛 感觉异常、嗅觉异常 疲劳 复视、视力模糊 油脂面容 体质量降低 病理基础 原发性非运动性症状 黑质和纹状体结构之外的相关神经核团和 结构的直接或间接受损 继发性非运动性症状 抗帕金森病药物的不良反应所引起 帕金森病病变（新认识） 首先在脑内开始吗？ 吸收毒素？ 吸入毒素？ 黑质并不是首先 受影响的部位 Braak Stages of CNS Pathology for PD 帕金森病病理分级: Braak 2003 帕金森病病理并非始于黑质致密部 n 运动前期1：(延髓:IX,X运动神经背核,前嗅核,嗅球und/oder 中央网状带/intermediate reticular zone)嗅觉； n 运动前期2：(延髓和桥脑被盖:尾状核、中缝核/caudal raphe nuclei, 巨细胞核/gigantocellular nucleus, 基底前脑/basal prosencephalon和中间皮质/ mesocortex, 蓝斑下区合成物 /coeruleus-subcoeruleus complex) 睡眠，头痛，运动减少，情 感 n 运动前期3：(+中脑:黑质致密部) 色觉，体温调节，认知，抑 郁，背疼； n 期4：四主症； n 期5：(新皮层) 运动波动，频发疲劳； n 期6：(新皮层) 错乱，视幻觉，痴呆，精神症状 非运动性症状的认识一诊断一治疗流程 n“认识”过程-仅仅起到一个线索的 作用 n“诊断”过程 定性问题-如何确认非运动性症状，分 清是原发性还是继发性 定量问题-确认后又如何量化非运动性 症状并评估其严重程度-量表 非运动性症状的认识一诊断一治疗流程 n如何“治疗” 药物治疗为主，同时辅以必要的康复治 疗甚至外科手术治疗 (1)辨证处理、对症加减 (2)早期服药、改善症状 (3)权衡利弊、调整用药 一.非运动症状自评量表NMSQuest 研 究 方 法 量表研究： 非运动症状自评量表NMSQuest 研究人群 n PD病人组:南京医科大学附属脑科 医院 帕金森专病门诊120例病人 n 对照组：102例健康中老年人 Chaudhuri KR ，et al. 2006 一般信息 PD组对照 总 数120102 男性比例（%）65%58% 年龄（岁）65.739.36岁64.5210.65 病程（年）3.763.19 平均HY值2.14 （1-5） 服用L-DOPA82%（28%单药 ） 服用DA激动剂42%（3%单药） PD病人 NMSQuest百分比分布（1） PD病人 NMSQuest百分比分布（2） NMS和病情严重性的关系 轻度，H-Y分期1，1.5和2期，中度，H-Y分期2.5和3期，重度H-Y分期4和5 期，KruskalWallis test ，pselegiline and amantadine Dopamine agonists and COMTinhibitors Standard levodopa) nCognitive deterioration-cholinesterase inhibitors nA compromise between motor function and mental state Initiated at low doses, Drug holidays should be avoided nNew atypical antipsychotics Clozapine(氯氮平 conventional analgesic treatments Pain Fatigue (33% to 58% ) nA sense of tiredness, lack of energy or total body give out nAnxiety and activities of daily life nDisease severity, and excessive daytime somnolence (EDS) pSleep, gender, age, depression. pMotor dysfunction or depression nTreatment poorly understood generally under-recognized no known treatment Conclusions PD Honeymoon period Dopa-resistant motor symptoms (speech impairment, abnormal posture and balance) Dopa-resistant non-motor signs (cognitive and neuropsychiatric impairment, autonomic dysfunction, sleep disorders) Drug-related side effects (psychosis, motor fluctuations, dyskinesias) Balanced in weighing motorand non-motor Reducing symptom severity-reduce disability Algorithm for diagnosing PD-D at Level I 1 A diagnosis of Parkinsons disease based on the Queens Square Brain Bank criteria for PD 2 PD developed prior to the onset of dementia 3 MMSE below 26 4 Cognitive deficits severe enough to impact daily living (Caregiver interview or Pill Questionnaire) 5 Impairment in at least two of the following tests: Months reversed or Seven backward Lexical fluency or Clock drawing MMSE Pentagons 3-Word recall PD Associated With a Decreased Global Cognitive Efficiency MiniMental Status Examination n Cutoff proposed: score 26 n below the age of 80 n at least 10 years of formal education Impairment in More Than One Cognitive Domain (-Attention ) Serial 7s of the MMSE nSubtract 7 starting at 100 nThe instructions should not be repeated. nCutoff proposed: At least two incorrect responses. Months reversed nGive the months of year backward, starting from December nCutoff proposed: Omission of two or more months, incorrect sequencing of the months, or failure to complete the test within 90 seconds Impairment in More Than One Cognitive Domain (-Executive Function ) Lexical Fluency nNumber of words beginning with the letter S in 1 minute. n Cutoff proposed: A score 9 words Clock Drawing Test n Draw a clock with the hands showing 10 past 2 n Cutoff proposed: Inability to insert the correct clock face numbers and/or the clock hands pointing to the correct time. Impairment in More Than One Cognitive Domain (-Visuo-Constructive Ability ) Drawing of the MMSE pentagons. nThe patients are asked to copy the two intercepting pentagons. nCutoff proposed: The copy should include two pentagons that overlap. Impairment in More Than One Cognitive Domain (-Memory Impairment ) n3-Word Recall of the MMSE nCutoff proposed: At least one missing word The recommended cut off is appropriate in patients below the age of 80 and in those with at least 10 years of formal education THE PILL QUESTIONNAIRE Question 1a: In patients with PD, which are the most accurate tools to screen for depression? Conclusions the Beck Depression Inventory (BDI) (one Class I) and the Hamilton Depression Rating Scale (HDRS) (two Class II) Based on one Class II study, the Montgomery Asberg Depression Rating Scale (MADRS) Recommendation. The BDI and HDRS should be considered (Level B). MADRS may be considered for (Level C). Question 1b: In patients with PD, which are the most accurate tools to screen for psychosis? Conclusion. Based on one Class IV study, there is insufficient evidence to support or refute PPRS as a screening tool for psychosis in PD (Level U). Recommendation. No recommendation is made Question 1c: In patients with PD, which are the most accurate tools to screen for dementia? Conclusion. The MMSE and CAMCog are probably useful for screening patients with PD and DSM-defined dementia (one Class I). The MMSE is as sensitive as the CAMCog and quicker to administer, but less specific. Recommendation. The MMSE and the CAMCog should be considered as screening tools for dementia in patients with PD (Level B). Question 2: In patients with PD, what is the best pharmacologic treatment for depression? Conclusions. Amitriptyline is possibly effective (Class II) . Insufficient evidence to support or refute the efficacy of other specific antidepressants. Anticholinergic side effects (potential worsening of cognition, orthostatic hypotension ,risk of falls. Recommendations. Amitriptyline may be considered (Level C). Although the highest level of evidence is for amitriptyline, it is not necessarily the first choice Insufficient evidence to make recommendations regarding other treatments for depression in PD. Absence of literature demonstrating clear efficacy of non- tricyclic antidepressants is not the same as absence of efficacy Question 2c. In patients with PD and psychosis, what is the best treatment? Conclusions. one Class I study and one Class II study demonstrated that clozapine is probably an effective treatment. Clozapine improved psychosis and resulted in improved motor function in some cases. One Class II study demonstrated that quetiapine possibly improves psychosis in PD. Two Class II studies demonstrated that olanzapine probably does not improve psychosis and worsens motor function Recommendations. clozapine should be considered (Level B). Clozapine use is associated with agranulocytosis that may be fatal. The absolute neutrophil count must be monitored. Monitoring requirements may vary according to country. For patients with PD and psychosis, quetiapine may be considered (Level C). For patients with PD and psychosis, olanzapine should not