Parkinson-plus syndrome

Parkinson-plus syndrome, also called atypical parkinsonism or disorders of multiple system degeneration, is a group of neurodegenerative diseases that combine classic parkinsonism with additional features that separate them from idiopathic Parkinson disease, namely multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration and dementia with Lewy bodies.帕金森叠加综合征（Parkinson-plus syndrome，PPS）又称非典型帕金森综合征或多系统变性疾病，是一组在经典帕金森综合征基础上叠加其他特征、从而与特发性帕金森病区分的神经退行性疾病，包括多系统萎缩、进行性核上性麻痹、皮质基底节变性与路易体痴呆。

The four disorders split into synucleinopathies, in which alpha-synuclein accumulates, and tauopathies, in which four-repeat tau accumulates, and they share a poor or short-lived response to levodopa and faster progression than Parkinson disease.这四种疾病分为突触核蛋白病（α-突触核蛋白沉积）与 tau 蛋白病（四重复 tau 沉积），共同点是对左旋多巴反应差或短暂、比特发性帕金森病进展更快。

Pooled prevalence is about 3.6 per 100,000 for multiple system atrophy, 6.9 per 100,000 for progressive supranuclear palsy and 3.9 per 100,000 for corticobasal syndrome, against 100 to 300 per 100,000 for Parkinson disease, and no disease-modifying therapy is available for any of them.汇总患病率约为多系统萎缩每 10 万人 3.6 例、进行性核上性麻痹 6.9 例、皮质基底节综合征 3.9 例，而帕金森病为每 10 万人 100–300 例，且四者均无改变疾病进程的治疗。

Terminology and classification

• The term Parkinson-plus came into use in the 1980s for parkinsonism of supposed neurodegenerative cause that mimics Parkinson disease while adding cerebellar or pyramidal signs, and atypical parkinsonism has become the more current label in Movement Disorder Society usage.Parkinson-plus 一词在 20 世纪 80 年代开始用于指称模拟帕金森病并附加小脑或锥体束征的推测神经退行性帕金森综合征，在运动障碍学会的用法中「非典型帕金森综合征」已成为更时新的名称。^[1]
• Levin and colleagues proposed in 2016 the pathogenic two-group scheme that is now standard, with dementia with Lewy bodies and multiple system atrophy on the synucleinopathy side and progressive supranuclear palsy and corticobasal degeneration on the tauopathy side.Levin 等 2016 年提出现已成为标准的双组病理方案：路易体痴呆与多系统萎缩属突触核蛋白病一侧，进行性核上性麻痹与皮质基底节变性属 tau 蛋白病一侧。^[2]
• Older lists also admitted Pick disease and olivopontocerebellar atrophy, the latter now recognised as a cerebellar presentation of multiple system atrophy, and frontotemporal dementia with parkinsonism linked to chromosome 17 appears in the differential literature.较旧的名单还收入皮克病与橄榄桥小脑萎缩，后者现被认定是多系统萎缩的小脑表现，伴 17 号染色体连锁的额颞叶痴呆伴帕金森综合征则见于鉴别文献。
• ICD-11 MMS 2025-01 provides a single group code, 8A00.1 atypical parkinsonism, whose synonym list includes Parkinson-plus syndrome, with 8A00.10 for progressive supranuclear palsy and 8A00.1Y covering corticobasal degeneration, whereas ICD-10 has no group rubric and assigns G23.1 to progressive supranuclear palsy, G23.2 and G23.3 to the parkinsonian and cerebellar types of multiple system atrophy and G23.8 to other basal ganglia degenerations.ICD-11 MMS 2025-01 提供了单一组码 8A00.1「非典型帕金森综合征」，其同义词表收录（Parkinson-plus syndrome）这一名称，其中 8A00.10 为进行性核上性麻痹、8A00.1Y 涵盖皮质基底节变性，而 ICD-10 没有组类目，仅将 G23.1 归于进行性核上性麻痹、G23.2 与 G23.3 归于多系统萎缩的帕金森型与小脑型、G23.8 归于其他基底节变性。
• Multiple system atrophy moved to the autonomic chapter of ICD-11 as 8D87.0, a reclassification that separates it from the movement disorder block, and dementia with Lewy bodies is coded 6D82 in the mental disorders chapter and 8A22 in the nervous system chapter.多系统萎缩在 ICD-11 中被移入自主神经章节作 8D87.0，这一重分类使其脱离运动障碍块，路易体痴呆则在精神障碍章节编为 6D82、在神经系统章节编为 8A22。
• Cross-references include Wikidata Q2915552 and MeSH D020734 Parkinsonian Disorders, while no MONDO term exists for the group itself, and the constituent diseases map to MONDO:0007803, MONDO:0019037, MONDO:0022308 and MONDO:0007488 respectively.交叉索引包括 Wikidata Q2915552 与 MeSH D020734「帕金森性疾病」，而该组本身没有 MONDO 术语，各成员分别对应 MONDO:0007803、MONDO:0019037、MONDO:0022308 与 MONDO:0007488。

History

• Dejerine and Thomas described the cerebellar form of olivopontocerebellar atrophy in 1900, and Frederic Lewy discovered the inclusion bodies that bear his name in 1912.1900 年 Dejerine 与 Thomas 描述了橄榄桥小脑萎缩的小脑型，1912 年 Frederic Lewy 发现了以他命名的包涵体。
• Shy and Drager reported the autonomic presentation in 1960, Adams and colleagues the striatonigral form in 1961, and Steele, Richardson and Olszewski defined progressive supranuclear palsy as a separate disease in 1964.Shy 与 Drager 于 1960 年报道了自主神经型，Adams 等 1961 年报道纹状体黑质型，Steele、Richardson 与 Olszewski 则在 1964 年将进行性核上性麻痹定义为独立疾病。^[3][4]
• Rebeiz, Kolodny and Richardson described corticodentatonigral degeneration with neuronal achromasia in 1967, Graham and Oppenheimer proposed multiple system atrophy as the umbrella term in 1969, and Kosaka gave the first autopsy account of diffuse Lewy body disease in 1976.Rebeiz、Kolodny 与 Richardson 于 1967 年描述了伴神经元无色变的皮质齿状核黑质变性，Graham 与 Oppenheimer 1969 年提出多系统萎缩作为总括术语，Kosaka 则于 1976 年给出弥漫性路易体病的首份尸检描述。^[5]
• Papp and colleagues identified glial cytoplasmic inclusions as the cellular marker of multiple system atrophy in 1989, the same year in which Gibb and Marsden named corticobasal degeneration and Quinn proposed the first diagnostic criteria for multiple system atrophy.Papp 等 1989 年鉴定出胶质细胞胞质内包涵体作为多系统萎缩的细胞标志，同年 Gibb 与 Marsden 命名了皮质基底节变性，Quinn 提出了多系统萎缩的首个诊断标准。^[6]
• Two consensus documents in 1996 retired the Shy-Drager name and launched the international criteria for dementia with Lewy bodies, and in 1997 and 1998 Spillantini and colleagues showed that alpha-synuclein is the main component of Lewy bodies and of the glial inclusions, placing multiple system atrophy among the synucleinopathies.1996 年的两份共识文件停用了 Shy-Drager 病名并启动了路易体痴呆的国际标准；1997 与 1998 年 Spillantini 等证明 α-突触核蛋白是路易体体与胶质包涵体的主要成分，从而把多系统萎缩归入突触核蛋白病。^{[7][8][9][10]}
• The diagnostic standards then matured through the Gilman 2008 consensus for multiple system atrophy, the Armstrong 2013 criteria for corticobasal degeneration, the McKeith 2017 fourth consensus for dementia with Lewy bodies, the Hoglinger 2017 Movement Disorder Society criteria for progressive supranuclear palsy and the Wenning 2022 Movement Disorder Society criteria for multiple system atrophy.诊断标准随后经 2008 年 Gilman 多系统萎缩共识、2013 年 Armstrong 皮质基底节变性标准、2017 年 McKeith 第四份路易体痴呆共识、2017 年 Höglinger 运动障碍学会进行性核上性麻痹标准与 2022 年 Wenning 运动障碍学会多系统萎缩标准而成熟。^{[11][12][13][14][15]}
• One classification was explicitly corrected: the Shy-Drager label was abandoned in favour of multiple system atrophy with parkinsonian or cerebellar subtypes, and the Lewy body variant of Alzheimer disease was discarded when MeSH created a separate Lewy body disease descriptor in 2000.有一处分类被明确修正：Shy-Drager 名称被弃用，改为多系统萎缩的帕金森型或小脑型亚型；路易体痴呆的阿尔茨海默病变体称号也在 2000 年 MeSH 设立独立路易体病描述词时被废止。

Epidemiology

• A 2024 systematic review pooled multiple system atrophy prevalence at 3.6 per 100,000 with 95 percent confidence interval 2.2 to 5.0 and incidence at 0.9 per 100,000 person-years, with crude estimates from 0.5 per 100,000 in Spain to 17 per 100,000 in Japan.2024 年的一项系统综述汇总多系统萎缩患病率为每 10 万人 3.6 例（95% 置信区间 2.2–5.0）、发病率为每 10 万人年 0.9 例，粗估计从西班牙的每 10 万人 0.5 例到日本的 17 例不等。^[16]
• For progressive supranuclear palsy the pooled prevalence is 6.92 per 100,000 and for corticobasal syndrome 3.91 per 100,000, and progressive supranuclear palsy is roughly ten times as common as corticobasal degeneration.进行性核上性麻痹的汇总患病率为每 10 万人 6.92 例，皮质基底节综合征为 3.91 例，前者患病率约为后者的十倍。^[17]
• Dementia with Lewy bodies shows a pooled incidence of 4.79 per 100,000 person-years across all ages and a prevalence of 352 per 100,000 above age 65 in a 2026 meta-analysis, making it the second most common neurodegenerative dementia after Alzheimer disease.路易体痴呆在全年龄段的汇总发病率为每 10 万人年 4.79 例，2026 年一项荟萃分析中 65 岁以上患病率为每 10 万人 352 例，使其成为仅次于阿尔茨海默病的第二常见神经退行性痴呆。^[18]
• Clinical diagnosis of Parkinson disease reaches a pooled accuracy of 80.6 percent across clinicopathological studies, and misassignment among Parkinson disease and the atypical disorders ranges from 7 to 35 percent.临床病理研究汇总显示帕金森病的临床诊断准确率为 80.6%，而帕金森病与非典型疾病之间的误配率为 7%–35%。^[19]
• About 24 percent of patients with multiple system atrophy or progressive supranuclear palsy are initially mislabelled as idiopathic Parkinson disease, and 18.8 percent of autopsy-confirmed multiple system atrophy had presented with a mimic phenotype.约 24% 的多系统萎缩或进行性核上性麻痹患者最初被误标为特发性帕金森病，18.8% 的尸检确诊多系统萎缩曾以拟表型就诊。^[20]
• Survival differs markedly from Parkinson disease, with median survival of 6 to 10 years in multiple system atrophy, about 7 years in progressive supranuclear palsy, 6 to 8 years in corticobasal degeneration and about 4 years after diagnosis in dementia with Lewy bodies.生存期与帕金森病差异显著：多系统萎缩中位生存 6–10 年，进行性核上性麻痹约 7 年，皮质基底节变性 6–8 年，路易体痴呆确诊后约 4 年。
• Most cases are sporadic, age at onset clusters in the sixth and seventh decades, and population surveillance relies on disease registries and the IHME Global Burden of Disease framework rather than on dedicated atypical parkinsonism reporting.多数病例为散发性，起病年龄集中于六七十岁，人群监测依赖疾病登记系统与 IHME 全球疾病负担框架，而非针对非典型帕金森综合征的专门报告。
• For scale, Parkinson disease affects more than 6 million people worldwide and the atypical disorders account for a small minority of all degenerative parkinsonism, so most parkinsonism cohorts are dominated by the idiopathic disease.作为量级参照，帕金森病全球患者超过 600 万，非典型疾病仅占全部退行性帕金森综合征的少数，因此多数帕金森综合征队列仍以特发性疾病为主。^[19]

Pathophysiology

• In multiple system atrophy the alpha-synuclein load sits predominantly in oligodendrocytes as glial cytoplasmic inclusions, also called Papp-Lantos bodies, with limited neuronal pathology, a pattern that sets it apart from Parkinson disease and dementia with Lewy bodies.在多系统萎缩中，α-突触核蛋白负荷主要以胶质细胞胞质内包涵体（又称 Papp-Lantos 体）形式位于寡突胶质细胞，神经元病变有限，这一模式使其与帕金森病和路易体痴呆区别开来。
• Progressive supranuclear palsy shows tufted astrocytes and globose neurofibrillary tangles built from four-repeat tau, while corticobasal degeneration shows astrocytic plaques and ballooned neurons, and both are therefore described as astrogliopathies.进行性核上性麻痹表现为由四重复 tau 构成的簇状星形胶质细胞与球样神经原纤维缠结，皮质基底节变性则表现为星形胶质细胞斑与气球样神经元，二者因此被描述为星形胶质细胞病。
• The parkinsonism of the group arises from postsynaptic striatal and basal ganglia degeneration rather than from the presynaptic dopamine terminal loss of Parkinson disease, which explains why levodopa helps only about 30 percent of multiple system atrophy patients and only transiently.该组的帕金森综合征源于突触后纹状体与基底节退变，而非帕金森病的突触前多巴胺终末丢失，这解释了为何左旋多巴仅对约 30% 的多系统萎缩患者有帮助且疗效短暂。
• Progressive supranuclear palsy additionally degenerates the pallidum, subthalamic nucleus and upper brainstem gaze centres, which produces the vertical gaze palsy and early falls that dominate its phenotype.进行性核上性麻痹还累及苍白球、底丘脑核与上位脑干凝视中枢，从而产生主导其表型的垂直凝视麻痹与早期跌倒。
• The origin of the alpha-synuclein in oligodendrocytes remains unresolved, because those cells produce little or none themselves, leaving neuronal uptake and prion-like spread as competing explanations.寡突胶质细胞中 α-突触核蛋白的来源仍未解决，因为这些细胞自身几乎不产生该蛋白，神经元摄取与朊病毒样播散是相互竞争的解释。
• Alzheimer disease mixes three- and four-repeat tau, whereas the tauopathies of this group carry four-repeat tau only, a distinction that guides the design of tau-directed antibodies and explains their failure so far.阿尔茨海默病混合三重复与四重复 tau，而该组的 tau 蛋白病只携带四重复 tau，这一区别指导了 tau 靶向抗体的设计，也解释了它们迄今的失败。

Clinical features

• Red flags for multiple system atrophy include early severe autonomic failure within five years, nocturnal stridor, disproportionate antecollis, orofacial levodopa-induced dystonia and inspiratory sighs, whereas progressive supranuclear palsy is flagged by vertical supranuclear gaze palsy, square-wave jerks, early axial rigidity, frontal dementia and falls within the first year.多系统萎缩的红旗征包括五年内早期严重自主神经衰竭、夜间喘鸣、不成比例的前冲型颈肌张力障碍、左旋多巴诱发的口面部肌张力障碍与吸气性叹息，而进行性核上性麻痹的红旗征为垂直核上性凝视麻痹、方波急跳、早期轴性肌强直、额叶型痴呆与首年内跌倒。^[19]
• Corticobasal degeneration declares itself through asymmetric limb rigidity and apraxia, cortical sensory loss, alien limb phenomenon, focal myoclonus and early cognitive or language decline, and dementia with Lewy bodies through fluctuating attention, recurrent visual hallucinations and REM sleep behaviour disorder.皮质基底节变性以不对称肢体强直与失用、皮质型感觉缺失、异己肢现象、局灶性肌阵挛及早期认知或语言衰退为特征，路易体痴呆则以注意波动、反复视幻觉与快速眼动期睡眠行为障碍为特征。
• Complications across the group include aspiration pneumonia as the leading terminal event, falls with fractures, orthostatic syncope, urinary retention and infection, and pressure ulcers in immobile patients.全组的并发症包括为首位终末事件的误吸性肺炎、伴骨折的跌倒、体位性晕厥、尿潴留与感染，以及卧床患者的压疮。
• Special populations include older adults in whom vascular parkinsonism coexists, and patients whose disease is unmasked or worsened by antipsychotics, antiemetics and other dopamine-blocking drugs.特殊人群包括血管性帕金森综合征并存的老年人，以及疾病被抗精神病药、止吐药等多巴胺阻断药物诱发或加重的患者。
• REM sleep behaviour disorder frequently precedes the synucleinopathy members by years and counts among the core clinical features of the 2017 criteria for dementia with Lewy bodies, giving a window for early recognition.快速眼动期睡眠行为障碍常早于突触核蛋白病成员数年出现，属于 2017 年路易体痴呆标准的核心临床特征之一，为早期识别提供了窗口。^[13]
• Dysarthria and dysphagia appear early in progressive supranuclear palsy in contrast to Parkinson disease, apraxia of speech marks the language presentations of corticobasal degeneration, and aspiration follows within a few years.进行性核上性麻痹的构音障碍与吞咽困难出现较早，与帕金森病相反，皮质基底节变性的语言表现以言语失用为标志，误吸在数年内随之发生。

Diagnosis

• The diagnosis rests on named criteria, namely the 2022 Movement Disorder Society criteria for multiple system atrophy, the 2017 criteria for progressive supranuclear palsy, the 2013 Armstrong criteria for corticobasal degeneration and the 2017 McKeith criteria for dementia with Lewy bodies, each with graded certainty levels.诊断依据具名标准，即 2022 年运动障碍学会多系统萎缩标准、2017 年进行性核上性麻痹标准、2013 年 Armstrong 皮质基底节变性标准与 2017 年 McKeith 路易体痴呆标准，各自设有分级确定性。^{[15][14][12][13]}
• Magnetic resonance imaging shows putaminal atrophy and the hot cross bun sign in multiple system atrophy, midbrain atrophy with the hummingbird sign in progressive supranuclear palsy and asymmetric frontoparietal atrophy in corticobasal degeneration.磁共振成像在多系统萎缩中显示壳核萎缩与十字面包征，进行性核上性麻痹显示中脑萎缩伴蜂鸟征，皮质基底节变性显示不对称的额顶叶萎缩。
• Dopamine transporter SPECT confirms degenerative parkinsonism but cannot separate Parkinson disease from the atypical disorders, while cardiac MIBG scintigraphy separates dementia with Lewy bodies, with reduced uptake, from multiple system atrophy, where uptake is preserved.多巴胺转运体 SPECT 可确认退行性帕金森综合征，但无法区分帕金森病与非典型疾病，而心脏 MIBG 闪烁显像可将摄取减低的路易体痴呆与摄取保留的多系统萎缩区分开。
• Differential diagnosis includes idiopathic Parkinson disease with its asymmetric onset, resting tremor and sustained levodopa response, drug-induced parkinsonism with a normal dopamine transporter scan, vascular parkinsonism with lower-body predominance and white matter disease, and normal pressure hydrocephalus with its gait, urinary and cognitive triad.鉴别诊断包括特发性帕金森病（不对称起病、静止性震颤与持续的左旋多巴反应）、药物性帕金森综合征（多巴胺转运体扫描正常）、血管性帕金森综合征（下肢为主伴白质病变）与正常压力脑积水（步态、泌尿与认知三联征）。
• At the pathology level corticobasal syndrome is a phenotype rather than a diagnosis, since autopsy series assign only 30 to 35 percent to corticobasal degeneration, 25 to 30 percent to progressive supranuclear palsy and 20 to 25 percent to Alzheimer disease, so the clinical label must not be equated with the histological entity.在病理层面，皮质基底节综合征是表型而非诊断，因为尸检系列中仅 30%–35% 归于皮质基底节变性、25%–30% 归于进行性核上性麻痹、20%–25% 归于阿尔茨海默病，因此临床标签不能等同于组织学实体。
• Polysomnography confirms REM sleep without atonia and supports the 2017 criteria, while routine blood tests, neurophysiology and imaging serve mainly to exclude Wilson disease, metabolic mimics and structural lesions.多导睡眠图证实快速眼动期肌张力缺失并支持 2017 年标准，而常规血液检查、神经电生理与影像主要用于排除威尔逊病、代谢性拟病与结构性病变。^[13]

Management

• No disease-modifying treatment exists for any member of the group, and the 2016 differential diagnosis and treatment review states plainly that available symptomatic treatments are of limited efficacy and supported only by low-level evidence.该组任何成员都没有改变疾病的治疗，2016 年的鉴别与治疗综述明确指出现有对症治疗疗效有限且仅有低级别证据支持。^[2]
• A levodopa trial remains worthwhile because about 30 percent of multiple system atrophy patients and some progressive supranuclear palsy parkinsonism subtypes respond at least transiently, and amantadine is a second-line option in progressive supranuclear palsy.左旋多巴试验仍有价值，因为约 30% 的多系统萎缩患者与部分进行性核上性麻痹帕金森亚型至少有短暂反应，金刚烷胺则是进行性核上性麻痹的二线选择。
• Botulinum toxin is first-line for sialorrhea in progressive supranuclear palsy and corticobasal syndrome under the 2021 CurePSP best-practice consensus, and the largest series reported improvement in 65.2 percent of treated patients with about four months of benefit.根据 2021 年 CurePSP 最佳实践共识，肉毒毒素是进行性核上性麻痹与皮质基底节综合征流涎的一线治疗，最大系列报告 65.2% 的受治患者改善、获益约四个月。^[21]
• Neurogenic orthostatic hypotension is treated with midodrine, droxidopa or fludrocortisone, and the droxidopa phase 3 trial that included multiple system atrophy patients improved the orthostatic hypotension questionnaire composite by 0.90 units.神经源性体位性低血压以米多君、屈昔多巴或氟氢可的松治疗，纳入多系统萎缩患者的屈昔多巴 3 期试验使体位性低血压问卷复合评分改善 0.90 个单位。^[22]
• Rivastigmine improved cognition and neuropsychiatric features in dementia with Lewy bodies, with 63 percent of treated patients reaching a 30 percent improvement on the neuropsychiatric inventory against 30 percent on placebo, without worsening parkinsonism.利伐斯的明改善路易体痴呆的认知与神经精神特征，63% 的受治患者在神经精神量表上达到 30% 改善，安慰剂组为 30%，且不加重帕金森综合征。^[23]
• The riluzole NNIPPS trial in multiple system atrophy and progressive supranuclear palsy was negative for survival, the clearest demonstration that broad neuroprotection has so far failed in this group.在多系统萎缩与进行性核上性麻痹中开展的利鲁唑 NNIPPS 试验在生存期上为阴性，最清楚地表明广谱神经保护在该组中迄今失败。^[24]
• Guidance for care comes from the 2016 Levin review, the 2019 treatment progress review, the 2021 CurePSP consensus and the 2024 Lancet Neurology review of multiple system atrophy, and multidisciplinary rehabilitation addresses gait, swallowing and communication.诊疗指引来自 2016 年 Levin 综述、2019 年治疗进展综述、2021 年 CurePSP 共识与 2024 年《柳叶刀·神经病学》多系统萎缩综述，多学科康复则针对步态、吞咽与交流。^[25][26]
• Non-drug care carries much of the burden, with physiotherapy for gait and balance, speech therapy for dysphagia and aspiration risk, nutritional support including percutaneous gastrostomy when swallowing fails, and early palliative involvement.非药物照护承担了大部分负担，包括针对步态与平衡的物理治疗、针对吞咽困难与误吸风险的语言治疗、吞咽失败时经皮胃造口等营养支持，以及早期舒缓疗护介入。

Research and controversies

• Emrusolmin, an oral small-molecule alpha-synuclein oligomer modulator, is being tested in the 56-week TOPAS-MSA phase 2 trial with 160 participants, the first large placebo-controlled disease-targeting study in multiple system atrophy.口服小分子 α-突触核蛋白寡聚体调节剂（emrusolmin）正在 56 周的 TOPAS-MSA 2 期试验中接受检验，共 160 名受试者，这是多系统萎缩首个大型安慰剂对照的靶向疾病研究。
• On the tau side the gosuranemab PASSPORT phase 2 trial in progressive supranuclear palsy was negative despite a 98 percent reduction in cerebrospinal fluid free N-terminal tau, a result that prompted a wide debate on whether tau immunotherapy is too late, aimed at the wrong epitope or the wrong target.在 tau 一侧，抗 tau 单克隆抗体（gosuranemab，BIIB092）的 PASSPORT 2 期试验在脑脊液游离 N 端 tau 降低 98% 的情况下仍然阴性，这一结果引发了关于 tau 免疫治疗是太迟、表位错误还是靶点错误的广泛争论。^[27]
• Neflamapimod, an oral p38 alpha kinase inhibitor, showed a 52 percent improvement on the clinical dementia rating scale sum of boxes in the extended RewinD-LB study in dementia with Lewy bodies and has advanced toward a phase 3 programme.口服 p38α 激酶抑制剂（neflamapimod）在路易体痴呆的 RewinD-LB 延长研究中使临床痴呆评定量表总分改善 52%，并已推进至 3 期项目。^[28]
• A first controversy is nosological, since dementia with Lewy bodies sits at the boundary of the group and the one-year rule that separates it from Parkinson disease dementia is acknowledged by the consensus itself to be arbitrary.第一重争议是分类学的：路易体痴呆位于该组的边界，而将其与帕金森病痴呆分开的一年规则被共识自身承认为武断。
• A second controversy is mechanistic, because the oligodendroglial alpha-synuclein of multiple system atrophy cannot be explained by local synthesis, and the choice between neuronal uptake and glial seeding determines whether anti-synuclein antibodies can work at all.第二重争议是机制性的：多系统萎缩的寡突胶质 α-突触核蛋白无法用原位合成解释，而在神经元摄取与胶质接种之间的选择决定了抗突触核蛋白抗体究竟能否起效。