进行性核上性麻痹研究新进展

进行性核上性麻痹为神经变性疾病,早期症状不典型,需与帕金森病、橄榄脑桥小脑萎缩、阿尔茨海默病、皮质基底节变性等疾病相鉴别。其临床表现包括垂直性核上性眼肌麻痹、帕金森综合征、轴性肌张力增高、姿势不稳、假性延髓性麻痹以及认知功能障碍等。影像学检查对诊断有重要作用。文中就进行性核上性麻痹的发病机制、临床表现、影像学特点、诊断标准等研究进展予以介绍。     

Utility of the Midbrain Tegmentum Diameter in the Differential Diagnosis of Progressive Supranuclear Palsy from Idiopathic Parkinson's Disease

Background and Purpose

Various magnetic resonance (MR) measurements have been proposed to aid in differentiating between progressive supranuclear palsy (PSP) and idiopathic Parkinson''s disease (IPD); however, these methods have not been compared directly. The aim of this study was to determine which measurement method exhibits the highest power to differentiate between PSP and IPD.

Methods

Brain MR images from 82 IPD and 29 PSP patients were analyzed retrospectively. T1-weighted 3D volumetric axial images, or sagittal images reconstructed from those axial images were examined. MR measurements included the length from the interpeduncular fossa to the center of the cerebral aqueduct at the mid-mammillary-body level, adjusted according to the anterior commissure-posterior commissure length (MB^Tegm), the ratio of the midbrain area to the pons area (M/P ratio) as measured by both Oba''s method (Oba M/P) and Cosottini''s method (Cosottini M/P), and a modified MR parkinsonism index (mMRPI).

Results

Receiver operating characteristic (ROC) analysis indicated that the areas under the ROC curves (AUCs) exceeded 0.70, with a high intrarater reliability for all MR measurement methods. ROC analyses of four MR measurements yielded AUCs of 0.69-0.76. At the cutoff value with the highest Youden index, mMRPI had the highest sensitivity, while Oba M/P offered the highest specificity. A comparison of the ROC analyses revealed that MB^Tegm was superior to mMRPI in differentiating PSP from IPD (p=0.049). There was no difference in discriminating power among Oba M/P, Cosottini M/P, and MB^Tegm.

Conclusions

Simple measurements of MB^Tegm on axial MR images at the mid-mammillary-body level are comparable to measurements of the M/P ratio with regard to their ability to discriminate PSP from IPD.     

Immunohistochemical Features which Distinguish Pallido-Nigro-Luysial Atrophy from Progressive Supranuclear Palsy

Abstract: Pallido-nigro-luysial atrophy (PNLA) and progressive supranuclear palsy (PSP) have similar clinical features and somewhat similar classical pathology. We describe here their differentiation on the basis of immunohistochemistry. We examined three autopsy cases of typical PSP and one case demonstrating PNLA. Biochemically, all four cases showed greatly depleted striatal catecholamines. Immunohistochemistry for complement, Tau and some other proteins revealed in all cases pathology beyond the classically described areas of involvement. PSP cases were characterized by the appearance of many Tau-positive, paired nucleated glia with astrocyte morphology in numerous brain areas; none were seen in the PNLA case. The PSP cases also showed many more complement activated oligodendrocytes and oligodendroglial microtubular masses than did the PNLA case. On the other hand, the PNLA case showed more abundant neuropil threads.     

Behavioral Changes as the Earliest Clinical Manifestation of Progressive Supranuclear Palsy

Background

The clinical and pathological heterogeneity of progressive supranuclear palsy (PSP) is well established. Even with a well-defined clinical phenotype and a thorough laboratory workup, PSP can be misdiagnosed, especially in its early stages.

Case Report

A 52-year-old woman, who we initially diagnosed with a behavioral variant of frontotemporal dementia developed parkinsonian features, which then progressed to gait instability and gaze abnormality.

Conclusions

We report herein a pathologically confirmed case of PSP presenting with behavioral changes including agitation and irritability, which eventually led to the cardinal symptoms of progressive supranuclear palsy.     

进行性核上性麻痹与多系统萎缩的头部MRI和FDG-PET比较

目的对比研究进行性核上性麻痹(PSP)与多系统萎缩(MSA)的脑干MRI表现和头部葡萄糖代谢特征。方法对11例PSP患者、37例MSA患者和43例健康对照进行头部MRI平扫检查,并计算MRI正中矢状面T1加权像上中脑截面面积,其中5例PSP和19例MSA进行了18F-FDG PET检查。结果(1)MRI:11例PSP正中矢状位T1加权像均可见中脑上缘平坦或凹陷表现,呈"蜂鸟征",而MSA患者和健康对照组未见上述表现。37例MSA患者中有34例轴位T2加权像桥脑可见"十字征"样长T2异常信号。PSP患者正中矢状位T1加权像上中脑截面面积分别低于MSA组和健康对照组(P<0.01)。(2)PET:PSP组主要表现为对称性额叶低代谢;MSA组主要表现为额、顶、颞叶普遍低代谢,纹状体对称性代谢降低,丘脑代谢高于纹状体。结论PSP中脑MRI特征和头部葡萄糖代谢特征与MSA和健康对照有明确差异,有助于PSP与MSA的鉴别诊断。     

Familial aggregation in Progressive Supranuclear Palsy and Corticobasal Syndrome

Background: Studies on familial aggregation might be of help to evaluate whether the genetic background has a key role in Progressive Supranuclar Palsy (PSP) and Corticobasal Syndrome (CBS). Only a few studies are available. Objective: To evaluate the prevalence of positive family history (FH) in PSP and CBS in a large sample of patients. Methods: Two hundred and thirty patients and 110 controls entered the study. Patients underwent an extensive clinical, neurological and neuropsychological assessment as well as a structural brain imaging study. A clinical follow‐up further confirmed the diagnosis. Familial aggregation was carefully recorded by a standardised questionnaire. Results: One hundred and twenty‐nine PSP (age at onset = 66.6 ± 7.3, female = 46.1%) and 101 CBS (age at onset = 62.8 ± 8.9, female = 41.6%) were consecutively enrolled. Positive FH was found in 31.8% of PSP (n = 41) and in 31.7% of CBS (n = 32). Familial aggregation was lower in the age‐matched control group compared to patient group (21.8%, P = 0.05). Patients with PSP had higher positive FH for Parkinsonism (63.4%) when compared to FH for dementia (36.6%). In CBS, FH was equally distributed between Parkinsonism (53.1%) and dementia (46.9%). In addition, FH was not associated with age at disease onset in PSP (FH+ versus FH−, 67.0 ± 7.3 vs. 66.7 ± 7.1, P = 0.788) and in CBS (62.6 ± 7.9 vs. 62.9 ± 9.5, P= 0.877). Conclusions: These results argue for familial aggregation in PSP and CBS, further underlying the importance of genetic background in these disorders. Further studies on possible genetic modulators or genetic epistasis contributing to PSP and CBS development are warranted.     

进行性核上性麻痹患者脑部葡萄糖代谢特征分析

目的：利用^18F-脱氧葡萄糖（^18F-FDG）正电子发射断层扫描成像（PET）分析进行性核上性麻痹（PSP）患者脑部葡萄糖代谢特征。方法：7例临床确诊的PSP患者（PSP组）和14例年龄匹配的健康对照者（对照组）行静息状态下^F—FDGPET脑成像,将两组的PET图像分别进行统计参数图（SPM）及尺度子轮廓模型／主要成分分析（SSM／PCA）研究,获得PSP患者脑部葡萄糖异常代谢图像并建立PSP脑代谢网络模式（PSPRP）。结果：SPM分析显示,与对照组比较,PSP组双侧内侧前额叶、腹外侧前额叶、尾状核、丘脑和中脑的葡萄糖代谢降低,双侧中央前回、顶上小叶、顶下小叶葡萄糖代谢增高。SSM／PCA分析显示PSPRP的特征表现为双侧内侧前额叶、腹外侧前额叶、尾状核、丘脑和中脑的葡萄糖代谢显著减低,而双侧顶叶代谢显著增高。PSP组的PSPRP表达值（1．711±1．218）明显高于对照组（0．043±O．496,t=-5．379,P=0．001）。结论：基于18F-FDGPET显像得到的脑部异常葡萄糖代谢特征可以有效鉴男IJPSP患者和健康对照者。     

Cerebrospinal Fluid Biomarkers of Synaptic Dysfunction are Altered in Parkinson's Disease and Related Disorders

Background

Synaptic dysfunction and degeneration are central contributors to the pathogenesis and progression of parkinsonian disorders. Therefore, identification and validation of biomarkers reflecting pathological synaptic alterations are greatly needed and could be used in prognostic assessment and to monitor treatment effects.

Objective

To explore candidate biomarkers of synaptic dysfunction in Parkinson's disease (PD) and related disorders.

Methods

Mass spectrometry was used to quantify 15 synaptic proteins in two clinical cerebrospinal fluid (CSF) cohorts, including PD (n₁ = 51, n₂ = 101), corticobasal degeneration (CBD) (n₁ = 11, n₂ = 3), progressive supranuclear palsy (PSP) (n₁ = 22, n₂ = 21), multiple system atrophy (MSA) (n₁ = 31, n₂ = 26), and healthy control (HC) (n₁ = 48, n₂ = 30) participants, as well as Alzheimer's disease (AD) (n₂ = 23) patients in the second cohort.

Results

Across both cohorts, lower levels of the neuronal pentraxins (NPTX; 1, 2, and receptor) were found in PD, MSA, and PSP, compared with HC. In MSA and PSP, lower neurogranin, AP2B1, and complexin-2 levels compared with HC were observed. In AD, levels of 14-3-3 zeta/delta, beta- and gamma-synuclein were higher compared with the parkinsonian disorders. Lower pentraxin levels in PD correlated with Mini-Mental State Exam scores and specific cognitive deficits (NPTX2; rho = 0.25–0.32, P < 0.05) and reduced dopaminergic pre-synaptic integrity as measured by DaTSCAN (NPTX2; rho = 0.29, P = 0.023). Additionally, lower levels were associated with the progression of postural imbalance and gait difficulty symptoms (All NPTX; β-estimate = −0.025 to −0.038, P < 0.05) and cognitive decline (NPTX2; β-estimate = 0.32, P = 0.021).

Conclusions

These novel findings show different alterations of synaptic proteins in parkinsonian disorders compared with AD and HC. The neuronal pentraxins may serve as prognostic CSF biomarkers for both cognitive and motor symptom progression in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Whole-Brain Magnetic Resonance Spectroscopy Reveals Distinct Alterations in Neurometabolic Profile in Progressive Supranuclear Palsy

Background

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian syndrome characterized by supranuclear gaze palsy, early postural instability, and a frontal dysexecutive syndrome. Contrary to normal brain magnetic resonance imaging in Parkinson's disease (PD), PSP shows specific cerebral atrophy patterns and alterations, but these findings are not present in every patient, and it is still unclear if these signs are also detectable in early disease stages.

Objective

The aim of the present study was to analyze the metabolic profile of patients with clinically diagnosed PSP in comparison with matched healthy volunteers and PD patients using whole-brain magnetic resonance spectroscopic imaging (wbMRSI).

Methods

Thirty-nine healthy controls (HCs), 29 PD, and 22 PSP patients underwent wbMRSI. PSP and PD patients were matched for age and handedness with HCs. Clinical characterization was performed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, PSP rating scale, and DemTect (test for cognitive assessment).

Results

In PSP patients a significant reduction in N-acetyl-aspartate (NAA) was detected in all brain lobes. Fractional volume of the cerebrospinal fluid significantly increased in PSP patients compared to PD and healthy volunteers.

Conclusions

In PSP much more neuronal degeneration and cerebral atrophy have been detected compared with PD. The most relevant alteration is the decrease in NAA in all lobes of the brain, which also showed a partial correlation with clinical symptoms. However, more studies are needed to confirm the additional value of wbMRSI in clinical practice. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Major Depressive Disorder Preceding the Onset of Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by vertical supranuclear palsy and parkinsonian symptoms. The neuropsychiatric symptoms of PSP include anhedonia, depressed mood and cognitive impairment. Patients with PSP have an increased risk for developing depressive disorders within the next year. However, it is rare to find that major depressive disorder was the antecedent diagnosis of a patient who was later diagnosed with PSP. We present here a patient who suffered from PSP with repetitive falls, a masked face and dysarthria after developing a major depressive disorder.