多系统萎缩的诊断进展

doi:10.3969/j.issn.1003-9198.2025.02.003

摘要/Abstract

摘要： 多系统萎缩(MSA)是一种快速进展的神经退行性疾病,主要表现为帕金森病样症状群、小脑性共济失调和自主神经功能障碍等多种临床症状。目前临床上用于诊断MSA的生物标志物缺乏特异性,早期诊断困难,容易误诊。MRI和脑脊液(CSF)检查可辅助诊断MSA,但成本较高且特异性低;MSA最新的早期检测技术α-突触核蛋白正电子发射计算机断层扫描(PET)成像应用于临床还需要一定时间;血液和尿液α-突触核蛋白检测技术有可能用于临床诊断;神经丝轻链(NfL)和胶质纤维酸性蛋白(GFAP)也可作为MSA诊断的生物标志物,但仍需进一步研究。研发用于MSA诊断的精准分子生物学标志物至关重要,它可以彻底改变MSA的诊断和治疗,有助于疾病的早期干预及改善预后。

关键词: 多系统萎缩, 诊断, 帕金森病, α-突触核蛋白

Abstract: Multiple system atrophy(MSA) is a rapidly progressive neurodegenerative disease characterized by a variety of clinical symptoms such as Parkinson's disease-like symptom clusters, cerebellar ataxia and autonomic dysfunction. At present, the biomarkers used in clinical diagnosis of MSA lack specificity, which makes early diagnosis difficult and easy to misdiagnose. MRI and cerebro spinal fluid(CSF) examination can assist in the diagnosis of MSA, but they are costly and have low specificity. It will take some time for the latest early detection technology of MSA, α-synuclein positron emission computed tomography (PET) imaging, to be applied in clinical practice. Blood and urine α-synuclein testing has the potential to be used in clinical diagnosis. Neurofilament light chain (NfL) and glial fibrillary acidic protein(GFAP) can also be used as biomarkers for the diagnosis of MSA, but further research is needed. The development of precise molecular biomarkers for the diagnosis of MSA is crucial, as it can revolutionize the diagnosis and treatment of MSA, and will facilitate early intervention and improve prognosis of the disease.

Key words: multiple system atrophy, diagnosis, parkinson's disease, α-synuclein

中图分类号:

R 741

李琳, 刘安如, 万丽君, 刘学伍. 多系统萎缩的诊断进展[J]. 实用老年医学, 2025, 39(2): 116-120.

LI Lin, LIU Anru, WAN Lijun, LIU Xuewu. Advances in the diagnosis of multiple system atrophy[J]. Practical Geriatrics, 2025, 39(2): 116-120.

参考文献

[1] FANCIULLI A, WENNING G K. Multiple-system atrophy[J]. N Engl J Med, 2015,372(14): 1375-1376.
[2] HANNA AL-SHAIKH R, WERNICK A I, STRONGOSKY A J, et al. Spinocerebellar ataxia type 6 family with phenotypic overlap with multiple system atrophy[J]. Neurol Neurochir Pol, 2020, 54(4): 350-355.
[3] KÜHNEL L, RAKET L L, ÅSTRÖM D O, et al. Disease progression in multiple system atrophy-novel modeling framework and predictive factors[J]. Mov Disord, 2022, 37(8): 1719-1727.
[4] WENNING G K, STANKOVIC I, VIGNATELLI L, et al. The movement disorder society criteria for the diagnosis of multiple system atrophy[J]. Mov Disord, 2022, 37(6): 1131-1148.
[5] KOGA S, DICKSON D W. Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy[J]. J Neurol Neurosurg Psychiatry, 2018, 89(2): 175-184.
[6] KOGA S, AOKI N, UITTI R J, et al. When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients[J]. Neurology, 2015, 85(5): 404-412.
[7] KOGA S, SEKIYA H, KONDRU N, et al. Neuropathology and molecular diagnosis of synucleinopathies[J]. Mol Neurodegener, 2021, 16(1): 83.
[8] DUTTA S, HORNUNG S, KRUAYATIDEE A, et al. α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson's disease from multiple system atrophy[J]. Acta Neuropathol, 2021, 142(3): 495-511.
[9] KOGA S, DICKSON D W. “Minimal change” multiple system atrophy with limbic-predominant α-synuclein pathology[J]. Acta Neuropathol, 2019, 137(1): 167-169.
[10] JAIN R S, KUMAR S, TEJWANI S. Medullary hot-cross bun sign in multiple system atrophy-cerebellar[J]. J Med Imaging Radiat Sci, 2016, 47(1): 113-115.
[11] RULSEHA M, KELLER J, RUSZ J, et al. Diffusion tensor imaging in the characterization of multiple system atrophy[J]. Neuropsychiatr Dis Treat, 2016, 12: 2181-2187.
[12] JELLINGER K. Evaluation of multiple system atrophy subtypes with FDG-PET[J]. Ann Indian Acad Neurol, 2021, 24(4): 468.
[13] ZHAO P, ZHANG B, GAO S, et al. Clinical features, MRI, and 18F-FDG-PET in differential diagnosis of Parkinson disease from multiple system atrophy[J]. Brain Behav, 2020, 10(11): e01827.
[14] KING A E, MINTZ J, ROYALL D R. Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders[J]. Mov Disord, 2011,26(7): 1218-1224.
[15] ROSHANBIN S, XIONG M, HULTQVIST G, et al. In vivo imaging of alpha-synuclein with antibody-based PET[J]. Neuropharmacology, 2022, 208: 108985.
[16] VERGNET S, HIVES F, FOUBERT-SAMIER A, et al. Dopamine transporter imaging for the diagnosis of multiple system atrophy cerebellar type[J]. Parkinsonism Relat Disord, 2019, 63: 199-203.
[17] WALLERT E D, VANDE GIESSEN E, KNOL R J J, et al. Imaging dopaminergic neurotransmission in neurodegenerative disorders[J]. J Nucl Med, 2022, 63(Suppl1): 27S-32S.
[18] OTANI R T V, YAMAMOTO J Y S, NUNES D M, et al. Magnetic resonance and dopamine transporter imaging for the diagnosis of parkinson's disease: a narrative review[J]. Arq Neuropsiquiatr, 2022, 80(5Suppl 1): 116-125.
[19] SCHWEIGHAUSER M, SHI Y, TARUTANI A, et al. Structures of α-synuclein filaments from multiple system atrophy[J]. Nature, 2020, 585: 464-469.
[20] KIELY A P, ASI Y T, KARA E, et al. α-synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy?[J]. Acta Neuropathol, 2013, 125(5): 753-769.
[21] STROHÄKER T, JUNG B C, LIOU S H, et al. Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts[J]. Nat Commun, 2019, 10: 5535.
[22] MARTINEZ-VALBUENA I, VISANJI N P, KIM A, et al. Alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy[J]. Transl Neurodegener, 2022,11(1): 7.
[23] KURAPOVA R, CHOULIARAS L, O'BRIENJ T. The promise of amplification assays for accurate early detection of α-synucleinopathies: a review[J]. Exp Gerontol, 2022, 165: 111842.
[24] LAURENS B, CONSTANTINESCU R, FREEMAN R, et al. Fluid biomarkers in multiple system atrophy: a review of the MSA biomarker initiative[J]. Neurobiol Dis, 2015, 80: 29-41.
[25] DUTTA S, HORNUNG S, TAHA H B, et al. Development of a novel electrochemiluminescence ELISA for quantification of α-synuclein phosphorylated at Ser¹²⁹ in biological samples[J]. ACS Chem Neurosci, 2023, 14(7): 1238-1248.
[26] LINCOLN S J, ROSS O A, MILKOVIC N M, et al. Quantitative PCR-based screening of alpha-synuclein multiplication in multiple system atrophy[J]. Parkinsonism Relat Disord, 2007, 13(6): 340-342.
[27] PENG C, GATHAGAN R J, LEE V M. Distinct α-Synuclein strains and implications for heterogeneity among α-Synucleinopathies[J]. Neurobiol Dis, 2018, 109(Pt B): 209-218.
[28] ZHANG L, CAO B, HOU Y, et al. Neurofilament light chain predicts disease severity and progression in multiple system atrophy[J]. Mov Disord, 2022, 37(2): 421-426.
[29] BARGAR C, DE LUCA C M G, DEVIGILI G, et al. Discrimination of MSA-P and MSA-C by RT-QuIC analysis of olfactory mucosa: the first assessment of assay reproducibility between two specialized laboratories[J]. Mol Neurodegener, 2021, 16(1): 82.
[30] OLSZEWSKA D A, MARTINEZ-VALBUENA I, VISANJI N, et al. A rapid, ultra-sensitive, RT-QuIC assay, with novel protocol, for MSA and PD using a single site skin biopsy and serum neurofilament light chain.(P1-1.Virtual)[J]. Neurology, 2022, 98(18_supplement):116.
[31] WANG Z, BECKER K, DONADIO V, et al. Skin α-synucleinaggregation seeding activity as a novel biomarker for parkinson disease[J]. JAMA Neurol,2020, 78(1): 1-11.
[32] MANNE S, KONDRU N, JIN H, et al. α-Synuclein real-time quaking-induced conversion in the submandibular glands of Parkinson's disease patients[J]. Mov Disord, 2020, 35(2): 268-278.
[33] HEGMANS J P J J, GERBER P J, LAMBRECHT B N. Exosomes[J]. Methods Mol Biol, 2008, 484: 97-109.
[34] GOOLLA M, CHESHIRE W P, ROSS O A,et al. Diagnosing multiple system atrophy: current clinical guidance and emerging molecular biomarkers[J]. Front Neurol, 2023, 14: 1210220.