Evolution of Clinical Outcome Measures and Biomarkers in Sporadic Adult-Onset Degenerative Ataxia.
multiple system atrophy
natural history
neurofilament light chain
sporadic ataxia
volumetric MRI
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
11
11
2022
received:
12
09
2022
accepted:
22
12
2022
medline:
18
4
2023
pubmed:
26
1
2023
entrez:
25
1
2023
Statut:
ppublish
Résumé
Sporadic adult-onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA-C) and sporadic adult-onset ataxia of unknown etiology (SAOA). To study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers. SPORTAX is a prospective registry of sporadic ataxia patients with an onset >40 years. Scale for the Assessment and Rating of Ataxia was the primary outcome measure. In subgroups, blood samples were taken and MRIs performed. Plasma NfL was measured via a single molecule assay. Regional brain volumes were automatically measured. To assess signal changes, we defined the pons and middle cerebellar peduncle abnormality score (PMAS). Using mixed-effects models, we analyzed changes on a time scale starting with ataxia onset. Of 404 patients without genetic diagnosis, 130 met criteria of probable MSA-C at baseline and 26 during follow-up suggesting clinical conversion to MSA-C. The remaining 248 were classified as SAOA. At baseline, NfL, cerebellar white matter (CWM) and pons volume, and PMAS separated MSA-C from SAOA. NfL decreased in MSA-C and did not change in SAOA. CWM and pons volume decreased faster, whereas PMAS increased faster in MSA-C. In MSA-C, pons volume had highest sensitivity to change, and PMAS was a predictor of faster progression. Fulfillment of possible MSA criteria, NfL and PMAS were risk factors, CWM and pons volume protective factors for conversion to MSA-C. This study provides detailed information on differential evolution and prognostic relevance of biomarkers in MSA-C and SAOA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
Sporadic adult-onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA-C) and sporadic adult-onset ataxia of unknown etiology (SAOA).
OBJECTIVES
To study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers.
METHODS
SPORTAX is a prospective registry of sporadic ataxia patients with an onset >40 years. Scale for the Assessment and Rating of Ataxia was the primary outcome measure. In subgroups, blood samples were taken and MRIs performed. Plasma NfL was measured via a single molecule assay. Regional brain volumes were automatically measured. To assess signal changes, we defined the pons and middle cerebellar peduncle abnormality score (PMAS). Using mixed-effects models, we analyzed changes on a time scale starting with ataxia onset.
RESULTS
Of 404 patients without genetic diagnosis, 130 met criteria of probable MSA-C at baseline and 26 during follow-up suggesting clinical conversion to MSA-C. The remaining 248 were classified as SAOA. At baseline, NfL, cerebellar white matter (CWM) and pons volume, and PMAS separated MSA-C from SAOA. NfL decreased in MSA-C and did not change in SAOA. CWM and pons volume decreased faster, whereas PMAS increased faster in MSA-C. In MSA-C, pons volume had highest sensitivity to change, and PMAS was a predictor of faster progression. Fulfillment of possible MSA criteria, NfL and PMAS were risk factors, CWM and pons volume protective factors for conversion to MSA-C.
CONCLUSIONS
This study provides detailed information on differential evolution and prognostic relevance of biomarkers in MSA-C and SAOA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
654-664Informations de copyright
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Références
Harding AE. "Idiopathic" late onset cerebellar ataxia. A clinical and genetic study of 36 cases. J Neurol Sci 1981;51:259-271.
Klockgether T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol 2010;9:94-104.
Tsuji S, Onodera O, Goto J, Nishizawa M. Sporadic ataxias in Japan--a population-based epidemiological study. Cerebellum 2008;7:189-197.
Muzaimi MB, Thomas J, Palmer-Smith S, et al. Population based study of late onset cerebellar ataxia in south East Wales. J Neurol Neurosurg Psychiatry 2004;75:1129-1134.
Leone M, Bottacchi E, D'Alessandro G, Kustermann S. Hereditary ataxias and paraplegias in Valle d'Aosta, Italy: a study of prevalence and disability. Acta Neurol Scand 1995;91:183-187.
Polo JM, Calleja J, Combarros O, Berciano J. Hereditary ataxias and paraplegias in Cantabria, Spain. An epidemiological and clinical study. Brain 1991;114(Pt 2):855-866.
Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008;71:670-676.
Osaki Y, Ben-Shlomo Y, Lees AJ, Wenning GK, Quinn NP. A validation exercise on the new consensus criteria for multiple system atrophy. Mov Disord 2009;24:2272-2276.
Miki Y, Foti SC, Asi YT, et al. Improving diagnostic accuracy of multiple system atrophy: a clinicopathological study. Brain 2019;142:2813-2827. https://doi.org/10.1093/brain/awz189
Wenning GK, Stankovic I, Vignatelli L, et al. The Movement Disorder Society criteria for the diagnosis of multiple system atrophy. Mov Disord 2022;37:1131-1148. https://doi.org/10.1002/mds.29005
Abele M, Minnerop M, Urbach H, Specht K, Klockgether T. Sporadic adult onset ataxia of unknown etiology: a clinical, electrophysiological and imaging study. J Neurol 2007;254:1384-1389.
Tsuchiya K, Ozawa E, Saito F, Irie H, Mizutani T. Neuropathology of late cortical cerebellar atrophy in Japan: distribution of cerebellar change on an autopsy case and review of Japanese cases. Eur Neurol 1994;34:253-262.
Ota S, Tsuchiya K, Anno M, Niizato K, Akiyama H. Distribution of cerebello-olivary degeneration in idiopathic late cortical cerebellar atrophy: clinicopathological study of four autopsy cases. Neuropathology 2008;28:43-50.
Kim M, Kim AR, Kim JS, et al. Clarification of undiagnosed ataxia using whole-exome sequencing with clinical implications. Parkinsonism Relat Disord 2020;80:58-64. https://doi.org/10.1016/j.parkreldis.2020.08.040
Giordano I, Harmuth F, Jacobi H, et al. Clinical and genetic characteristics of sporadic adult-onset degenerative ataxia. Neurology 2017;89(10):1043-1049.
Gilman S, Little R, Johanns J, et al. Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy. Neurology 2000;55:527-532.
Wirth T, Namer IJ, Monga B, et al. Progression of nigrostriatal denervation in cerebellar multiple system atrophy: a prospective study. Neurology 2022;98:232-236. https://doi.org/10.1212/WNL.0000000000013172
Wilke C, Bender F, Hayer SN, et al. Serum neurofilament light is increased in multiple system atrophy of cerebellar type and in repeat-expansion spinocerebellar ataxias: a pilot study. J Neurol 2018;265:1618-1624.
Zhang L, Cao B, Hou Y, et al. Neurofilament light chain predicts disease severity and progression in multiple system atrophy. Mov Disord 2022;37:421-426. https://doi.org/10.1002/mds.28847
Chelban V, Nikram E, Perez-Soriano A, et al. Neurofilament light levels predict clinical progression and death in multiple system atrophy. Brain 2022;145:4398-4408. https://doi.org/10.1093/brain/awac253
Singer W, Schmeichel AM, Shahnawaz M, et al. Alpha-synuclein oligomers and neurofilament light chain predict Phenoconversion of pure autonomic failure. Ann Neurol 2021;89:1212-1220. https://doi.org/10.1002/ana.26089
Burk K, Globas C, Wahl T, et al. MRI-based volumetric differentiation of sporadic cerebellar ataxia. Brain 2004;127:175-181.
Faber J, Giordano I, Jiang X, et al. Prominent white matter involvement in multiple system atrophy of cerebellar type. Mov Disord 2020;35:816-824. https://doi.org/10.1002/mds.27987
Paviour DC, Price SL, Jahanshahi M, Lees AJ, Fox NC. Longitudinal MRI in progressive supranuclear palsy and multiple system atrophy: rates and regions of atrophy. Brain 2006;129:1040-1049. https://doi.org/10.1093/brain/awl021
Reginold W, Lang AE, Marras C, Heyn C, Alharbi M, Mikulis DJ. Longitudinal quantitative MRI in multiple system atrophy and progressive supranuclear palsy. Parkinsonism Relat Disord 2014;20:222-225. https://doi.org/10.1016/j.parkreldis.2013.10.002
Savoiardo M, Strada L, Girotti F, et al. Olivopontocerebellar atrophy: MR diagnosis and relationship to multisystem atrophy. Radiology 1990;174:693-696.
Schulz JB, Klockgether T, Petersen D, et al. Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT. J Neurol Neurosurg Psychiatry 1994;57:1047-1056.
Schrag A, Kingsley D, Phatouros C, et al. Clinical usefulness of magnetic resonance imaging in multiple system atrophy. J Neurol Neurosurg Psychiatry 1998;65:65-71.
Abe K, Hikita T, Yokoe M, Mihara M, Sakoda S. The "cross" signs in patients with multiple system atrophy: a quantitative study. J Neuroimaging 2006;16:73-77. https://doi.org/10.1177/1051228405279988
Burk K, Buhring U, Schulz JB, Zuhlke C, Hellenbroich Y, Dichgans J. Clinical and magnetic resonance imaging characteristics of sporadic cerebellar ataxia. Arch Neurol 2005;62:981-985.
Carré G, Dietemann JL, Gebus O, et al. Brain MRI of multiple system atrophy of cerebellar type: a prospective study with implications for diagnosis criteria. J Neurol 2020;267:1269-1277. https://doi.org/10.1007/s00415-020-09702-w
Schmitz-Hubsch T, Du Montcel ST, Baliko L, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 2006;66:1717-1720.
Wenning GK, Tison F, Seppi K, et al. Development and validation of the unified multiple system atrophy rating scale (UMSARS). Mov Disord 2004;19:1391-1402.
Jacobi H, Rakowicz M, Rola R, et al. Inventory of non-ataxia signs (INAS): validation of a new clinical assessment instrument. Cerebellum 2013;12:418-428.
Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary care evaluation of mental disorders. Patient health questionnaire. JAMA 1999;282:1737-1744.
The EuroQol Group. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208.
Cortese A, Simone R, Sullivan R, et al. Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet 2019;51:649-658. https://doi.org/10.1038/s41588-019-0372-4
Traschütz A, Cortese A, Reich S, et al. Natural history, phenotypic Spectrum, and discriminative features of multisystemic RFC1 disease. Neurology 2021;96:e1369-e1382. https://doi.org/10.1212/WNL.0000000000011528
Herrmann L, Gelderblom M, Bester M, et al. Multisystemic neurodegeneration caused by biallelic pentanucleotide expansions in RFC1. Parkinsonism Relat Disord 2022;95:54-56. https://doi.org/10.1016/j.parkreldis.2022.01.001
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-424.
Harrison SM, Biesecker LG, Rehm HL. Overview of specifications to the ACMG/AMP variant interpretation guidelines. Curr Protoc Hum Genet 2019;103:e93. https://doi.org/10.1002/cphg.93
Wilke C, Haas E, Reetz K, et al. Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice. EMBO Mol Med 2020;12:e11803. https://doi.org/10.15252/emmm.201911803
Tustison NJ, Avants BB, Cook PA, et al. N4ITK: improved N3 bias correction. IEEE Trans Med Imaging 2010;29:1310-1320. https://doi.org/10.1109/TMI.2010.2046908
Buckner RL, Head D, Parker J, et al. A unified approach for morphometric and functional data analysis in young, old, and demented adults using automated atlas-based head size normalization: reliability and validation against manual measurement of total intracranial volume. Neuroimage 2004;23:724-738. https://doi.org/10.1016/j.neuroimage.2004.06.018
Iglesias JE, van Leemput K, Bhatt P, et al. Bayesian segmentation of brainstem structures in MRI. Neuroimage 2015;113:184-195. https://doi.org/10.1016/j.neuroimage.2015.02.065
Faber J, Kügler D, Bahrami E, et al. CerebNet: a fast and reliable deep-learning pipeline for detailed cerebellum sub-segmentation. Neuroimage 2022;264:119703.
Klockgether T, Lüdtke R, Kramer B, et al. The natural history of degenerative ataxia: a retrospective study in 466 patients. Brain 1998;121:589-600.
Abele M, Burk K, Schols L, et al. The aetiology of sporadic adult-onset ataxia. Brain 2002;125:961-968.
Montaut S, Diedhiou N, Fahrer P, et al. Biallelic RFC1-expansion in a French multicentric sporadic ataxia cohort. J Neurol 2021;268:3337-3343. https://doi.org/10.1007/s00415-021-10499-5
Aboud Syriani D, Wong D, Andani S, et al. Prevalence of RFC1-mediated spinocerebellar ataxia in a north American ataxia cohort. Neurol Genet 2020;6:e440. https://doi.org/10.1212/NXG.0000000000000440
Wan L, Chen Z, Wan N, et al. Biallelic intronic AAGGG expansion of RFC1 is related to multiple system atrophy. Ann Neurol 2020;88:1132-1143. https://doi.org/10.1002/ana.25902
Bogdan T, Wirth T, Iosif A, et al. Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study. J Neurol 2022;269:6354-6365. https://doi.org/10.1007/s00415-022-11253-1
Reetz K, Dogan I, Hilgers RD, et al. Progression characteristics of the European Friedreich's ataxia consortium for translational studies (EFACTS): a 2 year cohort study. Lancet Neurol 2016;15:1346-1354.