Clinical, Imaging, and Laboratory Markers of Premanifest Spinocerebellar Ataxia 1, 2, 3, and 6: A Systematic Review
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Background and Purpose Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of SCA1, -2, -3, and -6, and their associations with ataxia onset. Methods We included studies of the premanifest carriers of SCA published between January 1998 and December 2019 identified in Scopus and PubMed by searching for terms including ‘spinocerebellar ataxia’ and several synonyms of ‘preataxic manifestation’. We systematically reviewed the results obtained in studies categorized based on clinical, imaging, and laboratory markers. Results We finally performed a qualitative analysis of 48 papers. Common preataxic manifestations appearing in multiple SCA subtypes were muscle cramps, abnormal muscle reflexes, instability in gait and posture, lower Composite Cerebellar Functional Severity scores, abnormalities in video-oculography and transcranial magnetic stimulation, and gray-matter loss and volume reduction in the brainstem and cerebellar structures. Also, decreased sensory amplitudes in nerve conduction studies were observed in SCA2. Eotaxin and neurofilament lightchain levels were revealed as sensitive blood biomarkers in SCA3. Concerning potential predictive markers, hyporeflexia and abnormalities of somatosensory evoked potentials showed correlations with the time to ataxia onset in SCA2 carriers. However, no longitudinal data were found for the other SCA gene carriers. Conclusions Our results suggest that preataxic manifestations vary among SCA1, -2, -3, and -6, with some subtypes sharing specific features. Combining various markers into a standardized index for premanifest carriers may be useful for early screening and assessing the risk of disease progression in SCA carriers.
Abstract
Background and Purpose Premanifest mutation carriers with spinocerebellar ataxia (SCA) can exhibit subtle abnormalities before developing ataxia. We summarized the preataxic manifestations of SCA1, -2, -3, and -6, and their associations with ataxia onset. Methods We included studies of the premanifest carriers of SCA published between January 1998 and December 2019 identified in Scopus and PubMed by searching for terms including ‘spinocerebellar ataxia’ and several synonyms of ‘preataxic manifestation’. We systematically reviewed the results obtained in studies categorized based on clinical, imaging, and laboratory markers. Results We finally performed a qualitative analysis of 48 papers. Common preataxic manifestations appearing in multiple SCA subtypes were muscle cramps, abnormal muscle reflexes, instability in gait and posture, lower Composite Cerebellar Functional Severity scores, abnormalities in video-oculography and transcranial magnetic stimulation, and gray-matter loss and volume reduction in the brainstem and cerebellar structures. Also, decreased sensory amplitudes in nerve conduction studies were observed in SCA2. Eotaxin and neurofilament lightchain levels were revealed as sensitive blood biomarkers in SCA3. Concerning potential predictive markers, hyporeflexia and abnormalities of somatosensory evoked potentials showed correlations with the time to ataxia onset in SCA2 carriers. However, no longitudinal data were found for the other SCA gene carriers. Conclusions Our results suggest that preataxic manifestations vary among SCA1, -2, -3, and -6, with some subtypes sharing specific features. Combining various markers into a standardized index for premanifest carriers may be useful for early screening and assessing the risk of disease progression in SCA carriers.
참고문헌 (93)
- Parodi L, "Hereditary ataxias and paraparesias : clinical and genetic update", Curr Opin Neurol, 31, pp.462~471 (2018)
- Thomas EA, "Involvement of HDAC1 and HDAC3 in the pathology of polyglutamine disorders: therapeutic implications for selective HDAC1", HDAC3 inhibitors, 2014, pp.7, 634~661
- Schöls L, "Autosomal dominant cerebellar ataxias : clinical features, genetics, and pathogenesis", Lancet Neurol, 3, pp.291~304 (2004)
- Paulson H, "Ataxia and hereditary disorders", Neurol Clin, 19, pp.759~782 (2001)
- Rüb U, "Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7", Prog Neurobiol, 104, pp.38~66 (2013)
- Kim HJ, "SCA in Korea and its regional distribution : a multicenter analysis", Parkinsonism Relat Disord, 17, pp.72~75 (2011)
- Lee WY, "Frequency analysis and clinical characterization of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Korean patients", Arch Neurol, 60, pp.858~863 (2003)
- Jin DK, "Frequency of spinocerebellar ataxia types 1, 2, 3, 6, 7 and dentatorubral pallidoluysian atrophy mutations in Korean patients with spinocerebellar ataxia", J Neurol, 246, pp.207~210 (1999)
- Sullivan R, "Spinocerebellar ataxia : an update", J Neurol, 266, pp.533~544 (2019)
- Klockgether T, "Milestones in ataxia", Mov Disord, 26, pp.1134~1141 (2011)
- Okazawa H, "Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death", Neuron, 34, pp.701~713 (2002)
- La Spada AR, "Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7", Neuron, 31, pp.913~927 (2001)
- Matilla A, "The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1", Nature, 389, pp.974~978 (1997)
- Klockgether T, "Spinocerebellar ataxia", Nat Rev Dis Primers, 5, pp.24~ (2019)
- van de Warrenburg BP, "Age at onset variance analysis in spinocerebellar ataxias : a study in a Dutch-French cohort", Ann Neurol, 57, pp.505~512 (2005)
- Kim JY, "Molecular analysis of spinocerebellar ataxias in Koreans : frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7", Mol Cells, 12, pp.336~341 (2001)
- Maas RP, "The preclinical stage of spinocerebellar ataxias", Neurology, 85, pp.96~103 (2015)
- Schmitz-Hübsch T, "Scale for the assessment and rating of ataxia : development of a new clinical scale", Neurology, 66, pp.1717~1720 (2006)
- Lima M, "Towards the identification of molecular biomarkers of spinocerebellar ataxia type 3(SCA3)", Machado-Joseph disease(MJD), 2018, pp.1049, 309~319
- da Silva Carvalho G, "Cytokines in Machado Joseph disease", spinocerebellar ataxia 3, 2016, pp.15, 518~525
- Jacobi H, "Inventory of Non-Ataxia Signs(INAS) : validation of a new clinical assessment instrument", Cerebellum, 12, pp.418~428 (2013)
- Pearson CE, "Repeat instability : mechanisms of dynamic mutations", Nat Rev Genet, 6, pp.729~742 (2005)
- Stevanin G, "Clinical and molecular advances in autosomal dominant cerebellar ataxias : from genotype to phenotype and physiopathology", Eur J Hum Genet, 8, pp.4~18 (2000)
- Globas C, "Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6", Mov Disord, 23, pp.2232~2238 (2008)
- Velázquez-Pérez LC, "Spinocerebellar ataxia type 2 : clinicogenetic aspects, mechanistic insights, and management approaches", Front Neurol, 8, pp.472~ (2017)
- Velázquez-Pérez L, "Progression of early features of spinocerebellar ataxia type 2 in individuals at risk : a longitudinal study", Lancet Neurol, 13, pp.482~489 (2014)
- Chen JW, "Clinical characteristics, radiological features and gene mutation in 10 Chinese families with spinocerebellar ataxias", Chin Med J(Engl), 128, pp.1714~1723 (2015)
- Raposo M, "Nystagmus as an early ocular alteration in Machado-Joseph disease(MJD", SCA3), 2014, pp.14, 17~
- Mizushima K, "Analysis of spinocerebellar ataxia type 2 in Gunma Prefecture in Japan : CAG trinucleotide expansion and clinical characteristics", J Neurol Sci, 156, pp.180~185 (1998)
- Martin J, "Spinocerebellar ataxia type 7(SCA7)-correlations between phenotype and genotype in one large Belgian family", J Neurol Sci, 168, pp.37~46 (1999)
- Cancel G, "Molecular and clinical correlations in spinocerebellar ataxia 2 : a study of 32 families", Hum Mol Genet, 6, pp.709~715 (1997)
- Tezenas du Montcel S, "Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6", J Med Genet, 51, pp.479~486 (2014)
- Dziedzic T, "Biochemical and radiological markers of Alzheimer’s disease progression", J Alzheimers Dis, 50, pp.623~644 (2016)
- Braak H, "Staging of brain pathology related to sporadic Parkinson’s disease", Neurobiol Aging, 24, pp.197~211 (2003)
- Burciu RG, "Progression marker of Parkinson’s disease : a 4-year multi-site imaging study", Brain, 140, pp.2183~2192 (2017)
- Yang J, "Longitudinal progression markers of Parkinson’s disease : current view on structural imaging", Curr Neurol Neurosci Rep, 18, pp.83~ (2018)
- Odish OFF, "EEG may serve as a biomarker in Huntington’s disease using machine learning automatic classification", Sci Rep, 8, pp.16090~ (2018)
- Scarabino D, "Leukocyte telomere shortening in Huntington’s disease", J Neurol Sci, 396, pp.25~29 (2019)
- Wijeratne PA, "An image-based model of brain volume biomarker changes in Huntington’s disease", Ann Clin Transl Neurol, 5, pp.570~582 (2018)
- Jędrak P, "Mitochondrial alterations accompanied by oxidative stress conditions in skin fibroblasts of Huntington’s disease patients", Metab Brain Dis, 33, pp.2005~2017 (2018)
- Fazio P, "Novel imaging biomarkers for Huntington’s disease and other hereditary choreas", Curr Neurol Neurosci Rep, 18, pp.85~ (2018)
- Jacobi H, "Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study : analysis of baseline data", Lancet Neurol, 12, pp.650~658 (2013)
- Velázquez-Pérez L, "Comprehensive study of early features in spinocerebellar ataxia 2 : delineating the prodromal stage of the disease", Cerebellum, 13, pp.568~579 (2014)
- Velázquez-Pérez L, "Abnormal corticospinal tract function and motor cortex excitability in non-ataxic SCA2mutation carriers : a TMS study", Clin Neurophysiol, 127, pp.2713~2719 (2016)
- Park H, "Parkinsonism in spinocerebellar ataxia", Biomed Res Int, 2015, pp.125273~ (2015)
- Lindsay E, "Cognitive changes in the spinocerebellar ataxias due to expanded polyglutamine tracts : a survey of the literature", Brain Sci, 7, pp.83~ (2017)
- Velázquez-Pérez L, "Saccade velocity is reduced in presymptomatic spinocerebellar ataxia type 2", Clin Neurophysiol, 120, pp.632~635 (2009)
- Wu C, "Oculomotor deficits in spinocerebellar ataxia type 3 : potential biomarkers of preclinical detection and disease progression", CNS Neurosci Ther, 23, pp.321~328 (2017)
- Christova P, "Impaired eye movements in presymptomatic spinocerebellar ataxia type 6", Arch Neurol, 65, pp.530~536 (2008)
- Farrar MA, "Motor cortical dysfunction develops in spinocerebellar ataxia type 3", Clin Neurophysiol, 127, pp.3418~3424 (2016)
- "Rev Neurol", 1998, 955~963
- Velázquez Pérez L, "Electrophysiological features in patients and presymptomatic relatives with spinocerebellar ataxia type 2", J Neurol Sci, 263, pp.158~164 (2007)
- Velázquez-Pérez L, "Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence", Clin Neurophysiol, 128, pp.2493~2502 (2017)
- Rezende TJR, "Structural signature of SCA3 : from presymptomatic to late disease stages", Ann Neurol, 84, pp.401~408 (2018)
- Reetz K, "Brain atrophy measures in preclinical and manifest spinocerebellar ataxia type 2", Ann Clin Transl Neurol, 5, pp.128~137 (2018)
- Wu X, "Microstructural alterations in asymptomatic and symptomatic patients with spinocerebellar ataxia type 3 : a tract-based spatial statistics study", Front Neurol, 8, pp.714~ (2017)
- Falcon MI, "Early cerebellar network shifting in spinocerebellar ataxia type 6", Cereb Cortex, 26, pp.3205~3218 (2016)
- Mascalchi M, "Proton magnetic resonance spectroscopy in an Italian family with spinocerebellar ataxia type 1", Ann Neurol, 43, pp.244~252 (1998)
- Li QF, "Neurofilament light chain is a promising serum biomarker in spinocerebellar ataxia type 3", Mol Neurodegener, 14, pp.39~ (2019)
- Raposo M, "Accumulation of mitochondrial DNA common deletion since the preataxic stage of Machado-Joseph disease", Mol Neurobiol, 56, pp.119~124 (2019)
- de Assis AM, "Peripheral oxidative stress biomarkers in spinocerebellar ataxia type 3", Machado-Joseph disease, 2017, pp.8, 485~
- Nanetti L, "Stance instability in preclinical SCA1 mutation carriers : a 4-year prospective posturography study", Gait Posture, 57, pp.11~14 (2017)
- Velázquez-Pérez L, "Postural instability in prodromal spinocerebellar ataxia type 2 : insights into cerebellar involvement before onset of permanent ataxia", Cerebellum, 16, pp.279~281 (2017)
- Rochester L, "Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6", Mov Disord, 29, pp.252~255 (2014)
- Ilg W, "Individual changes in preclinical spinocerebellar ataxia identified via increased motor complexity", Mov Disord, 31, pp.1891~1900 (2016)
- Ilg W, "Specific influences of cerebellar dysfunctions on gait", Brain, 130(Pt 3), pp.786~798 (2007)
- Rodríguez-Labrada R, "Subtle rapid eye movement sleep abnormalities in presymptomatic spinocerebellar ataxia type 2 gene carriers", Mov Disord, 26, pp.347~350 (2011)
- Rodríguez-Labrada R, "Sleep spindles and K-complex activities are decreased in spinocerebellar ataxia type 2 : relationship to memory and motor performances", Sleep Med, 60, pp.188~196 (2019)
- Visser M, "Assessment of autonomic dysfunction in Parkinson’s disease : the SCOPA-AUT", Mov Disord, 19, pp.1306~1312 (2004)
- Montes BJ, "Disautonomic features in presyntomatic subjects and patients with type 2 spinocerebellar ataxia", Rev Mex Neuroci, 12, pp.76~81 (2011)
- Montes-Brown J, "Autonomic dysfunction in presymptomatic spinocerebellar ataxia type-2", Acta Neurol Scand, 125, pp.24~29 (2012)
- du Montcel ST, "Composite cerebellar functional severity score : validation of a quantitative score of cerebellar impairment", Brain, 131(Pt 5), pp.1352~1361 (2008)
- Schmitz-Hübsch T, "SCA Functional Index : a useful compound performance measure for spinocerebellar ataxia", Neurology, 71, pp.486~492 (2008)
- Yang ZH, "Metabolic profiling reveals biochemical pathways and potential biomarkers of spinocerebellar ataxia 3", Front Mol Neurosci, 12, pp.159~ (2019)
- van Gaalen J, "Abnormal eyeblink conditioning is an early marker of cerebellar dysfunction in preclinical SCA3 mutation carriers", Exp Brain Res, 237, pp.427~433 (2019)
- Velázquez-Perez L, "Motor decline in clinically presymptomatic spinocerebellar ataxia type 2 gene carriers", PLoS One, 4, pp.e5398~ (2009)
- Velázquez-Perez L, "Progression markers of Spinocerebellar ataxia 2. A twenty years neurophysiological follow up study", J Neurol Sci, 290, pp.22~26 (2010)
- Velázquez-Pérez L, "A comprehensive review of spinocerebellar ataxia type 2 in Cuba", Cerebellum, 10, pp.184~198 (2011)
- Velázquez-Pérez L, "Prodromal spinocerebellar ataxia type 2 : prospects for early interventions and ethical challenges", Mov Disord, 32, pp.708~718 (2017)
- Velázquez-Pérez L, "Central motor conduction time as prodromal biomarker in spinocerebellar ataxia type 2", Mov Disord, 31, pp.603~604 (2016)
- Velázquez-Pérez L, "Progression of corticospinal tract dysfunction in pre-ataxic spinocerebellar ataxia type 2 : a two-years follow-up TMS study", Clin Neurophysiol, 129, pp.895~900 (2018)
- Rodríguez-Díaz JC, "Neurorehabilitation therapy in spinocerebellar ataxia type 2 : a 24-week, rater-blinded, randomized, controlled trial", Mov Disord, 33, pp.1481~1487 (2018)
- Morlet É, "Neuroprotective effects of lithium : what are the implications in humans with neurodegenerative disorders?", Geriatr Psychol Neuropsychiatr Vieil, 16, pp.78~86 (2018)
- Duarte-Silva S, "Pharmacological therapies for Machado-Joseph disease", Adv Exp Med Biol, 1049, pp.369~394 (2018)
- Saute JAM, "Planning future clinical trials for Machado-Joseph disease", Adv Exp Med Biol, 1049, pp.321~348 (2018)
- Rubinsztein DC, "Diminishing return for mechanistic therapeutics with neurodegenerative disease duration? : there may be a point in the course of a neurodegenerative condition where therapeutics targeting disease-causing mechanisms are futile", Bioessays, 38, pp.977~980 (2016)
- Keiser MS, "Gene suppression strategies for dominantly inherited neurodegenerative diseases : lessons from Huntington’s disease and spinocerebellar ataxia", Hum Mol Genet, 25(R1), pp.R53~ (2016)
- Li X, "Toward therapeutic targets for SCA3 : insight into the role of Machado-Joseph disease protein ataxin-3 in misfolded proteins clearance", Prog Neurobiol, 132, pp.34~58 (2015)
- Yi J, "Sodium valproate alleviates neurodegeneration in SCA3", MJD via suppressing apoptosis and rescuing the hypoacetylation levels of histone H3 and H4, 2013, pp.8, e54792~
- Matilla-Dueñas A, "Handbook of the cerebellum and cerebellar disorders", pp.2370~2394 (2013), Springer
- Watson LM, "Polyglutamine disease : from pathogenesis to therapy", S Afr Med J, 102, pp.481~484 (2012)
- Almaguer-Mederos LE, "Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis", Clin Genet, 78, pp.169~174 (2010)
- Liberati A, "The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration", BMJ, 339, pp.b2700~ (2009)
