Semin Neurol
DOI: 10.1055/s-0043-1763511

Chi-Ying R. Lin

1   Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas

2   Department of Neurology, Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, Texas

,

Sheng-Han Kuo

3   Department of Neurology, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York

4   Initiative for Columbia Ataxia and Tremor, Columbia University Irving Medical Center, New York, New York

› Author Affiliations Funding/Disclosure Dr. Kuo has received funding from the National Institutes of Health: NINDS #R01 NS118179 (principal investigator), NINDS #R01 NS104423 (principal investigator), NINDS #R03 NS114871 (principal investigator), Parkinson's Foundation, National Ataxia Foundation, and International Essential Tremor Foundation. Dr. Kuo served as the Scientific Advisor for Praxis Precision Medicines and Sage Therapeutics.
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A variety of etiologies can cause cerebellar dysfunction, leading to ataxia symptoms. Therefore, the accurate diagnosis of the cause for cerebellar ataxia can be challenging. A step-wise investigation will reveal underlying causes, including nutritional, toxin, immune-mediated, genetic, and degenerative disorders. Recent advances in genetics have identified new genes for both autosomal dominant and autosomal recessive ataxias, and new therapies are on the horizon for targeting specific biological pathways. New diagnostic criteria for degenerative ataxias have been proposed, specifically for multiple system atrophy, which will have a broad impact on the future clinical research in ataxia. In this article, we aim to provide a review focus on symptoms, laboratory testing, neuroimaging, and genetic testing for the diagnosis of cerebellar ataxia causes, with a special emphasis on recent advances. Strategies for the management of cerebellar ataxia is also discussed.

Keywords ataxia - cerebellum - cerebellar ataxia Author Contribution

C.R.L. and S.H.K.: original draft and critical revision of the manuscript.

Publication History

Article published online:
24 February 2023

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  References 1 Kuo SH. Ataxia. Continuum (Minneap Minn) 2019; 25 (04) 1036-1054 2 Morel E, Armand S, Assal F, Allali G. Is frontal gait a myth in normal pressure hydrocephalus?. J Neurol Sci 2019; 402: 175-179 3 Nonnekes J, Růžička E, Serranová T, Reich SG, Bloem BR, Hallett M. Functional gait disorders: a sign-based approach. Neurology 2020; 94 (24) 1093-1099 4 Stolze H, Kuhtz-Buschbeck JP, Drücke H. et al. Gait analysis in idiopathic normal pressure hydrocephalus–which parameters respond to the CSF tap test?. Clin Neurophysiol 2000; 111 (09) 1678-1686 5 Luo L, Wang J, Lo RY. et al. The initial symptom and motor progression in spinocerebellar ataxias. Cerebellum 2017; 16 (03) 615-622 6 Chen ML, Lin CC, Rosenthal LS, Opal P, Kuo SH. Rating scales and biomarkers for CAG-repeat spinocerebellar ataxias: implications for therapy development. J Neurol Sci 2021; 424: 117417 7 Kwei KT, Kuo SH. An overview of the current state and the future of ataxia treatments. Neurol Clin 2020; 38 (02) 449-467 8 Trouillas P, Takayanagi T, Hallett M. et al; The Ataxia Neuropharmacology Committee of the World Federation of Neurology. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. J Neurol Sci 1997; 145 (02) 205-211 9 Schmitz-Hübsch T, Tezenas du Montcel S, Baliko L. et al. Reliability and validity of the International Cooperative Ataxia Rating Scale: a study in 156 spinocerebellar ataxia patients. Mov Disord 2006; 21 (05) 699-704 10 Hoche F, Guell X, Vangel MG, Sherman JC, Schmahmann JD. The cerebellar cognitive affective/Schmahmann syndrome scale. Brain 2018; 141 (01) 248-270 11 Amokrane N, Lin CR, Desai NA, Kuo SH. The impact of compulsivity and impulsivity in cerebellar ataxia: a case series. Tremor Other Hyperkinet Mov (N Y) 2020; 10: 43 12 Amokrane N, Viswanathan A, Freedman S. et al. Impulsivity in cerebellar ataxias: testing the cerebellar reward hypothesis in humans. Mov Disord 2020; 35 (08) 1491-1493 13 Carta I, Chen CH, Schott AL, Dorizan S, Khodakhah K. Cerebellar modulation of the reward circuitry and social behavior. Science 2019; 363 (6424): eaav0581 14 Chen TX, Lin CR, Aumann MA. et al. Impulsivity trait profiles in patients with cerebellar ataxia and parkinson disease. Neurology 2022; 99 (02) e176-e186 15 Heffley W, Song EY, Xu Z. et al. Coordinated cerebellar climbing fiber activity signals learned sensorimotor predictions. Nat Neurosci 2018; 21 (10) 1431-1441 16 Sendhilnathan N, Semework M, Goldberg ME, Ipata AE. Neural correlates of reinforcement learning in mid-lateral cerebellum. Neuron 2020; 106 (06) 1055 17 Wagner MJ, Kim TH, Savall J, Schnitzer MJ, Luo L. Cerebellar granule cells encode the expectation of reward. Nature 2017; 544 (7648): 96-100 18 Schmahmann JD, Pierce S, MacMore J, L'Italien GJ. Development and validation of a patient-reported outcome measure of ataxia. Mov Disord 2021; 36 (10) 2367-2377 19 Mitoma H, Manto M, Hampe CS. Time is cerebellum. Cerebellum 2018; 17 (04) 387-391 20 Dar MS. Ethanol-induced cerebellar ataxia: cellular and molecular mechanisms. Cerebellum 2015; 14 (04) 447-465 21 Luo J. Effects of ethanol on the cerebellum: advances and prospects. Cerebellum 2015; 14 (04) 383-385 22 Victor M, Adams RD, Mancall EL. A restricted form of cerebellar cortical degeneration occurring in alcoholic patients. AMA Arch Neurol 1959; 1 (06) 579-688 23 Haubek A, Lee K. Computed tomography in alcoholic cerebellar atrophy. Neuroradiology 1979; 18 (02) 77-79 24 Mitoma H, Manto M, Shaikh AG. Mechanisms of ethanol-induced cerebellar ataxia: underpinnings of neuronal death in the cerebellum. Int J Environ Res Public Health 2021; 18 (16) 8678 25 Setta F, Jacquy J, Hildebrand J, Manto MU. Ataxia induced by small amounts of alcohol. J Neurol Neurosurg Psychiatry 1998; 65 (03) 370-373 26 Shanmugarajah PD, Hoggard N, Currie S. et al. Alcohol-related cerebellar degeneration: not all down to toxicity?. Cerebellum Ataxias 2016; 3 (01) 17 27 Diener HC, Dichgans J, Bacher M, Guschlbauer B. Improvement of ataxia in alcoholic cerebellar atrophy through alcohol abstinence. J Neurol 1984; 231 (05) 258-262 28 Fein G, Greenstein D. Gait and balance deficits in chronic alcoholics: no improvement from 10 weeks through 1 year abstinence. Alcohol Clin Exp Res 2013; 37 (01) 86-95 29 Sosenko JM, Soto R, Aronson J, Kato M, Caralis PV, Ayyar DR. The prevalence and extent of vibration sensitivity impairment in men with chronic ethanol abuse. J Stud Alcohol 1991; 52 (04) 374-376 30 Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol 2007; 6 (05) 442-455 31 Desai SD, Shah DS. Atypical Wernicke's syndrome sans encephalopathy with acute bilateral vision loss due to post-chiasmatic optic tract edema. Ann Indian Acad Neurol 2014; 17 (01) 103-105 32 Divya MB, Kubera NS, Jha N, Jha AK, Thabah MM. Atypical neurological manifestations in Wernicke's encephalopathy due to hyperemesis gravidarum. Nutr Neurosci 2022; 25 (10) 2051-2056 33 Lin CY, Yoo JY, Doshi A, Colman R. Clinical reasoning: a 61-year-old man with conjugate gaze deviation, hemiparesis, and asymmetric reflexes. Neurology 2017; 89 (09) e105-e108 34 Jung YC, Chanraud S, Sullivan EV. Neuroimaging of Wernicke's encephalopathy and Korsakoff's syndrome. Neuropsychol Rev 2012; 22 (02) 170-180 35 Ramineni KK, Marupaka SK, Jakkani R, Ingle A. Wernicke encephalopathy with atypical findings on magnetic resonance imaging. Ann Indian Acad Neurol 2018; 21 (04) 328-330 36 Zuccoli G, Santa Cruz D, Bertolini M. et al. MR imaging findings in 56 patients with Wernicke encephalopathy: nonalcoholics may differ from alcoholics. AJNR Am J Neuroradiol 2009; 30 (01) 171-176 37 Kuo SH, Debnam JM, Fuller GN, de Groot J. Wernicke's encephalopathy: an underrecognized and reversible cause of confusional state in cancer patients. Oncology 2009; 76 (01) 10-18 38 Jones KS, Parkington DA, Cox LJ, Koulman A. Erythrocyte transketolase activity coefficient (ETKAC) assay protocol for the assessment of thiamine status. Ann N Y Acad Sci 2021; 1498 (01) 77-84 39 Leigh D, McBurney A, McIlwain H. Erythrocyte transketolase activity in the Wernicke-Korsakoff syndrome. Br J Psychiatry 1981; 139: 153-156 40 Pekovich SR, Martin PR, Singleton CK. Thiamine deficiency decreases steady-state transketolase and pyruvate dehydrogenase but not alpha-ketoglutarate dehydrogenase mRNA levels in three human cell types. J Nutr 1998; 128 (04) 683-687 41 Akhouri S, Kuhn J, Newton EJ. Wernicke-Korsakoff syndrome. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2022 42 Qudsiya Z, De Jesus O. Subacute combined degeneration of the spinal cord. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2022 43 Losa R, Sierra MI, Fernández A, Blanco D, Buesa JM. Determination of thiamine and its phosphorylated forms in human plasma, erythrocytes and urine by HPLC and fluorescence detection: a preliminary study on cancer patients. J Pharm Biomed Anal 2005; 37 (05) 1025-1029 44 Lu J, Frank EL. Rapid HPLC measurement of thiamine and its phosphate esters in whole blood. Clin Chem 2008; 54 (05) 901-906 45 Talwar D, Davidson H, Cooney J, St JO'Reilly D. Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay. Clin Chem 2000; 46 (05) 704-710 46 Wilkins A. Cerebellar dysfunction in multiple sclerosis. Front Neurol 2017; 8: 312 47 Anderson VM, Fisniku LK, Altmann DR, Thompson AJ, Miller DH. MRI measures show significant cerebellar gray matter volume loss in multiple sclerosis and are associated with cerebellar dysfunction. Mult Scler 2009; 15 (07) 811-817 48 Calabrese M, Mattisi I, Rinaldi F. et al. Magnetic resonance evidence of cerebellar cortical pathology in multiple sclerosis. J Neurol Neurosurg Psychiatry 2010; 81 (04) 401-404 49 Kutzelnigg A, Faber-Rod JC, Bauer J. et al. Widespread demyelination in the cerebellar cortex in multiple sclerosis. Brain Pathol 2007; 17 (01) 38-44 50 D'Ambrosio A, Pagani E, Riccitelli GC. et al. Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis. Mult Scler 2017; 23 (09) 1194-1203 51 Fritz NE, Edwards EM, Ye C. et al. Cerebellar contributions to motor and cognitive control in multiple sclerosis✰✰✰. Arch Phys Med Rehabil 2022; 103 (08) 1592-1599 52 Jaques CS, de Moraes MPM, Silva EAR. et al. Characterisation of ataxia in Sjogren's syndrome. J Neurol Neurosurg Psychiatry 2020; 91 (04) 446-448 53 Chen YW, Lee KC, Chang IW, Chang CS, Hsu SP, Kuo HC. Sjogren's syndrome with acute cerebellar ataxia and massive lymphadenopathy : a case report. Acta Neurol Taiwan 2013; 22 (02) 81-86 54 Chuah SL, Jobli AT, Wan SA, Teh CL. Cerebellar degeneration in primary Sjögren syndrome: a case report. J Med Case Reports 2021; 15 (01) 526 55 Farhat E, Zouari M, Abdelaziz IB. et al. Progressive cerebellar degeneration revealing Primary Sjögren Syndrome: a case report. Cerebellum Ataxias 2016; 3 (01) 18 56 Conway KS, Camelo-Piragua S, Fisher-Hubbard A, Perry WR, Shakkottai VG, Venneti S. Multiple system atrophy pathology is associated with primary Sjögren's syndrome. JCI Insight 2020; 5 (15) e138619 57 Bushara KO, Goebel SU, Shill H, Goldfarb LG, Hallett M. Gluten sensitivity in sporadic and hereditary cerebellar ataxia. Ann Neurol 2001; 49 (04) 540-543 58 Lin CY, Wang MJ, Tse W. et al. Serum antigliadin antibodies in cerebellar ataxias: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2018; 89 (11) 1174-1180 59 Newrick L, Hoggard N, Hadjivassiliou M. Recognition and management of rapid-onset gluten ataxias: case series. Cerebellum Ataxias 2021; 8 (01) 16 60 Benson BC, Mulder CJ, Laczek JT. Anti-gliadin antibodies identify celiac patients overlooked by tissue transglutaminase antibodies. Hawaii J Med Public Health 2013; 72 (9, Suppl 4): 14-17 61 Mitoma H, Hadjivassiliou M, Honnorat J. Guidelines for treatment of immune-mediated cerebellar ataxias. Cerebellum Ataxias 2015; 2 (01) 14 62 Payer J, Petrovic T, Lisy L, Langer P. Hashimoto encephalopathy: a rare intricate syndrome. Int J Endocrinol Metab 2012; 10 (02) 506-514 63 Rao RS, Sheshadri S, Bhattacharjee D, Patil N, Rao K. Progressive non-familial adult onset cerebellar degeneration: an unusual occurrence with Hashimoto's thyroiditis. Psychopharmacol Bull 2018; 48 (03) 42-46 64 Selim M, Drachman DA. Ataxia associated with Hashimoto's disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis. J Neurol Neurosurg Psychiatry 2001; 71 (01) 81-87 65 Ferracci F, Moretto G, Candeago RM. et al. Antithyroid antibodies in the CSF: their role in the pathogenesis of Hashimoto's encephalopathy. Neurology 2003; 60 (04) 712-714 66 Nakagawa H, Yoneda M, Fujii A, Kinomoto K, Kuriyama M. Hashimoto's encephalopathy presenting with progressive cerebellar ataxia. J Neurol Neurosurg Psychiatry 2007; 78 (02) 196-197 67 Castillo P, Woodruff B, Caselli R. et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol 2006; 63 (02) 197-202 68 Cornejo R, Venegas P, Goñi D, Salas A, Romero C. Successful response to intravenous immunoglobulin as rescue therapy in a patient with Hashimoto's encephalopathy. BMJ Case Rep 2010; 2010: bcr0920103332 69 Miske R, Hahn S, Rosenkranz T. et al. Autoantibodies against glutamate receptor δ2 after allogenic stem cell transplantation. Neurol Neuroimmunol Neuroinflamm 2016; 3 (04) e255 70 Shiihara T, Kato M, Konno A, Takahashi Y, Hayasaka K. Acute cerebellar ataxia and consecutive cerebellitis produced by glutamate receptor delta2 autoantibody. Brain Dev 2007; 29 (04) 254-256 71 Aly R, Emmady PD. Paraneoplastic cerebellar degeneration. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2022 72 McKeon A, Tracy JA, Pittock SJ, Parisi JE, Klein CJ, Lennon VA. Purkinje cell cytoplasmic autoantibody type 1 accompaniments: the cerebellum and beyond. Arch Neurol 2011; 68 (10) 1282-1289 73 Rydz D, Lin CY, Xie T, Cortes E, Vonsattel JP, Kuo SH. Pathological findings of anti-Yo cerebellar degeneration with Holmes tremor. J Neurol Neurosurg Psychiatry 2015; 86 (01) 121-122 74 Jarius S, Wildemann B. ‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook. J Neuroinflammation 2015; 12 (01) 168 75 Peter E, Do LD, Hannoun S. et al. Cerebellar ataxia with anti-DNER antibodies: outcomes and immunologic features. Neurol Neuroimmunol Neuroinflamm 2022; 9 (05) e200018 76 Dade M, Berzero G, Izquierdo C. et al. Neurological syndromes associated with anti-GAD antibodies. Int J Mol Sci 2020; 21 (10) 3701 77 Joubert B, Belbezier A, Haesebaert J. et al. Long-term outcomes in temporal lobe epilepsy with glutamate decarboxylase antibodies. J Neurol 2020; 267 (07) 2083-2089 78 Malter MP, Helmstaedter C, Urbach H, Vincent A, Bien CG. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann Neurol 2010; 67 (04) 470-478 79 Honnorat J, Saiz A, Giometto B. et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies: study of 14 patients. Arch Neurol 2001; 58 (02) 225-230 80 Ariño H, Gresa-Arribas N, Blanco Y. et al. Cerebellar ataxia and glutamic acid decarboxylase antibodies: immunologic profile and long-term effect of immunotherapy. JAMA Neurol 2014; 71 (08) 1009-1016 81 Kuchling J, Shababi-Klein J, Nümann A, Gerischer LM, Harms L, Prüss H. GAD antibody-associated late-onset cerebellar ataxia in two female siblings. Case Rep Neurol 2014; 6 (03) 264-270 82 Saiz A, Blanco Y, Sabater L. et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain 2008; 131 (Pt 10): 2553-2563 83 Espay AJ, Chen R. Rigidity and spasms from autoimmune encephalomyelopathies: stiff-person syndrome. Muscle Nerve 2006; 34 (06) 677-690 84 McKeon A, Robinson MT, McEvoy KM. et al. Stiff-man syndrome and variants: clinical course, treatments, and outcomes. Arch Neurol 2012; 69 (02) 230-238 85 Rosin L, DeCamilli P, Butler M. et al. Stiff-man syndrome in a woman with breast cancer: an uncommon central nervous system paraneoplastic syndrome. Neurology 1998; 50 (01) 94-98 86 Silverman IE. Paraneoplastic stiff limb syndrome. J Neurol Neurosurg Psychiatry 1999; 67 (01) 126-127 87 Tanaka H, Matsumura A, Okumura M, Kitaguchi M, Yamamoto S, Iuchi K. Stiff man syndrome with thymoma. Ann Thorac Surg 2005; 80 (02) 739-741 88 Thomas S, Critchley P, Lawden M. et al. Stiff person syndrome with eye movement abnormality, myasthenia gravis, and thymoma. J Neurol Neurosurg Psychiatry 2005; 76 (01) 141-142 89 Dalakas MC, Fujii M, Li M, Lutfi B, Kyhos J, McElroy B. High-dose intravenous immune globulin for stiff-person syndrome. N Engl J Med 2001; 345 (26) 1870-1876 90 Georgieva Z, Parton M. Cerebellar ataxia and epilepsy with anti-GAD antibodies: treatment with IVIG and plasmapheresis. BMJ Case Rep 2014; 2014: bcr2013202314 91 Jones AL, Flanagan EP, Pittock SJ. et al. Responses to and outcomes of treatment of autoimmune cerebellar ataxia in adults. JAMA Neurol 2015; 72 (11) 1304-1312 92 Sawaishi Y, Takada G. Acute cerebellitis. Cerebellum 2002; 1 (03) 223-228 93 Salas AA, Nava A. Acute cerebellar ataxia in childhood: initial approach in the emergency department. Emerg Med J 2010; 27 (12) 956-957 94 Bozzola E, Bozzola M, Tozzi AE. et al. Acute cerebellitis in varicella: a ten year case series and systematic review of the literature. Ital J Pediatr 2014; 40: 57 95 Malayala SV, Jaidev P, Vanaparthy R, Jolly TS. Acute COVID-19 cerebellitis: a rare neurological manifestation of COVID-19 infection. Cureus 2021; 13 (10) e18505 96 O'Neill KA, Polavarapu A. Acute cerebellar ataxia associated with COVID-19 infection in a 5-year-old boy. Child Neurol Open 2021; 8: X211066755 97 Povlow A, Auerbach AJ. Acute cerebellar ataxia in COVID-19 infection: a case report. J Emerg Med 2021; 60 (01) 73-76 98 Tomar LR, Shah DJ, Agarwal U, Batra A, Anand I. Acute post-infectious cerebellar ataxia due to COVID-19. Mov Disord Clin Pract (Hoboken) 2021; 8 (04) 610-612 99 Werner J, Reichen I, Huber M, Abela IA, Weller M, Jelcic I. Subacute cerebellar ataxia following respiratory symptoms of COVID-19: a case report. BMC Infect Dis 2021; 21 (01) 298 100 Altmann K, Koziol K, Palaver A. et al. Cytotoxic edema involving the corpus callosum and middle cerebellar peduncles in a young patient with mild COVID-19. Neurology 2022; (e-pub ahead of print) DOI: 10.1212/WNL.0000000000200816. 101 van Gaalen J, Kerstens FG, Maas RP, Härmark L, van de Warrenburg BP. Drug-induced cerebellar ataxia: a systematic review. CNS Drugs 2014; 28 (12) 1139-1153 102 Gürkov R. Amiodarone: a newly discovered association with bilateral vestibulopathy. Front Neurol 2018; 9: 119 103 Sarrazin S, Hein C, Delrieu J. et al. Amiodarone-induced ataxia: a case report of severe cerebellar dysfunction and review of literature. J Nutr Health Aging 2021; 25 (03) 284-286 104 Belli LS, De Carlis L, Romani F. et al. Dysarthria and cerebellar ataxia: late occurrence of severe neurotoxicity in a liver transplant recipient. Transpl Int 1993; 6 (03) 176-178 105 Kaleyias J, Faerber E, Kothare SV. Tacrolimus induced subacute cerebellar ataxia. Eur J Paediatr Neurol 2006; 10 (02) 86-89 106 Teimouri A, Ahmadi SR, Anavri Ardakani S, Foroughian M. Cyclosporine-A-based immunosuppressive therapy-induced neurotoxicity: a case report. Open Access Emerg Med 2020; 12: 93-97 107 Thompson CB, June CH, Sullivan KM, Thomas ED. Association between cyclosporin neurotoxicity and hypomagnesaemia. Lancet 1984; 2 (8412): 1116-1120 108 Graves TD, Condon M, Loucaidou M, Perry RJ. Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient. J Neurol Sci 2009; 285 (1–2): 238-240 109 Woodruff BK, Wijdicks EF, Marshall WF. Reversible metronidazole-induced lesions of the cerebellar dentate nuclei. N Engl J Med 2002; 346 (01) 68-69 110 Hamberg P, De Jong FA, Brandsma D, Verweij J, Sleijfer S. Irinotecan-induced central nervous system toxicity. Report on two cases and review of the literature. Acta Oncol 2008; 47 (05) 974-978 111 Hamberg P, Donders RC, ten Bokkel Huinink D. Central nervous system toxicity induced by irinotecan. J Natl Cancer Inst 2006; 98 (03) 219 112 Vaughn DJ, Jarvik JG, Hackney D, Peters S, Stadtmauer EA. High-dose cytarabine neurotoxicity: MR findings during the acute phase. AJNR Am J Neuroradiol 1993; 14 (04) 1014-1016 113 Adityanjee, Munshi KR, Thampy A. The syndrome of irreversible lithium-effectuated neurotoxicity. Clin Neuropharmacol 2005; 28 (01) 38-49 114 Decker BS, Goldfarb DS, Dargan PI. et al; EXTRIP Workgroup. Extracorporeal treatment for lithium poisoning: systematic review and recommendations from the EXTRIP workgroup. Clin J Am Soc Nephrol 2015; 10 (05) 875-887 115 Moon HJ, Jeon B. Can therapeutic-range chronic phenytoin administration cause cerebellar ataxia?. J Epilepsy Res 2017; 7 (01) 21-24 116 Lin CR, Viswanathan A, Chen TX. et al. Clinicopathological correlates of pyramidal signs in multiple system atrophy. Ann Clin Transl Neurol 2022; 9 (07) 988-994 117 Tu PH, Galvin JE, Baba M. et al. Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann Neurol 1998; 44 (03) 415-422 118 Revuelta GJ, Benatar M, Freeman A. et al. Clinical subtypes of anterocollis in parkinsonian syndromes. J Neurol Sci 2012; 315 (1–2): 100-103 119 Cortelli P, Calandra-Buonaura G, Benarroch EE. et al. Stridor in multiple system atrophy: consensus statement on diagnosis, prognosis, and treatment. Neurology 2019; 93 (14) 630-639 120 Miki Y, Foti SC, Asi YT. et al. Improving diagnostic accuracy of multiple system atrophy: a clinicopathological study. Brain 2019; 142 (09) 2813-2827 121 Wenning GK, Stankovic I, Vignatelli L. et al. The Movement Disorder Society criteria for the diagnosis of multiple system atrophy. Mov Disord 2022; 37 (06) 1131-1148 122 Gilman S, Wenning GK, Low PA. et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 2008; 71 (09) 670-676 123 Koga S, Aoki N, Uitti RJ. et al. When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology 2015; 85 (05) 404-412 124 Braune S, Reinhardt M, Schnitzer R, Riedel A, Lücking CH. Cardiac uptake of [123I]MIBG separates Parkinson's disease from multiple system atrophy. Neurology 1999; 53 (05) 1020-1025 125 Donadio V, Incensi A, Rizzo G. et al. Skin biopsy may help to distinguish multiple system atrophy-Parkinsonism from Parkinson's disease with orthostatic hypotension. Mov Disord 2020; 35 (09) 1649-1657 126 Haga R, Sugimoto K, Nishijima H. et al. Clinical utility of skin biopsy in differentiating between Parkinson's disease and multiple system atrophy. Parkinsons Dis 2015; 2015: 167038 127 Shahnawaz M, Mukherjee A, Pritzkow S. et al. Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy. Nature 2020; 578 (7794): 273-277 128 Eschlböck S, Wenning G, Fanciulli A. Evidence-based treatment of neurogenic orthostatic hypotension and related symptoms. J Neural Transm (Vienna) 2017; 124 (12) 1567-1605 129 Jordan J, Shibao C, Biaggioni I. Multiple system atrophy: using clinical pharmacology to reveal pathophysiology. Clin Auton Res 2015; 25 (01) 53-59 130 Perez-Lloret S,