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Kuhn J, Cascella M. Alexander disease. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 4, 2023.
Li R, Johnson AB, Salomons G, et al. Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. Ann Neurol. 2005;57(3):310-326. doi:10.1002/ana.20406
Yoshida T, Sasaki M, Yoshida M, et al. Nationwide survey of Alexander disease in Japan and proposed new guidelines for diagnosis. J Neurol. 2011;258(11):1998-2008. doi:10.1007/s00415-011-6056-3
Pareyson D, Fancellu R, Mariotti C, et al. Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature. Brain. 2008;131(Pt 9):2321-2331. doi:10.1093/brain/awn178
Sosunov A, Olabarria M, Goldman JE. Alexander disease: an astrocytopathy that produces a leukodystrophy. Brain Pathol. 2018;28(3):388-398. doi:10.1111/bpa.12601
Ahmad O, Rowe DB. Adult-onset Alexander’s disease mimicking degenerative disease. Pract Neurol. 2015;15(5):393-395. doi:10.1136/practneurol-2015-001144
Kang YR, Nam TS, Kim JM, et al. Older adult-onset Alexander disease with atypical clinicoradiological features: a case report. Front Neurol. 2023;14:1139047. doi:10.3389/fneur.2023.1139047
Muthusamy K, Sivadasan A, Dixon L, et al. Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions. Front Neurol. 2023;14:1219324. doi:10.3389/fneur.2023.1219324
Vaia Y, Mura E, Tonduti D. Type I Alexander disease: update and validation of the clinical evolution-based classification. Mol Genet Metab. 2023;138(3):107540. doi:10.1016/j.ymgme.2023.107540
Zampini L, Draghi L, Zanchi P. Developmental profiles in children and young adults with Alexander disease. Dev Neurorehabil. 2023;26(4):253-261. doi:10.1080/17518423.2023.2209834
Ruzhnikov MRZ, Brimble E, Hickey RE, Leukodystrophy Care N. Early signs and symptoms of leukodystrophies: A case-based guide. Pediatr Rev. 2021;42(3):133-146. doi:10.1542/pir.2019-0184
Zerem A, Libzon S, Ben Sira L, et al. Utility of genetic testing in children with leukodystrophy. Eur J Paediatr Neurol. 2023;45:29-35. doi:10.1016/j.ejpn.2023.05.008
Parikh S, Bernard G, Leventer RJ, et al. A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. Mol Genet Metab. 2015;114(4):501-515. doi:10.1016/j.ymgme.2014.12.434
Waldman A, Sollee J, Liu G, Cooper H, Vossough A. Novel classifications of Alexander disease based on MRI phenotypes. Presented at: 2019 Annual Meeting of the American Academy of Neurology; May 4-10, 2019; Philadelphia, PA.
van der Knaap MS, Naidu S, Breiter SN, et al. Alexander disease: diagnosis with MR imaging. AJNR Am J Neuroradiol. 2001;22(3):541-552.
Balbi P, Salvini S, Fundaro C, et al. The clinical spectrum of late-onset Alexander disease: a systematic literature review. J Neurol. 2010;257(12):1955-1962. doi:10.1007/s00415-010-5706-1
Adang LA, Sherbini O, Ball L, et al. Revised consensus statement on the preventive and symptomatic care of patients with leukodystrophies. Mol Genet Metab. 2017;122(1-2):18-32. doi:10.1016/j.ymgme.2017.08.006
Hagemann TL, Powers B, Lin NH, et al. Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment. Sci Transl Med. 2021;13(620):eabg4711. doi:10.1126/scitranslmed.abg4711
Clinicaltrials.gov. Bethesda, MD: National Library of Medicine (US). Identifier NCT04849741. A study to evaluate the safety and efficacy of zilganersen (ION373) in patients with Alexander disease (AxD). Accessed April 9, 2025. https://clinicaltrials.gov/study/NCT04849741.
Messing A. Alexander disease. Handb Clin Neurol. 2018;148:693-700. doi:10.1016/B978-0-444-64076-5.00044-2
Barczykowski AL, Foss AH, Duffner PK, Yan L, Carter RL. Death rates in the U.S. due to Krabbe disease and related leukodystrophy and lysosomal storage diseases. Am J Med Genet A. 2012;158A(11):2835-2842. doi:10.1002/ajmg.a.35624
Stellitano LA, Winstone AM, van der Knaap MS, Verity CM. Leukodystrophies and genetic leukoencephalopathies in childhood: a national epidemiological study. Dev Med Child Neurol. 2016;58(7):680-689. doi:10.1111/dmcn.13027
Srivastava S, Waldman A, Naidu S. Alexander Disease. In: Adam MP, Mirzaa GM, Pagon RA, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. November 15, 2002. Updated November 12, 2020.
National Organization for Rare Disorders. Alexander disease. https://rarediseases.org/rare-diseases/alexander-disease/. Accessed June 30, 2023.
Cohen L, Manin A, Medina N, et al. Argentinian clinical genomics in a leukodystrophies and genetic leukoencephalopathies cohort: Diagnostic yield in our first 9 years. Ann Hum Genet. 2020;84(1):11-28. doi:10.1111/ahg.12345
Heim P, Claussen M, Hoffmann B, et al. Leukodystrophy incidence in Germany. Am J Med Genet. 1997;71(4):475-478.
Schmidt JL, Pizzino A, Nicholl J, et al. Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing. Am J Med Genet A. 2020;182(8):1906-1912. doi:10.1002/ajmg.a.61641
Bonkowsky JL, Nelson C, Kingston JL, Filloux FM, Mundorff MB, Srivastava R. The burden of inherited leukodystrophies in children. Neurology. 2010;75(8):718-725. doi:10.1212/WNL.0b013e3181eee46b
Vanderver A, Hussey H, Schmidt JL, Pastor W, Hoffman HJ. Relative incidence of inherited white matter disorders in childhood to acquired pediatric demyelinating disorders. Semin Pediatr Neurol. 2012;19(4):219-223. doi:10.1016/j.spen.2012.10.001
Hagemann TL, Connor JX, Messing A. Alexander disease-associated glial fibrillary acidic protein mutations in mice induce Rosenthal fiber formation and a white matter stress response. J Neurosci. 2006;26(43):11162-11173. doi:10.1523/JNEUROSCI.3260-06.2006
Kiray H, Lindsay SL, Hosseinzadeh S, Barnett SC. The multifaceted role of astrocytes in regulating myelination. Exp Neurol. 2016;283(Pt B):541-549. doi:10.1016/j.expneurol.2016.03.009
Prust M, Wang J, Morizono H, et al. GFAP mutations, age at onset, and clinical subtypes in Alexander disease. Neurology. 2011;77(13):1287-1294. doi:10.1212/WNL.0b013e3182309f72
Joung J, Gallison K, Sollee JJ, et al. Acquisition and loss of developmental milestones and time to disease-related outcomes in cerebral Alexander disease. J Child Neurol. 2023;38(13-14):672-678. doi:10.1177/08830738231210040
van der Knaap MSV, J. Magnetic resonance of myelination and myelin disorders, 3rd ed. American Journal of Neuroradiology. 2006;27(4):947-948.
Arshiany H, Ezzatian B, Artounian V, Alizadeh F, Mohammadian F. Psychiatric onset Alexander disease: an important challenge in neuropsychiatric diagnosis: a case report. Basic Clin Neurosci. 2022;13(2):269-274. doi:10.32598/bcn.2021.1551.1
Anis S, Fay-Karmon T, Lassman S, et al. Adult-onset Alexander disease among patients of Jewish Syrian descent. Neurogenetics. 2023;24(4):303-310. doi:10.1007/s10048-023-00732-w
Bonkowsky JL, Edwards MR, Baker M, et al. Demographics and healthcare use in Alexander disease characterized from US national administrative data. Presented at: United Leukodystrophy Foundation Scientific Symposium; June 27, 2024; Itasca, IL.
Gavazzi F, Adang L, Waldman A, et al. Reliability of the telemedicine application of the Gross Motor Function Measure-88 in patients with leukodystrophy. Pediatr Neurol. 2021;125:34-39. doi:10.1016/j.pediatrneurol.2021.09.012
Pereira AC, Ribeiro MG, Araújo AP. Timed motor function tests capacity in healthy children. Arch Dis Child. 2016;101(2):147-151. doi:10.1136/archdischild-2014-307396
Pearson. Vineland Adaptive Behavior Scales Third Edition. Accessed May 29, 2025. https://www.pearsonassessments.com/en-us/Store/Professional-Assessments/Behavior/Vineland-Adaptive-Behavior-Scales-%7C-Third-Edition/p/100001622
Lin NH, Jian WS, Snider N, Perng MD. Glial fibrillary acidic protein is pathologically modified in Alexander disease. J Biol Chem. 2024;300(7):107402. doi:10.1016/j.jbc.2024.107402
Yang Z, Wang KK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 2015;38(6):364-374. doi:10.1016/j.tins.2015.04.003
Siracusa R, Fusco R, Cuzzocrea S. Astrocytes: role and functions in brain pathologies. Front Pharmacol. 2019;10:1114. doi:10.3389/fphar.2019.01114
Hagemann TL, Gaeta SA, Smith MA, Johnson DA, Johnson JA, Messing A. Gene expression analysis in mice with elevated glial fibrillary acidic protein and Rosenthal fibers reveals a stress response followed by glial activation and neuronal dysfunction. Hum Mol Genet. 2005;14(16):2443-2458. doi:10.1093/hmg/ddi248
Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A. Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet. 2001;27(1):117-120. doi:10.1038/83679
Messing A, Brenner M, Feany MB, Nedergaard M, Goldman JE. Alexander disease. J Neurosci. 2012;32(15):5017-23. doi:10.1523/JNEUROSCI.5384-11.2012
Sosunov AA, McKhann GM, 2nd, Goldman JE. The origin of Rosenthal fibers and their contributions to astrocyte pathology in Alexander disease. Acta Neuropathol Commun. 2017;5(1):27. doi:10.1186/s40478-017-0425-9
Yoshida T, Mizuta I, Saito K, et al. Effects of a polymorphism in the GFAP promoter on the age of onset and ambulatory disability in late-onset Alexander disease. J Hum Genet. 2013;58(9):635-638. doi:10.1038/jhg.2013.83
Yazdani PA, St-Jean ML, Matovic S, et al. The experience of parents of children with genetically determined leukoencephalopathies with the health care system: a qualitative study. J Child Neurol. 2023:8830738231176672. doi:10.1177/08830738231176672
Tsuji M, Tanaka M, Tanaka Y, et al. Autopsy report of a woman with infantile Alexander disease who survived 39 years. Neuropediatrics. 2020;51(4):298-301. doi:10.1055/s-0040-1705172
Zaver DB, Douthit NT. A novel mutation in the adult-onset Alexander's disease GFAP gene. Case Rep Med. 2019;2019:2986538. doi:10.1155/2019/2986538
Farina L, Pareyson D, Minati L, et al. Can MR imaging diagnose adult-onset Alexander disease? AJNR Am J Neuroradiol. 2008;29(6):1190-1196. doi:10.3174/ajnr.A1060
Namekawa M, Takiyama Y, Honda J, Shimazaki H, Sakoe K, Nakano I. Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature. BMC Neurol. 2010;10:21. doi:10.1186/1471-2377-10-21
Filippi M, Preziosa P, Banwell BL, et al. Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines. Brain. 2019;142(7):1858-1875. doi:10.1093/brain/awz144
Cai T, Jing S, Li Y, Wu J. A Case Report of Adult-onset Alexander disease with a tumor-like lesion in the lateral ventricle. Case Rep Neurol. 2021;13(2):355-360. doi:10.1159/000516256
Oshima Y, Takahashi-Iwata I, Sato S, Harada T, Yoshida T, Yabe I. Pearls & oy-sters: adult-onset Alexander disease with transient swelling of the medulla oblongata. Neurology. 2021;97(12):602-605. doi:10.1212/WNL.0000000000012268
Ziad F, Cypers G, Phillips M, et al. Adult-onset Alexander disease with unusual inflammatory features and a novel GFAP mutation in two patients. Neuropathol Appl Neurobiol. 2023;49(4):e12927. doi:10.1111/nan.12927
Graff-Radford J, Schwartz K, Gavrilova RH, Lachance DH, Kumar N. Neuroimaging and clinical features in type II (late-onset) Alexander disease. Neurology. 2014;82(1):49-56. doi:10.1212/01.wnl.0000438230.33223.bc
van der Knaap MS, Ramesh V, Schiffmann R, et al. Alexander disease: ventricular garlands and abnormalities of the medulla and spinal cord. Neurology. 2006;66(4):494-498. doi:10.1212/01.wnl.0000198770.80743.37
Yoshida T, Mizuta I, Yasuda R, Mizuno T. Clinical and radiological characteristics of older-adult-onset Alexander disease. Eur J Neurol. 2021;28(11):3760-3767. doi:10.1111/ene.15017
Yoshida T, Mizuta I, Yasuda R, Nakagawa M, Mizuno T. Characteristics of cerebral lesions in adult-onset Alexander disease. Neurol Sci. 2020;41(1):225-227. doi:10.1007/s10072-019-04048-2
Armangue T, Whitehead MT, Tonduti D, et al. Brainstem chipmunk sign: a diagnostic imaging clue across all subtypes of Alexander disease. AJNR Am J Neuroradiol. 2024;45(6):769-772. doi:10.3174/ajnr.A8220
Lynch DS, Wade C, Carlson AK, et al. Diagnosing Alexander disease in adults. Pract Neurol. Published online May 11, 2025. doi:10.1136/pn-2024-004490
Yoshida T, Mizuta I, Rei Y, et al. Revised guidelines for diagnosing Alexander disease and their validity. J Neurol Sci. 2017;381 (supplement):461-462.
Boronat S, Turon-Viñas E, Mac Manus N, et al. Response to amoxicillin and perampanel in infantile Alexander disease. Epilepsia Open. 2024;9(6):2505-2509. doi: 10.1002/epi4.13077
Keller SR, Mallack EJ, Rubin JP, et al. Practical approaches and knowledge gaps in the care for children with leukodystrophies. J Child Neurol. 2021;36(1):65-78. doi:10.1177/0883073820946154
Van Haren K, Bonkowsky JL, Bernard G, et al. Consensus statement on preventive and symptomatic care of leukodystrophy patients. Mol Genet Metab. 2015;114(4):516-526. doi:10.1016/j.ymgme.2014.12.433
Nanetti L, Kearney M, Boesch S, et al. Child-to-adult transition: a survey of current practices within the European Reference Network for Rare Neurological Diseases (ERN-RND). Neurol Sci. 2024;45(3):1007-1016. doi:10.1007/s10072-023-07101-3
Sarkar S, Sinha R, Chakraborty A, Khaitan T, Bhowmik B. Infantile Alexander disease: case report and review of literature. J Clin Diagn Res. 2017;11(6):ZD14–ZD15. doi:10.7860/JCDR/2017/26875.10106
Yuan Y, Wu Q, Huo L, Wang H, Liu X. Case report: Alexander’s disease with ‘head drop’ as the main symptom and literature review. Front Neurol. 2022;13:1002527. doi:10.3389/fneur.2022.1002527
Garcia Ayala ME, Serrano C, Labat E. Young woman with weakness progressing to quadriplegia: Is this multiple sclerosis or something else? A case report (2887). Neurology. 2020;94(15_Supplement). doi:10.1212/WNL.94.15_supplement.2887

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