Top

Published in:

Open Access 27-09-2023 | Leukodystrophy | Neurological Update

Update on leukodystrophies and developing trials

Authors: Giorgia Ceravolo, Kristina Zhelcheska, Violetta Squadrito, David Pellerin, Eloisa Gitto, Louise Hartley, Henry Houlden

Published in: Journal of Neurology | Issue 1/2024

Abstract

Leukodystrophies are a heterogeneous group of rare genetic disorders primarily affecting the white matter of the central nervous system. These conditions can present a diagnostic challenge, requiring a comprehensive approach that combines clinical evaluation, neuroimaging, metabolic testing, and genetic testing. While MRI is the main tool for diagnosis, advances in molecular diagnostics, particularly whole-exome sequencing, have significantly improved the diagnostic yield. Timely and accurate diagnosis is crucial to guide symptomatic treatment and assess eligibility to participate in clinical trials. Despite no specific cure being available for most leukodystrophies, gene therapy is emerging as a potential treatment avenue, rapidly advancing the therapeutic prospects in leukodystrophies. This review will explore diagnostic and therapeutic strategies for leukodystrophies, with particular emphasis on new trials.

Available only for authorised users

Vanderver A, Prust M, Tonduti D et al (2015) Case definition and classification of leukodystrophies and leukoencephalopathies. Mol Genet Metab 114(4):494–500. https://doi.org/10.1016/j.ymgme.2015.01.006CrossRefPubMedPubMedCentral

Kevelam SH, Steenweg ME, Srivastava S et al (2016) Update on leukodystrophies: a historical perspective and adapted definition. Neuropediatrics 47(6):349–354. https://doi.org/10.1055/s-0036-1588020CrossRefPubMed

Van Der Knaap MS, Bugiani M (2017) Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms. Acta Neuropathol (Berl) 134(3):351–382. https://doi.org/10.1007/s00401-017-1739-1CrossRefPubMed

Kevelam S, Steenweg M, Srivastava S et al (2016) Update on leukodystrophies: a historical perspective and adapted definition. Neuropediatrics 47(06):349–354. https://doi.org/10.1055/s-0036-1588020CrossRefPubMed

Ashrafi MR, Tavasoli AR (2017) Childhood leukodystrophies: a literature review of updates on new definitions, classification, diagnostic approach and management. Brain Dev 39(5):369–385. https://doi.org/10.1016/j.braindev.2017.01.001CrossRefPubMed

Numata Y, Gotoh L, Iwaki A et al (2014) Epidemiological, clinical, and genetic landscapes of hypomyelinating leukodystrophies. J Neurol 261(4):752–758. https://doi.org/10.1007/s00415-014-7263-5CrossRefPubMed

Ashrafi MR, Rezaei Z, Heidari M et al (2018) The first report of relative incidence of inherited white matter disorders in an Asian Country based on an Iranian Bioregistry System. J Child Neurol 33(4):255–259. https://doi.org/10.1177/0883073817751804CrossRefPubMed

Bonkowsky JL, Nelson C, Kingston JL, Filloux FM, Mundorff MB, Srivastava R (2010) The burden of inherited leukodystrophies in children. Neurology 75(8):718–725. https://doi.org/10.1212/WNL.0b013e3181eee46bCrossRefPubMedPubMedCentral

Ashrafi MR, Amanat M, Garshasbi M et al (2020) An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies. Expert Rev Neurother 20(1):65–84. https://doi.org/10.1080/14737175.2020.1699060CrossRefPubMed

10.

Van Der Knaap MS, Schiffmann R, Mochel F, Wolf NI (2019) Diagnosis, prognosis, and treatment of leukodystrophies. Lancet Neurol 18(10):962–972. https://doi.org/10.1016/S1474-4422(19)30143-7CrossRefPubMed

11.

Weerakkody Y, Yap J, Sciacca F et al Pelizaeus–Merzbacher disease. Reference Article, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/articles/7286. Case courtesy of Dr Yuranga Weerakkody. Radiopaedia.org, rID 7286

12.

Gaillard F, Knipe H, Glick Y et al Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Reference Article, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/articles/66933. Case courtesy of Dr Frank Gaillard. Radiopaedia.org, rID 66933

13.

Gaillard F, Weerakkody Y, Vadera S et al Vanishing white matter disease. Reference Article, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/articles/20903. Case courtesy of Dr Frank Gaillard. Radiopaedia.org, rID 20903

14.

Weerakkody Y, Yap J, Shrestha B et al X-linked adrenoleukodystrophy. Reference Article, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/articles/10259. Case courtesy of Dr Yuranga Weerakkody. Radiopaedia.org, rID 10259

15.

Walterfang M, Metachromatic leukodystrophy. Case Study, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/cases/15572. Case courtesy of Dr Y Mark Walterfang. Radiopaedia.org, rID 15572

16.

Fortin F Aicardi–Goutières syndrome. Case Study, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/cases/149902. Case courtesy of Dr Francis Fortin. Radiopaedia.org, rID 149902

17.

Gaillard F, El-Feky MR et al Canavan disease. Reference Article, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/articles/1045. Case courtesy of Dr Frank Gaillard. Radiopaedia.org, rID 1045

18.

Nassar D Cerebrotendinous xanthomatosis. Case Study, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/cases/165466. Case courtesy of Dr Aalaa Mohammed Nassar. Radiopaedia.org, rID 165466

19.

Lorensini B, Bell D, Hacking C et al Cystic leukoencephalopathy without megalencephaly. Reference Article, Radiopaedia.Org (Accessed on 02 Sep 2023). https://radiopaedia.org/articles/43625. Case courtesy of Dr Bruno Lorensini. Radiopaedia.org, rID 43625

20.

Maegawa GHB (2019) Lysosomal leukodystrophies lysosomal storage diseases associated with white matter abnormalities. J Child Neurol 34(6):339–358. https://doi.org/10.1177/0883073819828587CrossRefPubMedPubMedCentral

21.

Zalckvar E, Schuldiner M (2022) Beyond rare disorders: a new era for peroxisomal pathophysiology. Mol Cell 82(12):2228–2235. https://doi.org/10.1016/j.molcel.2022.05.028CrossRefPubMed

22.

DiMauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348(26):2656–2668. https://doi.org/10.1056/NEJMra022567CrossRefPubMed

23.

Mukherjee S, Ghosh A (2020) Molecular mechanism of mitochondrial respiratory chain assembly and its relation to mitochondrial diseases. Mitochondrion 53:1–20. https://doi.org/10.1016/j.mito.2020.04.002CrossRefPubMed

24.

Agamanolis DP (2018) Disorders of amino acid metabolism and Canavan disease. Developmental neuropathology. Wiley, New York, pp 403–415. https://doi.org/10.1002/9781119013112.ch33CrossRef

25.

Karikkineth AC, Scheibye-Knudsen M, Fivenson E, Croteau DL, Bohr VA (2017) Cockayne syndrome: clinical features, model systems and pathways. Ageing Res Rev 33:3–17. https://doi.org/10.1016/j.arr.2016.08.002CrossRefPubMed

26.

Scheper GC, van der Knaap MS, Proud CG (2007) Translation matters: protein synthesis defects in inherited disease. Nat Rev Genet 8(9):711–723. https://doi.org/10.1038/nrg2142CrossRefPubMed

27.

van der Knaap MS, Boor I, Estévez R (2012) Megalencephalic leukoencephalopathy with subcortical cysts: chronic white matter oedema due to a defect in brain ion and water homoeostasis. Lancet Neurol 11(11):973–985. https://doi.org/10.1016/S1474-4422(12)70192-8CrossRefPubMed

28.

Min R, van der Knaap MS (2018) Genetic defects disrupting glial ion and water homeostasis in the brain. Brain Pathol Zurich Switz 28(3):372–387. https://doi.org/10.1111/bpa.12602CrossRef

29.

Ferreira LMR, Li AM, Serafim TL, Sobral MC, Alpoim MC, Urbano AM (2020) Intermediary metabolism: an intricate network at the crossroads of cell fate and function. Biochim Biophys Acta Mol Basis Dis 1866(10):165887. https://doi.org/10.1016/j.bbadis.2020.165887CrossRefPubMed

30.

Yan H, Helman G, Murthy SE et al (2019) heterozygous variants in the mechanosensitive ion channel TMEM63A result in transient hypomyelination during infancy. Am J Hum Genet 105(5):996–1004. https://doi.org/10.1016/j.ajhg.2019.09.011CrossRefPubMedPubMedCentral

31.

Srivastava S, Waldman A, Naidu S (2020) Alexander disease. In: Adam MP, Mirzaa GM, Pagon RA et al (eds) GeneReviews^®. University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1172/. Accessed 25 June 2023

32.

Deginet E, Tilahun R, Bishaw S, Eshetu K, Moges A (2021) Probable vanishing white matter disease: a case report and literature review. Ethiop J Health Sci 31(6):1307–1310. https://doi.org/10.4314/ejhs.v31i6.28CrossRefPubMedPubMedCentral

33.

Shaimardanova AA, Chulpanova DS, Solovyeva VV et al (2020) Metachromatic leukodystrophy: diagnosis, modeling, and treatment approaches. Front Med 7:576221. https://doi.org/10.3389/fmed.2020.576221CrossRef

34.

Zhu J, Guo X, Ran N et al (2023) Leukoencephalopathy hypomyelination with brainstem and spinal cord involvement and leg spasticity caused by DARS1 mutations. Front Genet 13:1009230. https://doi.org/10.3389/fgene.2022.1009230CrossRefPubMedPubMedCentral

35.

Wenger DA, Luzi P, Rafi MA (2021) Advances in the diagnosis and treatment of Krabbe disease. Int J Neonatal Screen 7(3):57. https://doi.org/10.3390/ijns7030057CrossRefPubMedPubMedCentral

36.

Nie S, Chen G, Cao X, Zhang Y (2014) Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis 9(1):179. https://doi.org/10.1186/s13023-014-0179-4CrossRefPubMedPubMedCentral

37.

Singh R, Samanta D (2023) Pelizaeus–Merzbacher disease. In: StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK560522/. Accessed 26 June 2023

38.

Wei H, Moffett JR, Amanat M et al (2022) The pathogenesis of, and pharmacological treatment for, Canavan disease. Drug Discov Today 27(9):2467–2483. https://doi.org/10.1016/j.drudis.2022.05.019CrossRefPubMed

39.

Crow YJ (2005) Aicardi–Goutières syndrome. In: Adam MP, Mirzaa GM, Pagon RA et al (eds) GeneReviews^®. University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1475/. Accessed 25 June 2023

40.

Engelen M, Kemp S, De Visser M et al (2012) X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis 7(1):51. https://doi.org/10.1186/1750-1172-7-51CrossRefPubMedPubMedCentral

41.

Bradbury AM, Ream MA (2021) Recent advancements in the diagnosis and treatment of leukodystrophies. Semin Pediatr Neurol 37:100876. https://doi.org/10.1016/j.spen.2021.100876CrossRefPubMed

42.

Schiffmann R, Van Der Knaap MS (2009) Invited Article: An MRI-based approach to the diagnosis of white matter disorders. Neurology 72(8):750–759. https://doi.org/10.1212/01.wnl.0000343049.00540.c8CrossRefPubMedPubMedCentral

43.

Perrier S, Guerrero K, Tran LT et al (2023) Solving inherited white matter disorder etiologies in the neurology clinic: challenges and lessons learned using next-generation sequencing. Front Neurol 14:1148377. https://doi.org/10.3389/fneur.2023.1148377CrossRefPubMedPubMedCentral

44.

Soden SE, Saunders CJ, Willig LK et al (2014) Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med 6(265):265ra168. https://doi.org/10.1126/scitranslmed.3010076CrossRefPubMedPubMedCentral

45.

McInerney-Leo AM, Duncan EL (2020) Massively parallel sequencing for rare genetic disorders: potential and pitfalls. Front Endocrinol 11:628946. https://doi.org/10.3389/fendo.2020.628946CrossRef

46.

Muthusamy K, Sivadasan A, Dixon L et al (2023) Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions. Front Neurol 14:1219324. https://doi.org/10.3389/fneur.2023.1219324CrossRefPubMedPubMedCentral

47.

Moser AB, Kreiter N, Bezman L et al (1999) Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls. Ann Neurol 45(1):100–110. https://doi.org/10.1002/1531-8249(199901)45:1%3c100::aid-art16%3e3.0.co;2-uCrossRefPubMed

48.

Valianpour F, Selhorst JJM, van Lint LEM, van Gennip AH, Wanders RJA, Kemp S (2003) Analysis of very long-chain fatty acids using electrospray ionization mass spectrometry. Mol Genet Metab 79(3):189–196. https://doi.org/10.1016/s1096-7192(03)00098-2CrossRefPubMed

49.

Biochemical aspects of X‐linked adrenoleukodystrophy. https://doi.org/10.1111/j.1750-3639.2010.00391.x. Accessed 29 Aug 2023

50.

Moser HW, Moser AB, Frayer KK et al (1981) Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids. Neurology 31(10):1241–1249. https://doi.org/10.1212/wnl.31.10.1241CrossRefPubMed

51.

Suzuki K, Suzuki Y (1970) Globoid cell leucodystrophy (Krabbe’s disease): deficiency of galactocerebroside β-galactosidase*. Proc Natl Acad Sci USA 66(2):302–309. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC283044/. Accessed 2 Sept 2023

52.

Lamichhane A, Rocha Cabrero F (2023) Metachromatic leukodystrophy. In: StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK560744/. Accessed 2 Sept 2023

53.

Parikh S, Bernard G, Leventer RJ et al (2015) A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. Mol Genet Metab 114(4):501–515. https://doi.org/10.1016/j.ymgme.2014.12.434CrossRefPubMed

54.

Natowicz MR, Prence EM, Chaturvedi P, Newburg DS (1996) Urine sulfatides and the diagnosis of metachromatic leukodystrophy. Clin Chem 42(2):232–238CrossRefPubMed

55.

Lynch DS, Wade C, de Paiva ARB et al (2019) Practical approach to the diagnosis of adult-onset leukodystrophies: an updated guide in the genomic era. J Neurol Neurosurg Psychiatry 90(5):543–554. https://doi.org/10.1136/jnnp-2018-319481CrossRefPubMed

56.

Laugwitz L, Zizmare L, Santhanakumaran V et al (2022) Identification of neurodegeneration indicators and disease progression in metachromatic leukodystrophy using quantitative NMR-based urinary metabolomics. JIMD Rep 63(2):168–180. https://doi.org/10.1002/jmd2.12273CrossRefPubMedPubMedCentral

57.

Zhang Q, Li H, Zhang Z, Yang F, Chen J (2015) Serum metabolites as potential biomarkers for diagnosis of knee osteoarthritis. Dis Markers 2015:684794. https://doi.org/10.1155/2015/684794CrossRefPubMedPubMedCentral

58.

Weinstock NI, Wrabetz L, Feltri ML, Shin D (2016) Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease. J Neurosci Res 94(11):1094–1107. https://doi.org/10.1002/jnr.23789CrossRefPubMedPubMedCentral

59.

Federico A, Dotti MT (2001) Cerebrotendinous xanthomatosis. Neurology 57(9):1743. https://doi.org/10.1212/wnl.57.9.1743CrossRefPubMed

60.

Nie S, Chen G, Cao X, Zhang Y (2014) Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis 9:179. https://doi.org/10.1186/s13023-014-0179-4CrossRefPubMedPubMedCentral

61.

Dali CÍ, Barton NW, Farah MH et al (2015) Sulfatide levels correlate with severity of neuropathy in metachromatic leukodystrophy. Ann Clin Transl Neurol 2(5):518–533. https://doi.org/10.1002/acn3.193CrossRefPubMedPubMedCentral

62.

Turgeon CT, Orsini JJ, Sanders KA et al (2015) Measurement of psychosine in dried blood spots—a possible improvement to newborn screening programs for Krabbe disease. J Inherit Metab Dis 38(5):923–929. https://doi.org/10.1007/s10545-015-9822-zCrossRefPubMed

63.

Escolar M, Kiely B, Shawgo E et al (2017) Psychosine, a marker of Krabbe phenotype and treatment effect. Mol Genet Metab 121(3):271–278. https://doi.org/10.1016/j.ymgme.2017.05.015CrossRefPubMedPubMedCentral

64.

Beerepoot S, Heijst H, Roos B et al (2022) Neurofilament light chain and glial fibrillary acidic protein levels in metachromatic leukodystrophy. Brain J Neurol 145(1):105–118. https://doi.org/10.1093/brain/awab304CrossRef

65.

Jany PL, Agosta GE, Benko WS et al (2015) CSF and blood levels of GFAP in Alexander disease. ENeuro. https://doi.org/10.1523/ENEURO.0080-15.2015CrossRefPubMedPubMedCentral

66.

van Ballegoij WJC, van de Stadt SIW, Huffnagel IC et al (2020) Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy. Ann Clin Transl Neurol 7(11):2127–2136. https://doi.org/10.1002/acn3.51188CrossRefPubMedPubMedCentral

67.

Gómez J, Artigas L, Valls R, Gervas-Arruga J (2023) An in silico approach to identify early damage biomarker candidates in metachromatic leukodystrophy. Mol Genet Metab Rep 35:100974. https://doi.org/10.1016/j.ymgmr.2023.100974CrossRefPubMedPubMedCentral

68.

Caetano CM, Malchoff CD (2022) Daily glucocorticoid replacement dose in adrenal insufficiency, a mini review. Front Endocrinol 13:897211. https://doi.org/10.3389/fendo.2022.897211CrossRef

69.

von Jonquieres G, Rae CD, Housley GD (2021) Emerging concepts in vector development for glial gene therapy: implications for leukodystrophies. Front Cell Neurosci 15:661857. https://doi.org/10.3389/fncel.2021.661857CrossRef

70.

Ingusci S, Verlengia G, Soukupova M, Zucchini S, Simonato M (2019) Gene therapy tools for brain diseases. Front Pharmacol 10:724. https://doi.org/10.3389/fphar.2019.00724CrossRefPubMedPubMedCentral

71.

Sessa M, Lorioli L, Fumagalli F et al (2016) Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial. Lancet 388(10043):476–487. https://doi.org/10.1016/S0140-6736(16)30374-9CrossRefPubMed

72.

Kurtzberg J (2022) Gene therapy offers new hope for children with metachromatic leukodystrophy. Lancet Lond Engl 399(10322):338–339. https://doi.org/10.1016/S0140-6736(22)00057-5CrossRef

73.

Hordeaux J, Jeffrey BA, Jian J et al (2022) Efficacy and safety of a Krabbe disease gene therapy. Hum Gene Ther 33(9–10):499–517. https://doi.org/10.1089/hum.2021.245CrossRefPubMedPubMedCentral

74.

Naso MF, Tomkowicz B, Perry WL, Strohl WR (2017) Adeno-associated virus (AAV) as a vector for gene therapy. BioDrugs Clin Immunother Biopharm Gene Ther 31(4):317–334. https://doi.org/10.1007/s40259-017-0234-5CrossRef

75.

Herdt AR, Peng H, Dickson DW, Golde TE, Eckman EA, Lee CW (2023) Brain targeted AAV1-GALC gene therapy reduces psychosine and extends lifespan in a mouse model of Krabbe disease. Genes 14(8):1517. https://doi.org/10.3390/genes14081517CrossRefPubMedPubMedCentral

76.

Leone P, Shera D, McPhee SWJ et al (2012) Long-term follow-up after gene therapy for canavan disease. Sci Transl Med 4(165):165ra163. https://doi.org/10.1126/scitranslmed.3003454CrossRefPubMedPubMedCentral

77.

Amanat M, Nemeth CL, Fine AS, Leung DG, Fatemi A (2022) Antisense oligonucleotide therapy for the nervous system: from bench to bedside with emphasis on pediatric neurology. Pharmaceutics 14(11):2389. https://doi.org/10.3390/pharmaceutics14112389CrossRefPubMedPubMedCentral

78.

A study to evaluate the safety and efficacy of ION373 in patients with Alexander disease (AxD). NCT04849741

79.

Viking Therapeutics, Inc. (2023) Phase 1b, multi-center, randomized, double-blind, placebo-controlled, study to evaluate the safety, tolerability, PD and PK of VK0214, in subjects with the adrenomyeloneuropathy form (AMN) of X-linked adrenoleukodystrophy (X-ALD). clinicaltrials.gov. https://clinicaltrials.gov/study/NCT04973657. Accessed 29 Aug 2023

80.

A clinical study in male pediatric patients with cerebral X-linked adrenoleukodystrophy (Cald) to assess the effects of MIN-102 treatment on disease progression prior to human stem cell transplant (HSCT) (NEXUS). NCT04528706

81.

Pizcueta P, Vergara C, Emanuele M, Vilalta A, Rodríguez-Pascau L, Martinell M (2023) Development of PPARγ agonists for the treatment of neuroinflammatory and neurodegenerative diseases: leriglitazone as a promising candidate. Int J Mol Sci 24(4):3201. https://doi.org/10.3390/ijms24043201CrossRefPubMedPubMedCentral

82.

Schöls L (2023) Leriglitazone: frustration and hope in adrenoleukodystrophy. Lancet Neurol 22(2):103–105. https://doi.org/10.1016/S1474-4422(22)00518-XCrossRefPubMed

83.

OTL-200 in patients with late juvenile metachromatic leukodystrophy (MLD). NCT04283227

84.

Myrtelle Inc. (2023) Phase 1/2, open label, sequential cohort study of a single intracranial dose of AVASPA gene therapy for treatment of children with typical Canavan disease. clinicaltrials.gov. https://clinicaltrials.gov/study/NCT04833907. Accessed 29 Aug 2023

Title: Update on leukodystrophies and developing trials
Authors: Giorgia Ceravolo
Kristina Zhelcheska
Violetta Squadrito
David Pellerin
Eloisa Gitto
Louise Hartley
Henry Houlden
Publication date: 27-09-2023
Publisher: Springer Berlin Heidelberg
Keywords: Leukodystrophy
White Matter Alterations
Demyelinating Disease
Genetic Testing
Gene Therapy in Oncology
Published in: Journal of Neurology / Issue 1/2024
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-023-11996-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Update on leukodystrophies and developing trials

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2024

International survey on the implementation of the European and American guidelines on disorders of consciousness

Correction to: Synergistic effects of vagus nerve stimulation and antiseizure medication

Characterizing cognitive function in patients with autoimmune encephalitis: an Australian prospective study

Pooled analysis of patients with inherited prion disease caused by two- to twelve-octapeptide repeat insertions in the prion protein gene (PRNP)

Long-term outcome of natalizumab-associated progressive multifocal leukoencephalopathy in Austria: a nationwide retrospective study

The relationship between disease-specific psychosocial stressors and depressive symptoms in Huntington’s disease