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Acta Neuropathologica
Published in: Acta Neuropathologica 3/2017

Open Access 01-09-2017 | Review

Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms

Authors: Marjo S. van der Knaap, Marianna Bugiani

Published in: Acta Neuropathologica | Issue 3/2017

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Abstract

Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. The clinical course is mostly progressive, but may also be static or even improving with time. Progressive leukodystrophies are often fatal, and no curative treatment is known. The last decade has witnessed a tremendous increase in the number of defined leukodystrophies also owing to a diagnostic approach combining magnetic resonance imaging pattern recognition and next generation sequencing. Knowledge on white matter physiology and pathology has also dramatically built up. This led to the recognition that only few leukodystrophies are due to mutations in myelin- or oligodendrocyte-specific genes, and many are rather caused by defects in other white matter structural components, including astrocytes, microglia, axons and blood vessels. We here propose a novel classification of leukodystrophies that takes into account the primary involvement of any white matter component. Categories in this classification are the myelin disorders due to a primary defect in oligodendrocytes or myelin (hypomyelinating and demyelinating leukodystrophies, leukodystrophies with myelin vacuolization); astrocytopathies; leuko-axonopathies; microgliopathies; and leuko-vasculopathies. Following this classification, we illustrate the neuropathology and disease mechanisms of some leukodystrophies taken as example for each category. Some leukodystrophies fall into more than one category. Given the complex molecular and cellular interplay underlying white matter pathology, recognition of the cellular pathology behind a disease becomes crucial in addressing possible treatment strategies.
Literature
1.
2.
Agamanolis DP (2004) Pathology & genetics. Developmental neuropathology. ISN Neuropath, City
3.
4.
Anzil AP, Gessaga E (1972) Late-life cavitating dystrophy of the cerebral and cerebellar white matter. A form of sudanophil leucodystrophy. Eur Neurol 7:79–94PubMedCrossRef
5.
Axelsson R, Roytta M, Sourander P, Akesson HO, Andersen O (1984) Hereditary diffuse leucoencephalopathy with spheroids. Acta Psychiatr Scand Suppl 314:1–65PubMed
6.
Baba Y, Ghetti B, Baker MC, Uitti RJ, Hutton ML, Yamaguchi K, Bird T, Lin W, DeLucia MW, Dickson DW et al (2006) Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred. Acta Neuropathol 111:300–311. doi:10.​1007/​s00401-006-0046-z PubMedCrossRef
7.
Back SA, Luo NL, Borenstein NS, Volpe JJ, Kinney HC (2002) Arrested oligodendrocyte lineage progression during human cerebral white matter development: dissociation between the timing of progenitor differentiation and myelinogenesis. J Neuropathol Exp Neurol 61:197–211PubMedCrossRef
8.
Back SA, Tuohy TM, Chen H, Wallingford N, Craig A, Struve J, Luo NL, Banine F, Liu Y, Chang A et al (2005) Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nat Med 11:966–972. doi:10.​1038/​nm1279 PubMed
9.
10.
Barrallo-Gimeno A, Estevez R (2014) GlialCAM, a glial cell adhesion molecule implicated in neurological disease. Adv Neurobiol 8:47–59PubMedCrossRef
11.
12.
Barres BA, Hart IK, Coles HS, Burne JF, Voyvodic JT, Richardson WD, Raff MC (1992) Cell death and control of cell survival in the oligodendrocyte lineage. Cell 70:31–46PubMedCrossRef
13.
14.
15.
16.
Bielschowsky MH, Henneberg R (1928) Über familiäre diffuse Sklerose (Leukodystrophia cerebri progressiva hereditaria). J Psychol Neurol 36:131–181
17.
18.
Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S et al (2013) Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341:1233158. doi:10.​1126/​science.​1233158 PubMedCrossRef
19.
Bizzozero OA, Pasquini JM, Soto EF (1982) Differential effect of colchicine upon the entry of proteins into myelin and myelin related membranes. Neurochem Res 7:1415–1425PubMedCrossRef
20.
21.
Black DN, Booth F, Watters GV, Andermann E, Dumont C, Halliday WC, Hoogstraten J, Kabay ME, Kaplan P, Meagher-Villemure K et al (1988) Leukoencephalopathy among native Indian infants in northern Quebec and Manitoba. Ann Neurol 24:490–496. doi:10.​1002/​ana.​410240403 PubMedCrossRef
22.
Boor I, Nagtegaal M, Kamphorst W, van der Valk P, Pronk JC, van Horssen J, Dinopoulos A, Bove KE, Pascual-Castroviejo I, Muntoni F et al (2007) MLC1 is associated with the dystrophin-glycoprotein complex at astrocytic endfeet. Acta Neuropathol 114:403–410. doi:10.​1007/​s00401-007-0247-0 PubMedPubMedCentralCrossRef
23.
Boor PK, de Groot K, Waisfisz Q, Kamphorst W, Oudejans CB, Powers JM, Pronk JC, Scheper GC, van der Knaap MS (2005) MLC1: a novel protein in distal astroglial processes. J Neuropathol Exp Neurol 64:412–419PubMedCrossRef
24.
Borrett D, Becker LE (1985) Alexander’s disease. A disease of astrocytes. Brain 108(Pt 2):367–385PubMedCrossRef
25.
Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A (2001) Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet 27:117–120. doi:10.​1038/​83679 PubMedCrossRef
26.
Brignone MS, Lanciotti A, Macioce P, Macchia G, Gaetani M, Aloisi F, Petrucci TC, Ambrosini E (2011) The beta1 subunit of the Na, K-ATPase pump interacts with megalencephalic leucoencephalopathy with subcortical cysts protein 1 (MLC1) in brain astrocytes: new insights into MLC pathogenesis. Hum Mol Genet 20:90–103. doi:10.​1093/​hmg/​ddq435 PubMedCrossRef
27.
Brown WR, Moody DM, Thore CR, Challa VR (2000) Apoptosis in leukoaraiosis. AJNR 21:79–82PubMed
28.
Bruck W, Herms J, Brockmann K, Schulz-Schaeffer W, Hanefeld F (2001) Myelinopathia centralis diffusa (vanishing white matter disease): evidence of apoptotic oligodendrocyte degeneration in early lesion development. Ann Neurol 50:532–536PubMedCrossRef
29.
30.
31.
Bugiani M, Kevelam SH, Bakels HS, Waisfisz Q, Ceuterick-de Groote C, Niessen HW, Abbink TE, Lesnik Oberstein SA, van der Knaap MS (2016) Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL). Neurology 87:1777–1786. doi:10.​1212/​wnl.​0000000000003251​ PubMedCrossRef
32.
Bugiani M, Postma N, Polder E, Dieleman N, Scheffer PG, Sim FJ, van der Knaap MS, Boor I (2013) Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease. Brain 136:209–222. doi:10.​1093/​brain/​aws320 PubMedCrossRef
33.
Bugiani O, Borrone C (1976) Fucosidosis: a neuropathological study. Riv Patol Nerv Ment 97:133–141PubMed
34.
35.
Carson JH, Worboys K, Ainger K, Barbarese E (1997) Translocation of myelin basic protein mRNA in oligodendrocytes requires microtubules and kinesin. Cell Motil Cytoskeleton 38:318–328. doi:10.1002/(sici)1097-0169(1997)38:4%3c318:aid-cm2%3e3.0.co;2-#
36.
Charzewska A, Wierzba J, Izycka-Swieszewska E, Bekiesinska-Figatowska M, Jurek M, Gintowt A, Klosowska A, Bal J, Hoffman-Zacharska D (2016) Hypomyelinating leukodystrophies—a molecular insight into the white matter pathology. Clin Genet 90:293–304. doi:10.​1111/​cge.​12811 PubMedCrossRef
37.
38.
39.
Cho W, Messing A (2009) Properties of astrocytes cultured from GFAP over-expressing and GFAP mutant mice. Exp Cell Res 315:1260–1272PubMedCrossRef
40.
41.
Constantin G, Laudanna C, Baron P, Berton G (1994) Sulfatides trigger cytokine gene expression and secretion in human monocytes. FEBS Lett 350:66–70PubMedCrossRef
42.
43.
44.
Demerens C, Stankoff B, Logak M, Anglade P, Allinquant B, Couraud F, Zalc B, Lubetzki C (1996) Induction of myelination in the central nervous system by electrical activity. Proc Natl Acad Sci USA 93:9887–9892PubMedPubMedCentralCrossRef
45.
Depienne C, Bugiani M, Dupuits C, Galanaud D, Touitou V, Postma N, van Berkel C, Polder E, Tollard E, Darios F et al (2013) Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Lancet Neurol 12:659–668. doi:10.​1016/​s1474-4422(13)70053-x PubMedCrossRef
46.
47.
Dietrich J, Lacagnina M, Gass D, Richfield E, Mayer-Proschel M, Noble M, Torres C, Proschel C (2005) EIF2B5 mutations compromise GFAP+ astrocyte generation in vanishing white matter leukodystrophy. Nat Med 11:277–283. doi:10.​1038/​nm1195 PubMedCrossRef
48.
Dooves S, Bugiani M, Postma NL, Polder E, Land N, Horan ST, van Deijk AL, van de Kreeke A, Jacobs G, Vuong C et al (2016) Astrocytes are central in the pathomechanisms of vanishing white matter. J Clin Invest 126:1512–1524. doi:10.​1172/​jci83908 PubMedPubMedCentralCrossRef
49.
Duarri A, Lopez de Heredia M, Capdevila-Nortes X, Ridder MC, Montolio M, Lopez-Hernandez T, Boor I, Lien CF, Hagemann T, Messing A et al (2011) Knockdown of MLC1 in primary astrocytes causes cell vacuolation: a MLC disease cell model. Neurobiol Dis 43:228–238. doi:10.​1016/​j.​nbd.​2011.​03.​015 PubMedCrossRef
50.
Dubey M, Bugiani M, Ridder MC, Postma NL, Brouwers E, Polder E, Jacobs JG, Baayen JC, Klooster J, Kamermans M et al (2015) Mice with megalencephalic leukoencephalopathy with cysts: a developmental angle. Ann Neurol 77:114–131. doi:10.​1002/​ana.​24307 PubMedCrossRef
51.
52.
Ellison DL, Love S, Chimelli L, Harding BN, Lowe J, Vinters HV (2004) Neuropathology: a reference text of CNS pathology. Mosby Elsevier, City
53.
54.
55.
56.
Farina L, Pareyson D, Minati L, Ceccherini I, Chiapparini L, Romano S, Gambaro P, Fancellu R, Savoiardo M (2008) Can MR imaging diagnose adult-onset Alexander disease? AJNR 29:1190–1196. doi:10.​3174/​ajnr.​A1060 PubMedCrossRef
57.
Favre-Kontula L, Rolland A, Bernasconi L, Karmirantzou M, Power C, Antonsson B, Boschert U (2008) GlialCAM, an immunoglobulin-like cell adhesion molecule is expressed in glial cells of the central nervous system. Glia 56:633–645. doi:10.​1002/​glia.​20640 PubMedCrossRef
58.
59.
60.
61.
Fogli A, Rodriguez D, Eymard-Pierre E, Bouhour F, Labauge P, Meaney BF, Zeesman S, Kaneski CR, Schiffmann R, Boespflug-Tanguy O (2003) Ovarian failure related to eukaryotic initiation factor 2B mutations. Am J Hum Genet 72:1544–1550. doi:10.​1086/​375404 PubMedPubMedCentralCrossRef
62.
Fogli A, Wong K, Eymard-Pierre E, Wenger J, Bouffard JP, Goldin E, Black DN, Boespflug-Tanguy O, Schiffmann R (2002) Cree leukoencephalopathy and CACH/VWM disease are allelic at the EIF2B5 locus. Ann Neurol 52:506–510. doi:10.​1002/​ana.​10339 PubMedCrossRef
63.
Francalanci P, Eymard-Pierre E, Dionisi-Vici C, Boldrini R, Piemonte F, Virgili R, Fariello G, Bosman C, Santorelli FM, Boespflug-Tanguy O et al (2001) Fatal infantile leukodystrophy: a severe variant of CACH/VWM syndrome, allelic to chromosome 3q27. Neurology 57:265–270PubMedCrossRef
64.
Funfschilling U, Supplie LM, Mahad D, Boretius S, Saab AS, Edgar J, Brinkmann BG, Kassmann CM, Tzvetanova ID, Mobius W et al (2012) Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity. Nature 485:517–521. doi:10.​1038/​nature11007 PubMedPubMedCentral
65.
Gautier JC, Gray F, Awada A, Escourolle R (1984) Cavitary orthochromatic leukodystrophy in the adult. Oligodendroglial proliferation and inclusions. Rev Neurol (Paris) 140:493–501
66.
67.
Geren BB, Raskind J (1953) Development of the fine structure of the myelin sheath in sciatic nerves of chick embryos. Proc Natl Acad Sci USA 39:880–884PubMedPubMedCentralCrossRef
68.
69.
70.
71.
Girard PF, Tommasi M, Rochet M, Boucher M (1968) Leukoencephalopathy with large bilateral symmetrical cavitation. Post-traumatic decortication syndrome. Presse Med 76:163–166PubMed
72.
73.
Graveleau P, Gray F, Plas J, Graveleau J, Brion S (1985) Cavitary orthochromatic leukodystrophy with oligodendroglial changes. A sporadic adult case. Rev Neurol (Paris) 141:713–718
74.
75.
Haberland C, Brunngraber E, Witting L, Brown B (1973) The white matter in G M2 gangliosidosis. A comparative histopathological and biochemical study. Acta Neuropathol 24:43–55PubMedCrossRef
76.
77.
78.
79.
Haltia M, Rapola J, Santavuori P (1973) Infantile type of so-called neuronal ceroid-lipofuscinosis. Histological and electron microscopic studies. Acta Neuropathol 26:157–170PubMedCrossRef
80.
Hamilton EM, Polder E, Vanderver A, Naidu S, Schiffmann R, Fisher K, Raguz AB, Blumkin L, van Berkel CG, Waisfisz Q et al (2014) Hypomyelination with atrophy of the basal ganglia and cerebellum: further delineation of the phenotype and genotype-phenotype correlation. Brain 137:1921–1930. doi:10.​1093/​brain/​awu110 PubMedPubMedCentralCrossRef
81.
82.
83.
84.
Hanefeld F, Holzbach U, Kruse B, Wilichowski E, Christen HJ, Frahm J (1993) Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy. Neuropediatrics 24:244–248. doi:10.​1055/​s-2008-1071551 PubMedCrossRef
85.
86.
Harbord MG, Harden A, Harding B, Brett EM, Baraitser M (1990) Megalencephaly with dysmyelination, spasticity, ataxia, seizures and distinctive neurophysiological findings in two siblings. Neuropediatrics 21:164–168. doi:10.​1055/​s-2008-1071487 PubMedCrossRef
87.
88.
89.
Hinnebusch AG (2000) Translational control of gene expression. Cold Spring Harbor Laboratory Press, City
90.
Hoffman-Zacharska D, Mierzewska H, Szczepanik E, Poznanski J, Mazurczak T, Jakubiuk-Tomaszuk A, Madry J, Kierdaszuk A, Bal J (2013) The spectrum of PLP1 gene mutations in patients with the classical form of the Pelizaeus-Merzbacher disease. Med Wieku Rozwoj 17:293–300PubMed
91.
92.
93.
94.
Huttenlocher PR (2000) The neuropathology of phenylketonuria: human and animal studies. Eur J Pediatr 159(Suppl 2):S102–S106PubMedCrossRef
95.
Igisu H, Suzuki K (1984) Progressive accumulation of toxic metabolite in a genetic leukodystrophy. Science 224:753–755PubMedCrossRef
96.
97.
98.
Jenkinson EM, Rodero MP, Kasher PR, Uggenti C, Oojageer A, Goosey LC, Rose Y, Kershaw CJ, Urquhart JE, Williams SG et al (2016) Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts. Nat Genet 48:1185–1192. doi:10.​1038/​ng.​3661 PubMedPubMedCentralCrossRef
99.
Jepson S, Vought B, Gross CH, Gan L, Austen D, Frantz JD, Zwahlen J, Lowe D, Markland W, Krauss R (2012) LINGO-1, a transmembrane signaling protein, inhibits oligodendrocyte differentiation and myelination through intercellular self-interactions. J Biol Chem 287:22184–22195. doi:10.​1074/​jbc.​M112.​366179 PubMedPubMedCentralCrossRef
100.
101.
Kantor L, Harding HP, Ron D, Schiffmann R, Kaneski CR, Kimball SR, Elroy-Stein O (2005) Heightened stress response in primary fibroblasts expressing mutant eIF2B genes from CACH/VWM leukodystrophy patients. Hum Genet 118:99–106. doi:10.​1007/​s00439-005-0024-x PubMedCrossRef
102.
103.
Kevelam SH, Steenweg ME, Srivastava S, Helman G, Naidu S, Schiffmann R, Blaser S, Vanderver A, Wolf NI, van der Knaap MS (2016) Update on leukodystrophies: a historical perspective and adapted definition. Neuropediatrics 47:349–354. doi:10.​1055/​s-0036-1588020 PubMedCrossRef
104.
Kevelam SH, Taube JR, van Spaendonk RM, Bertini E, Sperle K, Tarnopolsky M, Tonduti D, Valente EM, Travaglini L, Sistermans EA et al (2015) Altered PLP1 splicing causes hypomyelination of early myelinating structures. Ann Clin Transl Neurol 2:648–661. doi:10.​1002/​acn3.​203 PubMedPubMedCentralCrossRef
105.
Kiely DG, Cargill RI, Struthers AD, Lipworth BJ (1997) Cardiopulmonary effects of endothelin-1 in man. Cardiovasc Res 33:378–386PubMedCrossRef
106.
107.
Kleijn M, Scheper GC, Voorma HO, Thomas AA (1998) Regulation of translation initiation factors by signal transduction. Eur J Biochem 253:531–544PubMedCrossRef
108.
Klein EA, Anzil AP (1994) Prominent white matter cavitation in an infant with Alexander’s disease. Clin Neuropathol 13:31–38PubMed
109.
Knopman D, Sung JH, Davis D (1996) Progressive familial leukodystrophy of late onset. Neurology 46:429–434PubMedCrossRef
110.
111.
112.
Koyama Y, Goldman JE (1999) Formation of GFAP cytoplasmic inclusions in astrocytes and their disaggregation by alphaB-crystallin. Am J Pathol 154:1563–1572PubMedPubMedCentralCrossRef
113.
114.
115.
Kuronen M, Hermansson M, Manninen O, Zech I, Talvitie M, Laitinen T, Grohn O, Somerharju P, Eckhardt M, Cooper JD et al (2012) Galactolipid deficiency in the early pathogenesis of neuronal ceroid lipofuscinosis model Cln8mnd: implications to delayed myelination and oligodendrocyte maturation. Neuropathol Appl Neurobiol 38:471–486. doi:10.​1111/​j.​1365-2990.​2011.​01233.​x PubMedCrossRef
116.
Lake B (1997) Greenfield’s neuropathology. Arnold pub, City
117.
118.
Lanciotti A, Brignone MS, Molinari P, Visentin S, De Nuccio C, Macchia G, Aiello C, Bertini E, Aloisi F, Petrucci TC et al (2012) Megalencephalic leukoencephalopathy with subcortical cysts protein 1 functionally cooperates with the TRPV4 cation channel to activate the response of astrocytes to osmotic stress: dysregulation by pathological mutations. Hum Mol Genet 21:2166–2180. doi:10.​1093/​hmg/​dds032 PubMedCrossRef
119.
Lanciotti A, Brignone MS, Visentin S, De Nuccio C, Catacuzzeno L, Mallozzi C, Petrini S, Caramia M, Veroni C, Minnone G et al (2016) Megalencephalic leukoencephalopathy with subcortical cysts protein-1 regulates epidermal growth factor receptor signaling in astrocytes. Hum Mol Genet 25:1543–1558. doi:10.​1093/​hmg/​ddw032 PubMedCrossRef
120.
121.
Laudanna C, Constantin G, Baron P, Scarpini E, Scarlato G, Cabrini G, Dechecchi C, Rossi F, Cassatella MA, Berton G (1994) Sulfatides trigger increase of cytosolic free calcium and enhanced expression of tumor necrosis factor-alpha and interleukin-8 mRNA in human neutrophils. Evidence for a role of L-selectin as a signaling molecule. J Biol Chem 269:4021–4026PubMed
122.
123.
124.
Lee KK, de Repentigny Y, Saulnier R, Rippstein P, Macklin WB, Kothary R (2006) Dominant-negative beta1 integrin mice have region-specific myelin defects accompanied by alterations in MAPK activity. Glia 53:836–844. doi:10.​1002/​glia.​20343 PubMedCrossRef
125.
Leegwater PA, Yuan BQ, van der Steen J, Mulders J, Konst AA, Boor PK, Mejaski-Bosnjak V, van der Maarel SM, Frants RR, Oudejans CB et al (2001) Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts. Am J Hum Genet 68:831–838. doi:10.​1086/​319519 PubMedPubMedCentralCrossRef
126.
127.
128.
Liu R, van der Lei HD, Wang X, Wortham NC, Tang H, van Berkel CG, Mufunde TA, Huang W, van der Knaap MS, Scheper GC et al (2011) Severity of vanishing white matter disease does not correlate with deficits in eIF2B activity or the integrity of eIF2B complexes. Hum Mutat 32:1036–1045. doi:10.​1002/​humu.​21535 PubMedCrossRef
129.
Lohmann K, Wilcox RA, Winkler S, Ramirez A, Rakovic A, Park JS, Arns B, Lohnau T, Groen J, Kasten M et al (2013) Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene. Ann Neurol 73:537–545. doi:10.​1002/​ana.​23829 PubMedCrossRef
130.
Lopez-Hernandez T, Ridder MC, Montolio M, Capdevila-Nortes X, Polder E, Sirisi S, Duarri A, Schulte U, Fakler B, Nunes V et al (2011) Mutant GlialCAM causes megalencephalic leukoencephalopathy with subcortical cysts, benign familial macrocephaly, and macrocephaly with retardation and autism. Am J Hum Genet 88:422–432. doi:10.​1016/​j.​ajhg.​2011.​02.​009 PubMedPubMedCentralCrossRef
131.
Lopez-Hernandez T, Sirisi S, Capdevila-Nortes X, Montolio M, Fernandez-Duenas V, Scheper GC, van der Knaap MS, Casquero P, Ciruela F, Ferrer I et al (2011) Molecular mechanisms of MLC1 and GLIALCAM mutations in megalencephalic leukoencephalopathy with subcortical cysts. Hum Mol Genet 20:3266–3277. doi:10.​1093/​hmg/​ddr238 PubMedCrossRef
132.
133.
134.
Magen D, Georgopoulos C, Bross P, Ang D, Segev Y, Goldsher D, Nemirovski A, Shahar E, Ravid S, Luder A et al (2008) Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy. Am J Hum Genet 83:30–42. doi:10.​1016/​j.​ajhg.​2008.​05.​016 PubMedPubMedCentralCrossRef
135.
Mahammad S, Murthy SN, Didonna A, Grin B, Israeli E, Perrot R, Bomont P, Julien JP, Kuczmarski E, Opal P et al (2013) Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation. J Clin Invest 123:1964–1975. doi:10.​1172/​jci66387 PubMedPubMedCentralCrossRef
136.
Marotti JD, Tobias S, Fratkin JD, Powers JM, Rhodes CH (2004) Adult onset leukodystrophy with neuroaxonal spheroids and pigmented glia: report of a family, historical perspective, and review of the literature. Acta Neuropathol 107:481–488. doi:10.​1007/​s00401-004-0847-x PubMedCrossRef
137.
Marteyn A, Sarrazin N, Yan J, Bachelin C, Deboux C, Santin MD, Gressens P, Zujovic V, Baron-Van Evercooren A (2016) Modulation of the innate immune response by human neural precursors prevails over oligodendrocyte progenitor remyelination to rescue a severe model of Pelizaeus-Merzbacher disease. Stem Cells 34:984–996. doi:10.​1002/​stem.​2263 PubMedCrossRef
138.
Merzbacher L (1910) Eine eigenartige familiärhereditäre Erkrankungform (Aplasia axialis extra-corticalis congenita). Z Gesamte Neurol Psychiat 3:1–138CrossRef
139.
140.
Mi S, Miller RH, Lee X, Scott ML, Shulag-Morskaya S, Shao Z, Chang J, Thill G, Levesque M, Zhang M et al (2005) LINGO-1 negatively regulates myelination by oligodendrocytes. Nat Neurosci 8:745–751. doi:10.​1038/​nn1460 PubMedCrossRef
141.
Miles L, DeGrauw TJ, Dinopoulos A, Cecil KM, van der Knaap MS, Bove KE (2009) Megalencephalic leukoencephalopathy with subcortical cysts: a third confirmed case with literature review. Pediatr Dev Pathol 12:180–186. doi:10.​2350/​08-06-0481.​1 PubMedCrossRef
142.
Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJ et al (2013) M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci 16:1211–1218. doi:10.​1038/​nn.​3469 PubMedPubMedCentralCrossRef
143.
Mitchison T, Kirschner M (1984) Dynamic instability of microtubule growth. Nature 312:237–242CrossRef
144.
145.
146.
Nahhas N, Conant A, Hamilton E, Curiel J, Simons C, van der Knaap M, Vanderver A (1993) TUBB4A-Related Leukodystrophy. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH et al (eds) GeneReviews(R). University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle, City
147.
Naidu S (1999) Clinical delineation of leukodystrophies. J Mol Neurosci 12:185–192CrossRef
148.
149.
150.
Neal JW, Cave EM, Singhrao SK, Cole G, Wallace SJ (1992) Alexander’s disease in infancy and childhood: a report of two cases. Acta Neuropathol 84:322–327PubMedCrossRef
151.
152.
Nicholas RS, Wing MG, Compston A (2001) Nonactivated microglia promote oligodendrocyte precursor survival and maturation through the transcription factor NF-kappa B. Eur J Neurosci 13:959–967PubMedCrossRef
153.
154.
Nilsson O, Svennerholm L (1982) Characterization and quantitative determination of gangliosides and neutral glycosphingolipids in human liver. J Lipid Res 23:327–334PubMed
155.
156.
Noble M, Murray K, Stroobant P, Waterfield MD, Riddle P (1988) Platelet-derived growth factor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/type-2 astrocyte progenitor cell. Nature 333:560–562. doi:10.​1038/​333560a0 PubMedCrossRef
157.
Nomura N, Miyajima N, Sazuka T, Tanaka A, Kawarabayasi Y, Sato S, Nagase T, Seki N, Ishikawa K, Tabata S (1994) Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1. DNA Res 1:27–35PubMedCrossRef
158.
Numata Y, Morimura T, Nakamura S, Hirano E, Kure S, Goto YI, Inoue K (2013) Depletion of molecular chaperones from the endoplasmic reticulum and fragmentation of the Golgi apparatus associated with pathogenesis in Pelizaeus-Merzbacher disease. J Biol Chem 288:7451–7466. doi:10.​1074/​jbc.​M112.​435388 PubMedPubMedCentralCrossRef
159.
Oldfors A, Tulinius M, Nennesmo I, Harding B (2004) Mitochondrial disorders. In: Pathology & genetics. Developmental neuropathology. ISN Neuropath, Basel, pp 296–302
160.
Oyanagi K, Kinoshita M, Suzuki-Kouyana E, Inoue T, Nakahara A, Tokiwai M, Arai N, Satoh JI, Aoki N, Jinnai K et al (2016) Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: Lesion staging and dynamic changes of axons and microglial subsets. Brain Pathol. doi:10.​1111/​bpa.​12443 PubMed
161.
162.
163.
164.
Pareyson D, Fancellu R, Mariotti C, Romano S, Salmaggi A, Carella F, Girotti F, Gattellaro G, Carriero MR, Farina L et al (2008) Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature. Brain 131:2321–2331. doi:10.​1093/​brain/​awn178 PubMedCrossRef
165.
Pascual-Castroviejo I, van der Knaap MS, Pronk JC, Garcia-Segura JM, Gutierrez-Molina M, Pascual-Pascual SI (2005) Vacuolating megalencephalic leukoencephalopathy: 24 year follow-up of two siblings. Neurologia 20:33–40PubMed
166.
167.
168.
169.
Pelizaeus F (1899) Überr eine eigenartige faimiliäre Entwicklungshemmung cornehmlich auf motorischem Gebiete. Archiv Psych 31:100
170.
Petito CK, Olarte JP, Roberts B, Nowak TS Jr, Pulsinelli WA (1998) Selective glial vulnerability following transient global ischemia in rat brain. J Neuropathol Exp Neurol 57:231–238PubMedCrossRef
171.
172.
173.
Powers JM (2004) Peroxisomal disorders. In: Pathology & genetics. Developmental neuropathology. JA Golden, BN Harding (eds). ISN Neuropath Press, Basel. pp.287–295
174.
Prass K, Bruck W, Schroder NW, Bender A, Prass M, Wolf T, Van der Knaap MS, Zschenderlein R (2001) Adult-onset Leukoencephalopathy with vanishing white matter presenting with dementia. Ann Neurol 50:665–668PubMedCrossRef
175.
176.
Proud CG (2001) Regulation of eukaryotic initiation factor eIF2B. Prog Mol Subcell Biol 26:95–114PubMedCrossRef
177.
178.
Purpura DP, Suzuki K (1976) Distortion of neuronal geometry and formation of aberrant synapses in neuronal storage disease. Brain Res 116:1–21PubMedCrossRef
179.
Rademakers R, Baker M, Nicholson AM, Rutherford NJ, Finch N, Soto-Ortolaza A, Lash J, Wider C, Wojtas A, DeJesus-Hernandez M et al (2011) Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet 44:200–205. doi:10.​1038/​ng.​1027 PubMedPubMedCentralCrossRef
180.
Rajasekharan S, Baker KA, Horn KE, Jarjour AA, Antel JP, Kennedy TE (2009) Netrin 1 and Dcc regulate oligodendrocyte process branching and membrane extension via Fyn and RhoA. Development 136:415–426. doi:10.​1242/​dev.​018234 PubMedCrossRef
181.
182.
Regier DS, Proia RL, D’Azzo A, Tifft CJ (2016) The GM1 and GM2 gangliosidoses: natural history and progress toward therapy. Pediatr Endocrinol Rev 13(Suppl 1):663–673PubMed
183.
Regier DS, Tifft CJ (1993) GLB1-related disorders. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH et al (eds) GeneReviews(R). University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle, City
184.
Ridder MC, Boor I, Lodder JC, Postma NL, Capdevila-Nortes X, Duarri A, Brussaard AB, Estevez R, Scheper GC, Mansvelder HD et al (2011) Megalencephalic leucoencephalopathy with cysts: defect in chloride currents and cell volume regulation. Brain 134:3342–3354. doi:10.​1093/​brain/​awr255 PubMedCrossRef
185.
186.
Rodriguez D, Gelot A, della Gaspera B, Robain O, Ponsot G, Sarlieve LL, Ghandour S, Pompidou A, Dautigny A, Aubourg P et al (1999) Increased density of oligodendrocytes in childhood ataxia with diffuse central hypomyelination (CACH) syndrome: neuropathological and biochemical study of two cases. Acta Neuropathol 97:469–480PubMedCrossRef
187.
Roman GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC (2002) Subcortical ischaemic vascular dementia. Lancet Neurol 1:426–436PubMedCrossRef
188.
189.
190.
Russo LS Jr, Aron A, Anderson PJ (1976) Alexander’s disease: a report and reappraisal. Neurology 26:607–614PubMedCrossRef
191.
192.
193.
194.
Schiffmann R, Moller JR, Trapp BD, Shih HH, Farrer RG, Katz DA, Alger JR, Parker CC, Hauer PE, Kaneski CR et al (1994) Childhood ataxia with diffuse central nervous system hypomyelination. Ann Neurol 35:331–340. doi:10.​1002/​ana.​410350314 PubMedCrossRef
195.
Schiffmann R, Tedeschi G, Kinkel RP, Trapp BD, Frank JA, Kaneski CR, Brady RO, Barton NW, Nelson L, Yanovski JA (1997) Leukodystrophy in patients with ovarian dysgenesis. Ann Neurol 41:654–661. doi:10.​1002/​ana.​410410515 PubMedCrossRef
196.
197.
Schmitt A, Gofferje V, Weber M, Meyer J, Mossner R, Lesch KP (2003) The brain-specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain. Glia 44:283–295. doi:10.​1002/​glia.​10304 PubMedCrossRef
198.
Sessa M, Lorioli L, Fumagalli F, Acquati S, Redaelli D, Baldoli C, Canale S, Lopez ID, Morena F, Calabria A 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 388:476–487. doi:10.​1016/​s0140-6736(16)30374-9 PubMedCrossRef
199.
200.
Simons C, Wolf NI, McNeil N, Caldovic L, Devaney JM, Takanohashi A, Crawford J, Ru K, Grimmond SM, Miller D et al (2013) A de novo mutation in the beta-tubulin gene TUBB4A results in the leukoencephalopathy hypomyelination with atrophy of the basal ganglia and cerebellum. Am J Hum Genet 92:767–773. doi:10.​1016/​j.​ajhg.​2013.​03.​018 PubMedPubMedCentralCrossRef
201.
Simons M, Kramer EM, Macchi P, Rathke-Hartlieb S, Trotter J, Nave KA, Schulz JB (2002) Overexpression of the myelin proteolipid protein leads to accumulation of cholesterol and proteolipid protein in endosomes/lysosomes: implications for Pelizaeus-Merzbacher disease. J Cell Biol 157:327–336. doi:10.​1083/​jcb.​200110138 PubMedPubMedCentralCrossRef
202.
Singhal BS, Gursahani RD, Udani VP, Biniwale AA (1996) Megalencephalic leukodystrophy in an Asian Indian ethnic group. Pediatr Neurol 14:291–296PubMedCrossRef
203.
Sirisi S, Folgueira M, Lopez-Hernandez T, Minieri L, Perez-Rius C, Gaitan-Penas H, Zang J, Martinez A, Capdevila-Nortes X, De La Villa P et al (2014) Megalencephalic leukoencephalopathy with subcortical cysts protein 1 regulates glial surface localization of GLIALCAM from fish to humans. Hum Mol Genet 23:5069–5086. doi:10.​1093/​hmg/​ddu231 PubMedCrossRef
204.
Skripuletz T, Hackstette D, Bauer K, Gudi V, Pul R, Voss E, Berger K, Kipp M, Baumgartner W, Stangel M (2013) Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain 136:147–167. doi:10.​1093/​brain/​aws262 PubMedCrossRef
205.
206.
Southwood CM, Garbern J, Jiang W, Gow A (2002) The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher disease. Neuron 36:585–596PubMedPubMedCentralCrossRef
207.
208.
Steenweg ME, Ghezzi D, Haack T, Abbink TE, Martinelli D, van Berkel CG, Bley A, Diogo L, Grillo E, Te Water Naude J et al (2012) Leukoencephalopathy with thalamus and brainstem involvement and high lactate ‘LTBL’ caused by EARS2 mutations. Brain 135:1387–1394. doi:10.​1093/​brain/​aws070 PubMedCrossRef
209.
Sugiura C, Miyata H, Oka A, Takashima S, Ohama E, Takeshita K (2001) A Japanese girl with leukoencephalopathy with vanishing white matter. Brain Dev 23:58–61PubMedCrossRef
210.
Sundal C, Jonsson L, Ljungberg M, Zhong J, Tian W, Zhu T, Linden T, Borjesson-Hanson A, Andersen O, Ekholm S (2014) Different stages of white matter changes in the original HDLS family revealed by advanced MRI techniques. J Neuroimaging 24:444–452. doi:10.​1111/​jon.​12037 PubMedCrossRef
211.
212.
Suzuki K, Suzuki K (2002). Lysosomal storage diseases. In: Greenfield’s Neuropathology. DI Grham, PL Lantos (eds). Arnold pub, London. pp.653-735.
213.
Suzuki K, Suzuki K (1996) The gangliosidoses. In: handbook of clinical neurology, RJ Vinken and GW Bruyn, Revised series Vol 22 (66) Neurodystrophies and neurolipidoses, HW Moser (ed) Elsevier Science B.V., Amsterdam, pp.247-280.
214.
Suzuki KV, Vanier M.T. (2004) Sphingolipidoses. In: Pathology & genetics. Developmental neuropathology. JA Golden, BN Arding (eds). ISN Neuropath, Basel. pp.235-236.
215.
Suzuki Y, Oshima A, Nanba E (2001) β-galactosidase deficiency (β-galactosidosis): GM1 gangliosidosis and Morquio B disease. In: The metabolic and molecular bases of inherited disease. CR Scriver, AL Beaudet, D Valle, WS Sly, B Childs, KW Kinzler, B Vogelstein (eds). McGraw-Hill, New York. pp.3775-3809.
216.
217.
Tang G, Perng MD, Wilk S, Quinlan R, Goldman JE (2010) Oligomers of mutant glial fibrillary acidic protein (GFAP) Inhibit the proteasome system in alexander disease astrocytes, and the small heat shock protein alphaB-crystallin reverses the inhibition. J Biol Chem 285:10527–10537. doi:10.​1074/​jbc.​M109.​067975 PubMedPubMedCentralCrossRef
218.
Tang G, Xu Z, Goldman JE (2006) Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. J Biol Chem 281:38634–38643. doi:10.​1074/​jbc.​M604942200 PubMedCrossRef
219.
Tang G, Yue Z, Talloczy Z, Goldman JE (2008) Adaptive autophagy in Alexander disease-affected astrocytes. Autophagy 4:701–703CrossRef
220.
221.
Teijido O, Martinez A, Pusch M, Zorzano A, Soriano E, Del Rio JA, Palacin M, Estevez R (2004) Localization and functional analyses of the MLC1 protein involved in megalencephalic leukoencephalopathy with subcortical cysts. Hum Mol Genet 13:2581–2594. doi:10.​1093/​hmg/​ddh291 PubMedCrossRef
222.
Tessitore A, Del PMM, Sano R, Ma Y, Mann L, Ingrassia A, Laywell ED, Steindler DA, Hendershot LM, d’Azzo A (2004) GM1-ganglioside-mediated activation of the unfolded protein response causes neuronal death in a neurodegenerative gangliosidosis. Mol Cell 15:753–766. doi:10.​1016/​j.​molcel.​2004.​08.​029 PubMedCrossRef
223.
224.
225.
Towfighi J, Young R, Sassani J, Ramer J, Horoupian DS (1983) Alexander’s disease: further light-, and electron-microscopic observations. Acta Neuropathol 61:36–42PubMedCrossRef
226.
Townsend JJ, Wilson JF, Harris T, Coulter D, Fife R (1985) Alexander’s disease. Acta Neuropathol 67:163–166PubMedCrossRef
227.
Townsend LE, Benjamins JA (1983) Effects of monensin on posttranslational processing of myelin proteins. J Neurochem 40:1333–1339PubMedCrossRef
228.
229.
Trapp BD, Nishiyama A, Cheng D, Macklin W (1997) Differentiation and death of premyelinating oligodendrocytes in developing rodent brain. J Cell Biol 137:459–468PubMedPubMedCentralCrossRef
230.
231.
van Berge L, Dooves S, van Berkel CG, Polder E, van der Knaap MS, Scheper GC (2012) Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA. Biochem J 441:955–962. doi:10.​1042/​bj20110795 PubMedCrossRef
232.
van der Knaap MS, Valk J (2005) GM1 gangliosidosis. In: Magnetic resonance of myelination and myelin disorders. Springer, Berlin Heidelberg New York. pp.96-102.
233.
van der Knaap MS, Barth PG, Gabreels FJ, Franzoni E, Begeer JH, Stroink H, Rotteveel JJ, Valk J (1997) A new leukoencephalopathy with vanishing white matter. Neurology 48:845–855PubMedCrossRef
234.
van der Knaap MS, Barth PG, Stroink H, van Nieuwenhuizen O, Arts WF, Hoogenraad F, Valk J (1995) Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children. Ann Neurol 37:324–334. doi:10.​1002/​ana.​410370308 PubMedCrossRef
235.
van der Knaap MS, Barth PG, Vrensen GF, Valk J (1996) Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course. Acta Neuropathol 92:206–212PubMedCrossRef
236.
237.
238.
van der Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J (1998) Phenotypic variation in leukoencephalopathy with vanishing white matter. Neurology 51:540–547PubMedCrossRef
239.
van der Knaap MS, Lai V, Kohler W, Salih MA, Fonseca MJ, Benke TA, Wilson C, Jayakar P, Aine MR, Dom L et al (2010) Megalencephalic leukoencephalopathy with cysts without MLC1 defect. Ann Neurol 67:834–837. doi:10.​1002/​ana.​21980 PubMed
240.
van der Knaap MS, Leegwater PA, Konst AA, Visser A, Naidu S, Oudejans CB, Schutgens RB, Pronk JC (2002) Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter. Ann Neurol 51:264–270PubMedCrossRef
241.
242.
van der Knaap MS, Naidu S, Breiter SN, Blaser S, Stroink H, Springer S, Begeer JC, van Coster R, Barth PG, Thomas NH et al (2001) Alexander disease: diagnosis with MR imaging. AJNR 22:541–552PubMed
243.
van der Knaap MS, Naidu S, Kleinschmidt-Demasters BK, Kamphorst W, Weinstein HC (2000) Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids. Neurology 54:463–468PubMedCrossRef
244.
van der Knaap MS, Naidu S, Pouwels PJ, Bonavita S, van Coster R, Lagae L, Sperner J, Surtees R, Schiffmann R, Valk J (2002) New syndrome characterized by hypomyelination with atrophy of the basal ganglia and cerebellum. AJNR 23:1466–1474PubMed
245.
246.
247.
van der Knaap MS, van Berkel CG, Herms J, van Coster R, Baethmann M, Naidu S, Boltshauser E, Willemsen MA, Plecko B, Hoffmann GF et al (2003) eIF2B-related disorders: antenatal onset and involvement of multiple organs. Am J Hum Genet 73:1199–1207. doi:10.​1086/​379524 PubMedPubMedCentralCrossRef
248.
van der Lei HD, Steenweg ME, Barkhof F, de Grauw T, d’Hooghe M, Morton R, Shah S, Wolf N, van der Knaap MS (2012) Characteristics of early MRI in children and adolescents with vanishing white matter. Neuropediatrics 43:22–26. doi:10.​1055/​s-0032-1307456 PubMedCrossRef
249.
van der Lei HD, van Berkel CG, van Wieringen WN, Brenner C, Feigenbaum A, Mercimek-Mahmutoglu S, Philippart M, Tatli B, Wassmer E, Scheper GC et al (2010) Genotype-phenotype correlation in vanishing white matter disease. Neurology 75:1555–1559. doi:10.​1212/​WNL.​0b013e3181f962ae​ PubMedCrossRef
250.
251.
van der Voorn JP, Pouwels PJ, Hart AA, Serrarens J, Willemsen MA, Kremer HP, Barkhof F, van der Knaap MS (2006) Childhood white matter disorders: quantitative MR imaging and spectroscopy. Radiology 241:510–517. doi:10.​1148/​radiol.​2412051345 PubMedCrossRef
252.
van der Voorn JP, Pouwels PJ, Kamphorst W, Powers JM, Lammens M, Barkhof F, van der Knaap MS (2005) Histopathologic correlates of radial stripes on MR images in lysosomal storage disorders. AJNR 26:442–446PubMed
253.
van Egmond ME, Pouwels PJ, Boelens JJ, Lindemans CA, Barkhof F, Steenwijk MD, van Hasselt PM, van der Knaap MS, Wolf NI (2013) Improvement of white matter changes on neuroimaging modalities after stem cell transplant in metachromatic leukodystrophy. JAMA Neurol 70:779–782. doi:10.​1001/​jamaneurol.​2013.​629 PubMedCrossRef
254.
Van Haren K, van der Voorn JP, Peterson DR, van der Knaap MS, Powers JM (2004) The life and death of oligodendrocytes in vanishing white matter disease. J Neuropathol Exp Neurol 63:618–630PubMedCrossRef
255.
van Heteren JT, Rozenberg F, Aronica E, Troost D, Lebon P, Kuijpers TW (2008) Astrocytes produce interferon-alpha and CXCL10, but not IL-6 or CXCL8, in Aicardi-Goutieres syndrome. Glia 56:568–578. doi:10.​1002/​glia.​20639 PubMedCrossRef
256.
van Kollenburg B, Thomas AA, Vermeulen G, Bertrand GA, van Berkel CG, Pronk JC, Proud CG, van der Knaap MS, Scheper GC (2006) Regulation of protein synthesis in lymphoblasts from vanishing white matter patients. Neurobiol Dis 21:496–504. doi:10.​1016/​j.​nbd.​2005.​08.​009 PubMedCrossRef
257.
258.
van Rappard DF, Bugiani M, Boelens JJ, van der Steeg AF, Daams F, de Meij TG, van Doorn MM, van Hasselt PM, Gouma DJ, Verbeke JI et al (2016) Gallbladder and the risk of polyps and carcinoma in metachromatic leukodystrophy. Neurology 87:103–111. doi:10.​1212/​wnl.​0000000000002811​ PubMedCrossRef
259.
Vanderver A, Prust M, Tonduti D, Mochel F, Hussey HM, Helman G, Garbern J, Eichler F, Labauge P, Aubourg P et al (2015) Case definition and classification of leukodystrophies and leukoencephalopathies. Mol Genet Metab 114:494–500PubMedPubMedCentralCrossRef
260.
261.
262.
263.
Watanabe I, Muller J (1967) Cavitating “diffuse sclerosis”. J Neuropathol Exp Neurol 26:437–455PubMedCrossRef
264.
Welch WJ (1992) Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. Physiol Rev 72:1063–1081PubMed
265.
Wibom R, Lasorsa FM, Tohonen V, Barbaro M, Sterky FH, Kucinski T, Naess K, Jonsson M, Pierri CL, Palmieri F et al (2009) AGC1 deficiency associated with global cerebral hypomyelination. N Engl J Med 361:489–495. doi:10.​1056/​NEJMoa0900591 PubMedCrossRef
266.
267.
Wohlwill FJ, Bernstein J, Yakovlev PI (1959) Dysmyelinogenic leukodystrophy; report of a case of a new, presumably familial type of leukodystrophy with megalobarencephaly. J Neuropathol Exp Neurol 18:359–383PubMedCrossRef
268.
269.
270.
Wong K, Armstrong RC, Gyure KA, Morrison AL, Rodriguez D, Matalon R, Johnson AB, Wollmann R, Gilbert E, Le TQ et al (2000) Foamy cells with oligodendroglial phenotype in childhood ataxia with diffuse central nervous system hypomyelination syndrome. Acta Neuropathol 100:635–646PubMedCrossRef
271.
272.
Yoshida K, Ikeda S, Kawaguchi K, Yanagisawa N (1994) Adult GM1 gangliosidosis: immunohistochemical and ultrastructural findings in an autopsy case. Neurology 44:2376–2382PubMedCrossRef
273.
274.
275.
276.
Metadata
Title
Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms
Authors
Marjo S. van der Knaap
Marianna Bugiani
Publication date
01-09-2017
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 3/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-017-1739-1

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