Neuroimaging-Befunde bei Mukopolysaccharidose: Was Sie wirklich wissen müssen

Das Zentralnervensystem ist bei den verschiedenen Typen der erblichen Stoffwechselkrankheit Mukopolysaccharidose in sehr unterschiedlichem Ausmaß beteiligt. Die Folge ist eine große Variationsbreite an klinischen Manifestationen. Deshalb ist es für den Radiologen wichtig, die Hauptmanifestationen der Erkrankung im Gehirn zu kennen. Dieser Artikel gibt anhand diverser Bildbeispiele einen Überblick über die typischen Neuroimaging-Befunde.

Abstract

Mucopolysaccharidosis (MPS) is an inherited metabolic disease and a member of the group of lysosomal storage disorders. Its hallmark is a deficiency of lysosomal enzymes involved in the degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs). The products of GAG degradation accumulate within lysosomes and in the extracellular space, thereby interfering with the degradation of other macromolecules. This process leads to chronic degeneration of cells, which in turn affects multiple organs and systems. There are seven distinct types of MPS (I, II, III, IV, VI, VII, and IX), which are divided into subtypes according to the deficient enzyme and the severity of the clinical picture. Although clinical manifestations vary considerably among the different types of MPS, the central nervous system (CNS) is characteristically affected, and magnetic resonance (MR) imaging is the method of choice to evaluate brain and spinal cord abnormalities. Enlarged perivascular spaces, white matter lesions, hydrocephalus, brain atrophy, cervical spinal canal stenosis with or without spinal cord compression and myelopathy, and bone abnormalities in the skull and spine (dysostosis multiplex) are typical imaging findings described in the literature and reviewed in this article. The differential diagnosis of MPS is limited because the constellation of imaging findings is highly suggestive. Thus, radiologists should be aware of its typical neuroimaging findings so they can recognize cases not yet diagnosed, exclude other metabolic diseases, monitor CNS findings over time, and assess treatment response.

Kernaussagen

• Die MPS ist eine erbliche Stoffwechselerkrankung aus der Gruppe der lysosomalen Speicherkrankheiten. Wichtigstes Kennzeichen ist ein Mangel an lysosomalen Enzymen, die an der Spaltung von Mukopolysacchariden (GAG) beteiligt sind. Partiell abgebaute GAG reichern sich in den Lysosomen und im Extrazellulärraum an und stören den Abbau anderer Makromoleküle. Dieser Prozess führt zu einer chronischen Degeneration von Zellen, die sich allmählich auf zahlreiche Organe und Organsysteme ausbreitet.

• Erweiterte perivaskuläre Räume, Läsionen der weißen Substanz, Hydrozephalus, Hirnatrophie und zervikale Spinalkanalstenose mit oder ohne Rückenmarkskompression bzw. Myelopathie sind typische Bildgebungsbefunde bei MPS. Zusätzlich sind bei diesen Patienten häufig auffällige Knochenbefunde an Schädel und Wirbelsäule (Dysostosis multiplex) vorhanden.

• Partiell abgebaute GAG reichern sich im ganzen Körper einschließlich der Leptomeningen an und behindern den Abfluss der interstitiellen Flüssigkeit aus dem Hirnparenchym mit der Folge der Erweiterung der perivaskulären Räume.

• In der MRT sind Läsionen der weißen Substanz zu beobachten. Am häufigsten betroffen ist die periventrikuläre weiße Substanz, doch können diese Läsionen überall im Gehirn auftreten. Häufig sind die Läsionen symmetrisch verteilt. Sie können miteinander verschmelzen und größer und diffuser werden, sodass sie das Beteiligungsmuster bei Leukodystrophie nachahmen.

• Die MPS ist mit einer Prädisposition der Patienten für eine atlantoaxiale Instabilität verbunden. Diese beruht auf einer Odontoiddysplasie in Verbindung mit einer Schlaffheit der Bänder. Zusammen mit weiteren Mechanismen können sie eine kompressionsbedingte Myelopathie verursachen.

Schlüsselwörter

Mukopolysaccharidose - klinische Befunde - Neuroimaging

Keywords

mucopolysaccharidosis - clinical manifestations - neuroimaging

• Literatur

• 1 Clarke LA. The mucopolysaccharidoses: a success of molecular medicine. Expert Rev Mol Med 2008; 10: e1
• 2 Giugliani R, Federhen A, Rojas MV. et al. Mucopolysaccharidosis I, II, and VI: brief review and guidelines for treatment. Genet Mol Biol 2010; 33: 589-604
• 3 Muenzer J. Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 2011; 50 (Suppl. 05) v4-v12
• 4 Barkovich AJ, Patay Z. Metabolic, toxic and inflammatory brain disorders. In: Barkovich AJ, Raybaud C. eds. Pediatric neuroimaging. 5th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2012: 81-239
• 5 Vedolin L, Schwartz IV, Komlos M. et al. Brain MRI in mucopolysaccharidosis: effect of aging and correlation with biochemical findings. Neurology 2007; 69: 917-924
• 6 Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr 2004; 144 (Suppl. 05) S27-S34
• 7 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD. Online mendelian inheritance in man. OMIM. Im Internet: http://omim.org (Stand: 30.08.2017)
• 8 Di Ferrante N. N-acetylglucosamine-6-sulfate sulfatase deficiency reconsidered. Science 1980; 210: 448
• 9 Wang RY, Cambray-Forker EJ, Ohanian K. et al. Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II. Mol Genet Metab 2009; 98: 406-411
• 10 Miebach E. Enzyme replacement therapy in mucopolysaccharidosis type I. Acta Paediatr Suppl 2005; 94: 58-60 ; discussion 57
• 11 Hobbs JR, Hugh-Jones K, Barrett AJ. et al. Reversal of clinical features of Hurler’s disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet 1981; 2: 709-712
• 12 White KK. Orthopaedic aspects of mucopolysaccharidoses. Rheumatology (Oxford) 2011; 50 (Suppl. 05) v26-v33
• 13 Cheon JE, Kim IO, Hwang YS. et al. Leukodystrophy in children: a pictorial review of MR imaging features. RadioGraphics 2002; 22: 461-476
• 14 Kirkpatrick K, Ellwood J, Walker RW. Mucopolysaccharidosis type I (Hurler syndrome) and anesthesia: the impact of bone marrow transplantation, enzyme replacement therapy, and fiberoptic intubation on airway management. Paediatr Anaesth 2012; 22: 745-751
• 15 Rasalkar DD, Chu WC, Hui J. et al. Pictorial review of mucopolysaccharidosis with emphasis on MRI features of brain and spine. Br J Radiol 2011; 84: 469-477
• 16 Zafeiriou DI, Batzios SP. Brain and spinal MR imaging findings in mucopolysaccharidoses: a review. AJNR Am J Neuroradiol 2013; 34: 5-13
• 17 Kwee RM, Kwee TC. Virchow-Robin spaces at MR imaging. RadioGraphics 2007; 27: 1071-1086
• 18 Zhang ET, Inman CB, Weller RO. Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in the human cerebrum. J Anat 1990; 170: 111-123
• 19 Schley D, Carare-Nnadi R, Please CP. et al. Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol 2006; 238: 962-974
• 20 Matheus MG, Castillo M, Smith JK. et al. Brain MRI findings in patients with mucopolysaccharidosis types I and II and mild clinical presentation. Neuroradiology 2004; 46: 666-672
• 21 Dekaban AS, Constantopoulos G. Mucopolysaccharidosis type I, II, IIIA and V: pathological and biochemical abnormalities in the neural and mesenchymal elements of the brain. Acta Neuropathol (Berl.) 1977; 39: 1-7
• 22 Finn CT, Vedolin L, Schwartz IV. et al. Magnetic resonance imaging findings in Hunter syndrome. Acta Paediatr 2008; 97: 61-68
• 23 Gabrielli O, Polonara G, Regnicolo L. et al. Correlation between cerebral MRI abnormalities and mental retardation in patients with mucopolysaccharidoses. Am J Med Genet A 2004; 125A: 224-231
• 24 van der Knaap MS, Valk J. Mucopolysaccharidoses. In: van der Knaap MS, Valk J. eds. Magnetic resonance of myelination and myelin disorders. 3rd ed. New York, NY: Springer; 2005: 123-132
• 25 Lee C, Dineen TE, Brack M. et al. The mucopolysaccharidoses: characterization by cranial MR imaging. AJNR Am J Neuroradiol 1993; 14: 1285-1292
• 26 Rauch RA, Friloux 3rd LA , Lott IT. MR imaging of cavitary lesions in the brain with Hurler/Scheie. AJNR Am J Neuroradiol 1989; 10 (Suppl. 05) S1-S3
• 27 Alqahtani E, Huisman TA, Boltshauser E. et al. Mucopolysaccharidoses type I and II: new neuroimaging findings in the cerebellum. Eur J Paediatr Neurol 2014; 18: 211-217
• 28 Manara R, Priante E, Grimaldi M. et al. Brain and spine MRI features of Hunter disease: frequency, natural evolution and response to therapy. J Inherit Metab Dis 2011; 34: 763-780
• 29 Steiner J, Adamsbaum C, Desguerres I. et al. Hypomelanosis of Ito and brain abnormalities: MRI findings and literature review. Pediatr Radiol 1996; 26: 763-768
• 30 Chow EW, Mikulis DJ, Zipursky RB. et al. Qualitative MRI findings in adults with 22q11 deletion syndrome and schizophrenia. Biol Psychiatry 1999; 46: 1436-1442
• 31 Carroll WJ, Woodruff WW, Cadman TE. MR findings in oculocerebrorenal syndrome. AJNR Am J Neuroradiol 1993; 14: 449-451
• 32 Shapiro E, Guler OE, Rudser K. et al. An exploratory study of brain function and structure in mucopolysaccharidosis type I: long term observations following hematopoietic cell transplantation (HCT). Mol Genet Metab 2012; 107: 116-121
• 33 Kumar M, Nasrallah IM, Kim S. et al. High-resolution magnetic resonance microscopy and diffusion tensor imaging to assess brain structural abnormalities in the murine mucopolysaccharidosis VII model. J Neuropathol Exp Neurol 2014; 73: 39-49
• 34 Satzer D, DiBartolomeo C, Ritchie MM. et al. Assessment of dysmyelination with RAFFn MRI: application to murine MPS I. PLoS One 2015; 10: e0116788
• 35 Murata R, Nakajima S, Tanaka A. et al. MR imaging of the brain in patients with mucopolysaccharidosis. AJNR Am J Neuroradiol 1989; 10: 1165-1170
• 36 Vedolin L, Schwartz IV, Komlos M. et al. Correlation of MR imaging and MR spectroscopy findings with cognitive impairment in mucopolysaccharidosis II. AJNR Am J Neuroradiol 2007; 28 (06) 1029-1033
• 37 Barone R, Parano E, Trifiletti RR. et al. White matter changes mimicking a leukodystrophy in a patient with mucopolysaccharidosis: characterization by MRI. J Neurol Sci 2002; 195: 171-175
• 38 Aliabadi H, Reynolds R, Powers CJ. et al. Clinical outcome of cerebrospinal fluid shunting for communicating hydrocephalus in mucopolysaccharidoses I, II, and III: a retrospective analysis of 13 patients. Neurosurgery 2010; 67: 1476-1481 ; discussion 1481 – 1482
• 39 Giugliani R, Harmatz P, Wraith JE. Management guidelines for mucopolysaccharidosis VI. Pediatrics 2007; 120: 405-418
• 40 Neto ÂR, Holanda GB, Farias MC. et al. Hydrocephalus in mucopolysaccharidosis type VI successfully treated with endoscopic third ventriculostomy. J Neurosurg Pediatr 2013; 11: 327-330
• 41 Lachman R, Martin KW, Castro S. et al. Radiologic and neuroradiologic findings in the mucopolysaccharidoses. J Pediatr Rehabil Med 2010; 3: 109-118
• 42 Beck M, Cole G. Disc oedema in association with Hunter’s syndrome: ocular histopathological findings. Br J Ophthalmol 1984; 68: 590-594
• 43 Żuber Z, Jurecka A, Jurkiewicz E. et al. Cervical spine MRI findings in patients with mucopolysaccharidosis type II. Pediatr Neurosurg 2015; 50: 26-30
• 44 Solanki GA, Martin KW, Theroux MC. et al. Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management. J Inherit Metab Dis 2013; 36: 339-355
• 45 Borlot F, Arantes PR, Quaio CR. et al. Mucopolysaccharidosis type IVA: evidence of primary and secondary central nervous system involvement. Am J Med Genet A 2014; 164A: 1162-1169
• 46 Möllmann C, Lampe CG, Müller-Forell W. et al. Development of a scoring system to evaluate the severity of craniocervical spinal cord compression in patients with mucopolysaccharidosis IVA (Morquio A syndrome). JIMD Rep 2013; 11: 65-72
• 47 Morishita K, Petty RE. Musculoskeletal manifestations of mucopolysaccharidoses. Rheumatology (Oxford) 2011; 50 (Suppl. 05) v19-v25
• 48 Natowicz MR, Short MP, Wang Y. et al. Clinical and biochemical manifestations of hyaluronidase deficiency. N Engl J Med 1996; 335: 1029-1033
• 49 Mut M, Cila A, Varli K. et al. Multilevel myelopathy in Maroteaux-Lamy syndrome and review of the literature. Clin Neurol Neurosurg 2005; 107: 230-235
• 50 Lyon G, Kolodny EH, Pastores GM. Late infantile progressive genetic encephalopathies (metabolic encephalopathies of the second year of life). In: Lyon G, Kolodny EH, Pastores GM. eds. Neurology of hereditary metabolic diseases of children. 3rd ed. New York, NY: McGraw-Hill; 2006: 179-242