Erkrankungen der weißen Substanz in der Bildgebung

Um Erkrankungen der weißen Substanz korrekt zu diagnostizieren, ist ein systematisches Vorgehen unter Berücksichtigung der Bildgebungsbefunde, der klinischen Merkmale und der Labordaten von entscheidender Bedeutung. Die genaue Kenntnis des pathologischen Substrats ist für das Verständnis der radiologischen Manifestationen fundamental. Die entsprechenden Fakten werden deshalb in diesem Beitrag strukturiert und nachvollziehbar aufbereitet.

Abstract

White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease). Infectious processes include Lyme disease (neuroborreliosis), progressive multifocal leukoencephalopathy, and human immunodeficiency virus (HIV) encephalopathy. Vascular processes include different types of small-vessel disease: arteriolosclerosis, cerebral amyloid angiopathy, cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), primary angiitis of the central nervous system, Susac syndrome, and neurolupus. Toxic-metabolic processes include osmotic myelinolysis, methotrexate leukoencephalopathy, and posterior reversible encephalopathy syndrome. The imaging spectrum can vary widely from small multifocal white matter lesions to confluent or extensive white matter involvement. Understanding the pathologic substrate is fundamental for understanding the radiologic manifestations, and a systematic approach to the radiologic findings, in correlation with clinical and laboratory data, is crucial for narrowing the differential diagnosis.

Kernaussagen

• Erkrankungen der weißen Substanz zeichnen sich durch ein verändertes Muster der Myelinisierung aus und umfassen ein breites Spektrum kongenitaler und erworbener Prozesse. Sie lassen sich in demyelinisierende und dysmyelinisierende Prozesse unterteilen. Demyelinisierende Erkrankungen können wiederum verschiedenen Kategorien zugeordnet werden.

• Bei multipler Sklerose handelt es sich um eine primäre demyelinisierende Erkrankung unbekannter Ätiologie, die durch perivenuläre Entzündung bzw. Demyelinisierung bei relativem Axonerhalt gekennzeichnet ist. In der MRT-Bildgebung stellt sie sich in Form von periventrikulären, juxtakortikalen, infratentoriellen und im Rückenmark lokalisierten Läsionen dar.

• TDL können mit Neoplasien mit hochgradiger Kontrastmittelanreicherung verwechselt werden. Mögliche Anhaltspunkte für die Diagnose bilden eine unvollständige ringförmige Anreicherung und/oder Diffusionsrestriktion, ein schwach ausgebildetes periläsionales Ödem, ein relativ geringer raumfordernder Effekt sowie ein geringes zerebrales Blutvolumen in der Perfusionsbildgebung.

• Die HIV-Enzephalopathie weist einige Gemeinsamkeiten mit der PML auf: Beide verursachen konfluierende Läsionen der weißen Substanz ohne signifikanten raumfordernden Effekt oder Kontrastmittelanreicherung. Jedoch sind die Läsionen bei PML eher peripher lokalisiert und asymmetrisch angeordnet, bei der HIV-Enzephalopathie hingegen eher zentral lokalisiert und symmetrisch verteilt.

• Mikroangiopathien stellen bei Weitem die häufigste Ursache von Erkrankungen der weißen Substanz dar und lassen sich in 6 verschiedene Typen unterteilen: Arteriolosklerose, zerebrale Amyloidangiopathie, hereditäre Vaskulopathien, inflammatorische Vaskulitiden, venöse Kollagenose und Sonstige.

Schlüsselwörter

autoimmunologisch vermittelte Erkrankungen der weißen Substanz - infektiöse Erkrankungen der weißen Substanz - vaskuläre Erkrankungen der weißen Substanz - toxisch-metabolische Erkrankungen der weißen Substanz - radiologisch-pathologische Korrelate

Keywords

autoimmune white matter diseases - infectious white matter diseases - vascular white matter diseases - toxic-metabolic white matter diseases - radiologic-pathologic correlation

• Literatur

• 1 Smith AB, Smirniotopoulos JG. Imaging evaluation of demyelinating processes of the central nervous system. Postgrad Med J 2010; 86: 218-229
• 2 Bakhti M, Aggarwal S, Simons M. Myelin architecture: zippering membranes tightly together. Cell Mol Life Sci 2014; 71: 1265-1277
• 3 Paz Soldán MM, Pirko I. Biogenesis and significance of central nervous system myelin. Semin Neurol 2012; 32: 9-14
• 4 Ragonese P, Aridon P, Salemi G. et al. Mortality in multiple sclerosis: a review. Eur J Neurol 2008; 15: 123-127
• 5 Karussis D. The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review. J Autoimmun 2014; 48–49: 134-142
• 6 Okuda DT. Unanticipated demyelinating pathology of the CNS. Nat Rev Neurol 2009; 5: 591-597
• 7 Williams R, Buchheit CL, Berman NEJ. et al. Pathogenic implications of iron accumulation in multiple sclerosis. J Neurochem 2012; 120: 7-25
• 8 Filippi M, Evangelou N, Kangarlu A. et al. Ultra-high-field MR imaging in multiple sclerosis. J Neurol Neurosurg Psychiatry 2014; 85: 60-66
• 9 Polman CH, Reingold SC, Banwell B. et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292-302
• 10 Montalban X, Tintoré M, Swanton J. et al. MRI criteria for MS in patients with clinically isolated syndromes. Neurology 2010; 74: 427-434
• 11 Cotton F, Weiner HL, Jolesz FA. et al. MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals. Neurology 2003; 60: 640-646
• 12 Tallantyre EC, Morgan PS, Dixon JE. et al. A comparison of 3 T and 7 T in the detection of small parenchymal veins within MS lesions. Invest Radiol 2009; 44: 491-494
• 13 Filippi M, Rocca MA. MR imaging of multiple sclerosis. Radiology 2011; 259: 659-681
• 14 Grabner G, Dal-Bianco A, Schernthaner M. et al. Analysis of multiple sclerosis lesions using a fusion of 3.0 T FLAIR and 7.0 T SWI phase: FLAIR SWI. J Magn Reson Imaging 2011; 33: 543-549
• 15 Lisanti CJ, Asbach P, Bradley Jr. WG. The ependymal “dot-dash” sign: an MR imaging finding of early multiple sclerosis. AJNR Am J Neuroradiol 2005; 26: 2033-2036
• 16 Roosendaal SD, Moraal B, Pouwels PJW. et al. Accumulation of cortical lesions in MS: relation with cognitive impairment. Mult Scler 2009; 15: 708-714
• 17 Filippi M, Rocca MA, Calabrese M. et al. Intracortical lesions: relevance for new MRI diagnostic criteria for multiple sclerosis. Neurology 2010; 75: 1988-1994
• 18 de Graaf WL, Kilsdonk ID, Lopez-Soriano A. et al. Clinical application of multi-contrast 7-T MR imaging in multiple sclerosis: increased lesion detection compared to 3 T confined to grey matter. Eur Radiol 2013; 23: 528-540
• 19 Lu Z, Zhang B, Qiu W. et al. Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis. PLoS One 2011; 6: e22766
• 20 Lycklama G, Thompson A, Filippi M. et al. Spinal-cord MRI in multiple sclerosis. Lancet Neurol 2003; 2: 555-562
• 21 Solomon AJ, Klein EP, Bourdette D. “Undiagnosing” multiple sclerosis: the challenge of misdiagnosis in MS. Neurology 2012; 78: 1986-1991
• 22 Al-Okaili RN, Krejza J, Wang S. et al. Advanced MR imaging techniques in the diagnosis of intraaxial brain tumors in adults. RadioGraphics 2006; 26: S173-S189
• 23 Cañellas AR, Gols AR, Izquierdo JR. et al. Idiopathic inflammatory-demyelinating diseases of the central nervous system. Neuroradiology 2007; 49: 393-409
• 24 Smirniotopoulos JG, Murphy FM, Rushing EJ. et al. Patterns of contrast enhancement in the brain and meninges. RadioGraphics 2007; 27: 525-551
• 25 Barnett Y, Sutton IJ, Ghadiri M. et al. Conventional and advanced imaging in neuromyelitis optica. AJNR Am J Neuroradiol 2014; 35: 1458-1466
• 26 Huh SY, Min JH, Kim W. et al. The usefulness of brain MRI at onset in the differentiation of multiple sclerosis and seropositive neuromyelitis optica spectrum disorders. Mult Scler 2014; 20: 695-704
• 27 Rovira À, Sastre-Garriga J, Auger C. et al. Idiopathic inflammatory demyelinating diseases of the brainstem. Semin Ultrasound CT MR 2013; 34: 123-130
• 28 Sahraian MA, Radue EW, Minagar A. Neuromyelitis optica: clinical manifestations and neuroimaging features. Neurol Clin 2013; 31: 139-152
• 29 Yonezu T, Ito S, Mori M. et al. “Bright spotty lesions” on spinal magnetic resonance imaging differentiate neuromyelitis optica from multiple sclerosis. Mult Scler 2014; 20: 331-337
• 30 Kister I, Herbert J, Zhou Y. et al. Ultrahigh-field MR (7 T) imaging of brain lesions in neuromyelitis optica. Mult Scler Int 2013; 2013: 398259
• 31 Nakamura M, Misu T, Fujihara K. et al. Occurrence of acute large and edematous callosal lesions in neuromyelitis optica. Mult Scler 2009; 15: 695-700
• 32 Tenembaum SN. Disseminated encephalomyelitis in children. Clin Neurol Neurosurg 2008; 110: 928-938
• 33 DeSanto J, Ross JS. Spine infection/inflammation. Radiol Clin North Am 2011; 49: 105-127
• 34 Smith AB, Smirniotopoulos JG, Rushing EJ. From the archives of the AFIP: central nervous system infections associated with human immunodeficiency virus infection – radiologic-pathologic correlation. RadioGraphics 2008; 28: 2033-2058
• 35 Hildenbrand P, Craven DE, Jones R. et al. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol 2009; 30: 1079-1087
• 36 Wardlaw JM, Smith EE, Biessels GJ. et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013; 12: 822-838
• 37 Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010; 9: 689-701
• 38 de Leeuw FE, de Groot JC, Achten E. et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001; 70: 9-14
• 39 Fazekas F, Chawluk JB, Alavi A. et al. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 1987; 149: 351-356
• 40 Wahlund LO, Barkhof F, Fazekas F. et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001; 32: 1318-1322
• 41 Duering M, Csanadi E, Gesierich B. et al. Incident lacunes preferentially localize to the edge of white matter hyperintensities: insights into the pathophysiology of cerebral small vessel disease. Brain 2013; 136 (Pt. 9) 2717-2726
• 42 Erro ME, Gállego J, Herrera M. et al. Isolated pontine infarcts: etiopathogenic mechanisms. Eur J Neurol 2005; 12: 984-988
• 43 Maillard P, Fletcher E, Harvey D. et al. White matter hyperintensity penumbra. Stroke 2011; 42: 1917-1922
• 44 Schmidt R, Schmidt H, Haybaeck J. et al. Heterogeneity in age-related white matter changes. Acta Neuropathol (Berl.) 2011; 122: 171-185
• 45 Doubal FN, Dennis MS, Wardlaw JM. Characteristics of patients with minor ischaemic strokes and negative MRI: a cross-sectional study. J Neurol Neurosurg Psychiatry 2011; 82: 540-542
• 46 Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013; 12: 483-497
• 47 Greenberg SM, Vernooij MW, Cordonnier C. et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009; 8: 165-174
• 48 Scheltens P, Pasquier F, Weerts JG. et al. Qualitative assessment of cerebral atrophy on MRI: inter- and intra-observer reproducibility in dementia and normal aging. Eur Neurol 1997; 37: 95-99
• 49 Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83: 124-137
• 50 Knudsen KA, Rosand J, Karluk D. et al. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001; 56: 537-539
• 51 Linn J, Halpin A, Demaerel P. et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74: 1346-1350
• 52 Chabriat H, Vahedi K, Iba-Zizen MT. et al. Clinical spectrum of CADASIL: a study of 7 families – cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Lancet 1995; 346: 934-939
• 53 Singhal S, Rich P, Markus HS. The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features. AJNR Am J Neuroradiol 2005; 26: 2481-2487
• 54 van den Boom R, Lesnik Oberstein SAJ, Ferrari MD. et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: MR imaging findings at different ages – 3rd–6th decades. Radiology 2003; 229: 683-690
• 55 Birnbaum J, Hellmann DB. Primary angiitis of the central nervous system. Arch Neurol 2009; 66: 704-709
• 56 Abdel Razek AAK, Alvarez H, Bagg S. et al. Imaging spectrum of CNS vasculitis. RadioGraphics 2014; 34: 873-894
• 57 Susac JO, Hardman JM, Selhorst JB. Microangiopathy of the brain and retina. Neurology 1979; 29: 313-316
• 58 Susac JO, Murtagh FR, Egan RA. et al. MRI findings in Susac’s syndrome. Neurology 2003; 61: 1783-1787
• 59 Kleffner I, Duning T, Lohmann H. et al. A brief review of Susac syndrome. J Neurol Sci 2012; 322: 35-40
• 60 Sarbu N, Alobeidi F, Toledano P. et al. Brain abnormalities in newly diagnosed neuropsychiatric lupus: systematic MRI approach and correlation with clinical and laboratory data in a large multicenter cohort. Autoimmun Rev 2015; 14: 153-159
• 61 Sibbitt Jr. WL, Brooks WM, Kornfeld M. et al. Magnetic resonance imaging and brain histopathology in neuropsychiatric systemic lupus erythematosus. Semin Arthritis Rheum 2010; 40: 32-52 [published correction appears in Semin Arthritis Rheum 2011; 40: 369]
• 62 Singh TD, Fugate JE, Rabinstein AA. Central pontine and extrapontine myelinolysis: a systematic review. Eur J Neurol 2014; 21: 1443-1450
• 63 Reddick WE, Glass JO, Helton KJ. et al. Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol 2005; 26: 1263-1269
• 64 Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol 2015; 14: 914-925
• 65 Johkura K, Naito M, Naka T. Cortical involvement in Marchiafava-Bignami disease. AJNR Am J Neuroradiol 2005; 26: 670-673
• 66 Tormoehlen LM. Toxic leukoencephalopathies. Neurol Clin 2011; 29: 591-605
• 67 Rimkus CdeM, Andrade CS, Leite CdaC. et al. Toxic leukoencephalopathies, including drug, medication, environmental, and radiation-induced encephalopathic syndromes. Semin Ultrasound CT MR 2014; 35: 97-117
• 68 Cummings M, Dougherty DW, Mohile NA. et al. Severe radiation-induced leukoencephalopathy: case report and literature review. Adv Radiat Oncol 2016; 1: 17-20