Abstract
Idiopathic inflammatory-demyelinating diseases (IIDDs) include a broad spectrum of central nervous system disorders that can usually be differentiated on the basis of clinical, imaging, laboratory and pathological findings. However, there can be a considerable overlap between at least some of these disorders, leading to misdiagnoses or diagnostic uncertainty. The relapsing-remitting and secondary progressive forms of multiple sclerosis (MS) are the most common IIDDs. Other MS phenotypes include those with a progressive course from onset (primary progressive and progressive relapsing) or with a benign course continuing for years after onset (benign MS). Uncommon forms of IIDDs can be classified clinically into: (1) fulminant or acute IIDDs, such as the Marburg variant of MS, Baló’s concentric sclerosis, Schilder’s disease, and acute disseminated encephalomyelitis; (2) monosymptomatic IIDDs, such as those involving the spinal cord (transverse myelitis), optic nerve (optic neuritis) or brainstem and cerebellum; and (3) IIDDs with a restricted topographical distribution, including Devic’s neuromyelitis optica, recurrent optic neuritis and relapsing transverse myelitis. Other forms of IIDD, which are classified clinically and radiologically as pseudotumoral, can have different forms of presentation and clinical courses. Although some of these uncommon IIDDs are variants of MS, others probably correspond to different entities. MR imaging of the brain and spine is the imaging technique of choice for diagnosing these disorders, and together with the clinical and laboratory findings can accurately classify them. Precise classification of these disorders may have relevant prognostic and treatment implications, and might be helpful in distinguishing them from tumoral or infectious lesions, avoiding unnecessary aggressive diagnostic or therapeutic procedures.
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References
Brinar VV (2004) Non-MS recurrent demyelinating diseases. Clin Neurol Neurosurg 106:197–210
Fukazawa T, Kikuchi S, Niino M et al (2004) Attack-related severity: a key factor in understanding the spectrum of idiopathic inflammatory demyelinating disorders. J Neurol Sci 225:71–78
Poser S, Luer W, Bruhn H, Frahm J, Bruck Y, Felgenhauer K (1992) Acute demyelinating disease. Classification and non-invasive diagnosis. Acta Neurol Scand 86:579–585
Charil A, Yousry TA, Rovaris M, Barkhof F, De Stefano N, Fazekas F et al (2006) MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation”. Lancet Neurol 5:841–852
Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46:907–911
Hawkins SA, McDonnell GV (1999) Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J Neurol Neurosurg Psychiatry 67:148–152
Pittock SJ, Mayr WT, McClelland RL et al (2004) Disability profile of MS did not change over 10 years in a population-based prevalence cohort. Neurology 62:601–606
Pittock SJ, McClelland RL, Mayr WT (2004) Clinical implications of benign multiple sclerosis: a 20-year population-based follow-up study. Ann Neurol 56:303–306
Brex PA, Ciccarelli O, O’Riordan JI, Sailer M, Thompson AJ, Miller DH (2002) A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 346:158–164
Compston A, Coles A (2002) Multiple sclerosis. Lancet 359:1221–1231
Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717
Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343:938–952
Tintore M, Rovira A, Rio J, Nos C, Grive E, Tellez N et al (2005) Is optic neuritis more benign than other first attacks in multiple sclerosis? Ann Neurol 57:210–215
Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Ebers GC, Johnson KP et al (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231
McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 50:121–127
Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L et al (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald criteria”. Ann Neurol 58:840–846
Ge Y (2006) Multiple sclerosis: the role of MR imaging. AJNR Am J Neuroradiol 27:1165–1176
Freedman MS, Blumhardt LD, Brochet B, Comi G, Noseworthy JH, Sandberg-Wollheim M et al (2002) International consensus statement on the use of disease-modifying agents in multiple sclerosis. Mult Scler 8:19–23
European Study Group on interferon beta-1b in secondary progressive MS (1998) Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet 352:1491–1497
Calabresi PA (2002) Considerations in the treatment of relapsing-remitting multiple sclerosis. Neurology 58(8 Suppl 4):S10–S22
Montalban X (2005) Primary progressive multiple sclerosis. Curr Opin Neurol 18:261–266
Stevenson VL, Miller DH, Rovaris M, Barkhof F, Brochet B, Dousset V et al (1999) Primary and transitional progressive MS: a clinical and MRI cross-sectional study. Neurology 52:839–845
Thompson AJ, Montalban X, Barkhof F, Brochet B, Filippi M, Miller DH et al (2000) Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol 47:831–835
Barkhof F (2002) The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol 15:239–245
Leary SM, Miller DH, Stevenson VL, Brex PA, Chard DT, Thompson AJ (2003) Interferon beta-1a in primary progressive MS: an exploratory, randomized, controlled trial. Neurology 60:44–51
Johnson MD, Lavin P, Whetsell WO Jr (1990) Fulminant monophasic multiple sclerosis, Marburg’s type. J Neurol Neurosurg Psychiatry 53:918–921
Bitsch A, Wegener C, da Costa C, Bunkowski S, Reimers CD, Prange HW, Bruck W (1999) Lesion development in Marburg’s type of acute multiple sclerosis: from inflammation to demyelination. Mult Scler 5:138–146
Capello E, Mancardi GL (2004) Marburg type and Balo’s concentric sclerosis: rare and acute variants of multiple sclerosis. Neurol Sci 25 (Suppl 4):S361–S363
Rodriguez M, Karnes WE, Bartleson JD, Pineda AA (1993) Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology 43:1100–1104
Weinshenker BG, O’Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW et al (1999) A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 46:878–886
Jeffery DR, Lefkowitz DS, Crittenden JP (2004) Treatment of Marburg variant multiple sclerosis with mitoxantrone. J Neuroimaging 14:58–62
Lhermitte F, Escourolle R, Hauw JJ, Gray F, Serdaru M, Lyon-Caen O (1981) Necrotic aspects of multiple sclerosis and Schilder’s disease. Rev Neurol (Paris) 137:589–600
Garell PC, Menezes AH, Baumbach G et al (1998) Presentation, management and follow-up of Schilder’s disease. Pediatr Neurosurg 29:86–91
Mehler MF, Rabinowich L (1989) Inflammatory myelinoclastic diffuse sclerosis (Schilder’s disease): neuroradiologic findings. AJNR Am J Neuroradiol 10:176–180
Sastre-Garriga J, Rovira A, Rio J, Tintore M, Grive E, Montalban X (2003) Clinically definite multiple sclerosis after radiological Schilder-like onset. J Neurol 250:871–873
Dresser LP, Tourian AY, Anthony DC (1991) A case of myelinoclastic diffuse sclerosis in an adult. Neurology 41:316–318
Eblen F, Poremba M, Grodd W, Opitz H, Roggendorf W, Dichgans J (1991) Myelinoclastic diffuse sclerosis (Schilder’s disease): cliniconeuroradiologic correlations. Neurology 41:589–591
Pretorius ML, Loock DB, Ravenscroft A, Schoeman JF (1998) Demyelinating disease of Schilder type in three young South African children: dramatic response to corticosteroids. J Child Neurol 13:197–201
Yao DL, Webster HD, Hudson LD, Brenner M, Liu DS, Escobar AI et al (1994) Concentric sclerosis (Balo): morphometric and in situ hybridization study of lesions in six patients. Ann Neurol 35:18–30
Gharagozloo AM, Poe LB, Collins GH (1994) Antemortem diagnosis of Balo concentric sclerosis: correlative MR imaging and pathologic features. Radiology 191:817–819
Stadelmann C, Ludwin S, Tabira T, Guseo A, Luchinetti CF, Leel-Ossy L et al (2005) Tissue preconditioning may explain concentric lesions in Baló’s type of multiple sclerosis. Brain 128:979–987
Korte JH, Bom EP, Vos LD, Breuer TJ, Wondergem JH (1994) Balo concentric sclerosis: MR diagnosis. AJNR Am J Neuroradiol 15:1284–1285
Wiendl H, Weissert R, Herrlinger U, Krapf H, Kuker W (2005) Diffusion abnormality in Balo’s concentric sclerosis: clues for the pathogenesis. Eur Neurol 53:42–44
Menge T, Hemmer B, Nessler S, Wiendl H, Neuhaus O, Hartung HP et al (2005) Acute disseminated encephalomyelitis: an update. Arch Neurol 62:1673–1680
Dale RC, de Sousa C, Chong WK, Cox TC, Harding B, Neville BG (2000) Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain 123:2407–2422
Hynson JL, Kornberg AJ, Coleman LT, Shield L, Harvey AS, Kean MJ (2001) Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology 56:1308–1312
Tenembaum S, Chamoles N, Fejerman N (2002) Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology 59:1224–1231
Dale RC, Branson JA (2005) Acute disseminated encephalomyelitis or multiple sclerosis: can the initial presentation help in establishing a correct diagnosis? Arch Dis Child 90:636–639
Caldemeyer KS, Smith RR, Harris TM, Edwards MK (1994) MRI in acute disseminated encephalomyelitis. Neuroradiology 36:216–220
Kesselring J, Miller DH, Robb SA, Kendall BE, Moseley IF, Kingsley D et al (1990) Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. Brain 113:291–302
O’Riordan JI, Gomez-Anson B, Moseley IF, Miller DH (1999) Long term MRI follow-up of patients with post infectious encephalomyelitis: evidence for a monophasic disease. J Neurol Sci 167:132–136
Honkaniemi J, Dastidar P, Kahara V, Haapasalo H (2001) Delayed MR imaging changes in acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 22:1117–1124
Mikaeloff Y, Adamsbaum C, Husson B, Vallee L, Ponsot G, Confavreux C et al (2004) MRI prognostic factors for relapse after acute CNS inflammatory demyelination in childhood. Brain 127:1942–1947
Krupp L, MacAllister W; on behalf of the International Pediatric MS Study Group (2006) Consensus definitions of acquired CNS demyelinating disorders of childhood. Mult Scler 16 [Suppl 1]:S23
Hartung HP, Grossman RI (2001) ADEM: distinct disease or part of the MS spectrum? Neurology 56:1257–1260
Shahar E, Andraus J, Savitzki D, Pilar G, Zelnik N (2002) Outcome of severe encephalomyelitis in children: effect of high-dose methylprednisolone and immunoglobulins. J Child Neurol 17:810–814
Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG (2002) Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 58:143–146
Marchioni E, Marinou-Aktipi K, Uggetti C, Bottanelli M, Pichiecchio A, Soragna D et al (2002) Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis. J Neurol 249:100–104
Apak RA, Anlar B, Saatci I (1999) A case of relapsing acute disseminated encephalomyelitis with high dose corticosteroid treatment. Brain Dev 21:279–282
Schwarz S, Mohr A, Knauth M, Wildemann B, Storch-Hagenlocher B (2001) Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology 56:1313–1318
Gibbs WN, Kreidie MA, Kim RC, Hasso AN (2005) Acute hemorrhagic leukoencephalitis: neuroimaging features and neuropathologic diagnosis. J Comput Assist Tomogr 29:689–693
Zagzag D, Miller DC, Kleinman GM, Abati A, Donnenfeld H, Budzilovich GN (1993) Demyelinating disease versus tumor in surgical neuropathology. Clues to a correct pathological diagnosis. Am J Surg Pathol 17:537–545
Kepes JJ (1993) Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients. Ann Neurol 33:18–27
Dagher AP, Smirniotopoulos J (1996) Tumefactive demyelinating lesions. Neuroradiology 38:560–565
Given CA, Stevens BS, Lee C (2004) The MRI appearance of tumefactive demyelinating lesions. AJR Am J Roentgenol 182:195–199
Cucurella MG, Rovira A, Grivé E, Tintoré M, Montalban X, Alonso J (2002) Serial proton spectroscopy, magnetization transfer ratio and T2 relaxation in pseudotumoral demyelinating lesions. NMR Biomed 15:284–292
Masdeu JC, Quinto C, Olivera C, Tenner M, Leslie D, Visintainer P (2000) Open-ring imaging sign: highly specific for atypical brain demyelination. Neurology 54:1427–1433
Schwartz KM, Erickson BJ, Lucchinetti C (2006) Pattern of T2 hypointensity associated with ring-enhancing brain lesions can help to differentiate pathology. Neuroradiology 48:143–149
Law M, Meltzer DE, Cha S (2002) Spectroscopic magnetic resonance imaging of a tumefactive demyelinating lesion. Neuroradiology 44:986–989
Butteriss DJ, Ismail A, Ellison DW, Birchall D (2003) Use of serial proton magnetic resonance spectroscopy to differentiate low grade glioma from tumefactive plaque in a patient with multiple sclerosis. Br J Radiol 76:662–665
De Stefano N, Caramanos Z, Preul MC, Francis G, Antel JP, Arnold DL (1998) In vivo differentiation of astrocytic brain tumors and isolated demyelinating lesions of the type seen in multiple sclerosis using 1H magnetic resonance spectroscopic imaging. Ann Neurol 44:273–278
Mao-Draayer Y, Braff S, Pendlebury W, Panitch H (2002) Treatment of steroid-unresponsive tumefactive demyelinating disease with plasma exchange. Neurology 59:1074–1077
Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG (1999) The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology 53:1107–1114
Beck RW, Trobe JD, Moke PS, Gal RL, Xing D, Bhatti MT et al (2003) High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial. Arch Ophthalmol 121:944–949
Rocca MA, Hickman SJ, Bö L, Agosta F, Miller DH, Comi G et al (2005) Imaging the optic nerve in multiple sclerosis. Mult Scler 11:537–541
Gass A, Moseley IF, Barker GJ, Jones S, MacManus D, McDonald WI, Miller DH (1996) Lesion discrimination in optic neuritis using high-resolution fat-suppressed fast spin-echo MRI. Neuroradiology 38:317–321
Hickman SJ, Miszkiel KA, Plant GT, Miller DH (2005) The optic nerve sheath on MRI in acute optic neuritis. Neuroradiology 47:51–55
Kupersmith MJ, Alban T, Zeiffer B, Lefton D (2002) Contrast-enhanced MRI in acute optic neuritis: relationship to visual performance. Brain 125:812–822
Davies MB, Williams R, Haq N, Pelosi L, Hawkins CP (1998) MRI of optic nerve and postchiasmal visual pathways and visual evoked potentials in secondary progressive multiple sclerosis. Neuroradiology 40:765–770
Miller DH, Ormerod IE, Rudge P, Kendall BE, Moseley IF, McDonald WI (1989) The early risk of multiple sclerosis following isolated acute syndromes of the brainstem and spinal cord. Ann Neurol 26:635–639
Sastre-Garriga J, Tintore M, Rovira A, Grive E, Pericot I, Comabella M et al (2003) Conversion to multiple sclerosis after a clinically isolated syndrome of the brainstem: cranial magnetic resonance imaging, cerebrospinal fluid and neurophysiological findings. Mult Scler 9:39–43
Bickerstaff ER, Cloake PC (1951) Mesencephalitis and rhombencephalitis. Br Med J 4723:77–81
Yaqub BA, al-Deeb SM, Daif AK, Sharif HS, Shamena AR, al-Jaberi M et al (1990) Bickerstaff brainstem encephalitis. A grave non-demyelinating disease with benign prognosis. J Neurol Sci 96:29–40
Stevenson VL, Ferguson SM, Bain PG (2003) Bickerstaff’s brainstem encephalitis, Miller Fisher syndrome and Guillain-Barre syndrome overlap with negative anti-GQ1b antibodies. Eur J Neurol 10:187
Winer JB (2001) Bickerstaff’s encephalitis and the Miller Fisher syndrome. J Neurol Neurosurg Psychiatry 71:433–435
Mondejar RR, Santos JM, Villalba EF (2002) MRI findings in a remitting-relapsing case of Bickerstaff encephalitis. Neuroradiology 44:411–414
Transverse Myelitis Consortium Working Group (2002) Proposed diagnostic criteria and nosology of acute transverse myelitis. Neurology 59:499–505
Lycklama G, Thompson A, Filippi M, Miller D, Polman C, Fazekas F et al (2003) Spinal-cord MRI in multiple sclerosis. Lancet Neurol 2:555–562
Dietemann JL, Thibaut-Menard A, Warter JM, Neugroschl C, Tranchant C, Gillis C, Eid MA, Bogorin A (2000) MRI in multiple sclerosis of the spinal cord: evaluation of fast short-tau inversion-recovery and spin-echo sequences. Neuroradiology 42:810–813
Campi A, Pontesilli S, Gerevini S, Scotti G (2000) Comparison of MRI pulse sequences for investigation of lesions of the cervical spinal cord. Neuroradiology 42:669–675
Ghezzi A, Bergamaschi R, Martinelli V, Trojano M, Tola MR, Merelli E et al (2004) Clinical characteristics, course and prognosis of relapsing Devic’s neuromyelitis optica. J Neurol 251:47–52
de Seze J (2003) Neuromyelitis optica. Arch Neurol 60:1336–1338
Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K et al (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112
Filippi M, Rocca MA, Moiola L et al (1999) MRI and magnetization transfer imaging changes in the brain and cervical cord of patients with Devic’s neuromyelitis optica. Neurology 53:1705–1710
Rocca MA, Agosta F, Mezzapesa DM et al (2004) Magnetization transfer and diffusion tensor MRI show gray matter damage in neuromyelitis optica. Neurology 62:476–478
Mandler RN, Davis LE, Jeffery DR, Kornfeld M (1993) Devic’s neuromyelitis optica: a clinicopathological study of 8 patients. Ann Neurol 34:162–168
O’Riordan JI, Gallagher HL, Thompson AJ, Howard RS, Kingsley DP, Thompson EJ et al (1996) Clinical, CSF, and MRI findings in Devic’s neuromyelitis optica. J Neurol Neurosurg Psychiatry 60:382–387
Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202:473–477
Weinshenker BG, Wingerchuk DM, Vukusic S, Linbo L, Pittock SJ, Lucchinetti CF et al (2006) Neuromyelitis optica IgG predicts relapse after longitudinally extensive transverse myelitis. Ann Neurol 59:566–569
Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG (2006) Revised diagnostic criteria for neuromyelitis optica. Neurology 66:1485–1489
Wingerchuk DM, Weinshenker BG (2005) Neuromyelitis optica. Curr Treat Options Neurol 7:173–182
Mandler RN, Ahmed W, Dencoff JE (1998) Devic’s neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 51:1219–1220
Cree BA, Lamb S, Morgan K, Chen A, Waubant E, Genain C (2005) An open label study of the effects of rituximab in neuromyelitis optica. Neurology 64:1270–1272
Lucchinetti CF, Kiers L, O’Duffy A, Gomez MR, Cross S, Leavitt JA et al (1997) Risk factors for developing multiple sclerosis after childhood optic neuritis. Neurology 49:1413–1418
Pirko I, Blauwet LK, Lesnick TG, Weinshenker BG (2004) The natural history of recurrent optic neuritis. Arch Neurol 61:1401–1405
Wingerchuk DM, Weinshenker BG (2003) Neuromyelitis optica: clinical predictors of a relapsing course and survival. Neurology 60:848–853
Kim KK (2003) Idiopathic recurrent transverse myelitis. Arch Neurol 60:1290–1294
Chan KH, Tsang KL, Fong GC, Cheung RT, Ho SL (2005) Idiopathic severe recurrent transverse myelitis: a restricted variant of neuromyelitis optica. Clin Neurol Neurosurg 107:132–135
Paty DW, Oger JJ, Kastrukoff LF, Hashimoto SA, Hooge JP, Eisen AA, Eisen KA, Purves SJ, Low MD, Brandejs V et al (1988) MRI in the diagnosis of MS: a prospective study with comparison of clinical evaluation, evoked potentials, oligoclonal banding, and CT. Neurology 38:180–185
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The authors thank Celine L. Cavallo for English language support.
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Cañellas, A.R., Gols, A.R., Izquierdo, J.R. et al. Idiopathic inflammatory-demyelinating diseases of the central nervous system. Neuroradiology 49, 393–409 (2007). https://doi.org/10.1007/s00234-007-0216-2
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DOI: https://doi.org/10.1007/s00234-007-0216-2