Книги по МРТ КТ на английском языке / MR Imaging in White Matter Diseases of the Brain and Spinal Cord - K Sartor Massimo Filippi Nicola De Stefano Vincent Dou

firmed in CT studies (Atlas et al. 1986). In the majority of patients with multiple lesions,at one single point of time, non-enhancing as well as enhancing lesions are present (Singh et al. 2000). The ratio between enhancing and non-enhancing lesions could be a useful criteria for the diagnosis of ADEM; however, this has not been evaluated yet. The pattern of contrast enhancement is not specific. Nodular, diffuse nodular, amorphous, gyral, spotty, and ring-like patterns of contrast enhancement have all been described. Recently, the ring-like pattern of contrast enhancement has been suggested as an important criteria for the differentiation between lymphoma (complete ring enhancement) and demyelinating lesions (“open ring sign”) (Masdeu et al. 2000). However, in patients with MS and ADEM, the contrast enhancement can also have the appearance of a complete ring (Lim et al. 2003). Therefore, the diagnostic value of the “open ring sign” is questionable.

Systematic short-time interval follow-up examinations have only been undertaken in a few selected patients (Honkaniemi et al. 2001). In most patients under therapy, at least a partial, rapid remission of size and number of the lesions can be seen. In ADEM, the lesions can disappear completely (O’Riordan et al. 1999). However, in some patients, new lesions may appear even after clinical recovery (Honkaniemi et al. 2001). There are also patients with new lesions at follow-up examinations without new clinical symptoms. It is not known whether these patients have a greater risk for the development of a clinically definite MS. Because of the lack of larger prospective, systematic MRI follow-up studies, a statement on the point of time of the appearance of these new lesions cannot be made. It has been repeatedly noted that new lesions predominantly appear within the first 4 weeks after the onset of symptoms.

17.11.3

New MRI Techniques

Because of the above outlined shortcomings of conventional MRI to achieve a definite diagnosis of ADEM, more specific methods that can potentially separate ADEM and other white matter diseases from MS are warranted. Currently, none exists. Hopefully, new MRI methods and the use of novel contrast agents such as small iron oxide particles might improve the diagnostic specificity of MRI in the future.

Using magnetization transfer and diffusion tensor MRI, Inglese et al. (2002) demonstrated in a small, heavily selected sample of patients after ADEM that, in contrast to a control group of patients with MS, the normal appearing brain tissue and spinal cord are spared from the pathological changes.All MR studies were performed after the acute phase of the disease. These results are in agreement with those of a recent MR follow-up study in which diffuse brain atrophy was detectable already within a 3-month period in untreated patients with an active relapsing remitting MS (Hardmeier et al. 2003). These studies offer the perspective that short-term MRI follow-up studies could separate the patients with MS from those with monophasic ADEM in whom an immunomodulatory long-term treatment would be improper.

There are only sparse reports on MR spectroscopy in ADEM. Bizzi et al. (2001) presented a patient with

ADEM who showed transient low levels of NAA on the initial MR spectroscopic imaging during the acute phase which normalized after clinical recovery. Unlike other demyelinating diseases, choline levels remained normal in all stages of the disease.Harada et al.(2000) compared the differences in water diffusion and lactate production in two patients with ADEM and acute necrotizing encephalopathy. In these two patients, the diffusion of brain water indicated the reversibility of neuronal impairment whereas the extent of lactate production did not correlate with the prognosis.

17.12

Variant of MS or Distinct Disease Entity?

The differentiation between ADEM and MS remains an unsolved issue. Possibly, in the future, new MRI techniques and innovative serological markers such as the presence of antimyelin antibodies may help to identify those patients with a monophasic disease who do not require preventive treatment already after the first episode of symptoms due to a demyelinating CNS syndrome and who could reliably be assured that they do not need to live with a possibly devastating disease.

Since the time of the first review on ADEM in 1931 (McAlpine 1931),it has,so far unsuccessfully,been re-

peatedly tried to identify reliable criteria for the differentiation between ADEM and MS. The larger followup examinations generally show a varying rate up to one third of all patients initially diagnosed with ADEM who later develop MS (Hynson et al. 2001; Rust et al. 1997; Schwarz et al. 2001). Moreover, terms such as Marburg disease, acute MS, multiphasic ADEM, which were often used as synonyms to ADEM, add to the confusion. Table 17.4 summarizes frequently assumed

criteria to distinguish the two diseases. However, it has to be emphasized that none of these unspecific criteria are evidence-based. Thus, these criteria may only provide hints toward the correct diagnosis. During or immediately after the first episode of a demyelinating CNS disease, a definite diagnosis of ADEM is probably not possible. So far, the differentiation between ADEM or the first symptom of an MS can only be ascertained after a longer follow-up.

References

Anlar B, Basaran C, Kose G et al (2003) Acute disseminated encephalomyelitis in children: outcome and prognosis. Neuropediatrics 34:194-199

Antel JP, Owens T (1999) Immune regulation and CNS autoimmune disease. J Neuroimmunol 100:181-189

Atlas SW, Grossman RI, Goldberg HI et al (1986) MR diagnosis of acute disseminated encephalomyelitis. J Comput Assist Tomogr 10:798-801

Baum PA, Barkovich AJ, Koch TK et al (1994) Deep gray matter involvement in children with acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 15:1275-1283

Berger T, Rubner P, Schautzer F et al (2003) Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med 349:139-145

Bizzi A, Ulug AM, Crawford TO et al (2001) Quantitative proton MR spectroscopic imaging in acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 22:1125-1130

Comi G, Filippi M, Barkhof F et al (2001) Effect of early inter-

feron treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357:1576-1582

Dale RC, de Sousa C, Chong WK et al (2000) Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain 123:2407-2422

Gupte G, Stonehouse M, Wassmer E et al (2003) Acute disseminated encephalomyelitis: a review of 18 cases in childhood. J Paediatr Child Health 39:336-342

Hahn CD, Miles BS, MacGregor DL et al (2003) Neurocognitive outcome after acute disseminated encephalomyelitis. Pediatr Neurol 29:117-123

Happe S, Husstedt IW (2000) Successful treatment of acute encephalomyelitis associated with common variable immunodeficiency syndrome (CVID): case report and review of the literature. J Neurol 247:562-565

Harada M, Hisaoka S, Mori K et al (2000) Differences in water diffusion and lactate production in two different types of postinfectious encephalopathy. J Magn Reson Imaging 11:559-563

Acute Disseminated Encephalomyelitis

Hardmeier M, Wagenpfeil S, Freitag P et al (2003) Atrophy is detectable within a 3-month period in untreated patients with active relapsing remitting multiple sclerosis. Arch Neurol 60:1736-1739

Hart MN, Earle KM (1975) Haemorrhagic and perivenous encephalitis: a clinical-pathological review of 38 cases. J Neurol Neurosurg Psychiatry 38:585-591

Höllinger P, Sturzenegger M, Mathis J et al (2002) Acute disseminated encephalomyelitis in adults: a reappraisal of clinical, CSF, EEG, and MRI findings. J Neurol 249:320-329 Honkaniemi J, Dastidar P, Kahara V, Haapasalo H (2001) Delayed MR imaging changes in acute disseminated

encephalomyelitis. AJNR Am J Neuroradiol 22:1117-1124 Hurst AE (1941) Acute haemorhagic leucoencephalitis: a pre-

viously undefined entitiy. Med J Aust 1:1-6

Hynson JL, Kornberg AJ, Coleman LT et al (2001) Clinical and neuroradiologic features of acute disseminated encephalomyelitis in children. Neurology 56:1308-1312.

Idrissova Zh R, Boldyreva MN, Dekonenko EP et al (2003) Acute disseminated encephalomyelitis in children: clinical features and HLA-DR linkage. Eur J Neurol 10:537-546

Inglese M, Salvi F, Iannucci G et al (2002) Magnetization transfer and diffusion tensor MR imaging of acute disseminated encephalomyelitis. AJNR Am J Neuroradiol 23:267-272

Jacobs LD, Beck RW, Simon JH et al (2000) Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 343:898-904

Jorens PG,VanderBorght A, Ceulemans B et al (2000) Encepha- lomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins. Neurology 54:1433-1441

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

Kesselring J, Miller DH, Robb SA et al (1990) Acute disseminated encephalomyelitis. MRI findings and the distinction from multiple sclerosis. Brain 113:291-302

Lim KE, Hsu YY, Hsu WC et al (2003) Multiple complete ring-shaped enhanced MRI lesions in acute disseminated encephalomyelitis. Clin Imaging 27:281-284

Lucchinetti C, Bruck W, Parisi J et al (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707-717

Lukes SA, Norman D (1983) Computed tomography in acute disseminated encephalomyelitis. Ann Neurol 13:567-572 Martino G, Adorini L, Rieckmann P et al (2002) Inflammation

in multiple sclerosis: the good, the bad, and the complex. Lancet Neurol 1:499-509

Masdeu JC, Quinto C, Tenner M et al (2000) Open-ring imaging sign. Neurology 54:1427-1433

McAlpine D (1931) Acute disseminated encephalomyelitis. Lancet 1:846-852

McDonald WI,Compston A,Edan G 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

Miller HG (1953) Acute disseminated encephalomyelitis treated with A.C.T.H. Brit Med J:177-183

Miller HG, Stanton JB, Gibbons JL (1956) Para-infectious encephalomyelitis and related symptoms. J Med 25:427505

Modi G, Mochan A, Modi M et al (2001) Demyelinating disor-

267

der of the central nervous system occurring in black South Africans. J Neurol Neurosurg Psychiatry 70:500-505

Murthy JM, Yangala R, Meena AK et al (1999) Clinical, electrophysiological and magnetic resonance imaging study of acute disseminated encephalomyelitis. J Assoc Physicians India 47:280-283

Murthy SN, Faden HS, Cohen ME et al (2002) Acute disseminated encephalomyelitis in children. Pediatrics 110:e21 Nadkarni N, Lisak RP (1993) Guillain-Barré syndrome (GBS)

with bilateral optic neuritis and central white matter disease. Neurology 43:842-843

Nasr JT, Andriola MR, Coyle PK (2000) ADEM: literature review and case report of acute psychosis presentation. Pediatr Neurol 22:8-18

Nishikawa M, Ichiyama T, Hayashi T et al (1999) Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis. Pediatr Neurol 21:583-586

O’Riordan JI, Gomez-Anson B, Moseley IF et al (1999) Long term MRI follow-up of patients with post infectious encephalomyelitis: evidence for a monophasic disease. J Neurol Sci 167:132-136

Pohl-Koppe A, Burchett SK, Thiele EA et al (1998) Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis. J Neuroimmunol 91:19-27

Poser CM (1989) Magnetic resonance imaging in asymptomatic disseminated vasculomyelinopathy. J Neurol Sci 94:69-77 Poser CM, Paty DW, Scheinberg L et al (1983) New diagnostic

criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227-231

Reik L (1980) Disseminated vasculomyelinopathy: An immune complex disease. Ann Neurol 7:291-296

Reis F, Kobayashi E, Maciel EP et al (1999) Ressonancia magnética e características clínicas em adultos com doencas desmielinizantes monofásicas. Encefalomielite aguda disseminada ou uma variante da esclerose múltipla? Arq Neuropsiquiatr 57:853-859

Rivers TM, Sprunt DH, Berry GP (1933) Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J Exp Med 58:39-53

Rust RS, Dodson W, Prensky A et al (1997) Classification and outcome of acute disseminated encephalomyelitis. Ann Neurol 42:491

Schwarz S, Knauth M, Schwab S et al (2000) Acute disseminated encephalomyelitis after parenteral therapy with herbal extracts: a report of two cases. J Neurol Neurosurg Psychiatry 69:516-518

Schwarz S, Mohr A, Knauth M et al (2001) Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology 56:1313-1318

Schwarz S, Zoubaa S, Knauth M et al (2002) Intravascular lymphomatosis presenting with a conus medullaris syndrome mimicking disseminated encephalomyelitis. Neuro-Oncol- ogy 4:187-191

Simon JH (2000) The contribution of spinal cord MRI to the diagnosis and differential diagnosis of multiple sclerosis. J Neurol Sci 172:S32-S35

Singh S, Alexander M, Korah IP (1999) Acute disseminated encephalomyelitis: MR imaging features. AJR 173:11011107

Storch MK, Stefferl A, Brehm U et al (1998) Autoimmunity to myelin oligodendrocyte glycoprotein in rats mimics the spectrum of multiple sclerosis pathology. Brain Pathol 8:681-694

268

Stratton KR, Howe CJ, Johnston RB (1994) Adverse events associated with childhood vaccines. Washington, National Academy Press

Tachovsky TG, Lisak RP, Koprowski H (1976) Circulating immune complexes in multiple sclerosis and other neurological diseases. Lancet 2:997-999

Takata T, Hirakawa M, Sakurai M et al (1999) Fulminant form of acute disseminated encephalomyelitis: successful treatment with hypothermia. J Neurol Sci 165:9497

S. Schwarz and M. Knauth

Tenembaum S, Chamoles N, Fejerman N (2002) Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology 59:1224-1231

Wang PN, Fuh JL, Liu HC et al (1996) Acute disseminated encephalomyelitis in middle-aged or elderly patients. Eur Neurol 36:219-223

Wildemann B, Jansen O, Haas J et al (2001) Rapid distinction of acute demyelinating disorders and central nervous system lymphoma by molecular analysis of cerebrospinal fluid cells. J Neurol 248:127-130

CONTENTS

18.1Introduction 269

18.2Multiple Sclerosis 269

18.2.1 Acute Disseminated Encephalomyelitis 272

18.2.2 Neuromyelitis Optica 273

18.3Transverse Myelitis 274

18.3.1 MRI Evaluation of Spinal Cord Damage in Relation to Function 275

18.4Conclusion 276 References 277

18.1 Introduction

Magnetic resonance imaging (MRI) has opened a new window on the visualization of abnormalities associated with white matter diseases in the brain. The contribution of MRI with regard to delineating such disorders in the spinal cord is even more impressive considering the fact that MRI has been the first technique to allow for a direct and detailed in vivo evaluation of morphological abnormalities of the spinal cord at all.Of course,MRI of the spinal cord still poses technical difficulties and may thus be more variable in quality than MRI of the brain.Not all pulse sequences which contribute to our understanding of cerebral disorders can easily and equally be applied to this region of the body. The small size of the cord, its position within the dural sac surrounded by pulsating cerebrospinal fluid (CSF), and the motion of the body and its organs during the examination are all factors that may degrade image quality and have to be considered in the examination protocol. Also

R. Bammer, PhD

Lucas MRS/I Center, Department of Radiology, Stanford,

California, USA

F. Fazekas, MD

Department of Neuroradiology, Medical University Graz,

Auenbruggerplatz 22, 8036 Graz, Austria

S. Strasser-Fuchs, MD

Department of Neurology, Medical University Graz,

Auenbruggerplatz 22, 8036 Graz, Austria

signal intensities and resulting contrasts between tissue classes generated by conventional sequences are somewhat different from the brain due to the specific texture of the cord. This is also relevant for the detection of lesions within the cord and necessitates the choice of appropriate sequences. A recent review addressed these technical aspects of spinal cord imaging especially with regard to multiple sclerosis (MS) as the most frequent demyelinating disease of the spinal cord (Lycklama et al. 2003).

Applying these techniques, characteristic MRI findings can be elicited for a distinction between the various demyelinating disorders of the cord and their separation from other diseases which may also affect the spinal cord (Fazekas and Kapeller 1999; Bot et al. 2002). Herein we concentrate especially on the patterns which are typically seen with the different so-called idiopathic inflammatory demyelinating disorders (Weinshenker and Miller 1998).Despite obvious specifics, it needs to be emphasized that the interpretation of MRI abnormalities must always take place in the context of clinical findings and, where necessary, together with other biological (e.g. CSF) and electrophysiologic investigations (Transverse Myelitis Consortium Working Group 1999). In addition to primarily diagnosis-related issues, we also review current possibilities for a quantitation of spinal cord damage from demyelinating diseases especially in relation to function, and we speculate on future prospects for the evaluation of this important part of the central nervous system by MRI.

18.2

Multiple Sclerosis

Multiple sclerosis most commonly causes distinct lesions within the spinal cord (Fazekas et al. 1999; Bot et al. 2004). These lesions typically occupy less than half of the cross-sectional area of the cord and affect both white and grey matter (Tartaglino et al.1995;

Thielen and Miller 1996).

With advancing disease focal MS lesions may merge to larger areas of high signal intensity (Fig. 18.4). A small proportion of MS patients also show only diffuse abnormalities of the spinal cord (Lycklama et al. 1997; Bot et al. 2004). These abnormalities consist mostly of a subtle increase of signal intensity on pro- ton-density-weighted images and have been observed especially in patients with high disability and a primary progressive course of the disease (Lycklama et al. 1998). MRI–histopathological correlations have shown that both diffuse and focal signal hyperintensities in the spinal cord correspond primarily to demyelination (Nijeholt et al. 2001). Axonal damage, however, appears to occur largely independent of intramedullary T2-hyperintensities (Bergers et al. 2002a). This may also explain why a large proportion of spinal cord lesions obviously remain asymptomatic and can at least partly account for reportedly disappointing correlations between clinical symptoms and imaging findings on conventional MRI of the spinal cord (Kidd et al. 1993; Lycklama et al. 1998; O’Riordan et al. 1998; Brex et al. 1999).

Some investigators have found a prevalence of up to 30-40% of spinal cord lesions in patients with a

clinically isolated syndrome suggestive of MS, i.e. at the first clinical presentation of the disease, and even in those presenting with optic neuritis (O’Riordan et al. 1998; Brex et al. 1999). In patients with established MS, the prevalence of intramedullary lesions increases to 80% and higher (Bot et al. 2004). Including diffuse cord changes, probably more than 90% of MS patients have some form of spinal involvement at some point in their disease (Lycklama et al. 1998).

In later stages of MS and with advanced disability spinal cord atrophy becomes readily apparent as well. Volume changes of the spinal cord, although occurring much earlier, can otherwise be reliably established only by the use of exact measurement techniques as described below. Distinct focal areas of cord atrophy are rarely seen except following recovery from very large MS lesions. Different from the brain, spinal cord lesions also do not evolve into socalled black holes, i.e. cystic lesions within the cord are not seen in typical MS. It is also common for the signal hyperintensity of spinal cord MS lesions to decrease over time, and together with the shrinkage of the lesion, causes them to disappear, or at least to

Fig. 18.4 Confluence of intramedullary lesions in a patient with secondary progressive MS

become very difficult to detect on routine follow-up scanning (Fig. 18.2).

Formal integration of spinal cord MRI findings in MS into current diagnostic criteria may still be viewed as suboptimal (McDonald et al.2001; Bot et al.2004; Miller et al. 2004). Earlier limitations regarding MRI examinations of the spinal cord at a high resolution with reproducibly good quality and a paucity of data regarding the diagnostic and prognostic value of the demonstration of MS lesions in the cord made the International Panel simply state that “one spinal cord lesion can be substituted for one brain lesion” (McDonald et al. 2001). Whether this substitution simply is additive to the number of total brain lesions or could also serve to fulfil the requirement of an infratentorial lesion, as defined by Barkhof’s criteria, remains unclear. Similarly, the proposed diagnostic criteria for primary progressive MS have remained somewhat vague (Thompson et al. 2000; McDonald

et al. 2001) but recognise the higher specificity of spinal cord lesions compared with brain lesions, as they do not occur with ageing per se (Thorpe et al. 1993). In addition to previous recommendations on the role of spinal cord MRI in the algorithm for MS diagnosis, which focussed primarily on the need to rule out other disorders (Fazekas et al. 1999), recent data also confirm a higher probability to prove disease dissemination in space by such examination. In a cohort of 104 patients with newly diagnosed MS, Bot et al. (2004) found that substitution of one spinal cord lesion for one brain lesion increased the sensitivity of the McDonald’s dissemination in space criteria from 66 to 85%, and it reached 94% when allowing for an unlimited substitution of brain lesions by spinal cord lesions. In a more selective manner such contribution has already been reported previously for patients with suspected MS, but no or only very few cerebral lesions (Thorpe et al. 1996b). Whether evidence for spinal cord lesions also conveys some prognostic information is still a matter of debate (Lycklama et al. 2003).

18.2.1

Acute Disseminated Encephalomyelitis

By definition, acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disorder which usually follows a viral infection (Wingerchuk 2003) or vaccination. Children are more frequently affected than adults. The MRI findings in the brain consist of multiple, frequently large lesions with perifocal oedema and contrast enhancement as evidence of their acute nature. Lesions can involve the cerebral white matter as well as the basal ganglia, the brain-stem and cerebellum and, according to their appearance and distribution, have been categorized into different patterns including a haemorrhagic variant (acute haemorrhagic encephalomyelitis; Tenenbaum et al. 2002). As part of the central nervous system, the spinal cord can also be involved. In comparison with MS, ADEM lesions of the spinal cord are typically larger and more oedematous (Fig. 18.5).The clinical presentation following a potentially triggering event and the absence of oligoclonal bands should point towards such a diagnosis. A corresponding MRI of the brain with multiple, exclusively acute-appearing lesions is also very suggestive of ADEM (Fig. 18.5).The notion that normalappearing brain white matter of ADEM patients is truly unaffected (Inglese et al. 2002), while in contrast more severe damage is found in the basal gan-