Chapter 1.2

Inflammatory Demyelinating Diseases

IstvanPirko1Charles R.G.Guttmann2 1Department of Neurology, Mayo Clinic, College of Medicine, Rochester, MN, USA    2Center for Neurological Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

Abstract

The spinal cord is commonly affected in inflammatory demyelinating diseases (IDD) of the central nervous system. In the most common IDD, multiple sclerosis (MS), the importance of spinal cord involvement is highlighted by the inclusion of characteristic cord lesions in its current diagnostic criteria. In neuromyelitis optica, longitudinally extensive spinal cord lesions over three or more segments are considered almost pathognomonic for the disease. In general, spinal cord lesion load shows a strong correlation with disability, and spinal cord-derived magnetic resonance imaging (MRI) measures are some of the strongest biomarkers of a disabling disease course. In progressive forms of MS, the clinical phenotype is consistent with a progressive myelopathy in most cases. These forms of MS, especially primary progressive MS, represent a major challenge for disease activity monitoring. Novel quantitative MRI metrics characterizing spinal cord involvement in MS are expected to find their way into routine clinical monitoring as they provide unique insight into tissue abnormalities, allowing for monitoring of disease progression and assessment of response to treatment. These techniques include magnetization transfer MRI, diffusion-weighted imaging, atrophy measurement techniques, T1 and T2 relaxometry, and magnetic resonance spectroscopy.

Keywords

Inflammatory myelopathyMultiple sclerosisNeuromyelitis opticaParaneoplastic myelopathyTransverse myelitis

Introduction

The spinal cord is a common site of involvement in inflammatory demyelinating diseases of the central nervous system (CNS). The most common such disease, multiple sclerosis, is the leading cause of nontraumatic disability in young adults, with an enormous socioeconomic impact.1 Neuromyelitis optica (NMO), an increasingly recognized and recently redefined condition, also has prominent and very characteristic spinal cord involvement, which is typically much more severe than MS-related transverse myelitis. The critical importance of spinal cord imaging in these conditions is also highlighted by the inclusion of spinal cord magnetic resonance imaging (MRI)-derived metrics in the internationally utilized diagnostic criteria of MS and NMO. However, with the constant evolution of the MS diagnostic criteria, new discoveries pertaining to the pathogenesis and biomarkers of NMO, and the evolving definitions of transverse myelitis, acute disseminated encephalomyelitis (ADEM), pediatric MS, and systemic autoimmune disease-associated and paraneoplastic myelopathies, one might feel overwhelmed when attempting to classify, characterize, diagnose, and manage these conditions. Neuroimaging, specifically MRI, plays a key role in the correct diagnosis of these conditions, and it provides a critically important aid for treatment monitoring. With the advent of advanced MRI techniques enabling quantitative analysis methods, MRI provides a reliable tool in monitoring and characterizing disease progression, and it also enables a unique insight into the generally poorly understood pathogenesis of these disorders. In this chapter, we will discuss the currently available and constantly evolving MRI-based quantitative tools. These will be discussed in the context of the most common forms of acute and subacute inflammatory myelopathies, including MS-related transverse myelitis, longitudinally extensive transverse myelitis (LETM) related to NMO and NMO spectrum disorder, and idiopathic inflammatory transverse myelitis in the context of MS and as a stand-alone condition. The vast majority of the published quantitative MRI literature clearly has focused on MS, with a smaller but growing proportion of studies related to NMO; for that reason, these two diseases are the main focus when we discuss quantitative methods. Finally, we will outline future perspectives and challenges in the evolving field of quantitative MRI in inflammatory myelopathies.

Classification of Inflammatory Myelopathies

While there is currently no single universally accepted and utilized classification of inflammatory myelopathies, one can consider several features of these conditions to establish clinically useful classifications. One such feature is the lesion location or “lesion type” (Table 1.2.1).2 In addition, an important classification strategy also followed in the recently published American Academy of Neurology guidelines is whether the TM episode is complete or partial,3 which is an especially helpful distinguishing feature at first presentation with transverse myelitis.   SPINAL CORD INVOLVEMENT IN INFLAMMATORY MYELOPATHIES: KEY POINTS AND FEATURES • Multiple sclerosis (MS): Patch-like lesions abutting the surface of the cord; in contact with cerebral spinal fluid (CSF); up to one-half of the axial crosscut surface is involved, but more commonly one-fourth to one-third • Neuromyelitis optica (NMO): Longitudinally extensive transverse myelitis—three or more segments long, “center of the cord” appearance on axial cuts, often involves more than 50% on axial cuts • Idiopathic transverse myelitis (TM): May be similar to MS or NMO-like lesions, without meeting the criteria for either; can be a clinically isolated syndrome (CIS) leading to MS, the first manifestation of NMO, or a stand-alone disease • Paraneoplastic myelopathies: Most commonly present as tractopathy

Transverse Myelitis: A Practical Definition Based on MRI

Transverse myelitis is a collective term for segmental inflammatory disorders of the spinal cord. While TM can be seen in the context of infections, which are typically easily recognized given the associated systemic features and/or CSF findings, most cases represent idiopathic inflammatory diseases, including MS, NMO, and less commonly ADEM, paraneoplastic disorders, or sarcoidosis. Metabolic diseases such as vitamin B12 or copper deficiency also may look like TM on conventional MRI, but even with conventional imaging usually there are clear clues regarding their noninflammatory nature. The most important classifying feature of idiopathic TM is based on its MRI appearance on axial and sagittal scans: lesions that encompass one-fourth to one-third of the cord crosscut surface area, typically abut the CSF, have a wedge-like appearance, and on sagittal images rarely extend beyond one or two segments are typical MS lesions. By contrast, lesions that are mostly gray matter centered, encompass one-half or more of the crosscut surface area, are longitudinally extensive usually beyond three segments, and during their acute stage are associated with mass effect are typical NMO lesions. TM lesions with NMO-like characteristics are often labeled as LETM.

TABLE 1.2.1

Classification of Inflammatory Myelopathies Based on Lesion Location

Complete All tracts Pyramidal, sensory, and autonomic dysfunction below lesion Trauma or acute necrotizing viral myelitis Bown–Séquard hemicord syndrome Ipsilateral corticospinal, posterior columns; contralateral spinothalamic Ipsilateral pyramidal weakness and loss of posterior column function; contralateral spinothalamic loss Multiple sclerosis, compression Anterior cord syndrome Bilateral anterior horn cells corticospinal tracts, spinothalamic and autonomic Acute bilateral flaccid weakness, loss of pain temperature, and sphincter and autonomic dysfunction; preservation of dorsal column modalities such as joint position sense Anterior spinal artery occlusion Posterior cord Bilateral posterior columns Bilateral loss of light touch, vibration, and joint position Vitamin B12 or copper deficiency (usually chronic) Central Crossing spinothalamic, corticospinal, and autonomic fibers Dissociated sensory loss (loss of pain and temperature with preserved vibration and joint position); pyramidal distribution weakness below lesion; autonomic dysfunction below the lesion Syrinx, neuromyelitis optica Conus medullaris Autonomic outflow and sacral spinal cord segments Early sphincter dysfunction, sacral sensory loss, and relatively mild motor dysfunction Postviral myelitis Cauda equina Spinal nerve roots of the cauda equina Early, often asymmetric flaccid weakness of the lower limbs; sensory loss in root distribution followed by autonomic dysfunction Acute...