RadioGraphics Update: White Matter Diseases with Radiologic-Pathologic Correlation

Abstract

Editor’s Note.—Articles in the RadioGraphics Update section provide current knowledge to supplement or update information found in full-length articles previously published in RadioGraphics. Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technologic advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article.

^©RSNA, 2020

Introduction

Over the last few years, many publications have been developed regarding follow-up of white matter diseases and their treatment (1). This update discusses the 2017 McDonald Criteria for the Diagnosis of Multiple Sclerosis (2) and the guidelines for MRI follow-up of multiple sclerosis (MS) on the basis of risk profile and therapy. There is also new knowledge regarding neuromyelitis optica spectrum disorders (NMOSDs), particularly the detection of anti–myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-Ab) as a distinct cause of central nervous system demyelination. A brief mention of important considerations regarding other diseases is included.

Multiple Sclerosis

Updated Diagnostic Criteria

MS remains the leading nontraumatic cause of disability in young adults, but the prognosis has improved dramatically in the last several years because of advances in immunotherapy. The latest diagnostic criteria are listed in the 2017 update of the 2010 McDonald criteria, which require two conditions: dissemination of lesions in space and in time. With regard to imaging, these criteria add cortical lesions to the classic locations (periventricular, juxtacortical, infratentorial, and spinal cord). Dissemination in space means that there is at least one lesion in at least two locations. Dissemination in time can be established on a single MR image, if there are both enhancing and nonenhancing lesions, or at follow-up MRI, if new lesions occur (2). Outside of these criteria, the central vein sign at T2^*-weighted MRI has recently been proposed as an MS biomarker (3).

Follow-up Recommendations

Disease-modifying therapies have evolved considerably, from moderately active drugs with few side effects to highly efficient immune-modulating drugs that have potentially severe reactions. Thus, new guidelines were developed for MRI follow-up of MS (Tables 1, 2). MRI is recommended before initiating or changing MS treatment and at 6 months after treatment initiation to allow the new drug to reach its therapeutic potential. Worsening of lesion activity at MRI is indicative of suboptimal response and could suggest the need for a treatment modification (4).

Table 1:

Recommendations for MRI Follow-up of MS

Table 2:

Standardization of MRI Acquisition Protocols

After the first follow-up, MRI is recommended annually for at least 1–2 years to exclude subclinical activity. Different monitoring scoring systems have been developed, with the best known (ie, the Rio, Prosperini, and Canadian systems) being based on the evaluation of MRI activity (new lesions seen with T2-weighted sequences, or lesion enhancement), although clinical parameters are also included (eg, recurrences, disability progression, neuropsychological assessment, and quality of life). MRI acquisition protocols should be standardized (Table 2) (4).

Monitoring for Opportunistic Infections

Patients at high risk (Table 1) should be followed with MRI every 3–4 months, including at least the use of T2-weighted fluid-attenuated inversion-recovery (FLAIR), T2-weighted, and diffusion-weighted sequences. In patients at high risk who switch treatment, MRI is recommended at treatment interruption and after initiation of the new drug. In patients who switch from natalizumab to fingolimod therapy, several cases of progressive multifocal leukoencephalopathy have been described. Other opportunistic infections can occur that are caused by a wide range of pathogens, such as varicella-zoster virus (in particular with fingolimod therapy). Many studies report treatment-related adverse events several months after initiation or discontinuation of treatment. Therefore, strict pharmacovigilance, including monitoring with MRI, should be performed in patients who change treatment (4,5).

Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica is now recognized as one end of neuromyelitis optica spectrum disorder (NMOSD), which encompasses patients who do not meet the original diagnostic criteria (Table 3). Three subgroups are defined by the presence of immunoglobulin G (IgG) antibody against aquaporin-4 (AQP4), which is positive (+) in 60%–70% of patients; the presence of MOG-Ab; and patients negative for both (5,6). Of the one-third of patients with NMOSD who do not have anti-AQP4 antibodies, a minority have MOG-IgG, reported as 7.4% of 215 patients with NMOSD in one series. The identification of clinically relevant MOG-IgG followed the development of cell-based assays using transfected cells. In contrast to NMOSD-AQP4+, MOG-Ab+ central nervous system (CNS) demyelination has a single or only a few attacks, a better prognosis, and other distinctive features (Table 4). The MONEM acronym is used for MOG-IgG–associated optic neuritis, encephalitis, and myelitis (7–9).

Table 3:

Diagnostic Criteria for NMOSD according to Anti-AQP4 Antibody Status

Table 4:

Features of AQP4-Ab+ Neuromyelitis Optica vs MOG-Ab+ CNS Demyelination

Regarding the pathologic findings, AQP4+ neuromyelitis optica/NMOSD is an astrocytopathy, while MOG-Ab+ CNS demyelination is an oligodendrocytopathy with complement activation driven by peripheral B cells and antibodies deposition, which has important therapeutic perspectives with the development of new treatments targeting B cells (8).

The proposed diagnostic criteria for MOG-Ab+ CNS demyelination are serum/cerebrospinal fluid MOG-IgG positivity, clinical features (any of the following: acute disseminating encephalomyelitis [ADEM], optic neuritis, transverse myelitis, or brain or brainstem demyelination), and exclusion of alternative diagnoses (9). MOG-IgG is not limited to NMOSD and has also been reported in MS and ADEM, which supports the hypothesis of a distinct entity of MOG-Ab+ CNS demyelination with varying phenotypes or clinical manifestations (7,9).

Acute Disseminated Encephalomyelitis

Typical ADEM is monophasic (90%) with a single episode of encephalopathy and multifocal neurologic deficits related to demyelinating lesions. If a relapse occurs within 3 months of the initial episode or within 4 weeks of discontinuing therapy, it is still considered part of the initial episode. Recurrent ADEM is defined by a new event at least 3 months after the initial episode and at least 4 weeks after the treatment interruption, with an identical clinical manifestation, affecting the same locations at MRI as the initial episode. Multiphasic ADEM is defined by one or more recurrences with encephalopathy and multifocal neurologic deficits, affecting new locations of the central nervous system. ADEM has a good prognosis in 70%–90% of cases, often with regression of lesions in the first 6 months (10).

Progressive Multifocal Leukoencephalopathy

Active progressive multifocal leukoencephalopathy (PML) manifests as increasing size and/or number of lesions at MRI within 3 months. C-reactive protein (CRP) in cerebrospinal fluid remains positive in about 75% of cases, and demyelination is usually permanent. Inactive PML is characterized by absence of worsening findings at MRI at a 3-month interval and negative CRP. PML still has no specific treatment, the goal being the restoration of immunity, which can stop disease progression (3,5).

Central Nervous System Vasculitis

Although radiologic findings of central nervous system vasculitis remain nonspecific, brain MRI has high negative predictive value. Brain MR angiography with new high-resolution black-blood sequences can show segmental vessel wall injury with contrast enhancement. Conventional angiography is recommended when clinical suspicion is associated with positive findings at MRI. Angiography may demonstrate multifocal narrowing of small or medium vessels; however, a brain biopsy may be necessary to confirm the diagnosis (11).

Conclusion

Our knowledge of white matter diseases is constantly evolving because of the discovery of new disease mechanisms, therapy advances, and refinements in MRI diagnosis and follow-up. In this context, a thorough understanding of MRI patterns is becoming increasingly important.