Visualizing the Central Nervous System: Imaging Tools for Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders

Abstract

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are autoimmune central nervous system conditions with increasing incidence and prevalence. While MS is the most frequent inflammatory CNS disorder in young adults, NMOSD is a rare disease, that is pathogenetically distinct from MS, and accounts for approximately 1% of demyelinating disorders, with the relative proportion within the demyelinating CNS diseases varying widely among different races and regions. Most immunomodulatory drugs used in MS are inefficacious or even harmful in NMOSD, emphasizing the need for a timely and accurate diagnosis and distinction from MS. Despite distinct immunopathology and differences in disease course and severity there might be considerable overlap in clinical and imaging findings, posing a diagnostic challenge for managing neurologists. Differential diagnosis is facilitated by positive serology for AQP4-antibodies (AQP4-ab) in NMOSD, but might be difficult in seronegative cases. Imaging of the brain, optic nerve, retina and spinal cord is of paramount importance when managing patients with autoimmune CNS conditions. Once a diagnosis has been established, imaging techniques are often deployed at regular intervals over the disease course as surrogate measures for disease activity and progression and to surveil treatment effects. While the application of some imaging modalities for monitoring of disease course was established decades ago in MS, the situation is unclear in NMOSD where work on longitudinal imaging findings and their association with clinical disability is scant. Moreover, as long-term disability is mostly attack-related in NMOSD and does not stem from insidious progression as in MS, regular follow-up imaging might not be useful in the absence of clinical events. However, with accumulating evidence for covert tissue alteration in NMOSD and with the advent of approved immunotherapies the role of imaging in the management of NMOSD may be reconsidered. By contrast, MS management still faces the challenge of implementing imaging techniques that are capable of monitoring progressive tissue loss in clinical trials and cohort studies into treatment algorithms for individual patients. This article reviews the current status of imaging research in MS and NMOSD with an emphasis on emerging modalities that have the potential to be implemented in clinical practice.

Keywords: magnetic resonance imaging; multiple sclerosis; neuroimaging; neuromyelitis optica spectrum disorders (NMOSD); optical coherence tomography.

Figure 1

Representative axial 3 T FLAIR-SWI images from individuals with (A) relapsing–remitting multiple sclerosis (RRMS; 28-year-old woman) and (B) AQP4-antibody-positive neuromyelitis optica spectrum disorder (AQP4+-NMOSD; 76-year-old woman). The central vein sign (red arrows) is present in the majority of MS lesions but not in white matter lesions in NMOSD. White boxes show magnified views of lesions in axial and sagittal plane. T, Tesla; FLAIR, fluid-attenuated inversion recovery; SWI, susceptibility-weighted imaging; RRMS, relapsing-remitting multiple sclerosis; AQP4-ab+, AQP4-antibody positive; NMOSD, neuromyelitis optica spectrum disorder.

Figure 2

MS-specific 7 T MR imaging markers displayed by T2*-weighted sequence. (A1) Lesions in relapsing-remitting MS commonly exhibit a central vein (red arrows). (A2) Hypointense rim structures (red arrow-heads) are prevalent in a subset of MS lesions. (A3) 7 T MRI allows for the delineation of gray matter lesions in great detail. (B1,B2) Central vein sign and hypointense rim structures are absent in lesions of AQP4+-NMOSD patients. (B3) Gray matter lesions are commonly absent in AQP4+-NMOSD. MS, multiple sclerosis; T, Tesla; FLAIR, fluid-attenuated inversion recovery; SWI, susceptibility-weighted imaging; RRMS, relapsing-remitting multiple sclerosis; AQP4-ab+, AQP4-antibody positive; NMOSD, neuromyelitis optica spectrum disorder. LGN, lateral geniculate nucleus; V1, primary visual cortex.

Figure 3

Diffusion-weighted imaging based probabilistic tractography allows for the delineation of the optic radiations displayed in (A1) sagittal and (A2) axial view. (B1) Diffusion tensor imaging (DTI) values along the optic radiation of an exemplary ON patient 3 years after attack (red) show decreased FA values compared to a healthy control (black) indicating trans-synaptic neurodegeneration after ON. (B2) MD values are pathologically increased in an exemplary ON patient almost throughout the entire course of the optic radiations compared to the exemplary healthy control. ON, optic neuritis; FA, fractional anisotropy; MD, mean diffusivity.

Figure 4

Representative T2-weighted spinal cord images from individuals. (A) Patient with relapsing–remitting multiple sclerosis (30-year-old woman) and MS-related myelitis and spinal cord imaging at (A1) 1 months, (A2) 2 months, (A3) 24 months, and (A4) 72 months after attack. Short extent (<3 segments) spinal cord lesion (red arrow) at C3 with typical morphology of MS-related myelitis. (B) Patient with AQP4-antibody-positive neuromyelitis optica spectrum disorder (36-year-old woman) and NMOSD-related LETM and spinal cord imaging at (B1) 2 months, (B2) 5 months, (B3) 12 months, and (B4) 60 months after attack. Spinal cord lesion (red arrows) with longitudinal morphology (C2-Th1; >3 segments) and subsequent atrophy (red arrow-heads) typical of NMOSD-related LETM. (C) Patient with MOG antibody associated disease (41-year-old woman) and MOGAD-related LETM and spinal cord imaging at (C1) 7 months, (C2) 8 months, (C3) 24 months, and (C4) 48 months after attack. Initial LETM (C3-C7; red arrows) with remarkable increase in length after relapse at month 8 (C2) (yellow arrows) and subsequent atrophy (red arrow-heads). RRMS, relapsing-remitting multiple sclerosis; AQP4-ab+, AQP4-antibody positive; NMOSD, neuromyelitis optica spectrum disorder; LETM, longitudinally-extensive transverse myelitis; MOGAD, myelin-oligodendrocyte-glycoprotein associated disease.

Figure 5

Representative OCT images from individuals with (A) relapsing–remitting multiple sclerosis with unilateral right-sided ON (RRMS; 41-year-old woman), (B) AQP4-antibody-positive neuromyelitis optica spectrum disorder with recurrent bilateral ON episodes (AQP4+-NMOSD; 25-year-old woman), and (C) MOG antibody associated disease with left-sided unilateral ON (MOGAD; 46-year-old man). OCT, optical coherence tomography; RRMS, relapsing-remitting multiple sclerosis; ON, optic neuritis; OD, right eye; OS, left eye; ILM, inner limiting membrane; RNFL, retinal nerve fiber layer; AQP4-ab+, AQP4-antibody positive; NMOSD, neuromyelitis optica spectrum disorder; MOGAD, myelin-oligodendrocyte-glycoprotein associated disease.