Increasing role of imaging in differentiating MS from non-MS and defining indeterminate borderline cases

Abstract

Multiple sclerosis (MS) is a heterogenous condition with differences between patients regarding disease presentation, imaging features, disease activity, prognosis and treatment responses. Following the discovery of new biomarkers, the concept of MS has evolved, with syndromes previously considered to be its variants now recognised as separate entities, including aquaporin-4 (AQP4)-antibody (Ab) neuromyelits optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-Ab disease (MOGAD). In line with their distinct pathology, the newly emerging conditions have imaging characteristics which are dissimilar to typical MS. Progress in reclassifying such demyelinating CNS conditions has highlighted the challenge in meaningful categorisation of atypical presentations at the borders of MS, such as antibody-negative neuromyelitis optica-like syndromes, tumefactive demyelinating lesions, or Balo's concentric sclerosis.In this review, we discuss the increasing role of imaging in distinguishing MS from non-MS CNS inflammatory/demyelinating conditions and defining undetermined borderline cases. This progress relies both on better characterisation of imaging features of these conditions on conventional imaging in terms of their appearance and location, as well as on the implementation of novel image acquisition and/or post-processing techniques allowing for more in-depth lesion assessment, including the presence of a central vein sign or paramagnetic rim.

Relapsing antibody-negative patients with features of neuromyelitis optica spectrum disorders: Differences in N-acetylaspartate level in the cervical spinal cord indicate distinct underlying processes

“…Antibody-negative patients with NMOSD features, 1 including bilateral simultaneous optic neuritis, recurrent isolated optic neurits, LETM, NMOSD-like brain lesions or absence of ovoid well-demarcated periventricular brain lesions, are among the most challenging to diagnose in neuroimmunology clinics as they might have atypical MS or ‘true’ NMOSD mediated by yet undiscovered antibodies. 4,17,18 Given the recent progress in the therapy of inflammatory/demyelinating diseases, characterisation of the antibody-negative overlap cohort is of crucial importance for disability prevention; however, the group has been largely understudied so far due to lack of biomarkers, difficulties in categorisation and the risk of erroneous diagnosis. We have recently implemented an unsupervised clustering approach and identified four hidden subgroups, which likely differ concerning the underlying disease process as suggested by differences in quantitative imaging parameters not used for subgroup identification.…”

MRI to differentiate multiple sclerosis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease

“…Overall, typical NMOSD lesions are extremely uncommon in MS and their presence should drive away the diagnosis of MS. Interestingly, some of these typical NMOSD lesions might be found in MOGAD (although not typically) and it could be associated with the route of entry of antibodies into the CNS, although their formation is not fully understood. 64 Therefore, typical NMOSD lesions should be promptly recognized in order to establish early diagnosis of NMOSD, thus making it possible to implement aggressive initial treatment and timely preventive longterm treatment to decrease further disability. 12…”

Diagnostic pitfalls in neuromyelitis optica spectrum disorders

“…N euromyelitis optica spectrum disorders (NMOsd), previously known as Devic disease, are autoimmune inflammatory disorders of the central nervous system (CNS) associated with astrocytic pathology, severe demyelination and axonal damage, classically characterised by optic neuritis (ON) and transverse myelitis attacks as well as seropositivity for antibodies against aquaporin 4 (AQP4-IgG) in the majority of cases (Wingerchuk, 2010;Wingerchuk et al, 2007). Despite distinct pathogenesis, clinical course, laboratory and magnetic resonance imaging (MRI) findings, in clinical practice NMOsd, particularly AQP4-IgG seronegative, may by confounded with multiple sclerosis (MS) and other CNS demyelinating diseases, or mimic their clinical features (Juryńczyk et al, 2021;Kim et al, 2017). The differences between NMOsd and other causes of CNS demyelination as well as the risk of misdiagnoses became a subject of various publications.…”