Myelitis features and outcomes in CNS demyelinating disorders: Comparison between multiple sclerosis, MOGAD, and AQP4-IgG-positive NMOSD

Abstract

Inflammatory myelopathies can manifest with a combination of motor, sensory and autonomic dysfunction of variable severity. Depending on the underlying etiology, the episodes of myelitis can recur, often leading to irreversible spinal cord damage and major long-term disability. Three main demyelinating disorders of the central nervous system, namely multiple sclerosis (MS), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4+NMOSD) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD), can induce spinal cord inflammation through different pathogenic mechanisms, resulting in a more or less profound disruption of spinal cord integrity. This ultimately translates into distinctive clinical-MRI features, as well as distinct patterns of disability accrual, with a step-wise worsening of neurological function in MOGAD and AQP4+NMOSD, and progressive disability accrual in MS. Early recognition of the specific etiologies of demyelinating myelitis and initiation of the appropriate treatment is crucial to improve outcome. In this review article we summarize and compare the clinical and imaging features of spinal cord involvement in these three demyelinating disorders, both during the acute phase and over time, and outline the current knowledge on the expected patterns of disability accrual and outcomes. We also discuss the potential implications of these observations for patient management and counseling.

Non‐demyelinating disorders mimicking and misdiagnosed asNMOSD:a literature review

“…MOGAD frequently has overlapping manifestations with NMOSD and represents a major differential diagnosis. MS typically presents with different clinical-MRI features in adults (e.g., less severe clinical attacks, short myelitis lesions on MRI) and is less likely to be misdiagnosed as NMOSD [5,[7][8][9]14].…”

“…However, MS patients may sometimes show preferential involvement of optic nerves and spinal cord, or multiple contiguous myelitis lesions that can resemble a longitudinally extensive lesion on MRI, that can mimic NMOSD [15]. The distinction may also be challenging in children with MS, in whom longitudinally extensive myelitis is more common than adults [9]. Once MS and MOGAD have been ruled out, we highlight a wide spectrum of rarer, non-demyelinating alternative diagnoses that are liable to be overlooked by clinicians (Table 2).…”

“…We included patients with alternative neurologic disorders reported as NMOSD mimics or misdiagnosed as NMOSD during the diagnostic work-up. We excluded cases of MS or MOGAD misdiagnosed as NMOSD because these represent entities that are already well-established as differential diagnoses in clinical practice [5,[7][8][9]. We also excluded cases with uncertain or poorly defined final diagnoses, as well as articles predating the discovery of AQP4-IgG [10].…”

“…Previous studies have suggested that patients with NMOSD are often misdiagnosed as having multiple sclerosis (MS) or other disorders [2][3][4][5], but only a few studies, other than case reports, have investigated what disorders are mistaken for NMOSD [6]. While MS and MOG-IgG-associated disease (MOGAD) represent the main differential diagnoses for NMOSD in clinical practice, and several studies have highlighted clinical-MRI differences between these three entities [7][8][9], non-demyelinating disorders that can mimic NMOSD are rare and likely underrecognized, which may lead to them being incorrectly diagnosed as seronegative NMOSD. We herein describe the main characteristics of non-demyelinating mimics of NMOSD reported in the literature, and highlight red flags that may help prevent misdiagnosis.…”

Upregulation of C-X-C motif chemokine 12 in the spinal cord alleviated the symptoms of experimental autoimmune encephalomyelitis in Lewis rats

“…As a common manifestation of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSDs), inflammatory demyelination make an important contribution to disability in the patients with demyelinating disorders ( Kearney et al, 2015 ; Ciccarelli et al, 2019 ; Fadda et al, 2022 ). Chemokines are considered to be essential mediators that are secreted by many kinds of cells to activate G protein-mediated signaling pathways ( Krumbholz et al, 2006 ; Huynh et al, 2020 ).…”