Differential diagnosis of neuromyelitis optica spectrum disorders

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system (CNS) mostly manifesting as optic neuritis and/or myelitis, which are frequently recurrent/bilateral or longitudinally extensive, respectively. As the autoantibody to aquaporin-4 (AQP4-Ab) can mediate the pathogenesis of NMOSD, testing for the AQP4-Ab in serum of patients can play a crucial role in diagnosing NMOSD. Nevertheless, the differential diagnosis of NMOSD in clinical practice is often challenging despite the phenotypical and serological characteristics of the disease because: (1) diverse diseases with autoimmune, vascular, infectious, or neoplastic etiologies can mimic these phenotypes of NMOSD; (2) patients with NMOSD may only have limited clinical manifestations, especially in their early disease stages; (3) test results for AQP4-Ab can be affected by several factors such as assay methods, serologic status, disease stages, or types of treatment; (4) some patients with NMOSD do not have AQP4-Ab; and (5) test results for the AQP4-Ab may not be readily available for the acute management of patients. Despite some similarity in their phenotypes, these NMOSD and NMOSD-mimics are distinct from each other in their pathogenesis, prognosis, and most importantly treatment. Understanding the detailed clinical, serological, radiological, and prognostic differences of these diseases will improve the proper management as well as diagnosis of patients.

Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans?

“…As vCJD macaques exhibit similar clinical signs and lesions as vCJD patients, one may assume at first that it will be also the case for atypical phenotypes. It is to note that the clinical signs exhibited by the macaques developing this myelopathy are evocative of certain human spinal cord diseases already described, including the rare flail arm syndrome of ALS [32,33], neuromyelitis optica (NMO) spectrum disorders [34], the recently described FOSMN [35] or necrotizing myelopathies [36]. However, the pathognomonic lesions of these aforementioned human spinal cord diseases under their classic forms are clearly distinct from the lesions that we observed in our myelopathic macaques, a priori infirming this comparison; nevertheless, the proportion of patients suffering from spinal cord diseases that are nowadays autopsied is very faint, and the diagnosis is thus mainly based on clinical and complementary examinations.…”

IL-2 and Mycobacterial Lipoarabinomannan as Targets of Immune Responses in Multiple Sclerosis Patients

“…In the initial disease phases, NMOSD presents similar symptoms to MS with the difference that the former involves immune-mediated demyelination and axonal damage targeting the AQP4 water channel predominantly contained within optic nerves and spinal cord, whereas the latter affects also the brain. As not all NMOSD patients develop anti-AQP4 Abs and false-positive results may be obtained in the case of other inflammatory diseases of the central nervous system (CNS) [28], the diseases are often mistakenly diagnosed and improperly treated, resulting in a rapid accumulation of disability. Therefore, patterns involving Abs against IL-2 and HERV-Wenv may be useful for an additional screening to confirm diagnostic outcomes based on standard criteria.…”

Primary central nervous system lymphoma with intramedullary spinal cord involvement mimicking inflammatory demyelinating disease

“…The patient was diagnosed with IDD of the CNS before confirmation of DLBCL on brain biopsy. PCNSL rarely mimics IDD, including MS, NMOSD, and acute transverse myelitis (TM) [6][7][8]. Both conditions can present with acute neurological signs of localized contrast-enhancing lesions in the CNS, with no detectable cause in a routine blood or CSF analysis [9].…”

“…In addition, involvement of the intramedullary spinal cord in PCNSL is uncommon and accounts for less than 1% of PCNSL cases [4][5][6]. Therefore, PCNSL involving the intramedullary spinal cord in a younger immunocompetent patient can be misdiagnosed as an inflammatory demyelinating disease (IDD) of the CNS, such as multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) [7,8]. Early diagnosis and treatment are important, as two-thirds of the immunocompetent PCNSL patients achieve complete response after treatment with methotrexate [2].…”