Necrotizing Myelopathy possibly related to the group defined as Neuromyelitis Optica Spectrum Disorders (NMOSD).
Our patient presented an acute, rapidly progressive myelitis involving both gray and white matter, with necrosis, macrophages and IgM deposits in lesion blood vessels extending over more than three vertebral segments. A coexisting old demyelinated plaque was also found in the cerebrum. Neither Optic neuritis nor NMO-IgG seropositivity was found.
Neuromyelitis Optica (NMO) is an infrequent autoimmune, inflammatory syndrome that affects the spinal cord and optic nerves causing Myelitis and Optic Neuritis. Lesional spectrum includes inflammatory, demyelinating or necrotic changes of white and gray matter, which can lead to visual loss and varying degrees of muscle weakness, among other clinical features. Many studies have shown that NMO has a relapsing course caused by attack to aquaporin-4 (AQP4), a water channel found astrocyte foot processes of the central nervous system at the level of the blood-brain barrier (6).
Definite clinical criteria for NMO diagnosis include presence of Acute Myelitis, Optic Neuritis, and at least two of the following: a) brain MRI not meeting diagnostic criteria for multiple sclerosis, b) contiguous spinal cord MRI lesion extending over ?3 vertebral segments, and/or c) NMO-IgG seropositive status (8). Early and accurate NMO diagnosis is important due to its rapid progression and poor prognosis in comparison to other myelopathies such as in Multiple Sclerosis (3, 8). Although this case did not present Optic Neuritis, thus precluding NMO diagnosis, absence of this finding may have been due to the short period of the clinical course (2). Our patient was seronegative for NMO-IgG, a feature that would separate the case from Neuromyelitis Optica or longitudinally extensive transverse myelitis with recurrent episodes. However, a certain number of seronegative NMO-IgG cases presenting clinical features of NMO have been described (7).
Most patients with NMO experience a relapsing course, in fact, in over 80% of cases, relapses of both Optic Neuritis and Myelitis will occur interspersed by intervals of months or years (1). Progression in NMO seems to be primarily related to relapsing frequency (10), although it has also been seen in long standing NMO cases with gradual progression, incomplete remission and cumulative neurologic disability (1).
Absence of brain lesions has recently been questioned as a necessary finding since the possibility of the presence of asymptomatic plaques (4, 6). Not only are asymptomatic brain lesions common in NMO, but also, when present, do not allow diagnosis to be ruled out entirely. Some patients with established NMO diagnosis presenting either asymptomatic or symptomatic brain lesions suggest current NMO diagnosis criteria should be revised (5). Imaging studies show mostly nonspecific lesions, some of which when located in the hypothalamus or brainstem may mimic typical Multiple Sclerosis (5).
Necrotizing Myelopathy can present as part of different conditions (i.e. ADEM, acute hemorrhagic leukoencephalopathy, paraneoplastic syndromes, etc) or in isolated fashion not related to other known concomitant diseases. It is characterized by recurrent, and in some cases gradual and progressive episodes. This raises the question as to whether these individuals may be suffering from a separate condition entirely, from a CNS manifestation of a systemic disease or from a variant of Multiple Sclerosis, or even from NMO (4).
Under histological examination, the tissue inflammation pattern found in these kinds of lesions includes extensive complement activation, sometimes with eosinophilia/neutrophil infiltration (4, 9) and vascular fibrosis in early active NMO. These lesions show co-localization with activated macrophages and C9 neo-antigen in perivascular regions associated with vascular hyalinization, suggesting CNS vasculature is an early and specific disease target. Ig deposits in these lesions are made up of IgM, and effectively fix complement, triggering myelin destruction, a process secondarily taken up by macrophages (4).
Although this patient did not present Optic Neuritis during his brief disease course and was seronegative for NMO-IgG; we believe that based on the fact that he presented Acute Myelitis, a contiguous spinal cord MRI lesion extending over ?3 vertebral segments, rapidly progressive clinical course with respiratory failure, characteristic spinal histopathology showing IgM blood vessel deposits, and an asymptomatic demyelinated plaque in the cerebrum, it is plausible to consider this case as possibly related to the disease group defined as Neuromyelitis Optica Spectrum Disorders (NMOSD) (3, 8) with negative NMO-IgG.
Contributed by Miguel A. Riudavets, MD; María Laura Tallone, MD; Jorge Correale, MD; Fernanda Díaz, MD; Gustavo Sevlever, MD, PhD