Absence of cortical demyelination in neuromyelitis optica

Abstract

Objective: To asses the presence of cortical demyelination in brains of patients with neuromyelitis optica (NMO). NMO is an autoimmune inflammatory demyelinating disease that specifically targets aquaporin-4-rich regions of the CNS. Since aquaporin-4 is highly expressed in normal cortex, we anticipated that cortical demyelination may occur in NMO.Methods: This is a cross-sectional neuropathologic study performed on archival forebrain and cerebellar tissue sections from 19 autopsied patients with a clinically and/or pathologically confirmed NMO spectrum disorder.Results: Detailed immunohistochemical analyses of 19 archival NMO cases revealed preservation of aquaporin-4 in a normal distribution within cerebral and cerebellar cortices, and no evidence of cortical demyelination. Conclusions:This study provides a plausible explanation for the absence of a secondary progressive clinical course in NMO and shows that cognitive and cortical neuroimaging abnormalities previously reported in NMO cannot be attributed to cortical demyelination. Lack of cortical demyelination is another characteristic that further distinguishes NMO from MS. Neurology Neuromyelitis optica (NMO) is an autoimmune inflammatory demyelinating relapsing disease of the CNS in which a disease-specific circulating autoantibody (NMO-immunoglobulin G [IgG]) binds to the aquaporin-4 (AQP4) water channel that is concentrated in the astrocytic foot processes.1-3 Increasing evidence supports a primary pathogenic role for this IgG. 4-6 Clinical, laboratory, neuroimaging, and pathologic features distinguish NMO from classic multiple sclerosis (MS). 7,8 Cognitive deficits and neuroimaging abnormalities have been described in normalappearing gray matter in NMO.9,10 Since AQP4 is heavily expressed in normal human cortex, 7,11 we anticipated finding cortical pathology in NMO. This study describes our findings from a systematic examination of NMO patients' brains for evidence of cortical demyelination.METHODS This cross-sectional neuropathologic study was performed on archival forebrain and cerebellar tissue obtained from 19 autopsied patients with a clinically and/or pathologically confirmed NMO spectrum disorder (NMOSD) 8 : NMO (n ϭ 16) or NMOSD (n ϭ 3; 2 relapsing longitudinally extensive transverse myelitis, 1 relapsing optic neuritis). Autopsies were performed at Mayo Clinic, Rochester, MN, or sent in from other institutions for diagnostic purposes between 1958 and 2009. The study was approved by the Institutional Review Board of Mayo Clinic, Rochester, MN. Clinical follow-up was obtained via review of medical records. Descriptive statistics were used to characterize the population demographics and number of blocks analyzed (table). Median age was 45 years at symptom onset (range 12-80) and 50 years at death (range 16 -80). Median disease duration was 36 months (range 8 -180). NMO-IgG serostatus was known in 6 cases (positive in 5, including all 3 NMOSD cases). Causes of death were

Olfactory dysfunction in neuromyelitis optica spectrum disorders

“…Accordingly, we inferred that atrophy might emerge in olfactory-related cerebral regions, accompanied by other cerebral regions, thereby contributing to olfactory dysfunction. Filippi et al [29] pointed that retrograde degeneration of neurons secondary to spinal cord and optic nerve lesions or GM lesions might be the reasons of normal-appearing GM damage in patients with NMO, and though no pathological findings supported cortical demyelination in NMOSD [4], Saji et al [30] concluded that the pathological process of cortical neurodegeneration contributed to cognitive impairment in NMOSDs, in line with the present imaging results. Brain Values are mean (SD) unless otherwise indicated.…”

“…Lesions present as a mirrored distribution of AQP-4, particularly adjacent to the ventricles [3]. Unlike in multiple sclerosis (MS), cortical lesions have not yet been detected in pathological and 7-T magnetic resonance imaging (MRI) studies on NMOSDs [4,5]. The characteristics of these lesions are distinctive in MS, which typically involves periventricular, juxtacortical, and infratentorial regions [6].…”

Gray Matter Volume Reduction Is Associated with Cognitive Impairment in Neuromyelitis Optica

“…This assertion is consistent with the findings of a pathologic study that failed to detect cortical changes that reflected axonal degeneration in patients with NMO. 32 Consequently, the primary neurodegenerative processes (neuronal loss) may at least partially account for the GMV reductions in patients with NMO. This hypothesis is confirmed by the results of a pathologic study that revealed a substantial cortical neuronal loss in NMO spectrum disorders.…”

A research update on the potential roles of aquaporin 4 in neuroinflammation

“…Cognitive dysfunction is found in approximately 30 % of pediatric MS children and adolescents [33]. In accordance with Popescu et al [24], it can be proposed that cortical demyelination only appears in MS, instead of NMO, and cognitive changes are correlated to cortical atrophy in MS, but not in NMO [34]. An EAE model is used to mimic MS pathophysiology.…”

“…The presence of anti-AQP4 IgG remains a powerful and useful differential diagnostic tool in daily clinical practice [23], although it remains a question whether the presence of the autoantibody against AQP4 is the cause of the disease or a collateral consequence of some secondary pathological mechanism. Popescu et al [24] provided a plausible explanation for the absence of a secondary progressive clinical course in NMO; they showed that cognitive and cortical neuroimaging abnormalities previously reported in NMO cannot be attributed to cortical demyelination. They suggested that the lack of cortical demyelination is another characteristic that further distinguishes NMO from MS.…”