Cognitive impairment and whole brain diffusion in patients with neuromyelitis optica after acute relapse
Highlights
► We investigate cognitive functions in NMO patients without visible brain lesions during acute relapse. ► We examine relationships between cognition and brain FA and MD using voxel-based analysis and region-of-interest analysis. ► Impaired learning and memory, information processing speed and attention occur in NMO patients without visible brain lesions. ► The impairment in immediate and short-term memory may be due to information encoding deficits during information acquisition. ► The corpus callosum may have local microscopic damages that play a role in cognitive impairments during acute relapse.
Introduction
Neuromyelitis optica (NMO) is an acute or subacute inflammatory demyelinating disease of central nervous system (CNS), with simultaneous or sequential involvement of the optic nerve and spinal cord. Controversy on whether NMO is a subtype of multiple sclerosis (MS) or a different disease has persisted for years. However, various studies provide supporting evidence that they are different diseases (e.g. (Argyriou & Makris, 2008; Lennon et al., 2004)). Both diseases share pathological characteristics, as they both reflect demyelination in CNS. Currently, conventional magnetic resonance imaging (MRI) (T1-weighted images before and after gadolinium infusion and T2-weighted and fluid-attenuated inversion recovery (FLAIR) images) unveiled visible brain lesions in patients with NMO (Cabrera-Gómez et al., 2007, Li et al., 2008). These findings support one of supportive criteria in the current diagnostic criteria for NMO, CNS involvement beyond the optic nerves and spinal cord is compatible with NMO, but onset brain MRI non-diagnostic for multiple sclerosis (Wingerchuk, Lennon, Pittock, Lucchinetti, & Weinshenker, 2006).
Although brain abnormalities in patients with NMO have been observed through imaging, whether they can result in cognitive impairment remains largely unknown. Significantly lower test scores in attention, information processing speed and memory have been reported in NMO patients, including some NMO patients with visible brain lesions observed on MRI (Blanc et al., 2008). It is still not clear whether NMO patients without visible lesions on conventional brain MRI have cognitive impairment. In recent years, microscopic damages in white matter connected to the spinal white matter tracts or the optic nerve of NMO patients without visible lesions on conventional brain MRI were observed on diffusion tensor imaging (DTI) (Lin et al., 2007, Yu et al., 2006, Yu et al., 2008). It was also found that there may be microscopic damages in normal-appearing brain tissues (NABT) on conventional brain MRI in NMO patients (Rocca et al., 2004, Yu et al., 2006). Considering that cognitive impairment in MS patients may occur at the early stages of the disease, even during the clinical isolated syndrome (CIS) (Feuillet et al., 2007, Potagas et al., 2008) and the radiologically isolated syndrome (RIS) (Lebrun, Blanc, Brassat, Zephir, & de Seze, 2010), we speculated that NMO patients without visible lesions on conventional brain MRI may also have cognitive impairments and the cause may be the microscopic damages in some regions of the brain. In the present study, we recruited NMO patients during acute relapse based on the current diagnostic criteria for NMO but excluded those patients with visible lesions on conventional brain MRI. We investigated the cognitive functions in NMO patients without visible lesions on conventional brain MRI and their relationships to fractional anisotropy (FA) and mean diffusivity (MD) using voxel-based analysis. This study may contribute to discover the early cognitive impairments and their neuropathological mechanisms in NMO patients during acute relapse.
Section snippets
Subjects
The inclusion criteria of this study were: (1) standard for the clinical diagnosis established by Wingerchuck et al. in 2006 (Wingerchuk et al., 2006); (2) age between 18 and 60 years, regardless of gender; (3) no corticosteroid and other immunosuppressants therapy in the last 8 weeks; (4) during an acute relapse. A relapse was defined as the development of new neurological symptoms or abrupt deterioration of existing symptoms lasting more than 24 h within the past 6 weeks; (5) no limit on duration
Differences in cognitive tests
The main demographic, clinical results of both groups are presented in Table 1. The results of the cognitive tests are summarized in Table 2. Patients with NMO showed significant differences compared with normal controls for the following tests scores after Bonferonni’s correction: Short-Delay Free Recall (SDFR) (P = 0.003), Short-Delay Cued Recall (SDCR) (P = 0.006) on the CVLT-II, the DST-backward (P < 0.001), the SDMT (P = 0.001), the 3-s PASAT (P = 0.002). We did not find significant differences
Discussion
In our study, we found that NMO patients without visible lesions on conventional brain MRI had impaired learning, memory, information processing speed, and attention compared with normal control subjects. The cognitive test scores were significantly correlated with FA and MD values in the local area of the corpus callosum, ACC, and MFC, particularly in the corpus callosum. A significant decrease in FA and MD values in different regions of the corpus callosum, such as the GCC, SCC, and BCC, was
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