White matter atrophy and cognitive dysfunctions in neuromyelitis optica

Abstract

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients, particularly in the WM.

Figure 1. White matter volume regional differences between the NMO group (n = 28) and the control group (n = 28) using VBM.

Note that the NMO group overall showed a decreased WM volume in the frontal and parietal lobes (including the superior longitudinal fascicle), corpus callosum, cerebellum, brainstem and optic chiasm compared to healthy control subjects. (P<0.05, false discovery rate, cluster size threshold >30 voxels).

Figure 2. Correlation between performance on PASAT 3 seconds and regional white matter volumes of 28 NMO patients, using VBM.

Note the correlations with corpus callosum and the pons. Statistical maps were thresholded without correction, with P value <0.001 and with a minimum cluster size of 30 voxels.

Figure 3. White matter volume regional differences between NMO patients with cognitive impairment (n = 15) and NMO patients without cognitive impairment (n = 13) using VBM.

Note that the NMO patients with cognitive impairment have a large decreased WM volume including brainstem, cerebellum, corticospinal tracts but also the important fascicles of the brain such as corpus callosum, superior longitudinal fascicle and inferior longitudinal fascicle. (P<0.05, false discovery rate, cluster size threshold >30 voxels). Sagittal view of the brain using xjview.