Cognitive and White Matter Tract Differences in MS and Diffuse Neuropsychiatric Systemic Lupus Erythematosus

B. Cesar; M.G. Dwyer; J.L. Shucard; P. Polak; N. Bergsland; R.H.B. Benedict; B. Weinstock-Guttman; D.W. Shucard; R. Zivadinov

doi:10.3174/ajnr.A4354

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Fig 1.
A comparison of lesion attenuation along WM tracts in patients with MS and those with NPSLE by using TBSS analysis. Red-highlighted areas show where patients with MS had significantly greater lesion attenuation than patients with NPSLE (P < .05). Patients with MS have significant lesion attenuation as shown in the left superior corona radiata and a small portion of the right posterior corona radiata.
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Fig 2.
Diffusion tensor imaging TBSS differences among patients with MS, patients with NPSLE with diffuse syndromes, and HCs, controlling for age and sex. The results are shown for FA, MD, RD, and AD differences between the studied groups (P < .05). Red-highlighted areas show where significantly lower FA was found in the second reported group, indicating less anisotropic diffusion. Blue-highlighted areas show significantly increased diffusivity in the second reported group, indicating more diffuse WM damage.
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Fig 3.
Details of TBSS FA comparison between patients with MS and those with NPSLE with diffuse syndromes. Red areas show where FA is significantly lower in patients with MS compared with patients with NPSLE in central white matter pathways, including the corpus callosum, inferior longitudinal fasciculus, and fronto-occipital fasciculus (P < .05).
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Fig 4.
Highlighted tracts display significant correlations between TBSS differences and performance on neuropsychological tests (P < .05). Red-highlighted tracts represent positive correlations, and blue-highlighted tracts represent negative correlations. For patients with MS, decreased neuropsychological scores significantly correlated with decreased FA and increased MD for each of the neuropsychological tests. For patients with NPSLE, decreased Delis-Kaplan Executive Function System scores significantly correlated with decreased FA. For HCs, increased PASAT scores correlated significantly with decreased MD. CVLT2 indicates California Verbal Learning Test, 2nd ed; BVMT-R, Brief Visuospatial Memory Test-Revised; D-KEFS, Delis-Kaplan Executive Function System; SDMT, Symbol Digit Modalities Test; dNPSLE, neuropsychiatric systemic lupus erythematosus with diffuse syndromes.

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Table 1:

Demographic and clinical characteristics of the study groups^{^a}

	MS (n = 30)	dNPSLE (n = 23)	HC (n = 43)	P Value^{^b}
Female sex (No.) (%)	23 (76.5%)	22 (95.7)	37 (86.0)	.150
Age (yr) (mean) (SD)	43.8 (8.6)	48.9 (12.5)	44.7 (9.8)	.170
Disease duration (yr) (mean) (SD)	11.7 (8)	15 (9.6)	NA	.237
SLAM checklist (mean) (SD)	NA	9.9 (4.9)	NA	NA
EDSS (median) (IQR)	3.3 (2.1–6.0)	NA	NA	NA

Note:—NA indicates not applicable; dNPSLE, neuropsychiatric systemic lupus erythematosus with diffuse syndromes; SLAM, systemic lupus activity measure; EDSS, Expanded Disability Status Scale; IQR, interquartile range.
↵a Disease-modifying medications for treatment of MS included interferon β (n = 18). natalizumab (n = 8), and glatiramer acetate (n = 4). Other treatment included antianxiety (dNPSLE, n = 2; MS, n = 0), antiepileptic (dNPSLE, n = 0; MS, n = 5), antidepressants (dNPSLE, n = 10: MS, n = 11), antifatigue (dNPSLE, n = 0; MS, n = 4), antispastic (dNPSLE, n = 0; MS, n = 8), antiparesthesia (dNPSLE, n = 0; MS, n = 8), hydroxychloroquine (Plaquenil) (dNPSLE, n = 21), imuran (dNPSLE, n = 4), immunosuppressive (dNPSLE, n = 21; MS, n = 5), steroids or nonsteroidal antiinflammatory drugs (dNPSLE, n = 17; MS n = 1).
↵b The χ² test was used to evaluate significant differences in sex distribution among the groups, and analysis of variance was used to evaluate significant differences in age and disease duration.

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Table 2:

Comparison of subject groups on neuropsychological measures^{^a}

	MS (Mean) (SD)	dNPSLE (Mean) (SD)	HC (Mean) (SD)	ANOVA (P Value)	MS vs HC (P Value)	dNPSLE vs HC (P Value)	MS vs dNPSLE (P Value)
SDMT	54.6 (16.1)	54.8 (10.3)	60.7 (10.4)	.091	.137	.373	1.0
CVLT2	49.3 (12.3)	50.35 (9.7)	57.9 (7.9)	.001	.003	.009	1.0
BVMT-R	21.7 (7.4)	24.3 (6.9)	26.9 (5.7)	.005	.004	.571	.359
D-KEFS	9.2 (2.8)	10.3 (2.6)	119 (2.2)	.011	.010	.252	.722
PASAT	41.6 (16)	42 (12.3)	48.3 (12.3)	.061	.111	.226	1.0

Note:—CVLT2 indicates California Verbal Learning Test, 2nd ed; BVMT-R, Brief Visuospatial Memory Test–Revised; D-KEFS, Delis-Kaplan Executive Function System; SDMT, Symbol Digit Modalities Test; dNPSLE, neuropsychiatric systemic lupus erythematosus with diffuse syndromes.
↵a Reported measures are raw scores. The statistical analysis among the groups was performed using 1-way analysis of covariance, adjusted for age and sex. Post hoc tests between the individual groups were performed using a Bonferroni correction.

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Table 3:

Comparison of conventional MRI characteristics among the study groups^{^a}

	MS (n = 30)	dNPSLE (n = 23)	HC (n = 43)	MS vs HCs^{^b} (P Value)	dNPSLE vs HCS^{^c} (P Value)	MS vs dNPSLE^{^d} (P Value)
T2 lesion number (mean) (SD)	31.1 (19.2)	11.7 (9.3)	7.9 (4.8)	<.0001	.06	<.0001
T2 lesion volume (mean) (SD)	15.2 (3.1)	1.9 (1.3)	1.6 (.4)	<.0001	.023	<.0001
Normalized WB volume (mean) (SD)	1490.4 (113.5)	1570.3 (79)	1596.5 (64.2)	<.0001	.465	.003
Normalized WM volume (mean) (SD)	784.5 (58.0)	829.3 (45.1)	849.0 (40.8)	<.0001	.285	.005
Normalized GM volume (mean) (SD)	704.0 (63.9)	751.5 (58.8)	755.3 (42)	.001	.964	.008

Note:—WB indicates whole-brain; dNPSLE, neuropsychiatric systemic lupus erythematosus with diffuse syndromes.
↵a The statistical analysis among the groups was performed using 1-way analysis of variance with post hoc Tukey correction, except for the T2 lesion number and volume, which were analyzed using the Mann-Whitney U test. All volumes are given in milliliters.
↵b P value for MS vs HCs.
↵c P value for SLE vs HCs.
↵d P value for MS vs SLE.

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Table 4:

Comparison of global white matter diffusion tensor imaging characteristics among the study groups^{^a}

	MS	dNPSLE	HC	MS vs HCs^{^b}	dNPSLE vs HCs^{^c}	MS vs dNPSLE^{^d}
FA (mean) (SD)	.398 (.006)	.411 (.004)	.418 (.002)	.001	.112	.310
MD × 10⁻³ (mean) (SD)	.786 (.009)	.775 (.008)	.734 (.008)	<.0001	.001	.780
AD × 10⁻³ (mean) (SD)	1.149 (.010)	1.150 (.012)	1.096 (.013)	.006	.003	.784
RD × 10⁻³ (mean) (SD)	.604 (.01)	.587 (.006)	.553 (.006)	<.0001	<.0001	.528

Note:—dNPSLE indicates neuropsychiatric systemic lupus erythematosus with diffuse syndromes.
↵a The statistical analysis between the groups was performed using 1-way analysis of variance controlling for age and sex. FA is a dimensionless measure. Diffusivity is given in square millimeters second⁻¹.
↵b P value for MS vs HCs.
↵c P value for SLE vs HCs.
↵d P value for MS vs SLE.