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Markedly Elevated Soluble Intercellular Adhesion Molecule 1, Soluble Vascular Cell Adhesion Molecule 1 Levels, and Blood-Brain Barrier Breakdown in Neuromyelitis Optica

Akiyuki Uzawa, MD; Masahiro Mori, MD, PhD; Saeko Masuda, MD; Satoshi Kuwabara, MD, PhD
Arch Neurol. 2011;68(7):913-917. doi:10.1001/archneurol.2011.148.
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Objective To evaluate the degree of blood-brain barrier disruption in patients with neuromyelitis optica (NMO) and to clarify whether the levels of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) in patients with NMO can be useful biomarkers for blood-brain barrier breakdown.

Design Descriptive historical cohort.

Setting Department of Neurology, Graduate School of Medicine, Chiba University.

Patients The levels of sICAM-1 and sVCAM-1 in 25 patients with NMO, 21 patients with multiple sclerosis, and 20 patients with other noninflammatory neurologic disorders in the serum and cerebrospinal fluid (CSF) were measured using a multiplexed fluorescent magnetic bead–based immunoassay.

Main Outcome Measures Levels of the soluble adhesion molecules in serum and CSF and their associations with blood-brain barrier disruption.

Results The CSF levels of sICAM-1 and sVCAM-1 increased in patients with NMO compared with patients with multiple sclerosis and other noninflammatory neurologic disorders (P < .001), and serum levels of sICAM-1 increased in patients with NMO compared with healthy control individuals (P = .003). The CSF sICAM-1 levels from patients with NMO were correlated with the albumin quotient (P = .02) and the presence of lesions detected via gadolinium-enhanced magnetic resonance imaging.

Conclusions Severe blood-brain barrier breakdown occurs in patients with NMO. Measuring adhesion molecules is useful to evaluate this barrier disruption.

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Figure 1. Soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) levels in cerebrospinal fluid (CSF) and serum. Measurements were obtained from 25 patients with neuromyelitis optica (NMO), 21 with multiple sclerosis (MS), 20 with other noninflammatory neurologic disorders (ONNDs), and 17 healthy control individuals (HCs). Dashed lines indicate the mean levels in each group. The levels of CSF sICAM-1 and sVCAM-1 were higher in patients with NMO than in those with MS or ONNDs (P < .001). The serum levels of sICAM-1 were higher in patients with NMO (P = .003) and ONNDs (P = .007) than those of HCs. * P < .001; ** P < .01.

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Figure 2. Correlations of soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) levels with clinical variables in patients with neuromyelitis optica (NMO). A-C: Correlations between the cerebrospinal fluid (CSF) sICAM-1 levels and albumin quotient (n = 15) (A), CSF cell counts (n = 25) (B), and CSF protein levels (n = 25) (C) in patients with NMO. D-F: Correlations between the CSF sVCAM-1 levels and albumin quotient (D), CSF cell counts (E), and CSF protein levels (F) in patients with NMO.

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Figure 3. Cerebrospinal fluid (CSF) soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) levels in patients with neuromyelitis optica (NMO) with or without lesions detected via gadolinium-enhanced magnetic resonance imaging (GdMRI). The CSF sICAM-1 (A) and sVCAM-1 (B) levels in patients with NMO with lesions (n = 14) and without lesions (n = 4) detected via GdMRI. Solid lines indicate the median levels in each group; bars, minimum and maximum values.

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