Pathological cerebrospinal fluid protein concentration and albumin quotient at relapse predicts short-term disability progression in multiple sclerosis: a retrospective single center observational study

Lara Diem; Maxine Bürge; Alexander Leichtle; Arsany Hakim; Andrew Chan; Anke Salmen; Maria-Eleptheria Evangelopoulos; Robert Hoepner

doi:10.1177/1756286420975909

Pathological cerebrospinal fluid protein concentration and albumin quotient at relapse predicts short-term disability progression in multiple sclerosis: a retrospective single center observational study

Ther Adv Neurol Disord. 2020 Dec 29:13:1756286420975909. doi: 10.1177/1756286420975909. eCollection 2020.

Authors

Lara Diem¹, Maxine Bürge², Alexander Leichtle³, Arsany Hakim⁴, Andrew Chan², Anke Salmen², Maria-Eleptheria Evangelopoulos², Robert Hoepner²

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, Bern, 3010, Switzerland.
² Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
³ University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁴ University Institute of Diagnostic and Interventional Neuroradiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.

Abstract

Background: Blood-brain barrier dysfunction in active multiple sclerosis (MS) lesions leads to pathological changes of cerebrospinal fluid (CSF). Theoretically, CSF analyses could help to predict relapse recovery and the course of disability. In this monocentric study, we investigated the impact of CSF findings assessed during the first relapse of MS on the short-term course of disability.

Methods: We performed a retrospective observational study including MS patients with available CSF data after onset of first MS relapse. Clinical symptoms had to be accompanied by gadolinium-enhanced lesion on magnetic resonance imaging. Expanded Disability Status Scale (EDSS) assessments at timepoint of relapse and after relapse recovery were studied to analyze disability. A two-step multivariate linear regression analysis adjusted for EDSS at spinal tab, duration of symptoms, sex, time until post relapse EDSS assessment, immunotherapy post relapse, and relapse treatment with glucocorticoids/plasma exchange to predict relapse associated disability was run.

Results: In the first step of the regression model, pathological albumin quotient (QAlb) [regression coefficient 0.50, 95% confidence interval (CI) (0.07-0.92), p = 0.02, n = 99] and CSF protein concentration [regression coefficient 0.84, 95% CI (0.33-1.35), p = 0.001, n = 99] predicted EDSS after relapse recovery. In the second step, the sum score of both predictors [range 0-2; n per value: 0 (n = 73), 1 (n = 10), 2 (n = 15)] confirmed the negative impact on course of disability after relapse [regression coefficient 0.38, 95% CI (0.13-0.62), p = 0.003, n = 98]. In this final multivariate linear regression model (p < 0.001; R ² 0.34), also EDSS at lumbar puncture [regression coefficient 0.58, 95% CI (0.35-0.81), p < 0.001, n = 98] and time between symptom onset and CSF evaluation [regression coefficient 0.03, 95% CI (0.006-0.048), p = 0.01, n = 98] forecast subsequent disability.

Discussion: Our study conducted in MS patients during first relapse confirmed that both increased CSF protein concentration and pathological QAlb have a negative impact on EDSS after relapse. As secondary finding, we identified time from symptom onset to lumbar puncture as predictor of disability recovery after relapse.

Keywords: EDSS; albumin quotient; cerebrospinal fluid; progression; protein.