Defining active progressive multiple sclerosis

Finn Sellebjerg; Lars Börnsen; Cecilie Ammitzbøll; Jørgen Erik Nielsen; Tua Vinther-Jensen; Lena Elisabeth Hjermind; Marina von Essen; Rikke Lenhard Ratzer; Per Soelberg Sørensen; Jeppe Romme Christensen

doi:10.1177/1352458517726592

Defining active progressive multiple sclerosis

Finn Sellebjerg, Lars Börnsen, Cecilie Ammitzbøll, Jørgen Erik Nielsen, Tua Vinther-Jensen, Lena Elisabeth Hjermind, Marina von Essen, Rikke Lenhard Ratzer, Per Soelberg Sørensen, Jeppe Romme Christensen

Department of Clinical Medicine

14 Citations (Scopus)

Abstract

BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS).

OBJECTIVE: To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria.

METHODS: Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary ( n = 26) and secondary progressive MS ( n = 26) and healthy controls ( n = 24).

RESULTS: Progressive MS patients had higher CSF cell counts, IgG-index, CHI3L1, MMP-9, CXCL13, NFL and MBP concentrations. Active patients were younger and had higher NFL, CXCL13 and MMP-9 concentrations than inactive patients. Patients with active disease according to consensus criteria or detectable CXCL13 or MMP-9 in CSF were defined as having combined active progressive MS. These patients had increased CSF cell counts, IgG-index and MBP, NFL and CHI3L1 concentrations. Combined inactive patients only had increased IgG-index and MBP concentrations.

CONCLUSION: Patients with combined active progressive MS show evidence of inflammation, demyelination and neuronal/axonal damage, whereas the remaining patients mainly show evidence of active demyelination. This challenges the idea that neurodegeneration independent of inflammation is crucial in disease progression.

Original language	English
Journal	Multiple Sclerosis
Volume	23
Issue number	13
Pages (from-to)	1727-1735
ISSN	1352-4585
DOIs	https://doi.org/10.1177/1352458517726592
Publication status	Published - 1 Nov 2017

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title = "Defining active progressive multiple sclerosis",

abstract = "BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS).OBJECTIVE: To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria.METHODS: Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary ( n = 26) and secondary progressive MS ( n = 26) and healthy controls ( n = 24).RESULTS: Progressive MS patients had higher CSF cell counts, IgG-index, CHI3L1, MMP-9, CXCL13, NFL and MBP concentrations. Active patients were younger and had higher NFL, CXCL13 and MMP-9 concentrations than inactive patients. Patients with active disease according to consensus criteria or detectable CXCL13 or MMP-9 in CSF were defined as having combined active progressive MS. These patients had increased CSF cell counts, IgG-index and MBP, NFL and CHI3L1 concentrations. Combined inactive patients only had increased IgG-index and MBP concentrations.CONCLUSION: Patients with combined active progressive MS show evidence of inflammation, demyelination and neuronal/axonal damage, whereas the remaining patients mainly show evidence of active demyelination. This challenges the idea that neurodegeneration independent of inflammation is crucial in disease progression.",

author = "Finn Sellebjerg and Lars B{\"o}rnsen and Cecilie Ammitzb{\o}ll and Nielsen, {J{\o}rgen Erik} and Tua Vinther-Jensen and Hjermind, {Lena Elisabeth} and {von Essen}, Marina and Ratzer, {Rikke Lenhard} and {Soelberg S{\o}rensen}, Per and {Romme Christensen}, Jeppe",

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doi = "10.1177/1352458517726592",

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T1 - Defining active progressive multiple sclerosis

AU - Sellebjerg, Finn

AU - Börnsen, Lars

AU - Ammitzbøll, Cecilie

AU - Nielsen, Jørgen Erik

AU - Vinther-Jensen, Tua

AU - Hjermind, Lena Elisabeth

AU - von Essen, Marina

AU - Ratzer, Rikke Lenhard

AU - Soelberg Sørensen, Per

AU - Romme Christensen, Jeppe

PY - 2017/11/1

Y1 - 2017/11/1

N2 - BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS).OBJECTIVE: To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria.METHODS: Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary ( n = 26) and secondary progressive MS ( n = 26) and healthy controls ( n = 24).RESULTS: Progressive MS patients had higher CSF cell counts, IgG-index, CHI3L1, MMP-9, CXCL13, NFL and MBP concentrations. Active patients were younger and had higher NFL, CXCL13 and MMP-9 concentrations than inactive patients. Patients with active disease according to consensus criteria or detectable CXCL13 or MMP-9 in CSF were defined as having combined active progressive MS. These patients had increased CSF cell counts, IgG-index and MBP, NFL and CHI3L1 concentrations. Combined inactive patients only had increased IgG-index and MBP concentrations.CONCLUSION: Patients with combined active progressive MS show evidence of inflammation, demyelination and neuronal/axonal damage, whereas the remaining patients mainly show evidence of active demyelination. This challenges the idea that neurodegeneration independent of inflammation is crucial in disease progression.

AB - BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS).OBJECTIVE: To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria.METHODS: Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary ( n = 26) and secondary progressive MS ( n = 26) and healthy controls ( n = 24).RESULTS: Progressive MS patients had higher CSF cell counts, IgG-index, CHI3L1, MMP-9, CXCL13, NFL and MBP concentrations. Active patients were younger and had higher NFL, CXCL13 and MMP-9 concentrations than inactive patients. Patients with active disease according to consensus criteria or detectable CXCL13 or MMP-9 in CSF were defined as having combined active progressive MS. These patients had increased CSF cell counts, IgG-index and MBP, NFL and CHI3L1 concentrations. Combined inactive patients only had increased IgG-index and MBP concentrations.CONCLUSION: Patients with combined active progressive MS show evidence of inflammation, demyelination and neuronal/axonal damage, whereas the remaining patients mainly show evidence of active demyelination. This challenges the idea that neurodegeneration independent of inflammation is crucial in disease progression.

U2 - 10.1177/1352458517726592

DO - 10.1177/1352458517726592

M3 - Journal article

C2 - 28831853

SN - 1352-4585

VL - 23

SP - 1727

EP - 1735

JO - Multiple Sclerosis Journal

JF - Multiple Sclerosis Journal

IS - 13

ER -

Defining active progressive multiple sclerosis

Abstract

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