Axonal damage accumulates in the progressive phase of multiple sclerosis: Three year follow up study

A. Petzold, M.J. Eikelenboom, G. Keir, D.J. Grant, R.H.C. Lazeron, C.H. Polman, B.M.J. Uitdehaag, E.J. Thompson, G. Giovannoni

Research output: Contribution to journalArticleAcademicpeer-review

94 Citations (Scopus)

Abstract

Background: Neurofilament phosphoforms (Nf) are principal components of the axoskeleton released during axonal injury. Cerebrospinal fluid (CSF) levels of Nf phosphoforms might be useful surrogate markers for disability in multiple sclerosis (MS), aid in distinguishing clinical subtypes, and provide valuable prognostic information. Method: Thirty four patients with MS were included in a three year follow up study along with 318 controls with other non-inflammatory neurological diseases. CSF levels of two Nf heavy chain (NfH) phosphoforms (NfHSM135, NfHSM134) were quantified at baseline and three year follow up using new ELISA techniques. Levels of NfH phosphoforms, the degree of phosphorylation (NfHSM134:NfHSM135 ratio), and changes in NfH levels between baseline and follow up (ΔNfH) were related to the clinical phenotype (RR or SP/PP), to three clinical scales (Kurtzke's EDSS, ambulation index (AI), and nine hole peg test (9HPT)), and to progression of disability. Results: A significantly higher proportion (59%) of patients with SP/PPMS experienced an increase in NfHSM135 levels between baseline and follow up compared with those with RRMS (14%, pSM134 levels at baseline were higher in patients with SP/PP (11 pg/ml) compared with RR (7 pg/ml, pSM135 levels were higher at follow up in SP/PP (129 pg/ml) compared with levels below assay sensitivity in RR (pSM135 correlated with the EDSS (rs = 0.54, ps = 0.42, ps = 0.59, pSM135 with all clinical scales at follow up suggests that cumulative axonal loss is responsible for sustained disability and that high NfHSM135 levels are a poor prognostic sign.

Original languageEnglish
Pages (from-to)206-211
Number of pages6
JournalJournal of Neurology, Neurosurgery & Psychiatry
Volume76
Issue number2
DOIs
Publication statusPublished - Feb 2005
Externally publishedYes

Fingerprint

Multiple Sclerosis
Cerebrospinal Fluid
Intermediate Filaments
Walking
Biomarkers
Enzyme-Linked Immunosorbent Assay
Phosphorylation
Phenotype
Wounds and Injuries

Cite this

Petzold, A. ; Eikelenboom, M.J. ; Keir, G. ; Grant, D.J. ; Lazeron, R.H.C. ; Polman, C.H. ; Uitdehaag, B.M.J. ; Thompson, E.J. ; Giovannoni, G. / Axonal damage accumulates in the progressive phase of multiple sclerosis: Three year follow up study. In: Journal of Neurology, Neurosurgery & Psychiatry. 2005 ; Vol. 76, No. 2. pp. 206-211.
@article{cd628016ea3e40dea13b0ff86a26c816,
title = "Axonal damage accumulates in the progressive phase of multiple sclerosis: Three year follow up study",
abstract = "Background: Neurofilament phosphoforms (Nf) are principal components of the axoskeleton released during axonal injury. Cerebrospinal fluid (CSF) levels of Nf phosphoforms might be useful surrogate markers for disability in multiple sclerosis (MS), aid in distinguishing clinical subtypes, and provide valuable prognostic information. Method: Thirty four patients with MS were included in a three year follow up study along with 318 controls with other non-inflammatory neurological diseases. CSF levels of two Nf heavy chain (NfH) phosphoforms (NfHSM135, NfHSM134) were quantified at baseline and three year follow up using new ELISA techniques. Levels of NfH phosphoforms, the degree of phosphorylation (NfHSM134:NfHSM135 ratio), and changes in NfH levels between baseline and follow up (ΔNfH) were related to the clinical phenotype (RR or SP/PP), to three clinical scales (Kurtzke's EDSS, ambulation index (AI), and nine hole peg test (9HPT)), and to progression of disability. Results: A significantly higher proportion (59{\%}) of patients with SP/PPMS experienced an increase in NfHSM135 levels between baseline and follow up compared with those with RRMS (14{\%}, pSM134 levels at baseline were higher in patients with SP/PP (11 pg/ml) compared with RR (7 pg/ml, pSM135 levels were higher at follow up in SP/PP (129 pg/ml) compared with levels below assay sensitivity in RR (pSM135 correlated with the EDSS (rs = 0.54, ps = 0.42, ps = 0.59, pSM135 with all clinical scales at follow up suggests that cumulative axonal loss is responsible for sustained disability and that high NfHSM135 levels are a poor prognostic sign.",
author = "A. Petzold and M.J. Eikelenboom and G. Keir and D.J. Grant and R.H.C. Lazeron and C.H. Polman and B.M.J. Uitdehaag and E.J. Thompson and G. Giovannoni",
year = "2005",
month = "2",
doi = "10.1136/jnnp.2004.043315",
language = "English",
volume = "76",
pages = "206--211",
journal = "Journal of Neurology, Neurosurgery & Psychiatry",
issn = "0022-3050",
publisher = "BMJ Publishing Group",
number = "2",

}

Petzold, A, Eikelenboom, MJ, Keir, G, Grant, DJ, Lazeron, RHC, Polman, CH, Uitdehaag, BMJ, Thompson, EJ & Giovannoni, G 2005, 'Axonal damage accumulates in the progressive phase of multiple sclerosis: Three year follow up study', Journal of Neurology, Neurosurgery & Psychiatry, vol. 76, no. 2, pp. 206-211. https://doi.org/10.1136/jnnp.2004.043315

Axonal damage accumulates in the progressive phase of multiple sclerosis: Three year follow up study. / Petzold, A.; Eikelenboom, M.J.; Keir, G.; Grant, D.J.; Lazeron, R.H.C.; Polman, C.H.; Uitdehaag, B.M.J.; Thompson, E.J.; Giovannoni, G.

In: Journal of Neurology, Neurosurgery & Psychiatry, Vol. 76, No. 2, 02.2005, p. 206-211.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Axonal damage accumulates in the progressive phase of multiple sclerosis: Three year follow up study

AU - Petzold, A.

AU - Eikelenboom, M.J.

AU - Keir, G.

AU - Grant, D.J.

AU - Lazeron, R.H.C.

AU - Polman, C.H.

AU - Uitdehaag, B.M.J.

AU - Thompson, E.J.

AU - Giovannoni, G.

PY - 2005/2

Y1 - 2005/2

N2 - Background: Neurofilament phosphoforms (Nf) are principal components of the axoskeleton released during axonal injury. Cerebrospinal fluid (CSF) levels of Nf phosphoforms might be useful surrogate markers for disability in multiple sclerosis (MS), aid in distinguishing clinical subtypes, and provide valuable prognostic information. Method: Thirty four patients with MS were included in a three year follow up study along with 318 controls with other non-inflammatory neurological diseases. CSF levels of two Nf heavy chain (NfH) phosphoforms (NfHSM135, NfHSM134) were quantified at baseline and three year follow up using new ELISA techniques. Levels of NfH phosphoforms, the degree of phosphorylation (NfHSM134:NfHSM135 ratio), and changes in NfH levels between baseline and follow up (ΔNfH) were related to the clinical phenotype (RR or SP/PP), to three clinical scales (Kurtzke's EDSS, ambulation index (AI), and nine hole peg test (9HPT)), and to progression of disability. Results: A significantly higher proportion (59%) of patients with SP/PPMS experienced an increase in NfHSM135 levels between baseline and follow up compared with those with RRMS (14%, pSM134 levels at baseline were higher in patients with SP/PP (11 pg/ml) compared with RR (7 pg/ml, pSM135 levels were higher at follow up in SP/PP (129 pg/ml) compared with levels below assay sensitivity in RR (pSM135 correlated with the EDSS (rs = 0.54, ps = 0.42, ps = 0.59, pSM135 with all clinical scales at follow up suggests that cumulative axonal loss is responsible for sustained disability and that high NfHSM135 levels are a poor prognostic sign.

AB - Background: Neurofilament phosphoforms (Nf) are principal components of the axoskeleton released during axonal injury. Cerebrospinal fluid (CSF) levels of Nf phosphoforms might be useful surrogate markers for disability in multiple sclerosis (MS), aid in distinguishing clinical subtypes, and provide valuable prognostic information. Method: Thirty four patients with MS were included in a three year follow up study along with 318 controls with other non-inflammatory neurological diseases. CSF levels of two Nf heavy chain (NfH) phosphoforms (NfHSM135, NfHSM134) were quantified at baseline and three year follow up using new ELISA techniques. Levels of NfH phosphoforms, the degree of phosphorylation (NfHSM134:NfHSM135 ratio), and changes in NfH levels between baseline and follow up (ΔNfH) were related to the clinical phenotype (RR or SP/PP), to three clinical scales (Kurtzke's EDSS, ambulation index (AI), and nine hole peg test (9HPT)), and to progression of disability. Results: A significantly higher proportion (59%) of patients with SP/PPMS experienced an increase in NfHSM135 levels between baseline and follow up compared with those with RRMS (14%, pSM134 levels at baseline were higher in patients with SP/PP (11 pg/ml) compared with RR (7 pg/ml, pSM135 levels were higher at follow up in SP/PP (129 pg/ml) compared with levels below assay sensitivity in RR (pSM135 correlated with the EDSS (rs = 0.54, ps = 0.42, ps = 0.59, pSM135 with all clinical scales at follow up suggests that cumulative axonal loss is responsible for sustained disability and that high NfHSM135 levels are a poor prognostic sign.

UR - http://www.scopus.com/inward/record.url?scp=12444288619&partnerID=8YFLogxK

U2 - 10.1136/jnnp.2004.043315

DO - 10.1136/jnnp.2004.043315

M3 - Article

C2 - 15654034

AN - SCOPUS:12444288619

VL - 76

SP - 206

EP - 211

JO - Journal of Neurology, Neurosurgery & Psychiatry

JF - Journal of Neurology, Neurosurgery & Psychiatry

SN - 0022-3050

IS - 2

ER -