title: CSF protein biomarkers for proximal axonal damage improve prognostic accuracy in the acute phase of Guillain-Barré syndrome.
abstract: Early predictors of prognosis in Guillain-Barré syndrome (GBS) are needed to identify patients who are likely to make a poor recovery and to guide therapeutic decision-making in the acute phase. Here we investigate whether axonal protein biomarkers released into the cerebrospinal fluid (CSF) following proximal axonal damage improve the early prognostic accuracy in GBS. A prospective multicenter study including 132 patients (38 GBS, 38 neurological controls, 42 headaches, 14 chronic inflammatory demyelinating neuropathy). CSF levels of axonal [neurofilament (NfH) and tau] and glial (S100B and glial fibrillary acidic protein) protein biomarkers were measured on admission. Nerve conduction studies were performed at the time of lumbar puncture and patients were classified according to neurophysiological criteria. Outcome was assessed on the Hughes functional score (F-score). Poor outcome was defined as the inability to walk independently (F-score > or = 3). High NfH levels (>0.73 ng/ml) predicted poor outcome (P = 0.01) with an odds ratio of 7.3 and correlated with the outcome F-score (R = 0.51, P < 0.01), as did hTau levels (R = 0.47, P < 0.01). Patients with poor outcome had significantly higher CSF NfH (median 1.78 ng/ml) when compared to those with good outcome (0.03 ng/ml) or all of the control groups (neurological controls 0.18 ng/ml, headaches 0.06 ng/ml, chronic inflammatory demyelinating neuropathy 0.05 ng/ml). Except for age (P < 0.05) and need for ventilatory support (P < 0.05), none of the other features reliably predicted outcome. Improved prognostic accuracy in the acute phase of GBS seems possible using CSF NfH levels.
authors.affiliation: Department of Neuroimmunology, Institute of Neurology and Tavistock Intensive Care Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdom. a.petzold@ion.ucl.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Petzold
authors.forename: J
authors.initials: J
authors.lastname: Brettschneider
authors.forename: K
authors.initials: K
authors.lastname: Jin
authors.forename: G
authors.initials: G
authors.lastname: Keir
authors.forename: N M F
authors.initials: NM
authors.lastname: Murray
authors.forename: N P
authors.initials: NP
authors.lastname: Hirsch
authors.forename: Y
authors.initials: Y
authors.lastname: Itoyama
authors.forename: M M
authors.initials: MM
authors.lastname: Reilly
authors.forename: A
authors.initials: A
authors.lastname: Takeda
authors.forename: H
authors.initials: H
authors.lastname: Tumani
mesh_terms: D000368:Aged; D001369:Axons / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid*; D020275:Guillain-Barre Syndrome / Q000134:cerebrospinal fluid* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid*; D009431:Neural Conduction / Q000502:physiology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D017063:Outcome Assessment, Health Care / Q000379:methods; D011446:Prospective Studies; D015203:Reproducibility of Results; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid*; D012720:Severity of Illness Index; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D016875:tau Proteins; C051774:neurofilament protein H