Research Article| Volume 352, ISSUE 1-2, P84-87, May 15, 2015

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Neurofilament light chain level in cerebrospinal fluid can differentiate Parkinson's disease from atypical parkinsonism: Evidence from a meta-analysis

Published:April 07, 2015DOI:


      • We investigated NFL concentration in CSF in PD, MSA and PSP using a meta-analysis.
      • Patients with MSA showed higher concentration of NFL in CSF than those with PD.
      • NFL concentration in CSF in PSP was significantly elevated relative to PD.


      A reliable test that facilitates the accurate diagnosis of Parkinson's and disorders will help with both, clinical management and therapeutic research. In this context, neurofilament light chain (NFL) is candidate for a biomarker in cerebrospinal fluid (CSF). A comprehensive literature search yielded 4 eligible studies. We expressed between-group difference of NFL concentration in CSF as the standardized mean difference. Four studies involved 166 Parkinson's disease (PD), 116 multiple system atrophy (MSA) and 73 progressive supranuclear palsy (PSP) patients. Patients with MSA showed higher concentration of NFL concentration in CSF than those with PD (standardized mean difference = 1.60, P < 0.0001). These studies were homogeneous (P = 0.17). NFL in CSF in PSP was significantly elevated relative to PD with homogeneous studies (standardized mean difference = 2.04, P < 0.0001; P = 0.99). The present meta-analysis suggested that NFL concentration in CSF in MSA and PSP was significantly increased relative to PD, and that this could help us to separate PD from atypical parkinsonian syndromes.


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        • Dickson D.W.
        Parkinson's disease and parkinsonism: neuropathology.
        Cold Spring Harb Perspect Med. 2012; 2: a009258
        • Schrag A.
        • Ben-Shlomo Y.
        • Quinn N.P.
        Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study.
        Lancet. 1999; 354: 1771-1775
        • Hughes A.J.
        • Ben-Shlomo Y.
        • Daniel S.E.
        • et al.
        What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathological study.
        Neurology. 2001; 57: S34-S38
        • Hughes A.J.
        • Daniel S.E.
        • Ben-Shlomo Y.
        • et al.
        The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service.
        Brain. 2002; 125: 861-870
        • Holmberg B.
        • Johnels B.
        • Ingvarsson P.
        • et al.
        CSF-neurofilament and levodopa tests combined with discriminant analysis may contribute to the differential diagnosis of Parkinsonian syndromes.
        Parkinsonism Relat Disord. 2001; 8: 23-31
        • Abdo W.F.
        • Bloem B.R.
        • Van Geel W.J.
        • et al.
        CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson's disease.
        Neurobiol Aging. 2007; 28: 742-747
        • Constantinescu R.
        • Rosengren L.
        • Johnels B.
        • et al.
        Consecutive analysis of cerebrospinal fluid axonal and glial markers in Parkinson's disease and atypical Parkinsonian disorders.
        Parkinsonism Relat Disord. 2010; 16: 142-145
        • Hall S.
        • Ohrfelt A.
        • Constantinescu R.
        • et al.
        Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders.
        Arch Neurol. 2012; 69: 1445-1452
        • Cochrane C.J.
        • Ebmeier K.P.
        Diffusion tensor imaging in parkinsonian syndromes: a systematic review and meta-analysis.
        Neurology. 2013; 80: 857-864
        • Sako W.
        • Murakami N.
        • Izumi Y.
        • et al.
        MRI can detect nigral volume loss in patients with Parkinson's disease: evidence from a meta-analysis.
        J Parkinsons Dis. 2014; 4: 405-411
        • Sako W.
        • Murakami N.
        • Izumi Y.
        • et al.
        The difference in putamen volume between MSA and PD: evidence from a meta-analysis.
        Parkinsonism Relat Disord. 2014; 20: 873-877
        • Gelb D.J.
        • Oliver E.
        • Gilman S.
        Diagnostic criteria for Parkinson's disease.
        Arch Neurol. 1999; 56: 33-39
        • Quinn N.
        Multiple system atrophy — the nature of the beast.
        J Neurol Neurosurg Psychiatry. 1989; (Special Supplemen): 78-89
        • Gilman S.
        • Wenning G.K.
        • Low P.A.
        • et al.
        Second consensus statement on the diagnosis of multiple system atrophy.
        Neurology. 2008; 71: 670-676
        • Litvan I.
        • Agid Y.
        • Calne D.
        • et al.
        Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele–Richardson–Olszewski syndrome): report of the NINDS-SPSP International Workshop.
        Neurology. 1996; 47: 1-9
        • Egger M.
        • Smith G.D.
        • Schneider M.
        • et al.
        Bias in meta-analysis detected by a simple, graphical test.
        BMJ. 1997; 315: 629-634
        • Scherling C.S.
        • Hall T.
        • Berisha F.
        • et al.
        Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration.
        Ann Neurol. 2014; 75: 116-126
        • Constantisnescu R.
        • Mondello S.
        Cerebrospinal fluid biomarker candidates for parkinsonian disorders.
        Front Neurol. 2013; 3: 187
        • Sako W.
        • Murakami N.
        • Izumi Y.
        • et al.
        Reduced alpha-synuclein in cerebrospinal fluid in synucleinopathies: evidence from a meta-analysis.
        Mov Disord. 2014; 29: 1599-1605
        • Quattrone A.
        • Nicoletti G.
        • Messina D.
        • et al.
        MR imaging index for differentiation of progressive supranuclear palsy from Parkinson disease and the Parkinson variant of multiple system atrophy.
        Radiology. 2008; 246: 214-221
        • Tang C.C.
        • Poston K.L.
        • Eckert T.
        • et al.
        Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis.
        Lancet Neurol. 2010; 9: 149-158
        • Nair S.R.
        • Tan L.K.
        • Ramli N.M.
        • et al.
        A decision tree for differentiating multiple system atrophy from Parkinson's disease using 3-T MR imaging.
        Eur Radiol. 2013; 23: 1459-1466