medwireNews: A simple blood test for neurofilament light chain (NfL) protein could help physicians distinguish atypical parkinsonian disorders from Parkinson’s disease (PD), study findings show.
The diagnostic accuracy of the test was between 81% and 91%, which is equally as high as the diagnostic accuracy achieved when measuring NfL protein in cerebrospinal fluid (CSF), report Oskar Hansson (Lund University, Sweden) and colleagues in Neurology.
Without the need for an invasive procedure such as lumbar puncture, they believe that “[t]his easily accessible biomarker of axonal degeneration may improve the diagnostic workup of patients with parkinsonian symptoms in specialized clinics as well as in [the] primary care setting.”
Using an ultrasensitive single molecular array immunoassay for NfL, the team tested the blood of 171 patients with PD, 19 with progressive supranuclear palsy, 30 with multiple system atrophy, five with corticobasal syndrome, and 53 healthy individuals.
The blood levels of NfL correlated significantly with CSF levels, and were significantly higher in people with atypical parkinsonian disorders than controls, whereas patients with PD had levels similar to those of controls.
NfL is a marker of degeneration of large myelinated axons, the researchers explain, and so the fact that it was increased in patients with atypical parkinsonian disorders and not those with PD “could be due in part to less severe and widespread axonal degeneration in PD compared to [atypical parkinsonian disorders].”
The average levels were around 10 pg/mL for PD patients and controls, compared with around 25 pg/mL for patients with progressive supranuclear palsy, 20 pg/mL for patients with multiple system atrophy and 27 pg/mL for those with corticobasal degeneration.
The researchers report that these findings were replicated in a separate cohort comprising 20 patients with PD, 29 with progressive supranuclear palsy, 30 with multiple system atrophy, 12 with corticobasal syndrome, and 26 healthy individuals.
The average disease duration of these patients and that of the original cohort was 4 to 6 years, but the team also found that blood NfL levels differentiated PD from atypical parkinsonian disorders in a third cohort of 109 patients (53 with PD) with disease duration of 3 years or less.
In terms of diagnosis, the specificity of the test ranged from 80% in the early disease cohort to 91% in the original cohort, and the sensitivity was 70% to 82%, respectively. The results were similar when the individual atypical parkinsonian disorder groups were compared with PD patients separately. But blood NfL levels could not distinguish between these other disorders, and clinicians would need to look for additional signs and symptoms to support a diagnosis, says the team.
They also note that absolute concentrations of NfL differed between the cohorts and so “development of a fully automated clinical grade assay and establishment of cutoff points would be necessary for implementation of blood-based NfL measurements in clinical practice.”
Guido Alves (Stavanger University Hospital, Norway) and Laura Bonanni (University G. d’Annunzio of Chieti-Pescara, Italy) add in a related editorial that the development of a clinical grade assay “should be done in patients whose diagnosis is pathologically proven, but also in those in the very earliest stages, including the premotor phase.”
They point out: “When disease-modifying treatments become available, diagnosing parkinsonian disorders correctly at early, possibly preclinical stages will be even more important.”
Support for NfL biomarker in primary progressive aphasia
In another study published in Neurology, blood levels of NfL have also been found useful for distinguishing between primary progressive aphasia (PPA) variants.
Markus Otto (University of Ulm, Germany) and colleagues found that serum NfL levels were significantly higher in 99 patients with PPA than in 35 healthy controls, and, at a cutoff of 25 pg/mL, distinguished between the two groups with 95% sensitivity and 70% specificity.
Significantly higher levels also distinguished the 40 patients with nonfluent/agrammatic variant and the 38 with semantic variant from the 21 with the logopenic variant. At a cutoff of 31 pg/mL, NfL identified these two groups pooled with 81% sensitivity and 67% specificity.
The researchers note that longitudinal increases in NfL were indicative of disease severity, correlating with pronounced progression of atrophy and functional performance decline, making it an objective disease status marker.
By Lucy Piper
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