Submitted by David Haustein, MD, and Andrew Tarulli, MD, News Science Editorial Board
Steinacker P, Feneberg E, Weishaupt J, et al. Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. J Neurol Neurosurg Psychiatry 2016;87:12-20.
In this prospective study, cerebrospinal fluid (CSF) and serum was collected from 455 patients: 253 patients with clinically definite or probable ALS or PLS, 85 with motor neuron disease mimics, and 117 with other neurodegenerative diseases. Elevated CSF but not serum neurofilament light chain (NfL) and phosphorylated heavy chain (pNfH) levels were found much more frequently in patients with motor neuron disease than in the comparison groups. A NfL cutoff level of 2200 pg/ml yielded a 77% sensitivity, 85% specificity, and 87% positive predictive value while a pNfH cutoff level of 560 pg/ml yielded an 83% sensitivity, 77% specificity, and 82% positive predictive value. Neurofilament levels were found to be elevated at earlier stages of the disease and to show a correlation with disease progression and duration.
Weydt P, Oeckl P, Huss A, et al. Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Ann Neurol 2016;79:152-158.
Serum and cererebrospinal (CSF) fluid neurofilament levels were investigated as potential ALS biomarkers in three subject groups: patients with familial ALS (patients, N = 64), asymptomatic familial ALS gene mutation carriers (carriers, N = 12), and first-degree relatives of mutation carriers without mutations themselves (controls, N = 19). Serum and CSF NfL and pNFH were increased tenfold in patients compared to both carriers and controls, but no differences were identified between carriers and controls. Consistent differences in NF levels were not identified between patients with C9orf72 and SOD1 mutations. Clear correlations between disease duration and severity and neurofilament levels were not identified in this study.
Comment: ALS biomarkers are desperately sought to help with definitive disease diagnosis, to offer insights into disease pathophysiology, and to serve as outcome measures in clinical trials. Neurofilaments are critical structural proteins in the central nervous system, and abnormalities are hypothesized to play a role in the pathogenesis of a variety of neurodegenerative diseases. They are potentially relevant to ALS because they are found within the ubiquitinated cytoplasmic inclusions of TDP43. The two studies summarized above investigate the use of neurofilament levels as biomarkers for motor neuron disease. The sensitivity, specificity, and predictive values were good in the first study; prospective data collection in patients referred specifically for an ALS diagnosis would be a logical next step. While neurofilament levels were not useful as markers of disease progression in the second study, analysis of longitudinal data points in the same subject may disclose a more obvious relationship.
About the AANEM News Science Editorial Board
The board helps to highlight significant, timely science news items for AANEM members. It reviews articles in journals and websites, identifies newsworthy items in the field, and writes article summaries.