Clinicians Work Up a Biomarker-Based Approach to Confirm ALS Diagnosis

Reducing the diagnostic delay? Increased levels of the neurofilament component pNfH may help neurologists confirm ALS diagnosis according to a new study. The levels of pNfH in the cerebrospinal fluid appear to be elevated in people with ALS due to their release by degenerating neurons (Brettschneider et al, 2006). Image: Cultured rat brain cells, Wikimedia Commons.

The diagnosis of ALS can take up to 12 months. To expedite this process, researchers are developing biomarkers that can help identify people with ALS. One of these emerging biomarkers, phosphorylated neurofilament H (pNFH), aims to do just that. But neurologists remain unsure about whether this approach can help differentially diagnose the disease.

Now, a research team led by VIB’s Philip Van Damme in Belgium, report that increased levels of pNfH in the CSF can differentiate people with ALS from disease mimics (DMs) at a sensitivity of 90.7% (CI 84.9%-94.8%) and a specificity of 88.0% (CI 75.7%-95.5%). 220 people with ALS and 50 people with DMs participated in the study. The levels of pNfH significantly correlated with the number of upper and lower motor neuron regions affected by the disease.

This increase, according to the study, can be detected after only 4 months, well before most people with ALS consult a neurologist. The results come at the heels of previous studies which suggest that levels of pNfH may help identify people with fast progression rates, key in stratifying patients in clinical trials (see January 2017 news; Lu et al., 2015).

The study is published on May 12 in Neurology.


To learn more about this approach, including an emerging diagnostic test being developed by Iron Horse Diagnostics, check out this recent news feature.


Poesen K, De Schaepdryver M, Stubendorff B, Gille B, Muckova P, Wendler S, Prell T, Ringer TM, Rhode H, Stevens O, Claeys KG, Couwelier G, D’Hondt A, Lamaire N, Tilkin P, Van Reijen D, Gourmaud S, Fedtke N, Heiling B, Rumpel M, Rödiger A, Gunkel A, Witte OW, Paquet C, Vandenberghe R, Grosskreutz J, Van Damme P. Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease. Neurology. 2017 May 12. [PubMed].

Further Reading

Brettschneider J, Petzold A, Süssmuth SD, Ludolph AC, Tumani H. Axonal damage markers in cerebrospinal fluid are increased in ALS. Neurology. 2006 Mar 28;66(6):852-6. [PubMed]

Lu CH, Petzold A, Topping J, Allen K, Macdonald-Wallis C, Clarke J, Pearce N, Kuhle J, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Greensmith L, Malaspina A. Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study. J Neurol Neurosurg Psychiatry. 2015 May;86(5):565-73. [PubMed]

diagnosis disease-als neurofilament pNfH topic-biomarkers topic-clinical
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