The diagnostic significance of neurofilament heavy chains in cerebrospinal fluid in amyotrophic lateral sclerosis

Abstract

Introduction. Early diagnosis of amyotrophic lateral sclerosis (ALS) is difficult because of the low sensitivity of clinical criteria at the early stages of the disease and the lack of reliable laboratory biomarkers. Neuron destruction leads to the release of excessively accumulated phosphorylated neurofilament heavy chains (pNFH) in the cerebrospinal fluid (CSF) and may potentially be used for early diagnosis of ALS. In addition, pNFH may have predictive significance.

Aim. To investigate the clinical significance of elevated neurofilament heavy chain levels in the CSF in ALS.

Materials and methods. The study included 33 patients with ALS diagnosed using the El Escorial criteria, 30 patients in the control group (post phlebectomy), as well as 28 patients in the comparison group: 16 patients with multiple sclerosis, 5 with autoimmune encephalitis, 1 with tick-borne encephalitis, 2 with primary lateral sclerosis, 1 with progressive muscle atrophy and 3 with other conditions (restless leg syndrome, compressive myelopathy and paraneoplastic cerebellar degeneration). All patients underwent a lumbar puncture, with pNFH levels measured using ELISA.

Results. A statistically significant difference in pNFH concentration was found between ALS patients and patients in the comparison group (p < 0.0001). At a threshold pNFH level, which was taken to be 0.785 ng/ml, the test sensitivity and specificity were 94% and 86%, respectively. Elevated pNFH levels in the CSF of patients with confirmed ALS were found in 94% of cases, compared with only 14% of patients in the comparison group. A statistically significant difference in pNFH concentration was found between the group with ALS and the control group (p < 0.0001). A negative correlation was found between pNFH level in the CSF and disease duration (r = –0.5172; p = 0.0029). A positive correlation was also found between the speed of disease progression and pNFH concentration (r = 0.5480; p = 0.001).

Conclusion. The results of this study demonstrate the high clinical significance of pNFH in the CSF in ALS.

For citation: Vladykina A.V., Nazarov V.D., Krasnov V.S., Koroleva E.I., Fedorova P.A., Moshnikova A.N., Mazing A.V., Lapin S.V., Emanuel V.L., Rudenko D.I., Stuchevskaya F.R., Zatakovenko S.M., Pavlova T.A., Alekseeva T.M., Goldobin V.V. [The diagnostic significance of neurofilament heavy chains in cerebrospinal fluid in amyotrophic lateral sclerosis]. Annals of clinical and experimental neurology. 2021; 15(1): 43–50. (In Russ.) https://doi.org/10.25692/ACEN.2021.1.5

About the authors

Anastasia V. Vladykina

Pavlov First St. Petersburg State Medical University, St. Petersburg

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

Vladimir D. Nazarov

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Vladimir S. Krasnov

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Ekaterina I. Koroleva

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Polina A. Fedorova

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Anna N. Moshnikova

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Aleksandra V. Mazing

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Sergey V. Lapin

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Vladimir L. Emanuel

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Dmitriy I. Rudenko

Pavlov First St. Petersburg State Medical University, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Fatima R. Stuchevskaya

Pavlov First St. Petersburg State Medical University, St. Petersburg; City Multidisciplinary Hospital № 2, St. Petersbur

Email: platonova@neurology.ru
Russian Federation

Sergey M. Zatakovenko

City Multidisciplinary Hospital № 2, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Tatyana A. Pavlova

Almazov National Medical Research Centre, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Tatyana M. Alekseeva

Almazov National Medical Research Centre, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

Vitaliy V. Goldobin

North-Western State Medical University named after I.I. Mechnikov, St. Petersburg

Email: platonova@neurology.ru
Russian Federation

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Copyright (c) 2021 Vladykina A.V., Nazarov V.D., Krasnov V.S., Koroleva E.I., Fedorova P.A., Moshnikova A.N., Mazing A.V., Lapin S.V., Emanuel V.L., Rudenko D.I., Stuchevskaya F.R., Zatakovenko S.M., Pavlova T.A., Alekseeva T.M., Goldobin V.V.

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