Plasma neurofilament light chain as a potential biomarker in Charcot-Marie-Tooth disease.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth (CMT) disease is a chronic, slowly progressing disorder. The lack of specific disease progression biomarkers limits the execution of clinical trials. However, neurofilament light chain (NfL) has been suggested as a potential biomarker for peripheral nervous system disorders. METHODS: Ninety-six CMT disease patients and 60 healthy controls were enrolled in the study. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Blood plasma NfL concentrations were measured using the single-molecule array NfL assay. RESULTS: The NfL concentration was significantly higher in the CMT disease patient group than in the controls (p < 0.001). Of the CMT disease patients, those with type CMTX1 had a higher NfL level than those in the two other analysed subgroups (CMT1A and other CMT disease types) (p = 0.0498). The NfL concentration had a significant but weak correlation with the CMTNSv2 (rs  = 0.25, p = 0.012). In one CMT disease patient with an extremely elevated NfL level, overlap with chronic inflammatory demyelinating polyneuropathy was suspected. Receiver operating characteristic analysis showed that an NfL concentration of 8.9 pg/ml could be used to discriminate CMT disease patients from controls, with an area under the curve of 0.881. CONCLUSIONS: Our study confirmed that the plasma NfL concentration is significantly higher in CMT disease patients than in controls. Plasma NfL concentration was found to significantly, albeit weakly, reflect the clinical severity of CMT disease. In the future, NfL may be used, either individually or collaboratively, as a biomarker in the clinical context of suspected CMT disease; however, several issues need to be addressed first.

Clinical Phenotyping and Biomarkers in Spinal and Bulbar Muscular Atrophy.

Background: Spinal and bulbar muscular atrophy (SBMA) or Kennedy disease [OMIM: 313200] is a rare X-linked neuromuscular disease. Patients commonly present with muscle cramps, tremors, leg weakness, dysarthria and dysphagia. Methods: We deeply phenotyped and evaluated the possible extent of affected systems in all patients with SBMA in Latvia (n = 5). In addition, neurophysiological studies and blood analyses were used to perform a molecular diagnosis and evaluate biochemical values. We analyzed neurofilament light (NfL) as a possible biomarker. Results: Neurological examination revealed typical SBMA clinical manifestations; all patients had small or large nerve fiber neuropathy. Three of five patients had increased neurofilament light levels. Conclusion: The study confirms the systemic involvement in patients suffering from SBMA. Increased NfL concentration was associated with either peripheral neuropathy or decreased body mass index. The complex phenotype of the disease should be kept in mind, as it could help to diagnose patients with SBMA.