Biomarkers of functional movement disorders - a systematic review

Functional movement disorders (FMD) are defined by diverse phenotypes of altered movements that lack corresponding pathology in an anatomical region, and are typically characterized by inconsistent findings on neurological examination.

While there are several suggestive clinical features indicating FMD, objective biomarkers are still lacking. We conducted a systematic review of the literature with an emphasis on literature published after February 2019 aiming to summarise current knowledge on biomarkers of FMD. We divided our findings into four main categories: genetic, biofluid, neuroimaging, and electrophysiological biomarkers. For the differential diagnosis of functional tremor, functional tic-like behaviours (FTLB), and functional myoclonus, previous studies support the use of electrophysiological biomarkers. Evidence from neuroimaging research supports the multi-network model of FMD as a condition affecting the attentional, sensorimotor, self-agency/multimodal integration, and limbic/salience circuits. Biomarkers such as neurofilament light chain, inflammatory, and autoimmune factors should still be considered experimental, since results are based on small sample sizes. There is preliminary evidence from a genetic study that in FMD there is a complex interaction between individual predisposing risk genes involved in the serotonergic pathway.

Although the diagnosis of FMD remains challenging, and depends mainly on clinical judgement, research is underway to identify potential biomarkers to improve diagnostic confidence. Previous studies indicate that, in addition to psychological symptoms, biological changes can be detected in patients with FMD. This is evidenced by different patterns of neurotransmission related to stress responses and emotional regulation.

We believe it is vital to conduct larger trials in diverse populations from different regions of the world in order to find more reliable biomarkers of FMD.