Predictors for α-synucleinopathies in isolated sleep behavior disorder with rapid eye movement

Reliable biomarkers can play an important role in predicting conversion to clinically manifest α-synucleinopathies in patients with isolated rapid eye movement sleep behavior disorder (RBD) and, according to a published review, can predict the subtype of α-synucleinopathies and response to treatment be essential. in neurology.

Previous studies have shown that RBD is a potential early sign of α-synucleinopathies, a group of neurodegenerative diseases characterized by abnormal accumulation of α-synuclein in the brain, including Parkinson’s disease, Lewy body dementia, and multiple system atrophy.

Potential biomarkers that predict conversion to clinically manifest α-synucleinopathies can help with early detection, assessment of response to therapy, and prediction of α-synucleinopathy subtypes. The current review focused on several categories of biomarkers and provided data on their potential utility and role in assessing diagnosis, prognosis, and response to disease-modifying therapy.

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The potential biomarkers were divided into 10 categories including neurophysiology, motor skills, cognition, olfactory sense, eye function, autonomic function, biofluids, neuroimaging, tissue biopsy, and genetic testing.

These biomarkers can be used to confirm an underlying α-synucleinopathy and to differentiate the subtypes of α-synucleinopathies (diagnostic), to predict the rate of phenoconversion and the severity of the disease (prognostic) to the progression of neurodegeneration and the response to it to monitor the treatment (monitoring or therapy-responsive) or to refine and improve the diagnostic, prognostic and monitoring functions (combined).

Rapid eye movement sleep without atony recorded during video polysomnography is the most readily available diagnostic biomarker. In patients with isolated RBD, motor abnormalities appear relatively late in the prodromal disease process and may indicate which patients are at greatest risk of phenoconversion in the near future. Quantitative motor tests are among the most powerful predictive markers of future phenoconversion.

Serum neuronal exosomal α-synuclein and spinal fluid conversion induced by tremors in real time can be used as valuable markers with high sensitivity and specificity.

There are no good imaging biomarkers to determine the neuropathological spread of α-synuclein in patients with isolated RBD. At this point in time, 123 I-N-ω-fluoropropyl-2β-carbomethoxy-3β- (4-iodophenyl) -nortropane (123 I-FPCIT) SPECT imaging is the most reliable prognostic marker for phenoconversion in this context.

Peripheral tissue biopsy, particularly skin biopsy, has shown promise as an in vivo diagnostic biomarker for isolated RBD. A transcutaneous punch biopsy of the submandibular gland under ultrasound guidance can be helpful.

The combination of several biomarkers can provide important data for diagnosis, prognosis and monitoring of therapy response.

“Future research will focus on longitudinal data of multiple biomarkers across multiple” [centers] worldwide, ”concluded the study researchers.

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Miglis MG, Adler CH, Antelmi E, et al. Biomarker for the conversion to α-synucleinopathy in isolated sleep behavior disorders caused by rapid eye movements. Lancet Neurol. 2021; 20 (8): 671-684. doi: 10.1016 / S1474-4422 (21) 00176-9