Some Parkinson’s Patients May Benefit from Non-dopaminergic Treatments

Non-dopaminergic treatments might be beneficial for Parkinson’s disease patients whose tremor is associated with a dysfunction of the serotonergic system, an area of the brain directly connected to serotonin interactions.

A study with that finding, “Progression of tremor in early stages of Parkinson’s disease: a clinical and neuroimaging study,” was published in the journal Brain.

The pathological hallmark of Parkinson’s disease is degeneration of a part of the brain called the substantia nigra, which contains dopaminergic neurons (nerve cells responsible for releasing the neurotransmitter dopamine that acts as a central power-driver for brain activity).

Dysfunction of dopaminergic neurons can lead to tremors, which can be clinically classified as rest (occurring when the muscle is relaxed and the most common in Parkinson’s), postural (occurring when a person maintains a position against gravity, such as holding the arms outstretched), or kinetic (associated with any voluntary movement, such as moving the wrists up and down or closing and opening the eyes).

The mechanism behind the occurrence of rest tremors in Parkinson’s disease remains poorly understood. It is known, however, that rest tremors often are less responsive to dopamine replacement therapy, suggesting that dopamine deficiency alone does not determine tremor severity.

The serotonergic system, which originates from an area of the brain called the brainstem raphe nuclei, is known to be disrupted in Parkinson’s disease. Nerve cells that make up the serotonergic system, and can be found within the raphe nuclei, have serotonin transporters, which are small proteins responsible for the transport of the neurotransmitter serotonin and the correct communication between nerve cells.

Dysfunction of these molecules is known to increase the severity of rest tremor in Parkinson’s patients.

In this study, researchers used clinical and imaging data from the Parkinson’s Progressive Markers Initiative database to assess for the prevalence and progression of resting tremor, postural tremor, and kinetic tremor during early Parkinson’s disease.

Clinical analysis of tremors was conducted on 378 patients: 87.8% presented with tremor at baseline; rest tremor occurred in 69.6% of patients at baseline; and 67.9% at follow-up. Postural and kinetic tremors occurred in about 50% of patients at both baseline and follow-up.

Data revealed that, as disease progressed, dysfunction of both the serotonergic system and the dopaminergic system could contribute to the occurrence of rest tremors. In fact, patients with fewer available serotonin transporters had more severe resting tremors. Additionally, severity of the tremors  also was higher in patients with higher raphe nuclei dysfunction and connected to a poorer response to dopaminergic therapy.

Based on this clinical data, the authors believe that non-dopaminergic treatments might be beneficial for patients whose tremor is associated with a dysfunction of the serotonergic system, in particular that associated with a raphe-predominant dysfunction.