DBS can ease familial and idiopathic Parkinson’s symptoms equally

Study in 97 patients with and without LRRK2 or PRKN gene mutations

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Subthalamic deep brain stimulation (DBS) may bring benefits to people with Parkinson’s regardless of whether the disease is caused by a gene mutation or appears in patients with no associated mutations, a study in Spain found.

Researchers investigated this surgical treatment’s use in people with LRRK2 and PRKN mutations —  two of the most common causes of familial Parkinson’s — and a larger patient group with idiopathic disease, or Parkinson’s whose cause is not clearly known.

These findings could be of importance, as recent studies reported differences in responses to DBS, the researchers noted. While they were independent of patients’ “genetic status … a genotype-phenotype [disease characteristics] relationship has been established with both disease progression and response to treatment, which might be relevant in the context of DBS and optimal candidate selection for the surgery.”

The study, “Analysis of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with monogenic PRKN and LRRK2 forms of Parkinson’s disease,” was published as a short communication in Parkinsonism & Related Disorders.

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DBS is a treatment option for patients with longer disease duration

Parkinson’s results from the progressive loss of nerve cells that produce dopamine, and the disease can be due to a mix of genetic and environmental factors. Dopamine is a major brain chemical messenger involved in movement control.

Various disease treatments aim to help patients in managing the range of Parkinson’s motor and nonmotor symptoms. They include surgical treatments such as DBS, usually offered to people with a longer disease duration.

DBS involves implanting one or more small wires (called electrodes) into the deep structures of the brain to stimulate those regions with electrical impulses. The electrodes are connected to a pulse generator, which is powered by a battery.

Subthalamic DBS is applied to a small, egg-shaped brain structure called the subthalamic nucleus, and it has been shown to ease motor and non-motor symptoms and improve quality of life in people with advanced Parkinson’s. The subthalamic region is involved in the regulation of motor control and is a key area affected by the disease.

Subthalamic DBS also can lower the medication doses needed for symptom control, leading to a lesser risk of side effects such as dyskinesia, or involuntary movements.

While many factors can determine how well a patient responds to DBS, previous work has shown the surgery can ease motor and nonmotor symptoms in early-onset Parkinson’s patients regardless of known disease-causing mutations.

Researchers at institutes in Oviedo, Spain, looked at data from 97 Parkinson’s patients with or without known disease-causing mutations who had undergone subthalamic DBS at a university hospital there between February 2000 and June 2021.

Of them, 74 patients had idiopathic Parkinson’s and 23 had familial disease, with 15 patients carrying mutations in the LRRK2 gene and the other eight in the PRKN gene.

At the time of the surgery, patients’ mean age was 59.5 and they had been living with the disease for a mean of nearly 13 years. All responded to levodopa, the mainstay Parkinson’s treatment, but they experienced motor fluctuations or dyskinesia as a side effect.

The researchers looked for differences in the levodopa equivalent dose (the combined total of Parkinson’s medications), motor symptoms, ability to perform daily activities, and disease severity between idiopathic patients and those with disease-causing mutations up to one year after DBS.

Lesser motor symptoms, lower levodopa equivalent doses one year after surgery

In both groups, DBS was associated with significant reductions in the levodopa equivalent dose and motor symptoms, as assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) Part 3, results showed. Notably, the surgery’s effects did not differ significantly between patients with and without disease-associated mutations.

Patients’ ability to perform daily life activities — measured using the UPDRS Part 2 and the Schwab and England Scale — showed similar trends, improving significantly and to the same extent in both groups up to one year after DBS.

The only significant difference between these groups was seen in scores on the Hoehn and Yahr Scale, a measure of disease severity. People with disease-causing mutations had significantly lower scores, reflecting less severe disease, than did those with idiopathic disease at six months post-surgery. However, this difference lost significance at one year.

“Despite this statistically significant finding at six months post DBS evaluation, it should be noted that from a clinical point of view this significance is minimal,” the researchers added.

Patients with LRRK2 or PRKN gene mutations had “good clinical, motor, and pharmacologic response” to DBS, the team concluded, adding that the response was similar to that of people with idiopathic Parkinson’s.

Larger studies that follow patients over longer periods are needed to confirm these findings and to better understand the role of genetic factors in response to subthalamic DBS, the scientists added.