Mania After DBS Tied to Stimulating Specific Brain Regions, Study Finds

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Among people with Parkinson’s undergoing deep brain stimulation (DBS), those who receive stimulation in a certain brain region — the medial and ventral subthalmic nucleus — are more likely to develop a distressing side effect known as mania, a yearlong study in more than 100 DBS patients reported.

Results suggest that changing the location of electrical stimulation, paired with sensible adjustments to medications, can effectively manage mania in Parkinson’s patients who experience this DBS side effect.

The study, “Limbic stimulation drives mania in STN-DBS in Parkinson disease: a prospective study,” was published in the Annals of Neurology.

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DBS is a treatment approach for people in more advanced disease stages that involves surgically implanting a device that provides electrical stimulation to specific regions of the brain. While DBS can effectively ease some Parkinson’s symptoms, mania — unusual and distressingly high elevations in mood and energy — can follow the procedure.

Risk factors for this side effect have not been thoroughly studied.

A team led by scientists in France analyzed data covering 111 Parkinson’s patients treated with DBS targeting the specific brain region called the subthalmic nucleus (STN), often a DBS target for Parkinson’s. These people, who underwent the surgery between May 2015 and January 2020, were followed as part of the PREDI-STIM study (NCT02360683) into subthalamic stimulation.

Eighteen patients (16.2%) developed mania, with most experiencing this emotional side effect within a week of starting on DBS. The others began with mania after an adjustment made to the location of the stimulating device in the brain. All but one of these 18 mania patients were male.

The researchers conducted a battery of statistical analyses looking for factors associated with mania risk. Results showed no association between mania risk and any pre-surgery factors, including patient age, disease duration, symptom severity, medication use, and psychiatric health problems.

Overall, postoperative mania is frequent and cannot be anticipated based on individual  clinical characteristics, in line with studies indicating manic behaviors in 15 to 40% of patients undergoing STN-DBS,” the researchers wrote.

However, a clear pattern was observed based on where in the subthalmic nucleus the leads providing electrical stimulation were placed.

Specifically, 15 patients with mania (15 out of 18, or 83%) had leads in the medial (middle) and ventral (lower) part of the STN, compared with less than half (47%) of those who did not develop mania. The medial and ventral STN region is involved in the limbic system, a group of brain regions that help in processing emotion and behavior.

Clinical management of mania generally involved changing the location of the electrical leads and/or temporarily adjusting patients’ medications (e.g., stopping or reducing doses of dopamine agonists that can cause or worsen manic symptoms). These adjustments stopped manic behaviors for all affected patients.

Most found that this side effect resolved within a few weeks. Mania persisted for almost two months in three patients and for three to five months in two others before ending.

“Our study clearly emphasizes the major role of stimulating the ventromedial part of the STN as a trigger of mania, especially for bilateral stimulation of the limbic STN territory, independently of clinical factors,” the researchers wrote.

“The switch to a more dorsal [upper, opposite of ventral] stimulation is a safe and effective strategy, besides discerning adjustment of oral medication, guaranteeing long-term motor and nonmotor benefits without reemergent mania,” they added. “This strategy should be applied without delay once the first signs of mania occur because of possible devastating consequences of prolonged or persistent mania for the patient, his caregiver and relatives.”

The team noted that Parkinson’s symptom severity after DBS did not differ between patients who did or did not develop mania.

“Importantly, patients with mania had similar motor and nonmotor benefits one year after STN-DBS surgery, even though dopamine agonists were considerably reduced or stopped, demonstrating that the occurrence of mania in the immediate or short-term postoperative period is not a prognostic [influencing] factor of outcome for STN-DBS implantation,” the scientists wrote.