Subthalamic DBS Effect on Impulsive, Compulsive Behaviors Predicted by Comprehensive Assessments

In the cohort of 14 patients with preoperative impulsive and compulsive behavior burden, 6 patients demonstrated clinically relevant improvement on QUIP-RS, while 1 worsened and 7 remained stable.

Patients with Parkinson disease (PD) who had higher preoperative impulsive and compulsive behavior (ICB) burden and lower doses of dopamine agonists (DA) demonstrated more favorable ICB outcomes following subthalamic nucleus-deep brain stimulation (STN-DBS), whereas those with more severe baseline attention/memory deficits experienced worse outcomes.1

In the post-hoc analysis, individuals who had higher baseline Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS) scores and lower baseline levodopa-equivalent daily dose dopamine agonists (LEDD-DA) were associated with greater QUIP-RS improvements. Thus, the findings from this prospective, open-label multicenter study highlight the importance of a comprehensive assessment of patients’ motor and nonmotor profiles before DBS surgery.

Lead author Anna Sauerbier, MD, MBBS, clinical research fellow, King’s College London, and colleagues assessed 55 patients preoperatively and at 6-month follow-up postoperatively as a way to investigate clinical predictors of STN-DBS effects on ICB. They analyzed between-group differences on several clinical scales, including the QUIP-RS, PD Questionnaire-8 (PDQ-8 SI), Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale (UPDRS), along with LEDD total (LEDD-total) and LEDD-DA.

At baseline, 38.9% (n = 14) of patients reported ICB. The most frequently reported included ponding and hobbyism (31.4%), eating disorders (16.2%), hypersexuality (5.4%), and excessive shopping (5.4%). While QUIP-RS total score did not change at follow-up in the overall cohort, those who reported having clinically relevant ICB, the QUIP-RS total improved significantly (before: 30.5 [±10.7]; afterward: 24.1 [±14.0]; P = .044). Investigators noted that there was considerable interindividual variability of QUIP-RS outcomes, as 29.1% (n = 16) of those experienced a clinically relevant improvement while 27.3% (n = 15) showed a clinically relevant worsening in QUIP-RS total score.

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The investigators concluded that "further studies in larger cohorts analyzing a wide range of motor and [nonmotor symptoms] may better predict patients’ postoperative risk of developing ICDs. The overall aim of this line of research is a better selection of patients for DBS therapy."

Clinically relevant improvement on QUIP-RS was observed in 6 of the 14 patients who reported preoperative ICB (median baseline QUIP-RS score, 29.5; interquartile range [IQR], 21.5-40.25). Worsening was found in 1 patient (median baseline QUIP-RS score, 48), whereas 7 patients reported stable changes (median baseline QUIP-RS score, 24; IQR, 20-36).

From baseline to 6-month follow-up, those in the overall cohort showed significant improvement on several secondary outcomes, including PDQ-8, NMSS total, UPDRS-II, UPRDS-IV, Hoehn and Yahr scale, LEDD total, and LEDD-DA. Those with preoperative ICB had similar significant improvements, except with just trends observed for PDQ-8 SI and UPDRS-IV and no significant outcome on UPDRS-II.

In comparison with those in the QUIP-RS improvement group, Individuals who had worsened scores demonstrated higher LEDD-DA (321.9 mg [±139.2] vs 180.3 mg [±156.1]; P = .021), a lower QUIP-RS total (12.1 [±13.6] vs 21.8 [10.6]; P = .009), and higher NNMSS attention/memory domain scores (5.1 [±4.4] vs 2.8 [±5.1]; P = .043) at baseline.

The data published also coincided with the limited literature published on STN-DBS effects on ICB. Data from Rossi, et al. found that despite relatively unchanged LEDD following STN-DBS, ICD symptoms trended towards improvement, although worsening and emergence of new ICDs occurred as well.2 Additionally, more recent research helped identify a mechanistic substrate of neuropsychiatric improvement with STN-DBS and suggested that tractography could be used to predict the incidence of adverse neuropsychiatric effects.3

REFERENCES
1. Sauerbier A, Loehrer P, Jost ST, et al. Predictors of short-term impulsive and compulsive behavior after subthalamic stimulation in Parkinson disease. J Neurol Neurosurg Psychiatry. Published online September 11, 2021. doi:10.1136/jnnp-2021-326131
2. Rossi JP, De Jesus S, Hess CW, et al. Measures of impulsivity in Parkinson disease decrease after DBS in the seting of stable dopamine therapy. Parkinsonism Relat Disord. 2017 November; 44:13-17. doi:10.1016/j.parkreldis.2017.08.006
3. Mosley PE, Paliwal S, Robinson K, et al. The structural connectivity of subthalamic deep brain stimulation correlates with impulsivity in Parkinson disease. Brain. 2020 July; 143(7):2235-2254