Early Intervention of Deep Brain Stimulation Results in Improvements in Motor, Non-Motor Symptoms of Parkinson Disease

Andrea Kuhn, MD

Findings from a retrospective study of patients with early-onset Parkinson disease (EOPD) who were less than 45 years old showed that intervention with deep brain stimulation of the subthalamic nucleus (STN-DBS) can significantly improve motor and non-motor symptoms, as well as reduce neuropsychiatric features.

Motor scores, assessed using the Unified Parkinson’s Disease Rating Scale(UPDRS)-III, was explored under 4 different conditions with and without medication and stimulation: STIM-ON/MED-ON; STIM-OFF/MED-ON; STIM-ON/MED-OFF, and STIM-OFF/MED-OFF, respectively. At 12-month follow-up, mean motor scores had improved by 52.4 (±17.6%) points in the STIM-ON/MED-OFF state compared with MED-OFF state at baseline (P = .00). At the same time, the levodopa equivalent dosage (LEDD) was significantly reduced by 58.5 (±32.5%) after surgery.

Senior investigator Andrea Kuhn, MD, professor and head, Movement Disorders and Neuromodulation, Charitdé University Hospital, Berlin, and colleagues concluded that "Physicians as well as patients have an utmost interest in possible predictors for the putative DBS outcome in a cohort with such a highly complex clinical profile. Longitudinal monitoring of DBS-EOPD-patients over long-term intervals with standardized comprehensive clinical assessment, accurate phenotypic characterization and documentation of clinical outcomes might help to gain insights into disease etiology, to contextualize genomic information and to identify predictors of optimal DBS candidates as well as those in danger of deterioration and/or non-response in the future."

The analysis included follow-up data of 46 patients with EOPD who were operated on between 2012 and 2020. Patients had a mean disease duration of 12.9 (±5.9) years and a mean age at surgery of 51.0 (±8.8) years. PD-associated gene mutations were found in 15% of the cohort. Preoperative motor assessment included performance of a standardized levodopa challenge by use of the UPDRS III without dopaminergic substitution for at least 12 hours (MED-OFF) and after 200 mg of soluble levodopa (MED-ON), as well as assessment of the UPDRS II and IV.

In terms of non-motor symptoms, treatment with STN-DBS resulted in significant improvements in UPDRS I by 2.5 (±7.5) points after 12 months (P = .045). While changes in activities of daily living (UPDRS II) did not reach statistical significance, investigators did identify significant changes in neuropsychiatric evaluation for impulsive control disorder. Using the QUIP-Rating scale, patients treated with STN-DBS saw significant reductions of 6.6 (±16.1) points (P = .002). Additionally, at the 12-month follow-up, quality of life was significantly improved as well, as shown by a change from 38.9 (±14.9) points to 28.8 (±18.0) points on PDQ39.

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As for safety, in the first year after implantation, 7 adverse events (AEs) occurred, including dyskinesia (n = 3), dysarthria (n = 3), and accidental STIM-OFF (n = 1). Nine serious AEs were recorded, the most frequent being postoperative confusion, occurring in 3 patients, that was resolved after 3-5 days. One patient attempted suicide after newly started DA-therapy and resulting impulsivity 11 months after electrode implantation.

After 12 months of DBS, the total number of motor and/or neuropsychiatric additional comorbidities diminished from 64 to 17. Additionally, patients on DBS showed stable cognition throughout the study, demonstrated by scores on Mini-Mental State Examination (baseline vs 12 months: 28.7 vs 28.5 points; P = .47) and DemTect (14.2 vs 14.4 points; P = .53). Mood, measured by the BDI-II, and apathy, measured by the Starkstein-Apathy-Scale, revealed no significant changes at 12-month follow-up.

Investigators also performed a subanalysis of patients with (Mut+ :n = 7) and without (Mut– :n = 14) using the Wilcoxon Mann-Whitney test. Patients with PD-gene-mutation tended to be younger at surgery and to have a shorter disease duration in comparison to the Mut– patients. After 12 months of treatment with STN-DBS, Mut+ patients presented a significantly reduced LEDD (952.9 [±611.3] mg/d vs 469 [±450.7] mg/d; P = .025) and motor score (UPDRS II: 51.0 [±18] vs 32.1 [±1.6]; P = .025), with no significant changes in non-motor symptoms.

REFERENCE
1. Krause P, Reimer J, Kaplan J, et al. Deep brain stimulation in early onset Parkinson’s disease. Front Neurol. 2022;13. doi:10.3389/fneur.2022.1041449.