Management of Impulse Control and Related Disorders in Parkinson's Disease: An Expert Consensus.

BACKGROUND: Impulse-control and related behavioral disorders (ICBDs) significantly impact the lives of Parkinson's disease (PD) patients and caregivers, with lasting consequences if undiagnosed and untreated. While ICBD pathophysiology and risk factors are well-studied, a standardized severity definition and treatment evidence remain elusive. OBJECTIVE: This work aimed to establish international expert consensus on ICBD treatment strategies. To comprehensively address diverse treatment availabilities, experts from various continents were included. METHODS: From 2021 to 2023, global movement disorders specialists engaged in a Delphi process. A core expert group initiated surveys, involving a larger panel in three iterations, leading to refined severity definitions and treatment pathways. RESULTS: Experts achieved consensus on defining ICBD severity, emphasizing regular PD patient screenings for early detection. General treatment recommendations focused on continuous monitoring, collaboration with significant others, and seeking specialist advice for legal or financial challenges. For mild to severe ICBDs, gradual reduction in dopamine agonists was endorsed, followed by reductions in other PD medications. Second-line treatment strategies included diverse approaches like reversing the last medication change, cognitive behavior therapy, subthalamic nucleus deep brain stimulation, and specific medications like quetiapine, clozapine, and antidepressants. The panel reached consensus on distinct treatment pathways for punding and dopamine dysregulation syndrome, formulating therapy recommendations. Comprehensive discussions addressed management strategies for the exacerbation of either motor or non-motor symptoms following the proposed treatments. CONCLUSION: The consensus offers in-depth insights into ICBD management, presenting clear severity criteria and expert consensus treatment recommendations. The study highlights the critical need for further research to enhance ICBD management. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Subthalamic stimulation has acute psychotropic effects and improves neuropsychiatric fluctuations in Parkinson's disease.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for motor complications in Parkinson's disease (PD). However, its effects on neuropsychiatric symptoms remain disputed. The aim of this study was to evaluate the effects of STN-DBS on neuropsychiatric symptoms in PD. Methods: We retrospectively assessed 26 patients with PD who underwent a preoperative levodopa challenge and postoperative levodopa and stimulation challenges 1 year after STN-DBS. Based on the Neuropsychiatric Fluctuations Scale, Neuropsychiatric State Scores and Neuropsychiatric Fluctuation Indices (NFIs) were calculated. Mixed-effects models with random effects for intercept were used to examine the association of Neuropsychiatric State Score and NFI with the different assessment conditions. Results: In acute challenge conditions, there was an estimated increase of 15.9 points in the Neuropsychiatric State Score in stimulation ON conditions (95% CI 11.4 to 20.6, p<0.001) and 7.6 points in medication ON conditions (95% CI 3.3 to 11.9, p<0.001). Neuropsychiatric fluctuations induced by levodopa, quantified with NFI, decreased by 35.54% (95% CI 49.3 to 21.8, p<0.001) 1 year after STN-DBS. Conclusions: Bilateral STN-DBS at therapeutic parameters has acute psychotropic effects similar to levodopa and can modulate and decrease levodopa-induced neuropsychiatric fluctuations.

Deep Brain Stimulation: When to Test Directional?

Background: Directional deep brain stimulation (DBS) allows for steering of the stimulation field, but extensive and time-consuming testing of all segmented contacts is necessary to identify the possible benefit of steering. It is therefore important to determine under which circumstances directional current steering is advantageous. Methods: Fifty two Parkinson's disease patients implanted in the STN with a directional DBS system underwent a standardized monopolar programming session 5 to 9 months after implantation. Individual contacts were tested for a potential advantage of directional stimulation. Results were used to build a prediction model for the selection of ring levels that would benefit from directional stimulation. Results: On average, there was no significant difference in therapeutic window between ring-level contact and best directional contact. However, according to our standardized protocol, 35% of the contacts and 66% of patients had a larger therapeutic window under directional stimulation compared to ring-mode. The segmented contacts warranting directional current steering could be predicted with a sensitivity of 79% and a specificity of 57%. Conclusion: To reduce time required for DBS programming, we recommend additional directional contact testing initially only on ring-level contacts with a therapeutic window of less than 2.0 mA.

Assessment of Affective-Behavioral States in Parkinson's Disease Patients: Towards a New Screening Tool.

BACKGROUND: Assessment of affective-behavioral states in patients with Parkinson's disease (PD) undergoing deep brain stimulation (DBS) is essential. OBJECTIVE: To analyze well-established questionnaires as a pilot-study with the long term aim to develop a screening tool evaluating affective-behavioral dysfunction, including depression, anxiety, apathy, mania, and impulse control disorders, in PD patients screened for DBS. METHODS: Two hundred ninety-seven inpatients with PD underwent standardized neuropsychiatric testing including German versions of Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Apathy Evaluation Scale, Self-Report Manic Inventory, and Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale, to assess appropriateness for DBS. Statistical item reduction was based on exploratory factor analysis, Cronbach's alpha, item-total correlations, item difficulty, and inter-item correlations. Confirmatory factor analysis was conducted to assess factorial validity. An expert rating was performed to identify clinically relevant items in the context of PD and DBS, to maintain content validity. We compared the shortened subscales with the original questionnaires using correlations. To determine cutoff points, receiver operating characteristics analysis was performed. RESULTS: The items of the initial questionnaires were reduced from 129 to 38 items. Results of confirmatory factor analyses supported the validity of the shortened pool. It demonstrated high internal consistency (Cronbach's alpha = 0.72-0.83 across subscales), and the individual subscales were correlated with the corresponding original scales (rs = 0.84-0.95). Sensitivities and specificities exceeded 0.7. CONCLUSION: The shortened item pool, including 38 items, provides a good basis for the development of a screening tool, capturing affective-behavioral symptoms in PD patients before DBS implantation. Confirmation of the validity of such a screening tool in an independent sample of PD patients is warranted.

Reckless Generosity, Parkinson's Disease and Dopamine: A Case Series and Literature Review.

BACKGROUND: Impulse control disorders (ICDs) are a frequent side effect of dopamine replacement therapy (DRT) in Parkinson's disease (PD). Reckless generosity might expand the spectrum of known ICDs. CASES: Over 18 months, we encountered three PD patients exhibiting reckless generosity under DRT, leading to disastrous financial and social consequences. LITERATURE REVIEW: Except for another case series describing reckless generosity in three PD patients, only one study has examined generosity in PD patients; with findings suggesting that PD patients with ICDs are less sensitive to the aversive aspects of the lack of reciprocation in social settings. Studies with healthy individuals suggest that increased availability of dopamine might reduce social discounting and promote egalitarian behavior, and thereby increase generous behavior towards strangers. Genetic studies show that polymorphisms in dopamine D4 receptors influence generous behavior. CONCLUSIONS: Reckless generosity in PD patients with DRT might be underreported and should therefore be carefully be screened for by clinicians. A potential mechanism underlying this ICD-related behavior might be a sensitization of the mesolimbic and mesocortical dopaminergic system, leading to reduced social discounting and maladaptive reward-learning. Further research is needed to investigate the prevalence and underlying mechanisms of reckless generosity in PD patients.

Management of Impulse Control Disorders with Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

Impulse Control Disorders (ICDs) and related disorders are common side effects of dopaminergic treatment in Parkinson's Disease (PD) and are associated with negative effects on mental and physical health, quality of life and interpersonal relationships. Current management options are limited, as a reduction of dopaminergic medication often leads to worsening of motor symptoms or dopamine agonist withdrawal syndrome. The aim of this review was to investigate if ICDs improve, worsen, or remain stable after Subthalamic Nucleus Deep Brain Stimulation (STN-DBS). We reviewed retrospective, prospective and randomized-controlled studies published between 2000 and 2019 examining the effect of STN-DBS on one or more ICDs. The number of participants, time of follow-up, methods used to measure ICDs, type of ICDs, the incidence of ICDs before STN-DBS, the incidence of improvement (remission or reduction) of ICDs after STN-DBS, the incidence of de novo ICDs after STN-DBS, stimulation parameters, lead position, change in motor score and change in medication are reported for each study. Available studies suggest that ICDs improve after STN-DBS in most patients and that persisting new-onset ICDs induced by STN-DBS are rare. However, more randomized-controlled studies are needed to confirm the findings and to further investigate the underlying mechanisms.