Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Meta‐Analysis

Zoon, Thomas J.C.; Rooijen, Geeske van; Balm, Georgina M.F.C.; Bergfeld, Isidoor O.; Daams, Joost G.; Krack, Paul; Denys, Damiaan; Bie, Rob M.A. de

doi:10.1002/mds.28390

Cited by 45 publications

(31 citation statements)

References 74 publications

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“…8 However, apathy increases on average after STN-DBS compared to the preoperative state. 87,88 In the most recent meta-analysis, 87 postoperative apathy was not statistically correlated with a reduction in dopamine replacement therapy, leading to speculations regarding a direct apathy-inducing effect of STN-DBS per se. 87 However, meta-analysis of the literature is limited in determining the causal underpinnings.…”

Section: The Risk Of Postoperative Apathymentioning

confidence: 99%

Changing Gears – DBS For Dopaminergic Desensitization in Parkinson's Disease?

Weiß

Volkmann

Fasano

et al. 2021

Annals of Neurology

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In Parkinson's disease, both motor and neuropsychiatric complications unfold as a consequence of both incremental striatal dopaminergic denervation and intensifying long‐term dopaminergic treatment. Together, this leads to ‘dopaminergic sensitization’ steadily increasing motor and behavioral responses to dopaminergic medication that result in the detrimental sequalae of long‐term dopaminergic treatment. We review the clinical presentations of ‘dopaminergic sensitization’, including rebound off and dyskinesia in the motor domain, and neuropsychiatric fluctuations and behavioral addictions with impulse control disorders and dopamine dysregulation syndrome in the neuropsychiatric domain. We summarize state‐of‐the‐art deep brain stimulation, and show that STN‐DBS allows dopaminergic medication to be tapered, thus supporting dopaminergic desensitization. In this framework, we develop our integrated debatable viewpoint of “changing gears”, that is we suggest rethinking earlier use of subthalamic nucleus deep brain stimulation, when the first clinical signs of dopaminergic motor or neuropsychiatric complications emerge over the steadily progressive disease course. In this sense, subthalamic deep brain stimulation may help reduce longitudinal motor and neuropsychiatric symptom expression – importantly, not by neuroprotection but by supporting dopaminergic desensitization through postoperative medication reduction. Therefore, we suggest considering STN‐DBS early enough before patients encounter potentially irreversible psychosocial consequences of dopaminergic complications, but importantly not before a patient shows first clinical signs of dopaminergic complications. We propose to consider neuropsychiatric dopaminergic complications as a new inclusion criterion in addition to established motor criteria, but this concept will require validation in future clinical trials. ANN NEUROL 2021;90:699–710

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Section: The Risk Of Postoperative Apathymentioning

confidence: 99%

Changing Gears – DBS For Dopaminergic Desensitization in Parkinson's Disease?

Weiß

Volkmann

Fasano

et al. 2021

Annals of Neurology

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“…In agreement with these human studies, our results could suggest that STN lesion affects USV emotional decoding, thereby blunting the emotion contagion induced by USV listening, and in fine, the behavioural response to those USV. In PD patients, STN-DBS can also induce apathy [58,59], while in rats, STN lesion blunts emotional response to hedonic and aversive stimuli [42]. This general diminished affective state could account for the dampened response to USV.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a vocal signature in the rat and its reinforcing effects: a key role for the subthalamic nucleus

et al. 2021

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Although rodents have a well-structured vocal form of communication, like humans and non-human primates, there is, to date, no evidence for a vocal signature in the well-known 50- and 22-kHz ultrasonic vocalizations (USVs) emitted by rats. Here, we show that rats can recognize the identity of the USV emitter since they choose to preferentially self-administer playback of 50-kHz USVs emitted by a stranger rat over those of their cagemate. In a second experiment, we show that only stranger, but not familiar, 50-kHz USVs reduce cocaine self-administration. Finally, to study the neurobiological substrate of these processes, we have shown that subthalamic nucleus (STN)-lesioned rats did not lever press much for any USV playback, whatever their emotional valence, nor did they seem able to differentiate familiar from stranger peer. Advocating for the existence of a vocal signature in rats, these results highlight the importance of ultrasonic communication in the socio-affective influence of behaviour, such as the influence of proximal social factors on drug consumption and confirm the role of the STN on this influence.

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“…In their study, a significant improvement of neuropsychiatric fluctuations and impulse control disorders in PD over time could be detected after deep brain stimulation [ 58 ]. On the other hand, DBS in the subthalamic nucleus may increase apathy and depressive symptoms, leading to reduced HR-QoL in PwP and increased caregiver burden [ 59 , 60 , 61 ]. Therefore, considering DBS as a therapeutical option in PD with neuropsychiatric symptoms should weigh the possible advantages and disadvantages of this intervention.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychiatric Symptoms in Parkinson’s Disease Patients Are Associated with Reduced Health-Related Quality of Life and Increased Caregiver Burden

et al. 2022

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting in reduced health-related quality of life (HR-QoL) of people with PD (PwP) and their caregivers. Furthermore, there is an accumulating burden on caregivers of patients in advanced stages of the disease. In previous studies, motor- and non-motor-symptoms of PwP have been identified to contribute to reduced HR-QoL and an increased caregiver burden. This cross-sectional observational study aimed to study the influence of neuropsychiatric symptoms measured with the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s Disease (SEND-PD) questionnaire on the HR-QoL of PwP, as well as the caregiver burden. Analyses revealed a significant association between SEND-PD subscale mood/apathy and reduced HR-QoL in PwP, measured by the Parkinson’s disease quality of life questionnaire (PDQ-8) (p < 0.001). Furthermore, mood/apathy was significantly correlated with caregiver burden (p = 0.001) in the multiple linear regression analysis. Hence, neuropsychiatric symptoms were found to have a profound impact on the HR-QoL of PwP, as well as on caregiver burden. Since neuropsychiatric symptoms were one of the main predictors for caregiver burden, physicians of PwP should treat these symptoms to stabilize caregiver burden, as well as HR-QoL in PwP and their caregivers.

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Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Meta‐Analysis

Cited by 45 publications

References 74 publications

Changing Gears – DBS For Dopaminergic Desensitization in Parkinson's Disease?

Changing Gears – DBS For Dopaminergic Desensitization in Parkinson's Disease?

Evidence for a vocal signature in the rat and its reinforcing effects: a key role for the subthalamic nucleus

Neuropsychiatric Symptoms in Parkinson’s Disease Patients Are Associated with Reduced Health-Related Quality of Life and Increased Caregiver Burden

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