Apathy following subthalamic stimulation in Parkinson disease: A dopamine responsive symptom

Abstract

To evaluate the effects of the dopamine D2-D3 agonist ropinirole in patients who developed apathy after complete withdrawal from dopaminergic medication following successful subthalamic nucleus (STN) stimulation for advanced Parkinson disease (PD). We assessed apathy (Apathy Scale, Apathy Inventory), mood (Montgomery-Asberg Depression Rating Scale), cognitive functions (Mattis Dementia rating scale, frontal score, executive tests) and motor state (UPDRS-III) in 8 PD patients treated with STN stimulation without dopaminergic treatment and who became apathetic. Assessments were made at baseline and after 6 weeks of ropinirole treatment (7.2 +/- 5.9 mg/d; range 1-18 mg/d). Apathy improved with ropinirole in all but 1 patient (54 +/- 24%; range 0-78%). Mood also improved (75 +/- 31%; range 0-100%), but not in correlation with the change in apathy. Cognitive performance was not modified. Stimulation contacts were located within the STN in all patients except the one who remained apathetic in spite of ropinirole treatment (zona incerta). We suggest that apathy, which was compensated for by an enhancement of D2-D3 receptor stimulation in PD patients with STN stimulation: (1) depends on a dopaminergic deficit in associativo-limbic areas of the brain and (2) can be avoided if a dopaminergic agonist is administered postoperatively.

Apathy in Parkinson's disease: clinical features, neural substrates, diagnosis, and treatment

“…In this 12 week prospective, placebocontrolled, randomised, double-blinded trial, 109 the SAS score was reduced by 34·6% in the piribedil group (n=19) compared with 3·2% in the placebo group (n=18; p=0·015) (Level B, one Class I study). In an open-label study, 108 the dopamine D2 and D3 receptor agonist ropinirole proved to be effi cacious in eight patients with apathy after STN-DBS, as shown by substantial decreases in SAS scores after 6 months of treatment. The average score on the SAS decreased from 21·4 (SD 4·0) to 9·9 (SD 6·1) after ropinirole-ie, an improvement of 54% (SD 24%; range 0-78%).…”

“…92,[104][105][106] However, with regard to the on-period motivational aspects of the antiparkinsonian drugs, a slowly progressive desensitisation of the psychotropic eff ects of dopaminergic treatment after drug decrease 107 explains why the hypodopaminergic withdrawal syndrome in patients on chronic STN-DBS typically occurs with a substantial delay of several months after surgery 83,92 (unlike the much more acute withdrawal syndrome after cessation of dopamine agonists in patients not receiving chronic STN-DBS). 93 The potential to reverse postoperative apathy after D2 or D3 receptor stimulation with oral dopamine receptor agonists 108,109 clearly suggests a Parkinson's disease-related symptom that has been unmasked by a decrease in drug treatment. That is, postoperative apathy is not induced by current diff usion to non-motor territories of the subthalamic nucleus, as had been postulated in the absence of an association between reduction in drug treatment and occurrence of apathy.…”

Cognitive and Behavioural Changes After Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease

“…In 7 out of 8 Parkinsonian patients (in which the stimulation contacts were located within the subthalamic nucleus), ropinirole induced an improvement of apathy, while only one patient (in whom the stimulation contacts were located within the zona incerta) remained apathetic. This study suggests that in Parkinsonian patients treated by subthalamic implants apathy may result from a dopaminergic deficiency in associative limbic areas and can be effectively treated in most patients by dopaminergic agonists administered postoperatively (Czernecki et al, 2008).…”

“…The effects of a 6-week treatment with the dopamine D2-D3 agonist ropinirole was investigated in 8 Parkinsonian patients who developed apathy after complete withdrawal from dopaminergic medication, following successful subthalamic implants (Czernecki et al, 2008). In 7 out of 8 Parkinsonian patients (in which the stimulation contacts were located within the subthalamic nucleus), ropinirole induced an improvement of apathy, while only one patient (in whom the stimulation contacts were located within the zona incerta) remained apathetic.…”

Postoperative management of deep brain stimulation in Parkinson’s disease

“…Apathy, defined as lack of interest and motivation, is one of the most frequent psychiatric sideeffects of STN DBS (Funkiewiez et al, 2004;Volkmann et al, 2010). Postoperative apathy is related to excessive withdrawal of dopaminergic treatment (Thobois et al, 2010) and responds well to dopamine agonist drugs (Czernecki et al, 2008). Because of its frequency, delayed appearance, association with other POSTOPERATIVE MANAGEMENT OF DEEP BRAIN STIMULATION IN PARKINSON'S DISEASE 137 hypodopaminergic symptoms, impact on quality of life, and potential reversibility, apathy needs to be screened for systematically, especially during the first year of postoperative follow-up (Thobois et al, 2010;Lhommée et al, 2012).…”