Young age and severity of motor function are risk factors for psychosis after subthalamic nucleus deep brain stimulation for Parkinson's disease

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for motor symptoms in advanced Parkinson’s disease (PD). Various postoperative psychiatric symptoms have been reported following STN-DBS, including delirium, mania, depressive states, aggression, hallucinations, and delusions. We retrospectively analyzed delirium and psychosis after DBS in a consecutive series of patients who underwent bilateral STN-DBS for treatment of PD. This is a retrospective observational study. Delirium was defined according to the Diagnostic and Statistical Manual of Mental Disorders (5th Edition), and postoperative psychosis was defined as organic hallucination based on ICD-10. Patients with major psychiatric problems (e.g., severe depressive episodes, schizophrenia) were excluded. We enrolled 143 patients (75 males, 68 females) who underwent bilateral STN-DBS for PD between August 2015 and September 2018 at Juntendo University Hospital. Before DBS, we assessed the MiniMental State Examination (MMSE), Montreal Cognitive Assessment Japanese version, Frontal Assessment Battery (FAB), Delirium Rating Scale, and Unified Parkinson’s Disease Rating Scale Part III of the International Parkinson and Movement Disorder Society (MDS-UPDRS III). The UPDRS ratio was calculated as follows: [(MDS-UPDRS IIIoff) – (MDS-UPDRS IIIon)/(MDS-UPDRS IIIoff)]. We calculated the levodopa equivalent daily dose (LEDD) three times: before DBS, and 14 and 21 days after DBS. We defined ‘change over time in LEDD’ as [(LEDDbaseline) – (LEDD14 days after DBS)]/(LEDDbaseline), and ‘proportion of dopamine agonist (DA)’ as [(DA LEDD)/(total LEDD)]. The clinical features of the patients are summarized in Table S1. Of the 143 patients, six (4.2%) patients had psychosis after DBS, all within a day after increasing the stimulation. Four patients recovered within several weeks. One patient left the hospital with psychotic symptoms. One patient died by suicide (Table S2). Five of six patients with postoperative psychosis had preoperative pareidolia. Minor preoperative hallucinations may be associated with postoperative psychosis. We reinitiated the stimulation immediately after the psychosis, and DAs were decreased or stopped. If the symptoms still did not improve, patients were treated with antipsychotic medications. We gradually increased the stimulation after the symptoms improved or disappeared (Table S2). In addition, five of six patients with postoperative psychosis presented with dyskinesia, suggesting that postoperative psychosis was associated with dopamine sensitivity. Patients with psychosis were significantly younger than patients with no psychosis (P = 0.0485) (Fig. S1). The MDS-UPDRS III score in the medication-off period before DBS was significantly higher in patients with postoperative psychosis than in patients with no psychosis (P = 0.00136) (Fig. S1). LEDD at 14 and 21 days after DBS was not significantly different in the psychosis group compared to the no psychosis group (Table S1). To compare changes in dopamine over time from baseline to 14 days after DBS, we calculated the change over time in total LEDD [(baseline – 14 days after DBS)/baseline]. We found no significant difference between patients with and without psychosis. It is said that DAs are related to hallucinations and delusions. We compared the proportion of DAs in the total LEDD, which was calculated as (DA LEDD)/ (total LEDD). The proportion of DAs in the psychosis group was significantly higher than in the no psychosis group at 14 days after DBS (t[141] = −2.082, P = 0.0391). However, we found no significant difference between the psychosis and no psychosis groups before surgery (Table S1 and Fig.S1). Age, MMSE, and FAB in patients with delirium were significantly different from patients with no delirium (p[age] = 0.000545, p[MMSE] = 0.0140, p[FAB] = 0.0180) (Table S3). The incidence of hallucination in patients with PD receiving medical treatment is 16.2%, and the incidence of postoperative delirium in elderly non-PD individuals is 10–70%. Our results suggest that DBS surgery did not confer a higher risk of postoperative mental confusion. Shiina (2015) evaluated 32 patients who underwent DBS. At 3 months, 12 patients with psychiatric symptoms had worsened due to DBS. At one year, six patients had some psychiatric symptoms caused by DBS. In our study, continuing DAs without reducing the dose after surgery was a trigger for postoperative psychotic symptoms. Further studies are needed to reveal the mechanisms involved. We identified three interesting differences between psychosis and delirium. First, patients with psychosis were younger than patients with no psychosis. On the other hand, patients with delirium were older than patients with no delirium. Second, cognitive function was related to delirium but not postoperative psychosis. Third, the time of onset was different for delirium compared to psychosis. Delirium was detected immediately after surgery, but psychosis occurred after increasing stimulation. Further studies are needed to reveal the mechanisms involved.