|Year : 2021 | Volume
| Issue : 3 | Page : 191-198
Effects of bilateral STN-DBS on psychiatric profile, cognitive aspects, and quality of life in patients with parkinson's disease
Rajesh Alugolu1, S Pavan1, Padmaja Gaddamanugu2, Swapnil Kolpakwar1, Vijaya Saradhi Mudumba1, Rukmini Mridula2, Rupam Borgohain2
1 Department of Neurosurgery, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
|Date of Submission||13-Jun-2021|
|Date of Decision||12-Nov-2021|
|Date of Acceptance||18-Nov-2021|
|Date of Web Publication||27-Dec-2021|
Department of Neurosurgery, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082, Telangana
Source of Support: None, Conflict of Interest: None
Background: Apart from motor manifestations, Parkinson's disease (PD) and associated treatment modalities including DBS are associated with less studied psychiatric and cognitive symptoms. Aim: This study aims to evaluate psychiatric profile, cognition, and quality of life in patients with advanced PD and the effects on STN-DBS on them. Study Design: A prospective, single center, observational study using a direct, structured interview of PD patients. Materials and Methods: All consecutive patients undergoing bilateral STN-DBS between the period June 2017 and December 2019 were evaluated with mini international neuropsychiatric interview (MINI), Addenbrooke's Cognitive Examination (ACE), and PD questionnaire-39 (PDQ-39) before surgery. All these patients were evaluated at 6 weeks postsurgery with MINI and with MINI, ACE and PDQ-39 at 6 months postsurgery. Lead position in magnetic resonance imaging was correlated with psychiatric manifestations. Paired t-test and Wilcoxon sign-rank test were used to study the difference between means. Results: There were a total of 40 cases operated in the study period. There were two patients who had cerebral hemorrhage and two had leads removed due to infection and these patients were excluded from the final analysis. Out of 36 patients, depression was noted in 7 (19.4%), psychosis in 5 (13.8%), anxiety in 10 (27.7%), and suicidal ideation in 2 (5.5%) cases. Postoperatively, 85% of patients with depression, 80% with psychosis, and 80% of patients with anxiety disorders improved. One patient developed new-onset depression and one patient developed visual hallucination. Two patients had acute deterioration in the immediate postoperative period. The patient who developed depression and hallucination had their leads medially located. Mild cognitive decline was noted in verbal fluency which was significant (P = 0.003), and however, there was a significant improvement in quality of life (P = 0.001). Conclusions: Bilateral STN-DBS is a safe and effective therapeutic option and improves psychiatric disorders if the leads are appropriately placed. Although mild cognitive decline occurs, there is overall significant improvement in quality of life.
Keywords: Addenbrooke's cognitive examination, MINI, Parkinson's disease, Parkinson's disease questionnaire-39, psychiatric disorder, STN-DBS
|How to cite this article:|
Alugolu R, Pavan S, Gaddamanugu P, Kolpakwar S, Mudumba VS, Mridula R, Borgohain R. Effects of bilateral STN-DBS on psychiatric profile, cognitive aspects, and quality of life in patients with parkinson's disease. J Neurobehav Sci 2021;8:191-8
|How to cite this URL:|
Alugolu R, Pavan S, Gaddamanugu P, Kolpakwar S, Mudumba VS, Mridula R, Borgohain R. Effects of bilateral STN-DBS on psychiatric profile, cognitive aspects, and quality of life in patients with parkinson's disease. J Neurobehav Sci [serial online] 2021 [cited 2022 May 26];8:191-8. Available from: http://www.jnbsjournal.com/text.asp?2021/8/3/191/333758
| Introduction|| |
Parkinson's disease (PD) is considered one of the most common neurodegenerative motor disorders. It affects 1% of the population over the age of 50 years. It predominantly affects motor functioning which results in bradykinesia, rigidity, and resting tremor. However, it is also known to cause problems with cognition, mood, and behavior which are known as nonmotor manifestations.,
Bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) is known to be valid and relatively safe therapeutic option for the treatment of motor symptoms with low cognitive and behavioral morbidity. Neuropsychological evidence seems to be consistent, which indicates substantial safety of the surgical procedure, and postsurgical cognitive deterioration is comparatively rare. Nevertheless, psychiatric and behavioral effects of this surgical procedure are still inconclusive.
A wide and heterogeneous range of complications ranging from mild to severe depressive episodes, apathy, hypomania/mania, aggressive, and psychotic episodes in the postoperative period have been reported.
We undertook this study to evaluate the effects of bilateral subthalamic nucleus deep brain stimulation on psychiatric profile, cognition, and quality of life, in a prospective cross-sectional study, in patients undergoing STN-DBS in PD and to evaluate the lead position and its correlation with the psychiatric symptomatology.
| Materials and Methods|| |
This study was performed in line with the principles of the Declaration of Helsinki, as revised in 2013. The study was approved by the institutional Ethics Committee of NIMS institutional Ethics committee and Approval No EC/NIMS/1965/2017, dated 25.05.2017. This was a prospective, single-center, observational study which employed a direct, structured interview of PD patients. The study was approved by the Institutional Ethics Committee. An informed written consent by the subjects was obtained for thesis study as well as for the surgical intervention.
A total of 40 patients were prospectively enrolled in the study. Two patients expired of intracerebral bleed and two patients required lead removal due to infection. Remaining 36 patients were followed up for 6 months. Of the 36 patients, 23 patients were male and 13 were female.
All idiopathic PD patients who were found eligible as per CAPSIT-PD5 protocol and were willing to undergo STN-DBS surgery from June 2017 to December 2019 were included in the study.
- Patients who were not stable at the end of 6 months were excluded from the study
- Leads removed due to infection, malfunction, etc.,
- Medical comorbidities with poor medical health
- Psychiatric profiling of patient was done with MINI international neuropsychiatric interview version 7.0.1 which is based on DSM V criteria. (Permission obtained from Dr. Sheehan, Emeritus Professor, University of South Florida, USA, for academic purpose)
- Cognitive assessment using Addenbrooke's Cognitive Examination-III (ACE-III) was performed when the patient was in “ON” state.
- Quality of life assessment using PD questionnaire-39 (PDQ-39) questionnaire in the “ON” state.
Six weeks: Psychiatric profile with MINI.
Six months: Psychiatric profile with MINI, cognition with ACE-III, and quality of life-PDQ-39.
All patients were operated by a single neurosurgeon. Stereotactic surgery was performed using CRW™-Illuminant frame Integra®, USA, using five channel intraoperative microelectrode recording and macroelectrode stimulation. Final lead placement (Medtronic, United Kingdom) in bilateral subthalamic nuclei was based on intraoperative recording and stimulation effects. Postoperative magnetic resonance imaging (MRI) was performed in all cases before implantable pulse generator (Medtronic Activa® P C, United Kingdom) implantation and stimulation to check the position of the leads.
Patients were maintained on monopolar stimulation with frequency of 130–180 Hz, pulse width of 60–90 μs, and amplitude ranging from 2.5 to 4.0V based on response.
Postoperative MRI was obtained and lead positions were checked in relation to the red nucleus. As size and shape of STN varies, we modified the division of STN. A horizontal line (A), tangential line to the anterior tip of red nucleus was drawn. Another tangential line was drawn on the lateral surface of the red nucleus (B). A point 3 mm lateral to the junction of A and B was the target. Line A was extended laterally to divide STN into anterior (ventral) and posterior (dorsal) segments. Another perpendicular line to line A at the target point divided it into medial and lateral compartments. Lead positions in postoperative MRI were correlated with the psychiatric manifestations.
Postoperative lead position was checked on T2-weighted axial imaging and lead position was designated as anterior, medial, posterior, lateral, and central (if at target) based on the quadrants divided [Figure 1].
|Figure 1: Postoperative T2 axial magnetic resonance imaging with subdivision of STN, A – horizontal line, B – vertical line; AL: Anterolateral, AM: Anteromedial, PL: Posterolateral, PM: Posteromedial, C: Central|
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Statistical analysis was done using SPSS software version 21.0.(IBM SPSS Statistics, English version 21.). Continuous variables were presented as mean ± standard deviation paired t-test and Wilcoxon sign-rank test were used to study the difference between means. All tests were two sided and P < 0.05 was considered statistically significant.
| Results|| |
Mean duration of disease was 8.5 years (range 4–12 years). No significant relation could be noted between age, duration of illness, sex, and psychiatric illness. Patients were evaluated individually for psychiatric illness [Table 1]. Paired t-test and Wilcoxon sign-rank test were used to study the difference between means of following disease preoperatively and postoperatively.
Out of 36 patients, 7 (19.4%) had depression preoperatively. Among them, 5 (13.8%) had mild depression and 2 (5.5%) had moderate form of depression. None of the patients had any severe form of depression. Postoperatively, six patients had improvement and one patient developed new-onset depression at the end of 6 months follow-up.
Psychosis and hallucinations
Psychosis was present in 5 (13.8%) patients, of whom two patients had acute deterioration of their symptoms in the immediate postoperative period. Both patients returned to their preoperative status within 72 h. One patient had new-onset visual hallucinations at the end of 6 months follow-up [Figure 2].
|Figure 2: Psychiatric manifestations in preoperative and postoperative period. SI: Suicidal ideation, PD: Panic disorder, OCD: Obsessive compulsive disorder, GAD: Generalized anxiety disorder|
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Suicidal ideation and panic disorder
Mild suicidal ideation was seen in two patients. One patient improved after surgery within 6 weeks while other patient still remained the same. Panic disorder was noted in two patients out of which one patient improved after the surgery at the end of 6 weeks. Agoraphobia and obsessive compulsive disorder were noted in the same patient which improved by 6 weeks.
Social phobia and anxiety
Social phobia was noted in three patients and two patients improved at 6 weeks follow-up and one patient remained the same. Generalized anxiety disorder was noted in two patients before surgery and both patients improved postoperatively [Figure 2].
Cognition was assessed by ACE-III preoperatively and at 6 months after the surgery. Of the various subscales tested, verbal fluency was decreased which was significant (P = 0.003). Rest of all subscales, there was no significant difference noted. When all the subscales were combined, there was a significant decrease in cognition (P = 0.001) noted [Table 2].
Quality of life
Quality of life assessment was done with PDQ-39 preoperatively and at 6 months following the surgery. Except for social support, all other subscales improved significantly [Table 3].
Lead positions were checked based on the quadrant division system described previously [Figure 1]. Postoperatively, two patients had developed new-onset symptoms. Both the patients had leads in anteromedial quadrant. Lead positions of all patients with psychiatric manifestations are presented in [Table 4].
|Table 4: Lead positions with pre- and post-operative psychiatric manifestations|
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| Discussion|| |
PD has been associated with significant nonmotor and cognitive symptoms along with motor manifestations. This, in turn, affects the overall quality of life of the individual. Variable results have been noted in literature pertaining to changes in these manifestations after deep brain stimulation [Table 5]. The present study aimed and evaluated the prevalence of psychiatric manifestations in a group of PD patients presenting for deep brain stimulation and evaluated them in terms of cognition as well as quality of life, both preoperatively and after 6 months of surgery.
|Table 5: Postoperative changes in depression, psychosis, anxiety, and suicide in various studies|
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Improvement in depression has been studied and reported extensively in cases of advanced PD after undergoing DBS. However, reports of new onset of depression and deterioration have also been noted. Houeto et al. reported 30% improvement in depression and new-onset depression in 4% of patients postsurgery. Smeding et al. observed new-onset depression in 3% of patients in postsurgery cases. Castelli et al. reported improvement in 20% of cases and stable course of their depression in the post-operative period (70%) and deterioration in 10% cases. STN-DBS also may improve both mood and anxiety. This is by affecting probably the signaling features of the motor, associative, and limbic circuitry that project to and/or receive input from the STN or by neurotransmission. The exact mechanism remains unknown, but it is hypothesized to reduce disturbances in basal ganglia thalamocortical network (acts as a traffic controller) activity by increasing both excitatory and inhibitory signaling in the STN and adjacent fiber tracts. Although, STN-DBS improves motor manifestations, changes in motor function are not found to correlate with changes in nonmotor symptoms. This suggests that these effects occur independently at an individual level. On evaluation of lead position in case with new-onset depression, it was noted that leads were located in anteromedial quadrant bilaterally and the subsequent activation of limbic circuits could have caused new-onset depression [Table 5].
Postoperative psychosis following STN-DBS has been reported to vary from 1.5% to 4%., Psychosis before stimulation can be attributed to lesionectomy effect of the lead. We noted psychosis in 13.8% of patients and 11% of patients improved at 6 weeks follow-up. One patient had medication induced psychosis due to pramipexole, and following surgery, the medication was switched to levodopa leading to an improvement in symptoms. Improvement in this situation could be attributed to modification of medication postsurgery. Acute deterioration of psychosis noted in 5.5% of patients, returned to base line within 72 h. Bilateral frontal edema due to lead passage, pneumocephalus, and lesion can also cause worsening of the symptoms. New-onset psychosis was seen in about 2.7% of patients, however, after 6 months of surgery in the form of visual hallucinations. Unfortunately, we were unable to determine the cause of these hallucinations.
At 1 year follow-up, anxiety improves along with other mood disorders and the result is more favorable if there is early improvement within 3 months. We noted improvement in anxiety in 80% of patients with no new-onset anxiety symptoms. Houeto et al., however, reported new-onset anxiety in 4% of the patients. Randomized controlled study of 156 patients by Witt et al. comparing STN-DBS with best medical treatment (BMT) available demonstrated Class I data of improvement in anxiety scales at 6-month follow-up after performing DBS. The cause of improvement is not understood completely, but reduced disturbances in basal ganglia thalamocortical network activity could be an important factor. New-onset anxiety has been commonly attributed to fear pertaining to the failure of the device.
Suicide risk has been a matter of considerable debate with varied reports of prevalence, ranging from 4% to 10%., Meta-analysis by Appleby et al. showed that most of the PD patients who underwent thalamic or GPi stimulation reported a suicidal ideation/attempt at 0.3%–0.7% and a completed suicide rate 0.16%–0.32%. They reported dissociation of depression and suicidal risk with improvement of depression, however, the risk of suicide remains same and improved motor outcomes actually led to less monitoring of patients by caregivers. In a randomized controlled study by Weintraub et al., they reported no increased rates of suicidal ideation post-DBS at 6 months. Suicidal ideation in our study was noted in 5.5%, of which 2.7% of patients improved after surgery while 2.7% of patients remained the same. There were no suicidal attempts in our study [Table 5]. Major decrease in dopaminergic medications following the surgery can result in apathy, increased rates of depression. The above factors can contribute toward increased suicidal ideation. Neurological or medical complications are also listed as potential factors for increase in suicidal risk.
PD, is a neurodegenerative disorder, will have a progressive decline in cognition, but following a surgical procedure, the decline is rare. Funkiewiez et al. reported in follow-up of patients for 1 year and 3 years after surgery, there was no significant change noted in the overall cognition. Although, the verbal fluency decreased significantly at 1-year follow-up and remained the same at 3 years. In our study, we found mild decrease in attention, memory, visuospatial, and language functions but these were not demonstrated to be statistically significant. Verbal fluency and overall cognition were significantly decreased after surgery [Table 6]. In a recent meta-analysis by Kurtis et al. concluded after STN-DBS, there is Level I and II type evidence consistently reporting moderate decrease in verbal fluency, as well as a mild reduction in abstract reasoning, working memory and executive functions. However, this mild cognitive deterioration is not known to be clinically relevant. In RCT study by Witt et al., compared with best medical treatment with a follow up of 6 months after STN DBS, concluded no significant decline in overall cognition but a significant decrease was noted in verbal fluency. This decrease albeit had no effect on quality of life. In comparison, medical treatment group had no decline in cognition or verbal fluency. This indicates that the decline was not because of disease progression, but rather the effect of surgery itself. Castelli et al. compared STN-DBS with medical treatment with a follow-up of 3 years and observed no significant overall decline in the cognition in both groups. However, there was significant decline in the DBS group in fluency task. Okun et al. compared with STN-DBS and GPi DBS with a follow-up of 7 months and did not find any difference in overall cognition between the groups as well as pre- and post-operative states. However, the mean letter fluency scores decreased in STN-DBS group when compared to GPi DBS group and the difference was significant.
Quality of life
The main objective of DBS hinges on improving quality of life and minimizing motor symptoms of PD. Erola et al. reported improvement across all subscales at 1 month follow-up and significant improvement is seen in ADL, emotional well-being, stigma, and bodily discomfort. At 12 months follow-up, communication was in fact worse than preoperative status, but had not reached statistical significance. In the present study, patients were evaluated at baseline and 6 months postsurgery. All subscales improved and were statistically significant except for social support which decreased from baseline, but the difference was not significant [Table 7]. Similar findings were noted previously.,
Lead position has been correlated with psychiatric manifestations. Furthermore, ventral or medially located leads having more propensity of causing mood-related symptoms. Okun et al. in COMPARE trial obtained precise locations of these implanted leads with a high-resolution computed tomography (CT) scan which was fused to the preoperative MRI and used an orthogonal Cartesian coordinate system. Based on these tools, they noticed that patients who were less happy and less energetic had leads in ventral location when compared to those patients who had optimal lead location. However, no measurement was done for medial and lateral variation in the above study. In our study, we used postoperative T2-weighted axial image at the red nucleus level to map quadrants of the STN [Figure 1]. Based on the lead locations, patient who had new onset depression had anteromedially placed leads according to the quadrant system. Sudhyadhom et al. used postoperative MRI with overlaid Schaltenbrand and Bailey Atlas More Details to accurately locate the lead after surgery and noticed similar findings. They hypothesized, there could be a spread of current to the limbic circuits which could cause mood disorders and these were seen in patients in medially placed leads. Abulseoud et al. used COMPASS surgical planning software and evaluated the effects of different position of the lead and stimulation effects. They reported abrupt pleasant sensations transient difficulty in emotional recognition, hypomania, and mania which were reproducible with bilateral stimulation of the medial STN. However, their evaluation was only for transient stimulation and long-term effects cannot be concluded from their study. We noticed new-onset visual hallucinations in a patient after the surgery who had his leads located in the medial region. Beside the known activation of limbic areas, it is also possible that STN stimulation induces the activation of extrastriate visual or the lateral temporal cortex. This has been observed by functional MRI and single-photon emission CT in patients with the Charles Bonnet syndrome.
| Conclusions|| |
Bilateral subthalamic nucleus deep brain stimulation improves the psychiatric profile and quality of life significantly with a negative impact on cognition in some of the patients. Medially placed leads are more likely to cause psychiatric disturbances.
Patient informed consent
There is no need for patient informed consent.
Ethics committee approval
The study was approved by the institutional Ethics Committee of NIMS institutional Ethics committee and Approval No EC/NIMS/1965/2017, dated 25.05.2017.
Financial support and sponsorship
No funding was received.
Conflicts of interest
There are no conflicts of interest to declare.
Author contribution subject and rate
- Alugolu Rajesh (25%): Design the research
- Pavan S (15%): Data collection and analyses
- Padmaja Gaddamanugu (15%): Design the research
- Swapnil Kolpakwar (15%): Wrote the manuscript
- M.Vijaya Saradhi (10%): data analyses
- Rukmini Mridula (10%): data analyses
- Rupam Borgohain (10%): data analyses
Authors are pleased to acknowledge Dr. Kode Sashanka, Ms. Syed Tazeem Fathima, and Mr. Santosh Kumar for their invaluable support for conduction of this study.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]