Dear Editor,

Parkinson’s disease (PD) results from the pathological loss or degeneration of dopaminergic neurons in the substantia nigra of the midbrain and the development of neuronal Lewy bodies [1]. In addition to the classical motor symptoms, PD patients also exhibit a variety of non-motor symptoms (NMS). Deep brain stimulation (DBS) is an approved therapy for patients with PD. The beneficial effect of DBS on motor symptoms in PD is well established; however, the impact of DBS on NMS remains to be determined. There is increasing evidence regarding the beneficial effect of DBS on NMS.

Our prospective study was conducted in the Departments of Neurology and Neurosurgery at the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru, India. The study was approved by the Institute Ethics Committee [No. NIMH/DO/IEC (BS&NS DIV)/2018-19]. All patients with PD underwent DBS at our institute and were included in the study after providing written informed consent. Demographic characteristics, clinical characteristics, and scores on motor symptoms and NMS scales were collected, and the data were entered into a Microsoft Excel spreadsheet. The motor severity scales that were used included the unified Parkinson’s Disease Rating Scale part III (UPDRS part III) and Hoehn and Yahr Stage. Various NMS were assessed using the following scales: the Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ), Non-Motor Symptoms Scale (NMSS), Parkinson’s Disease Quality of Life–39 (PDQ-39), Hospital Anxiety and Depression Scale (HADS), Non-Motor Symptom Questionnaire (NMSQ), and Questionnaire for Impulsive Compulsive Disorder in Parkinson’s Disease Rating Scale (QUIP). The anxiety and depression scores were calculated separately using the HADS. These scales were administered at baseline before DBS as well as at 2 months and at 6 months following DBS.

Nineteen patients who underwent bilateral subthalamic nucleus (STN) DBS were included in the study. The mean follow-up duration at the 1st visit was 2.18 ± 0.38 months, and the mean follow-up duration at the 2nd visit was 7.11 ± 1.85 months. Males (n = 14) outnumbered females (n = 5) in the present study. The mean age at disease onset was 38.53 ± 9.22 years (range: 15–56 years). The majority of the patients who underwent DBS had early-onset PD (52.63%), whereas late-onset PD was observed in approximately 47.37% of patients.

A statistically significant improvement was observed for the UPDRS part III score at the 1st visit and at the 2nd visit. There was also a significant reduction in the total levodopa equivalent daily dose (T-LEDD) from the pre-DBS value.

Cognition status assessed by the MoCA did not change over the 6-month period after DBS. None of the patients experienced any worsening of cognition following DBS. The ESS score improved in 11 patients, remained at the status quo in 6 patients and worsened in one patient. Overall, there was a significant improvement in the ESS score at 6 months after DBS. Thirteen (68.42%) patients had poor sleep quality as assessed by the PSQI before DBS, which decreased to 10 (52.63%) after 2 months and subsequently to 6 (31.58%) after 6 months of DBS. There was a nonsignificant improvement in the RBDSQ score. The anxiety and depression scores also improved significantly after DBS. In the mood or cognition domain of the NMS questionnaire, most of the patients (n = 15) showed improvements at 2 months after DBS. After 6 months, mood improved in the majority of patients (n = 16). After analyzing scores in individual domains, it was evident that most of the domains (except memory) improved at 2 months and 6 months after DBS. NMSS scores also significantly improved following DBS. There was a significant reduction in impulse control disorders (ICDs) after DBS according to the QUIP score (p < 0.001).

The mean scores in all domains of the PDQ-39 showed a declining trend after DBS, except for social support, which remained unchanged, and cognition, which initially improved at 2 months but subsequently decreased at 6 months. However, the total PDQ-39 score significantly improved (Table 1, Supplementary Figures 1 and 2 in the online-only Data Supplement). There was no correlation between improvements in motor symptoms and NMS or between changes in LEDD and NMS.

Studies have shown that cognitive impairment after STN-DBS predominantly involves verbal fluency [2]. This was not observed in our study. DBS also has a favorable effect on sleep quality. It increases the total sleep duration and duration of nonrapid eye movement sleep. However, it does not have any effect on periodic limb movements, apnea or RBD [3].

STN-DBS also improves depression and other mood disorders. It is proposed that stimulation of the limbic territory of the STN and modulation of monoaminergic circuits could explain the improvement in depression after DBS. Similar to our study, DBS also improved most of the domains of the NMSS in a questionnaire-based assessment. The NMSS total score and the sleep/fatigue, urinary and miscellaneous domains showed the most significant improvement after STN-DBS [4]. In addition, the frequency of ICDs also decreases following STN-DBS [5]. Only one patient developed an ICD post DBS. The significant improvements in motor symptoms and NMS after DBS could partly explain the improvements in overall quality of life. Nonmotor fluctuations (NMF) are the other group of symptoms seen in patients with PD. DBS has also been shown to improve the NMF of sensory symptoms, pain, dysautonomia and cognitive domains [6]. However, psychiatric fluctuations respond less consistently to DBS. In comparison to studies on the effects of STN-DBS on NMS, there is a paucity of data on the impact of globus pallidum internus (GPi) DBS on these symptoms. There are very few studies that have compared STN versus GPi DBS on NMS. Some data suggest that GPi targeting may have a favorable effect on mood and behavior. There was no discrepancy between the different items on the NMSS or NMSQ and the other scales. Our patients were young, and performing genetic testing would have helped in prognostication. In our country, PD occurs almost a decade earlier than in the Western population, which may explain some disparities observed in other studies [7].

In conclusion, our study demonstrated that STN-DBS affected NMS even at 6 months after DBS. Significant improvements were noted in sleep problems, quality of life, anxiety, depression, ICDs and various domains of the NMSS. However, further studies with large sample sizes and long follow-up periods are needed to determine the impact of DBS on NMS in PD patients.

Supplementary Materials

Notes

Ethics Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all the patients included in the study. The study was approved by the Institute Ethics Committee [No. NIMH/DO/IEC (BS&NS DIV)/2018-19].

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Author Contributions

Conceptualization: Tanaya Mishra, Nitish Kamble, Pramod Kumar Pal. Data curation: Tanaya Mishra, Nitish Kamble. Formal Analysis: Tanaya Mishra, Nitish Kamble, Amitabh Bhattacharya. Investigation: Tanaya Mishra, Nitish Kamble, Amitabh Bhattacharya. Methodology: Tanaya Mishra, Nitish Kamble, Amitabh Bhattacharya. Project administration: Dwarakanath Srinivas, Ravi Yadav, Pramod Kumar Pal. Resources: Dwarakanath Srinivas, Ravi Yadav, Pramod Kumar Pal. Software: Nitish Kamble, Amitabh Bhattacharya. Supervision: Dwarakanath Srinivas, Ravi Yadav, Pramod Kumar Pal. Validation: Dwarakanath Srinivas, Ravi Yadav, Pramod Kumar Pal. Visualization: Tanaya Mishra, Nitish Kamble, Dwarakanath Srinivas, Ravi Yadav, Pramod Kumar Pal. Writing—original draft: Tanaya Mishra, Nitish Kamble. Writing—review & editing: Dwarakanath Srinivas, Ravi Yadav, Pramod Kumar Pal.

Acknowledgments

None

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