A prospective pilot study of the effects of deep brain stimulation on olfaction and constipation in Parkinson’s disease

Abstract

Background:

Previous studies suggest deep brain stimulation of the subthalamic nucleus (STN-DBS) may improve olfaction and constipation in PD, using subjective measures. Objective: To utilize objective measures to assess olfaction and constipation in PD following STN-DBS.

Methods:

In this prospective pilot study, olfaction (University of Pennsylvania Smell Identification Test [UPSIT]), bowel symptoms (ROME III questionnaires, daily bowel diaries, 100mm visual analog scales for satisfaction with treatment and bowel habits), and motor manifestations of PD were evaluated before and after STN-DBS. Levodopa equivalent daily dose (LEDD) was calculated.

Results:

Ten patients (8 men, mean age 67.4±6.0 years) with mean PD duration of 7.5±3.7 years underwent bilateral STN-DBS, with mean follow-up of 3 months for all measures, except 7 months follow-up for bowel diaries. There was improvement in the Unified Parkinson’s Disease Rating Scale motor “off” scores (33.7±6.7 before and 16.1±10.8 after, P=0.001). Mean UPSIT scores (20.0±6.6 versus 17.5±5.7, P=0.03) worsened from severe to total hyposmia. Seven patients had baseline constipation and completed bowel diaries. There was improvement in number of complete spontaneous bowel motions (CBSM) per week (2.2±1.9 before versus 4.7±2.4 after, P=0.04), satisfaction with treatment of constipation (44±27 before versus 64±25 after, P=0.02), and with bowel motions (33±22 before and 48±20 after, P=0.2). However, laxative use (P=0.15) and LEDD (P=0.15) were unchanged.

Conclusion:

Olfaction worsened while symptoms of constipation improved but did not resolve after STN-DBS.

Introduction

Parkinson’s Disease (PD) is a neurodegenerative disorder with both motor and non-motor features[1]. Over 70% of patients have reduced olfaction, which also affects the appreciation of taste, and can reduce their quality of life [2]. Up to 70% of PD patients report constipation, which may severely impair their quality of life[3].

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective therapy for specified motor complications of PD, including medication-refractory tremor, motor fluctuations, or disabling dyskinesia[4]. There is emerging, albeit weak, evidence that STN-DBS may also improve selective non-motor symptoms of PD, including hyposmia and bowel dysfunction [5–8]. The effects of STN-DBS on olfaction has been evaluated with self-rated assessments, supplemented with limited objective measurements in some studies [5, 9, 10]. Assessment for constipation utilized questions such as “do you have constipation” rather than with daily bowel diaries that document bowel habits [7, 11–13]. Daily bowel diaries provide a more refined assessment of symptoms and, in particular, the day-to-day variability in bowel habits [14].

Hence, we conducted a pilot study to prospectively assess the effects of STN-DBS on bowel habits and olfaction in patients with PD and constipation, using detailed objective measures.

Materials and Methods

Study design

This prospective pilot study was conducted at Mayo Clinic in Rochester, MN between October 2016 and March 2019. The study was approved by the Institutional Review Board at Mayo Clinic. All participants provided informed consent. Surveys and tests were administered at baseline before STN-DBS, and 3 or more months after STN-DBS.

Study subjects

All patients with idiopathic PD between the ages of 18 and 80 years who were being evaluated for DBS, and had symptoms of chronic constipation, were eligible to participate in this study. The inclusion criteria were: a diagnosis of idiopathic PD, based on UK Brain Bank criteria[15]; referral for STN-DBS for medication-resistant motor fluctuations and/or dyskinesia and/or tremor; no changes in PD medications for 3 weeks prior to the study; and chronic constipation for at least 3 months, as suggested by a modified Rome III questionnaire [16] (i.e., 2 or more of the following 6 symptoms: (i) less than 3–4 bowel motions/week, (ii) often or usually have a sense of incomplete emptying after a bowel movement, (iii) often or usually need to strain excessively during a bowel movement, (iv) often or usually had hard or lumpy stools, (v) often or usually have a sense of anal blockage during bowel movement, (vi) and ever need to use anal digitation to enable defecation.

The exclusion criteria were: (i) cognitive impairment, dementia, unstable psychiatric or other disorder that contraindicated STN-DBS, or clinician opinion that the patient would be unable to comply with the study, (ii) another likely cause for constipation (e.g. opioids), and (iii) another cause for impaired olfaction (i.e., head injury, active sinusitis, or current smoking).

Patients who were eligible and consented to participate underwent baseline assessments on the same day.

Assessment of Parkinson’s disease and olfaction

The duration of PD, indication for deep brain stimulation (DBS), and Unified Parkinson’s Disease Rating Scale [UPDRS] part III motor scores off and on medication were recorded. The levodopa equivalent dosage was calculated [17]. The 40-Item University of Pennsylvania Smell Identification Test (UPSIT) was administered according to the manufacturer’s instructions [18]. This test incorporates 40 “scratch-and-smell” odors and is validated for PD[19]. Subjects were presented with a freshly scratched odor-impregnated panel on up to two occasions and asked to choose one of four possible answers. The number of correctly identified odors determines the UPSIT score, which ranges from 0 to 40. Anxiety and depression were evaluated with the Hospital Anxiety and Depression Scale (HADS)[20]. For both subscales (i.e., anxiety and depression), scores of 0–7, 8–10, and 11–21 were respectively normal, borderline, and abnormal.

Assessment of bowel symptoms

The Rome III criteria were assessed at baseline and at follow-up 3 months after STN-DBS. Participants recorded every bowel event in a bowel diary for 4 consecutive weeks at baseline and after STN-DBS. A bowel event was defined as any attempt to defecate and/or a fecal incontinent episode. For each bowel event, participants recorded the circumstances before the event (i.e., straining, digital manipulation, or laxative use), stool leakage, Bristol stool form (1 = pellets, 7 = watery) [21], duration on the toilet, sense of complete evacuation, worst pain, and worst urgency. The data were summarized as the number of spontaneous bowel movements (SBM) and complete spontaneous bowel movements (CSBM). A bowel movement was considered to be spontaneous if the bowel movement was not preceded by the intake of a laxative agent or enema within a period of 24 hours. A SBM was considered complete (i.e., a CSBM) if the subject responded “yes” to the question pertaining to the sense of complete evacuation. Patients graded the severity of their constipationon a 6-point Likert scale as: “I am not troubled by constipation”, “very mild” (can usually be ignored), “mild” (can be ignored if you don’t think about it), “moderate” (cannot be ignored, but does not affect your lifestyle), “severe” (affects your lifestyle) or “very severe” (markedly affects your lifestyle). Finally, patients responded to the following questions, “How satisfied are you with your bowel movements?” and “How satisfied are you with the current treatment of your constipation?” on a 100 mm visual analogue scale (VAS).

Medications

Patients were permitted to continue their bowel regimen (i.e., fiber, bulk laxatives, stool softeners, probiotics, or polyethylene glycol 3350) at the same dose and frequency throughout the study. No patients were on prescription medications to treat constipation. Consistent with current guidelines, patients were permitted to use rescue medications (i.e., bisacodyl 5 mg tablet or 10 mg suppository or up to 2 Fleet’s enemas) for severe constipation (i.e., 72 hours after the last bowel movement or when symptoms became intolerable)[22].

Deep brain stimulation (DBS) surgery

All of the DBS procedures were performed by the same experienced DBS neurosurgeon, with Medtronic (Medtronic Inc., Minneapolis, MN) DBS equipment using established methods [23]. On the morning of the operation, a MRI brain scan was performed. Thereafter, a stereotactic frame was placed. Stimulation leads were placed in bilateral subthalamic nuclei (STN) during a single operation. Lead placement was guided by microelectrode recordings. Pulse generators and lead extensions were implanted approximately 2 weeks later. The patients returned to clinic for monopolar review approximately 2 weeks afterwards, and subsequent programming of DBS parameters at approximately 3 monthly intervals, optimized to treat PD motor symptoms with minimization of stimulation-related side effects.

Statistical analysis

The proportions of patients who had symptoms of constipation before and after DBS were compared with McNemar’s test. The frequency of SBM and CSBM per week was compared with paired t-tests. UPSIT scores were analyzed by a paired t-test and further characterized into tiers of normal or abnormal olfactory function according to age and sex. The HADS scores were compared via a paired t-test and classified as normal, borderline, or abnormal using the standardized scoring sheet. Correlations and comparison of unpaired data were evaluated using Spearman’s Rho and Mann-Whitney U tests. LEDD was determined for PD medications using a validated online calculator. (https://www.Parkinson’ssmeasurement.org/toolBox/levodopaEquivalentDose.htm). Data are summarized as Mean ± SEM.

Results

Demographic and clinical features

Of the 15 recruited patients, 4 withdrew as they did not wish to complete post-operative questionnaires and bowel diaries, and 1 was lost to follow up. Ten participants (8 men, all Caucasians, mean age 67.4 ± 6.0) years) completed the study and are included in the analysis (Table 1). They had PD for 7.5 ± 3.7 years and mean baseline UPDRS part III scores of 33.7 ± 6.7 and 10.4 ± 6.2 off and on medications.

Table 1.

Baseline demographics and PD characteristics of all patients.

Patient	Sex	Age	PD duration (years)	DBS indication	PD Meds	LEDD Pre-DBS	LEDD Post-DBS	UPDRS part 3 Off/On Medication
1	F	66	7	Fluctuations, dyskinesia	L-dopa IR, L-dopa CR, ropinirole	1600	1450	36/11
2	M	63	10	Fluctuations, dyskinesia	L-dopa IR	1800	500	28/8
3	F	71	5	Fluctuations, dyskinesia	L-dopa IR, amantadine, ropinirole	2820	1600	28/5
4	M	78	2	Fluctuations	L-dopa IR, L-dopa CR	2625	2050	38/11
5	M	73	13	Fluctuations, dyskinesia	L-dopa IR, ropinirole	1240	1160	23/9
6	M	63	8	Tremor, dyskinesia	L-dopa IR	1200	1600	46/24
7	M	67	5	Tremor, dyskinesia	L-dopa IR	1000	1050	32/17
8	M	57	8	Tremor, fluctuations, dyskinesia	L-dopa IR, rotigotine, rasagiline	2620	2460	40/3
9	M	71	13	Tremor	L-dopa CR, entacapone	1000	1000	32/6
10	M	65	4	Tremor	L-dopa IR, ropinirole	1120	1320	33/11
	Mean	67.4	7.5			1702.5	1419.0	33.7/10.4
	STD	6.0	3.7			726.8	555.9	6.7/6.2

PD, Parkinson’s disease; DBS, deep brain stimulation; LEDD, levodopa dose equivalence; UPDRS, Unified Parkinson’s Disease Rating Scale; L-dopa, carbidopa levodopa; IR, immediate release; CR, controlled release.

Before DBS, all patients were being treated with carbidopa-levodopa. Six patients received at least one additional dopaminergic medication. Three months after DBS, 3 patients had discontinued at least 1 medication. While the LEDD score was lower after DBS, differences were not significant [baseline LEDD 1702.5 ± 726.8 versus 1419 ± 555.9 (P=0.15) post-DBS].

The mean post-operative follow-up duration was 3 months for clinical assessment and DBS programming, UPDRS part 3, Rome III, UPSIT, and HADS questionnaires; and 7 months for the bowel diaries because of delayed patient completion.

Effects of DBS on olfaction

All 10 participants completed the UPSIT before and after DBS at the 3 month follow-up visit. The mean baseline score was 20.0 ± 6.6, indicative of severe hyposmia. Following DBS, the score declined to 17.5 ± 5.7 (P=0.03), indicative of total hyposmia (Figure 1a).

Fig. 1.

(A) UPSIT scores before and after DBS (n=10). Patient 4 and 10 had the same pre- and post-scores so they appear as 1 line. (B) Number of CSBM per week before and after STN-DBS (n=7). Triangles represent patients constipated at baseline and at follow up. The plain lines represent patients constipated at baseline and with resolution at follow-up.

STN, subthalamic nucleus; DBS, deep brain stimulation; UPSIT, University of Pennsylvania Smell Identification Test.

Effects of DBS on motor symptoms, anxiety and depression

STN-DBS was accompanied by an improvement in the UPDRS motor “off” scores (33.7±6.7 before and 16.1±10.8 after (P=0.001). The only exception was Case 5 in whom gait and the post-operative off score worsened from 23 to 25. This was attributed to suboptimal right-sided electrode lead placement and capsular side effects, despite intraoperative attempts to reposition the electrode from an anterolateral to posteromedial direction due to brain shift during the procedure. The DBS stimulation parameters are listed in Table 2. These were relatively homogenous across patients.

Table 2.

Constipation olfaction, mood, UPDRS part III, and laxative use amongst participants, at baseline compared with post-surgical follow-up; and final DBS programming stimulation parameters.

	Rome III Constipated (Y/N)		SBM/week		CSBM/week		# of Laxatives/week		UPSIT		HADS-Anxiety		HADS-Depression		UPDRS part 3 Off/On Meds		#DBS Final Stimulation Parameters
Patient	Pre	Post	Pre	Post	Pre	Post	Pre	Post	Pre	Post	Pre	Post	Pre	Post	Pre	Post
1	Y	N	7.0	6.7	1.9	5.1	0.6	0.3	28	28	7	7	7	7	36/11	24 off	L: +C −2, 2.0V R: +C −10, 2.0V
2	Y	N	4.5	7.3	1.0	7.0	2.5	0.0	21	19	2	2	2	0	28/8	3 off	L: +2 −1, 2.3V R: +10 −9, 2.3V
3	Y	N	1.9	5.8	1.3	5.8	2.5	6.6	21	13	0	1	1	2	28/5	3 off	L: +C −1, 1.5V R: +C −10, 0.0V
4	Y	Y	4.8	2.7	2.6	2.3	2.2	4.3	13	13	5	4	10	6	38/11	23 off	L: +1 −3, 2.1V R: +10 −8, 2.1V
5	N	N	-	-	-	-	-	-	19	15	4	4	5	6	23/9	25 off	L: +C −2, 1.5V R: +10 −11, 1.5V
6	N	N	-	-	-	-	-	-	31	24	5	3	3	1	46/24	6 off	L: +C −2, 2.25V R: +C −9, 2.2V
7	Y	Y	7.7	8.9	2.7	6.4	0.2	0.0	11	11	9	3	2	6	32/17	8 off	L: +C −1, 1.65V R: +C −11, 1.9V
8	Y	N	8.1	7.0	5.9	5.8	0.0	0.0	25	23	9	8	7	8	40/3	34 off	L: +C −1, 2.5V R: +10 −9, 2.5V
9	Y	N	-	-	-	-	-	-	18	16	8	8	8	8	32/6	14 off	L: +C −2, 2.15V R: +11 −10 +9, 2.1V
10	Y	N	0.0	0.5	0.0	0.5	7.0	7.5	13	13	9	8	4	4	33/11	21 off	L: +C −11, 1.5V R: +C −3, 1.5V
Mean			4.9	5.6	2.2	4.7	2.2	2.7	20	17.5	5.8	4.8	4.9	4.8	33.7/10.4	16.1
SEM			1.2	1.1	0.7	0.9	0.9	1.3	6.6	5.7	3.2	2.7	3.0	2.9	6.7/6.2	10.8

Patients 5, 6 and 9 were excluded from the analysis of bowel functions if bowel diaries were incomplete or if patients did not meet Rome 3 criteria for a diagnosis of functional constipation at baseline.

^#All stimulation parameters utilized pulse width 60μs and frequency 130 Hz. For patient 10, the electrode numbering is switched for the left and right sides, as the electrodes were inserted into the opposite port.

L, Left; R, Right; SBM, Spontaneous Bowel Motion; CSBM, Complete Spontaneous

Bowel Motion; UPSIT, University of Pennsylvania Smell Identification Test; HADS, Hospital Anxiety and Depression Score; UPDRS, Unified Parkinson’s Disease Rating Scale.

Anxiety (5.8 ± 3.2 versus 4.8 ± 2.7, P=0.14) and depression scores (4.9 ± 3.0 versus 4.8 ± 2.9, P=0.89) were not significantly different before versus after STN-DBS (Table 2).

Baseline bowel habits

Based on the screening bowel questionnaire, constipation symptoms included infrequent bowel movements (80%), hard or lumpy stools (100%), excessive straining (80%), sense of anal blockage (40%), anal digitation (30%) during defecation, and a sense of incomplete emptying after defecation (50%). On the baseline Rome III questionnaire, which was administered on the same day, 2 patients (Cases 5 and 6, Table 2) did not fulfill Rome III criteria for constipation because their answers to 3 questions changed from “often” or “usually” to “never” or “sometimes”. Moreover, these patients had 6.3 and 7.3 CSBMs/week (Figure 1a), which is considerably greater than the normal value of ≥ 3 CSBMs/week. One patient (Case 9) did not return the follow-up bowel diary.

Effects of DBS on bowel habits

Constipation, as defined by the Rome III criteria, resolved in 5 of the 8 affected patients (63%, P=0.03) 3 months after DBS. A smaller proportion of patients reported excessive straining to defecate “often” or “usually” after DBS (88% versus 25%, P=0.03). The proportion of patients who reported the sensation of incomplete emptying often or usually also declined but differences were not significant (50% versus 13%, P=0.08). Differences in the proportion of patients who reported fewer than 3 BM per week (29% versus 57%, P=0.2), hard or lumpy stools often or usually (88% versus 38%, P=0.1), the sensation of anal blockage often or usually (0% versus 0%, P=1.0), or the need for digitation (13% versus 13%, P=1.0) were not significant after versus before DBS. On a 6-point Likert scale, the severity of constipation improved from 4 ± 1 to 3± 1 (P=0.02).

Because 1 patient did not return the follow-up bowel diary (Case 9, Table 2), pre- and post STN-DBS bowel diaries were available in 7 patients with baseline constipation. The mean follow-up was 7 months for the diaries because 2 patients (Cases 1 and 8) were reluctant to complete the diaries after surgery. Compared to baseline, the number of SBM was unchanged (4.9 ± 3.0 versus 5.6 ± 2.9, P=0.4) but the number of CSBM increased (2.2 ± 1.9 versus 4.7 ± 2.4, P=0.04, Table 2 and Figure 1a). DBS was associated with a reduction in the proportion of bowel motions that were associated with straining (28% ± 12% versus 7% ± 4%, P=0.09) and the sense of incomplete evacuation (50% ± 9% versus 20% ± 5%, P=0.03, Table 3). Other bowel diary parameters were not different before versus after DBS.

Table 3.

Bowel symptoms as per 4-week bowel diary recorded at baseline and at follow-up for the patients with constipation as per Rome III criteria (n=7).

Bowel symptom	Baseline		Follow-up		P Value
	(Mean)	(SEM)	(Mean)	(SEM)
Stool frequency (per day)	1.1	0.0	1.2	0.1	0.34
Stool frequency (CV [%])	16%	8%	21%	9%	0.73
Bristol stool form score	2.1	0.3	2.7	0.2	0.15
Maximum proportionate stool-form score (%)	55%	8%	62%	8%	0.54
Sense of incomplete evacuation (%)	50%	9%	20%	5%	0.03
Rectal urgency (%)	71%	9%	72%	10%	0.91
Straining to begin (%)	28%	12%	7%	4%	0.09
Straining to end (%)	1%	1%	0%	0%	0.36
Postprandial bowel movements (%)	29%	10%	33%	9%	0.60

CV (%), percent coefficient of variation; SEM, standard error of mean.

After STN-DBS, the VAS scores for satisfaction with the treatment of constipation improved from 44 ± 27 mm to 64 ± 25 mm (P=0.02), and satisfaction with bowel motions also improved from 33 ± 22 to 48 ± 20 (P=0.2). However, the number of laxatives used per week was not different before versus after treatment (2.2 ± 2.4 versus 2.7 ± 3.4, P=0.5).

In an exploratory analysis, age was not correlated with change in SBM (P=1.0) or CSBM (P=0.8). Furthermore, median (interquartile range) age was not different in those whose constipation did and did not resolve (66 [62 – 71] versus 73 [67 – 78], P=0.2). However, the change in UPDRS part 3 was strongly and inversely correlated with change in SBM/week (ρ = −0.76, P=0.046) and CSBM/week ((ρ = −0.76, P=0.046).

Discussion

The rationale for studying the effects of DBS on both constipation and olfaction was: 1) these are two of the most prevalent non-motor features of PD, and negatively impact quality of life, 2) other studies simultaneously assessed the effect of DBS on these symptoms, albeit in a subjective fashion and 3) they readily lend themselves to objective assessment via UPSIT, bowel diaries and bowel symptom questionnaires. This prospective pilot study found that hyposmia objectively worsened, while some symptoms of constipation objectively improved after STN-DBS. However, laxative use, dopaminergic medications, depression, and anxiety were unchanged after DBS.

Olfaction significantly worsened from severe to total hyposmia after DBS. These findings contrast with prior studies, which used subjective questions, limited instruments (e.g., 12-item UPSIT), and reported conflicting outcomes of DBS on olfaction, including early post-operative improvement [9, 10, 24, 25]. Although our findings may be due to natural disease progression, the significant decline within months suggests DBS was time-locked to directly worsened olfaction. Possible pathophysiological mechanisms include lead penetrance through the frontal lobe or a direct effect of stimulation on the STN or its connections. An anatomical substrate for impaired olfaction in PD is atrophy of the orbitofrontal cortex[26] although the DBS lead trajectory is distant from this region. Interestingly, clinically effective bilateral STN-DBS for PD has been associated with decreased regional cerebral metabolic activity on 18F-Fluorodeoxyglucose PET in the orbitofrontal cortex[27], which could suggest a downstream effect of STN stimulation. There was no change in mood in our cases, although depression can be associated with reduced olfactory performance [28]. We did not perform neuropsychometric evaluation at follow-up, although none of the patients had cognitive decline post-operatively to suggest this as an explanation for worsening olfaction.

Before DBS, 80% of patients each reported infrequent bowel movements and excessive straining on the screening questionnaire. These are the most frequently used symptoms to define constipation in PD[29]. However, only 4 of the 9 (44%) patients who completed bowel diaries had <3 SBMs/week during the baseline period. Furthermore, 1 of the 2 patients who reported < 3 bowel movements per week on Rome III questionnaires actually had ≥3 SBMs/week during the baseline diary period. A similar discrepancy between the self-reported (ie, by questionnaire) and actual frequency (ie, by bowel diaries) of bowel movements has been observed in idiopathic chronic constipation[30]. This phenotype of frequent unsatisfactory bowel motions has been described in patients with PD[31] and underscores the need to inquire about other symptoms of constipation as documented in this study.

Although symptoms of constipation improved after STN-DBS, the magnitude of improvement varied among the assessments. The VAS scores for satisfaction with bowel habits and with treatment of constipation significantly improved after STN-DBS. While the minimal clinically important difference for these instruments is unknown, the magnitude of improvement is considerable; for example the average VAS score for satisfaction with the treatment of constipation improved from 44 to 66. Likewise, the average number of CSBMs increased significantly from 2.8 to 4.8/week. Of the individual symptoms, excessive straining improved but other symptoms (ie, anal digitation and blockage, hard stools) did not. Overall, constipation defined by Rome criteria resolved in 63% of affected patients.

PD is associated with both dyssynergic defecation and slow colonic transit[29]. Either can underlie constipation. It is conceivable that indirect or direct effects of STN-DBS could ameliorate these dysfunctions and improve bowel symptoms. This is supported by lower UPDRS part 3 scores, indicating milder PD motor features, correlating with a higher number of SBM and CSBM. The improvement in UPDRS motor scores may translate to improved mobility, although extrapolating from other studies, improved mobility probably has modest effects on bowel habits in constipated patients[32]. Alternatively, by reducing motor fluctuations or motor off-state severity, DBS may improve the rectoanal coordination that is necessary for normal defecation [33]. Additionally, stimulation of the STN may activate autonomic centers or the dorsal motor vagal nucleus, and thus improve gastrointestinal motor features [34]. Dopaminergic medication intake was not associated with changes in bowel symptoms; the lack of significant reduction in LEDD score can be explained by the gradual taper of medication while stimulation parameters were being optimized in the early post-operative period.

The encouraging preliminary findings from this and earlier studies need to be confirmed by larger future studies that assess gastrointestinal symptoms, colonic transit, and anorectal functions before and after STN-DBS [35–37].

The study was limited by small sample size, lack of subject diversity (predominantly Caucasian males), lack of a control group, and short follow-up. Patients were reluctant to complete daily bowel diaries for 1 month before and after DBS and required follow-up phone-calls to do so. This resulted in a mean delay of 4 months between the completion of follow-up diaries and the remaining tests; this was also a barrier to study recruitment and retention. The improvement in bowel symptoms may reflect a placebo effect. However, if there were a substantial placebo effect, olfaction might also have improved.

The strengths of the study are the prospective single-center design using a comprehensive uniform dataset and validated objective measures for assessment of constipation, olfaction, and mood for all participants. Future confirmation of these findings would benefit from a larger controlled study, with greater sex and racial diversity, that also investigates the effects of stimulating the globus pallidus interna. Assessments of colonic transit and anorectal functions may identify the mechanisms by which STN-DBS improves bowel habits [37]. A reassessment of constipation and anosmia after turning off DBS may be useful to assess the effects of stimulation rather than the lesion induced by DBS. The effects of DBS on other non-motor features, such as autonomic and urinary symptoms and their objective tests should also be evaluated.

In this pilot study, olfaction worsened after STN-DBS in PD, while some symptoms of constipation and satisfaction with bowel habits improved. These findings were not associated with changes in laxative use, PD medications, or mood. These preliminary findings should be confirmed by a larger study with longer follow-up.

Highlights.

• Studies report STN-DBS subjectively improves constipation and olfaction in PD

• This study objectively assessed olfaction and constipation pre and post STN-DBS

• Symptoms of constipation, and satisfaction with bowel habits, improved after surgery

• Olfaction worsened after surgery

• These findings were not associated with changes in laxative use or PD medications