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Abstract

Background

The complexity of gastrointestinal (GI) disorders associated with Parkinson's disease (PD) and the significant interactions between GI medications and the dopaminergic axis necessitates expert management. The integrated care model for disorders of the brain-gut interaction (DBGI) has advantages, however, has not been applied in concurrent DBGI and PD.

Objective

To test the hypothesis that our Parkinson's Research and Integrated Support Model (PRISM) will reduce symptom severity and improve the quality of life (QOL) in patients with GI symptoms associated with PD.

Methods

Patients with refractory GI symptoms referred to the PRISM clinic were evaluated and treated by the integrated efforts of movement disorder specialists, neurogastroenterologists, dietitians, occupational therapists, speech-swallow therapists, and neuroscientists. Patients underwent a battery of GI symptoms and QOL questionnaires and personalized actionable biomarkers (motility testing and swallowing studies). Inflammatory markers and stool tests were collected. An individualized standard of care treatment was established based on the specific DBGI diagnosis uncovered during the PRISM evaluation.

Results

44 adult PD patients with GI complaints were evaluated. The most common symptoms included constipation (97%), dysphagia (61%), and gastroesophageal reflux (34%). Actionable biomarkers were highly positive revealing esophageal dysmotility (20/21, 95%), slow-transit constipation (40/42, 90%), intestinal methanogen overgrowth (7/8, 87%), gastroparesis (17/20, 85%), oropharyngeal dysphagia (28/44, 63%), and dyssynergic defecation (27/42, 61%). GI symptom severity and QOL significantly improved (p < 0.05) as measured by all questionnaires.

Conclusions

More severely affected patients with Parkinson's treated with the Fixel PRISM approach showed significant improvements in GI symptom frequency, severity, and QOL.

Plain language summary

Many persons with Parkinson's disease experience severe gastrointestinal symptoms including constipation, difficulty swallowing, and bloating. These symptoms impact the quality of life for persons living with Parkinson's disease, however, are often overlooked and may require specialized care. Recognizing the need for more comprehensive gastrointestinal care for persons with Parkinson's disease, clinicians at the Norman Fixel Institute for Neurologic Diseases developed the Parkinson's Research and Integrated Support Model (PRISM). PRISM is novel clinic which uses an interdisciplinary team of movement disorder experts, neurogastroenterologists, dietitians, occupational therapists, speech-swallow therapists, and neuroscientists to address complex gastrointestinal symptoms associated with Parkinson's disease. The clinic is designed to be person-centric and to occur in a single visit. In this study, 44 persons with Parkinson's disease who were resistant to treatment of their GI dysfunction by a movement disorders neurologist were treated in the PRISM clinic between August 2021 and March 2024. This cohort experienced significant improvements in gastrointestinal symptoms including constipation, as well as overall quality of life, highlighting the importance of interdisciplinary gastrointestinal care for persons with Parkinson's disease.

Keywords

Parkinson's disease constipation gastroenterology integrated care

Introduction

Parkinson's disease (PD) is a chronic neurodegenerative condition characterized by the loss of nigrostriatal dopaminergic innervation as well as degeneration in multiple motor and non-motor basal ganglia circuits. PD manifests with the development of classic motor symptoms including bradykinesia, rigidity, resting tremors, postural instability, and dystonia, though the patterns of symptoms are frequently variable between persons and may change with disease progression. Nonmotor symptoms including psychiatric disturbances, sleep disorders, mood disorders, and gastrointestinal (GI) symptoms are commonly present across all stages of PD and can significantly impact quality of life (QOL).¹ The entire GI system has been shown to be potentially affected in PD, and common manifestations include constipation, dysphagia, and gastroparesis.²

Constipation has been described as the most frequent autonomic symptom of PD, occurring in up to 80%.² Constipation is a clinical diagnosis, but its symptoms do not always correlate with the underlying type—whether slow transit or defecatory disorder/dyssynergia—which is crucial for selecting the appropriate treatment, such as medications or pelvic floor physical therapy. The type of constipation can be confirmed by kidney, ureter, bladder abdominal X-ray (KUB), external anal sphincter electromyography, the balloon distension/expulsion tests, and anorectal manometry (ARM).³ ARM and KUB are useful to triage rectal evacuation disorders and slow transit constipation.^4,5 Dysphagia and gastroparesis are other common GI symptoms which may manifest in advanced PD, frequently heralding disease progression and potential future complications.^6,7 Gastroparesis, in particular, can disrupt medication absorption, leading to erratic drug levels, which may increase the daily duration of OFF states or worsen the severity of OFF episodes in patients experiencing motor fluctuations.^8,9

In recent years, there has been a shift toward providing persons with integrated care, where providers work together as a unified team on all aspects of treatment. By leveraging the expertise of providers from multiple health disciplines, integrated care models aim to provide more holistic and personalized care which can be tailored to the unique needs of a patients.¹⁰ Integrated care has been utilized in a variety of medical specialties including oncology, surgery, primary care, internal medicine, and psychiatry, and it is associated with fewer hospital readmission rates, shorter hospital stays, improved overall survival, and improved patient outcomes.^11–21 However, there has been a slow shift in recent years among experts toward integrated care for patients with severe GI symptomatology. This approach differs from multidisciplinary care, which involves a team of healthcare professionals from various specialties working independently to treat a patient, each focusing on their specific area of expertise. Integrated care, in contrast, is a more holistic approach where professionals coordinate efforts, share information, and create a unified treatment plan that addresses overall health needs.²²

The complexity and severity of GI dysfunction in PD frequently requires expert clinical management. However, there is a paucity of information on the outcomes of integrated care for patients with PD patients and GI symptoms. The Norman Fixel Institute for Neurological Diseases operates in a service and science hub model,²³ and the PRISM system was layered into the existing infrastructure to support interdisciplinary care.²³ The goal of development and deployment of the PRISM model was to establish an integrated clinic to comprehensively evaluate and to treat GI symptoms with an overarching goal of impacting QOL (Figure 1). The research aspect of the PRISM approach was focused on the use of data for quality improvement projects as well as the collection of microbiome data for future correlations. We hypothesized that our integrated holistic approach based on global GI inventories for unresponsive symptoms would improve GI symptom severity and overall QOL. We sought in this project to detail and to share critical aspects of the model including clinic development, clinic flow, impact on GI symptom severity, frequency of symptoms, and QOL. Finally, we endeavored to record and share the challenges associated with establishing a PRISM clinic, including future research directions.

Figure 1.

Overview of how integrated care is achieved with the PRISM approach. Figure created with BioRender.

Methods

Clinic design

The PRISM Clinic was established in August 2021 at the Norman Fixel Institute for Neurologic Diseases at the University of Florida in Gainesville to care for people with PD presenting with severe or difficult to treat GI symptoms. Movement disorder physicians carefully screened patients and generated a referral to the PRISM Clinic when conservative measures performed solely by the movement disorder specialist including dietary modifications, hydration, exercise, and a trial of one or two first-line pharmacologic agents were insufficient or resulted in persistent or worsening GI symptoms. At each PRISM visit, patients were evaluated and treated by an integrated team consisting of movement disorder experts, neurogastroenterologists, dietitians, occupational therapists, speech-swallow therapists, and neuroscientists who each collected data for clinical and potential future research use (Table 1). Unlike traditional multidisciplinary care, the PRISM approach ensured that all team members actively collaborated during the same PRISM clinical session to formulate an organized, uniform, individualized, and standardized treatment plan. Meetings with the entire interdisciplinary team were conducted after each PRISM clinic to discuss patients assessed as well as upcoming patients for the next clinic. Additionally, monthly meetings with the entire team are conducted to resolve outstanding issues or clinical concerns. An overview of the PRISM clinic flow is presented in Figure 2. Six to eight patients were scheduled monthly using this integrated approach. A pragmatic point of care evaluation with KUB was done during the index visit to calculate the Leech score (LS)²⁴ and the rectal gas transaxial area (RGTA)⁵ to screen for slow transit constipation and defecatory disorders respectively. Patients with overt gastroparesis or esophageal dysphagia symptoms underwent a 4-h solid gastric emptying study (GES) and esophagogastroduodenoscopy (EGD) respectively. A yearly screening for oropharyngeal and esophageal disorders was done with videofluoroscopic swallow study (VFSS) with esophagram. See details for comprehensive testing in Table 2.

Figure 2.

PRISM clinic flow.

Table 1.

Sub-specialty providers and their clinical roles.

Provider	Role
Movement disorders specialist (MD)	Medically manage symptoms of PD and related comorbidities including medication adjustments, advanced PD therapies, and lifestyle changes Refer patients to the PRISM clinic
Gastroenterologist (MD)	Perform GI evaluation including imaging studies (e.g., KUB and esophagram), motility testing (e.g., esophageal manometry and ARM), and endoscopy (e.g., EGD and colonoscopy). Formulate step-up treatment with lifestyle changes (e.g., mechanical anti-reflux measures), diet as treatment (e.g., mediterranean diet), pharmacologic intervention (e.g., secretagogue for constipation), and endoscopic therapy (e.g., Esophageal dilation for strictures)
Registered Dietitian	Symptom management (e.g., integration of meal timing with medication schedules, texture-modified diet, weight fluctuations) Provide nutrition education and counseling (e.g., encourage healthy eating habits, cooking demonstrations, meal preparation tips, tools for tracking dietary intake, online resources and support groups) Help patients and families develop a personalized nutrition plan to improve GI functioning (e.g., high-calorie, low-protein meal plan and gastroparesis diet)
Occupational therapist	Assess a person's abilities to perform activities of daily living, paying special attention to the intersections between PD and GI dysfunction Evaluate fine motor skills, gross motor skills, functional mobility, coordination, and balance. Environmental assessment (e.g., home safety, workplace, and community mobility evaluation) Work with patients and families to develop personalized strategies to improve independence and QOL (e.g., environment modifications, adaptive devices, assistive technology)
Pelvic Floor/Health Therapist	Evaluate and treat pelvic floor dysfunction or pain that relates to bowel, bladder and/or sexual function Treat pelvic floor dysfunction with internal and external manual therapy, pelvic floor training, home exercise prescriptions, and transcutaneous electrical nerve stimulation
Speech-swallow therapist	Assess speech and swallow function (e.g., VFSS) Provide targeted interventions to improve swallowing function, reduce risk of aspiration, and enhance nutritional intake (e.g., swallowing techniques, strengthening exercises) Treat swallow dysfunction with electrical stimulation therapy and adaptive eating utensils
Neuroscientist	Perform, analyze, and interpret the results of fecal biomarker analysis (e.g., genetic factors, cellular and molecular mechanisms)
Clinical research coordinator	Administer standardized questionnaires at each visit Coordinate scheduling with patients and organize monthly PRISM clinic team meetings

Table 2.

Clinical indications for GI testing.

Test	Clinical Indications
VFSS	Several studies have reported the need for feeding tubes as a marker for later and for end-stage disease and have shown associations with worse PD survival.^25,26 As such, VFSS testing is conducted yearly to triage oropharyngeal dysfunction and aspiration.²⁷ Examples of oropharyngeal dysfunction includes choking while swallowing, hoarse voice, throat clearing behavior that affects QOL, and/or aspiration pneumonia episode(s).
Abdominal KUB x-ray	KUB can reveal a large stool burden even when PD patients deny constipation or report diarrhea.^28,29 KUB-based LS and RGTA have an acceptable positive predictive value identifying slow-transit constipation (SLC) and defecatory disorders (DD) respectively.^30–33 Thus, all patients underwent KUB to screen the type of constipation.
EGD	Esophageal dysphagia, odynophagia, GERD unresponsive to proton pump inhibitors, nausea/vomiting, and gastroparesis to rule out obstructive causes, and upper GI symptoms associated with weight loss.
ARM	Fecal incontinence, fecal seepage, constipation not responding to first-line therapy, symptoms or imaging suggesting a defecatory disorder.
NM 4-h solid GES	Nausea with or without vomiting and/or early satiety (especially with weight loss) that is refractory to medication.
Hydrogen breath test (HBT)	Hydrogen breath test is performed to evaluate for small intestinal bacterial overgrowth (SIBO)/intestinal methanogen overgrowth (IMO). IMO in particular, is associated with slow intestinal transit and constipation.³⁴ Treating IMO can improve intestinal transit times and constipation.
TBE	Dysphagia, clinical suspicion for esophageal motility disorders
HRM	Used in patients with symptoms of dysphagia and reflux symptoms in whom endoscopy and imaging are unrevealing. HRM assesses esophageal peristalsis, intraluminal pressures, and bolus resistance (outflow obstruction). In patients with oropharyngeal dysphagia symptoms, it can help to determine upper esophageal sphincter abnormalities and triage patients that may benefit from dilation or myotomy. It is the gold standard for the evaluation of esophageal motility disorders such Achalasia.

Patients with PD were administered standard questionnaires at the start of each visit with guidance provided by a clinical research assistant. Care-partner assistance was used to answer questions only when needed. The standardized questionnaires included the Digestion-associated Quality of Life Questionnaire (DQLQ),³⁵ the Gastrointestinal Symptoms Rating Scale (GSRS),³⁶ and the novel in-house questionnaire, the Gainesville Gastrointestinal Symptom Inventory (GGSI). The GGSI was created to gauge GI symptom severity and the impact these symptoms have on QOL and the scale was constructed using Rome IV definitions.³⁷ The GGSI was composed of 7 arms to assess (1) dysphagia, (2) reflux symptoms, (3) dyspepsia/upset stomach, (4) constipation, (5) abdominal pain, (6) diarrhea, and (7) other miscellaneous information (Supplemental Figure 1). GI severity questions were answered on a scale of 0–3 points where never = 0 points, 1 day = 1 point, 2–3 days = 2 points, and 4 days or more = 3 points. QOL effect was evaluated by the following scale: 1 = never or not bothersome, 2 = Mild. not affecting daily activities/meals, 3 = Moderate. Limits some meals/daily activities, 4 = Severe. Limits most meals/daily activities. To minimize recall bias, only symptoms experienced 7 days prior to GGSI administration were considered. The total GGSI score was calculated by adding the total number of points for sections 1–6. A higher GGSI score reflected more severe symptoms and worse overall QOL. Patient responses were collected and stored in REDCap (Research Electronic Data Capture) and on the EPIC Electronic Medical Records.

Patients were additionally sent home with stool collection kits for fecal biomarker analysis to assess microbiota, inflammatory markers, permeability markers, and short-chain fatty acids. Fecal biomarker analysis data was the only test ordered solely for research purposes, and patients who declined to participate were still able to experience integrated care in our clinic. The MyChart patient portal powered by Epic (TM Epic Systems Corporation) was used in the short-term to follow-up with biomarker results and to develop a plan. Standard of care treatment was administered based on diagnosis, and follow-up appointments were scheduled based on acuity and response to treatment. Clinical research assistants contacted patients before and after their scheduled PRISM visit to answer questions and inform patients of care expectations.

Present study

A retrospective IRB approved (IRB202201172) chart review was conducted on patients evaluated in the PRISM clinic between August 2021 and March 2024. Patients were included in the cohort if they met the following criteria: (a) over the age of 18, (b) previous diagnosis of PD, (c) presented to our clinic with GI dysfunction, and (d) completed the GSRS, DQLQ, and the GGSI. Patients with atypical parkinsonism or any other movement disorder were excluded from the analysis. Demographic information, prevalence of GI symptoms, initial visit questionnaire scores, return visit questionnaire scores, and total number of specialized GI tests were collected from individual medical records. Key outcome variables for the analysis included the difference in total GI symptoms scores as measured by the GGSI and total QOL score as measured by the GGSI. Secondary outcome variables included the difference in initial and return visit GGSI individual arm scores, the DQLQ scores, and the GSRS scores.

Results were reported as means (SD), frequencies, and percentages unless otherwise stated. Paired t-tests were used for all comparisons. Normality was established with a Shapiro-Wilk test. For data that was not normally distributed, (GGSI abdominal pain scores, GGSI diarrhea scores, and all GSRS sub-scores) a Wilcoxon Signed Rank Test was utilized, and data was reported as median (IQR). All statistical analyses were conducted in SigmaPlot 15.

Results

There were 50 adult patients with PD and severe GI symptoms reviewed, and 44 patients were included in the analysis. Six patients were excluded because their GSRS, DQLQ, and/or GGSI records were incomplete. The mean age was 70 (±8.78) years, and 22 were female. The average PD duration was 6.8 years and the mean Hoehn and Yahr scale score was 2.45 (±0.91). Most patients (n = 31, 70.4%) did not receive deep brain stimulation (DBS). Of the original 44, 15 (34.1%) were seen at follow-up with an average of 200 days between the initial and return visit. The most common GI complaints in the cohort were constipation (97%), dysphagia (61%), gastroesophageal reflux disease (GERD) (34%), and bloating (20%). Other complains included stool incontinence, dyspepsia (11%), abdominal pain (9%), and diarrhea in 2 (4%). Ancillary testing results (Table 3) revealed esophageal dysmotility (20/21, 95%), slow-transit constipation (40/42, 90%), Intestinal methanogen overgrowth (7/8, 87%), gastroparesis (17/20, 85%), oropharyngeal dysphagia (28/44, 63%), and dyssynergic defecation (27/42, 61%). 31 patients (62%) provided informed consent for fecal biomarker analysis. Of these, 12 samples (5 PD, 7 healthy control) were returned. No repeat samples were collected from any patients.

Table 3.

Ancillary test results.

Chronic Constipation
Test and Disorder	Frequency Administered	Abnormal Test
KUB	42 (95.5%)	42 (100%)
STC		40 (90.9%)
DD		27 (61.4%)
Combined STC and DD		26 (59.1%)
ARM (DD)	14 (31.8%)	12 (85.7%)
Hydrogen Breath Test (SIBO, IMO)	8 (18.2%)	7 (87.5%)
Dysphagia
VFSS (oropharyngeal dysphagia)	44 (100%)	28 (63.4%)
HRM (DD)	21 (47.7%)	20 (95.2%)
Gastroparesis
Gastric emptying study (gastroparesis)	20 (45.5%%)	17 (85%)

Values are reported as n (%). Frequency administered is calculated from the total number of patients in the analysis. KUB slow transit constipation (STC) is defined as a LS > 7. KUB defecatory disorder (DD) is defined as an RGTA if >9 mm². Gastroparesis is defined as >10% retention at 4-h on NM 4-h solid gastric emptying study.

At the initial visit, the median number of hard stools per week was 2, median number of skipped bowel movements (BM) per week was 2, and median number of incomplete BMs per week was 2. At the return visit, the median number of hard stools per week decreased to 0.5, the median number of skipped BMs per week to 1, and the median number of incomplete BMs per week to 1.5. For the 15 patients who had a follow-up visit, the GGSI GI symptoms score (p = 0.006), the GGSI QOL score (p = 0.002), the GGSI dysphagia arm score (p = 0.049), and the GGSI constipation arm score (p < 0.001) all significantly decreased at the return visit (Table 4, Figure 3). The DQLQ (p = 0.021) and GSRS scores (p = 0.016) similarly decreased significantly at the return visit (Table 5).

Figure 3.

Line graph of initial and return visit questionnaire scores.

Table 4.

Initial and return GGSI scores.

	Initial GGSI (n = 15)	Return GGSI (n = 15)	P-value
GI Symptoms Total Score	8.422 (2.174)	5.924 (1.530)	0.006
Dysphagia Arm Score	2.971 (0.767)	0.915 (0.236)	0.049
Reflux Arm Score	2.059 (0.532)	0.743 (0.192)	0.796
Nausea Arm Score	2.554 (0.659)	0.990 (0.256)	0.217
Constipation Arm Score	2.908 (0.751)	0.799 (0.206)	<0.001
Abdominal Pain Arm Score	0 (0–2)	0 (1–3)	0.391
Diarrhea Arm Score	0 (0–2)	1 (1–1)	0.808
QOL Total Score	4.454 (1.150)	2.808 (0.725)	0.002

The GI symptoms total score is broken into dysphagia, reflux, nausea, constipation, abdominal pain, and diarrhea subscores. GGSI scores are presented as mean (standard deviation) or median (interquartile range).

Table 5.

Initial and return DQLQ and GSRS scores.

	Initial (n = 15)	Return (n = 15)	P-value
DQLQ	2.196 (0.567)	1.925 (0.497)	0.021
GSRS Total Score	23.20 (13.487)	8.267 (7.255)	<0.001
Reflux Score	0 (0–2.5)	0 (0–0)	0.038
Indigestion Score	1.5 (1–2.25)	0.25 (0–1)	<0.001
Constipation Score	1.2 (0.9–2.432)	0.567 (0.333–1.167)	0.014
Abdominal Pain Score	0.67 (0–2.34)	0 (0–0)	0.012
Diarrhea Score	0 (0–1.67)	0 (0–0.67)	0.399

GSRS score is broken into reflux, indigestion, constipation, abdominal pain, and diarrhea subscores. DQLQ and GSRS scores are presented as mean (standard deviation). GSRS subscores are reported as median (interquartile range).

Discussion

The complexity and severity of GI disorders associated with PD, especially constipation, significantly affects QOL and in severe cases require expert clinical management.¹ We have developed an integrated clinic that combines specialized expertise, innovative application of GI diagnostic tools and tests, as well as patient-centered care in a deliberate effort to address the complex needs of those with severe GI symptoms. Our data demonstrated that patients with severe GI symptoms treated with the PRISM approach had significant improvements on GI symptom frequency, severity, and overall QOL which was confirmed by using multiple questionnaires.

The most common symptoms presented in our cohort included constipation (97%), dysphagia (61%), and GERD (34%). The most common actionable biomarkers applied included VFSS (100%), KUB (96%), and esophageal HRM (47%). The pragmatic point of care approach of the index visit (standard questionnaires, KUB, VFSS) and the effectiveness of the personalized PRISM approach highlights its potential for replication in other healthcare settings to benefit a broader population of PD patients.

The findings of this study suggest patients treated in our clinic experience significantly worse symptoms and GI dysfunction than the general population of patients with PD.³⁸ The KUB performed in 95% of patients showed abnormalities in 100% of cases. 87% of patients tested in our clinic demonstrated delayed gastric emptying on NM 4-h solid GES. While some studies have reported delayed gastric emptying in up to 50% of PD patients,^39,40 others have found no significant differences compared to age-matched controls.^41–43 Interestingly, the cardinal symptoms of gastroparesis including nausea and vomiting were not as prevalent in this cohort. This may reflect the heterogenous nature of PD, individual compensatory mechanisms to reduce unwanted GI symptoms, medication interactions, or severity of other common, more bothersome GI symptoms such as severe constipation. However, the diagnosis of gastroparesis is critical because the efficacy of PD medications can be affected by gastric emptying times.⁴² VFSS detected oropharyngeal dysfunction in 63% of tested patients, exceeding prior estimates of 35–55% in PD.^44–46 ARM findings were abnormal in 85% of tested patients, suggesting that defecatory disorders are common in patients with severe constipation, with prevalence exceeding literature estimates by up to 19%.^47–50 Lastly, HBT results were abnormal in 87% of patients, exceeding previously reported small intestinal bacterial and methanogen overgrowth prevalence rates in PD, ranging from 25.3% to 70%.^51–53 It is likely that the prevalence of these symptoms is greater in our cohort compared to the general population of PD because the PRISM clinic is designed for PD patients with severe GI dysfunction failing first line therapies. These findings reinforce the importance of comprehensive GI evaluations in PD patients, as motility disorders, defecatory disorders, and bacterial/methanogen overgrowth appear to be more widespread than previously reported. Furthermore, the results of this analysis highlight how GI symptoms rarely present alone but rather, as complex upper and lower syndromes. Many patients in this cohort presented with a constellation of symptoms that include constipation, dysphagia, and bloating. This finding suggests that the entire GI system is affected in PD rather than isolated organs and clinicians should consider addressing GI symptoms in a systemic, holistic manner.

Our paper represents one of the early attempts at implementing an integrated care model specifically tailored to PD patients with severe refractory GI symptoms. The PRISM Clinic model was meticulously designed following the guidelines outlined by Radder et al.⁵⁴ to minimize delays in receiving specialized PD care, while also improving patient access and leveraging the Fixel Service and Science hub model.²³ The streamlined referral process, guided by movement disorders specialists, prioritizes individuals with the most pressing needs, and thus minimizes delays in receiving crucial treatments. Proper evaluation and testing facilitated an enhanced understanding of the multifactorial nature of GI dysfunction in PD with the aim of implementing a combination of dietary, pharmacological, and psychological therapies. Constant communication between patients and clinical research staff before and after PRISM clinic visits facilitated a supportive and collaborative relationship between patients and providers, which may have reduced appointment cancellations and improved compliance to treatment regimens. Furthermore, monthly meetings involving the entire integrative team ensured regular updates on patient progress, refinement of treatment strategies, and interdisciplinary feedback to align care plans across specialties. The integration of multiple same-day appointments and diagnostic procedures additionally optimized efficiency while minimizing inconvenience. This pathway facilitated a timely diagnosis and intervention strategy and enabled more effective management.

The novel GGSI questionnaire we developed has yet to be validated, however we chose the items to be more PD specific and to provide information to aid clinicians in decision making.^35,55 The GGSI was unique compared to the other questionnaires as it combined evaluation of GI symptom severity and QOL metrics into one objective questionnaire. This combined approach minimized the need to administer multiple questionnaires and thus may have the potential to reduce fatigue. The GGSI additionally presented clinical questions in simple language to enable comprehension and accurate documentation of symptoms. Future research aims to validate the GGSI to improve reliability and sensitivity in assessing GI symptoms and QOL in PD patients. Validation studies will also provide insight in GGSI interpretation, including what scores are correlated with mild, moderate, and severe symptoms in PD patients.

In our experience, the creation of a novel, integrated specialty clinic presented clinicians and researchers with unique challenges. The process of scheduling had to accommodate the patient with the disease and provider availability, minimize wait times, and effectively manage unexpected changes or cancellations.⁵⁶ Depending on availability, it may not in every case be possible to schedule the entire team or anticipate the procedures which will be required on a single visit. Patients traveling from distant locations, those working, those with other health problems or family obligations had to be accommodated. The future use of telemedicine and remote assessment may be a potential solution to some of the logistical challenges.

The optimal frequency of PRISM clinic dates per month to maximize access to care while efficiently utilizing clinic resources will need to be better defined. Holding one clinic day a month led to increased waiting times, which created barriers to access. These barriers were mitigated by encouraging a direct channel of communication with clinical coordinators and providers by remote access using the MyChart patient portal powered by Epic (TM Epic Systems Corporation).

Collecting fecal samples for fecal biomarker analysis created unique challenges for both clinical and research aims. Obtaining consent for fecal biomarker analysis and providing stool collection kits was initiated in August 2023. Fecal collection kits were mailed or provided to patients in the PRISM clinic. While no conclusions can be drawn at this stage regarding this ancillary investigation, it has been difficult to obtain a sufficient sample size due to issues with constipation and other confounding factors. Stool samples can prove difficult to collect, patients frequently forget to collect their stool, and some perceive that handling stool may be unhygienic and embarrassing.⁵⁷ Additionally, patients with severe constipation may not produce enough stool for collection or may be in pain while producing stool and thus disregard collection. These challenges, combined with the lack of time to collect stools, led to delays in obtaining fecal biomarker data to share with clinicians and to use for research. To address these challenges, we use convenient, at-home microbiome kits for collections and plan to educate patients on the timing of collection to ease these issues. We will continue to collaborate with our multidisciplinary team (e.g., nurses, dietitians, and physiotherapists) to manage constipation more effectively and facilitate stool collection. Furthermore, we are hopeful that in 2025, with increased staffing, we will be able to collect more samples to run microbiota and biomarker analyses. Future studies will aim to evaluate the results of our fecal biomarker analyses as well as strategies to improve recruitment rates to better understand the efficacy of our service and science hub model.

Despite these challenges, we found that the integrative approach, guided by standardized protocols, facilitated a more comprehensive and structured evaluation for our patients. This likely improved diagnostic accuracy and treatment consistency, making the process more efficient and accessible for patients. Moreover, we believe that the expertise of individual providers in PD-related GI issues—when applied within a shared protocol—resulted in better outcomes compared to independent assessments by non-specialists. The integrated nature of the clinic allowed for a holistic approach, incorporating nutritional, psychological, and rehabilitative support which not only enhanced diagnostic precision, but also contributed to overall improvements in patient QOL.

While it is possible that the improvements in our patients’ symptoms may have been due to the utilization of medical interventions available outside of an integrated care model, this clinic's success was likely facilitated by the combination of unique resources including funding to create integrative centers, neurogastroenterology testing availability, clinical expertise with PD, and the use of clinical coordinators. Smaller and non-university based medical centers with less access to funding and to specialists may not be able to recapitulate this model. Neuro-gastroenterologists in particularly are especially scarce worldwide, representing a minority of all GI providers.^58,59 Future studies should evaluate long term complications, morbidity and mortality rates, and hospitalization records of PRISM patients. We should thus examine associated healthcare costs before recommending this model to a larger number of centers.

A limited number of PD patients with refractory GI symptoms were referred to our clinic, inducing a selection bias and effectively limiting the sample size of this analysis. The small sample size in this analysis reflects the early stage of our clinic's development rather than the potential patient population, as our clinic is unique in focusing on GI symptoms in PD. However, this relatively small number of patients facilitated an opportunity to refine our clinic flow, optimize diagnostic tools, and to evaluate longitudinal preliminary patient outcomes. Given the results of this pilot study, we plan to expand our clinic to a larger number of patients.

Furthermore, interview-style questionnaires can introduce bias, which may affect the accuracy and reliability of results.⁶⁰ Interview-style questionnaires, while valuable for data collection, are prone to several biases that can impact the reliability and validity of the results including interviewer bias (the interviewer's behavior, tone, or phrasing can influence the respondent's answers), response bias (respondents may provide answers they think are socially desirable or acceptable rather than their true feelings), recall bias (respondents may have difficulty accurately remembering past events or experiences), sampling bias (if the sample is not representative of the larger population, the results may be skewed), confirmation bias (interviewers may unintentionally seek out information that confirms preconceived notions), and cultural bias (cultural differences can affect the interpretation and responses to questions). Addressing these biases through careful design and implementation of interview-style questionnaires will be essential.

One key area for future research will be to validate the GGSI constructed for this clinic as the field needs more diagnostic and screening instruments validated in PD populations. Because levodopa has the potential to affect gastrointestinal motility and growing evidence suggests that GI health influences drug pharmacokinetics, it would be valuable to investigate whether improvements in quality of life observed in patients treated with this interdisciplinary approach are associated with enhanced dopa-responsiveness, potentially mediated by changes in levodopa equivalent daily dose or absorption. Additionally, the effect of DBS on GI symptoms in PD is under-investigated. Current studies lack rigorous design, show weak retrospective correlations, and do not assess GI motility or systematically evaluate the effects of medications and DBS settings. To bridge this gap in the literature, a thorough assessment of postoperative GI symptomatology through analysis of GI symptom questionnaire and biomarkers following DBS therapy will be necessary.

Conclusion

Patients with severe GI symptoms and PD cared for using the PRISM approach experienced positive impacts on the overall severity of gastrointestinal symptoms and QOL. The model is a promising approach to enhance care and outcomes in this population, though scalability, cost and long-term benefits in reducing GI related hospitalizations will require further study.

Supplemental Material

sj-pdf-1-pkn-10.1177_1877718X251335047 - Supplemental material for The fixel GI Parkinson's research and integrated support model (PRISM)

Supplemental material, sj-pdf-1-pkn-10.1177_1877718X251335047 for The fixel GI Parkinson's research and integrated support model (PRISM) by Grace Hey, Manuel Amaris, Matthew Beke, Nur Walker-Pizarro, Candice Rogers, Vinata Vedam-Mai, Rachael Dorsey, Nicole Herndon, Michael S Okun and Adolfo Ramirez-Zamora in Journal of Parkinson's Disease

Footnotes

Acknowledgments

The authors have no acknowledgments to report.

ORCID iDs

Grace Hey

Manuel Amaris

Matthew Beke

Nur Walker-Pizarro

Vinata Vedam-Mai

Michael S Okun

Adolfo Ramirez-Zamora

Ethical considerations

IRB approval was obtained to perform the research outlined in this manuscript (IRB202201172). We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Consent to participate

Informed consent was obtained from all research participants.

Consent for publication

Not applicable

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Ramirez-Zamora has received research support from the Parkinson's Foundation and consulting honoraria from Medtronic Inc, Boston Scientific, Cerevel therapeutics, Blue Rock Therapeutic, Iota Inc, and Signant Health in the past 12 months. Dr. Okun serves as Medical Advisor the Parkinson's Foundation, and has received research grants from NIH, Parkinson's Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. Dr. Okun's research is supported by: R01 NS131342 NIH R01 NR014852, R01NS096008, UH3NS119844, U01NS119562. Dr. Okun has received royalties for publications with Hachette Book Group, Demos, Manson, Amazon, Smashwords, Books4Patients, Perseus, Robert Rose, Oxford and Cambridge (movement disorders books). The institution and not Dr. Okun receives grants from industry. All other authors have no additional financial disclosures to report.

Data availability

Our data cannot be shared because it contains Protected Health Information which we are not permitted to disclose outside of individuals who are listed on the approved research protocol.

Supplemental material

Supplemental material for this article is available online.

References

Chaudhuri

Schapira

. Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment. Lancet Neurol 2009; 8: 464–474.

Bock

Brown

Zhang

, et al. Association of motor and nonmotor symptoms with health-related quality of life in a large online cohort of people with Parkinson disease. Neurology 2022; 98: e2194–e2203.

Jost

Schrank

Herold

, et al. Functional outlet obstruction: anismus, spastic pelvic floor syndrome, and dyscoordination of the voluntary sphincter muscles. Definition, diagnosis, and treatment from the neurologic point of view. Scand J Gastroenterol 1999; 34: 449–453.

Cangemi

Flanagan

Barshop

, et al. Colonic stool burden a useful surrogate for slow transit constipation as determined by a radiopaque transit study. Am J Gastroenterol 2019; 114: 519–523.

Park

Khemani

Acosta

, et al. Rectal gas volume: Defining cut-offs for screening for evacuation disorders in patients with constipation. Neurogastroenterol Motil 2017; 29.

Sobotka

Chen

, et al. Altered pharyngeal muscles in Parkinson disease. J Neuropathol Exp Neurol 2012; 71: 520–530.

Gong

Gao

Liu

, et al. The prevalence and associated factors of dysphagia in Parkinson's disease: a systematic review and meta-analysis. Front Neurol 2022; 13: 1000527.

Heetun

Quigley

. Gastroparesis and Parkinson's disease: a systematic review. Parkinsonism Relat Disord 2012; 18: 433–440.

Soliman

Coffin

Gourcerol

. Gastroparesis in Parkinson disease: pathophysiology, and clinical management. Brain Sci 2021; 11: 831.

10.

Choi

Pak

. Multidisciplinarity, interdisciplinarity and transdisciplinarity in health research, services, education and policy: 1. Definitions, objectives, and evidence of effectiveness. Clin Invest Med 2006; 29: 351–364.

11.

Herkert

Kraal

Spee

, et al. Quality assessment of an integrated care pathway using telemonitoring in patients with chronic heart failure and chronic obstructive pulmonary disease: protocol for a quasi-experimental study. JMIR Res Protoc 2020; 9: e20571.

12.

Lanning

Longstaff

Jones

, et al. Modern innovative solutions in improving outcomes in chronic obstructive pulmonary disease (MISSION COPD): mixed methods evaluation of a novel integrated care clinic. Interact J Med Res 2019; 8: e9637.

13.

Vohs

Shi

Holmes

, et al. Novel approach to integrating mental health care into a primary care setting: development, implementation, and outcomes. J Clin Psychol Med Settings 2023; 30: 3–16.

14.

Stoltenberg

Kennedy

Rico

, et al. Developing a novel integrated geriatric palliative care consultation program for the emergency department. J Am Coll Emerg Physicians Open 2022; 3: e12860.

15.

Vedel

De Stampa

Bergman

, et al. A novel model of integrated care for the elderly: COPA, coordination of professional care for the elderly. Aging Clin Exp Res 2009; 21: 414–423.

16.

Ahmadi

Mbuagbaw

Finley

, et al. Impact of the integrated comprehensive care program post-thoracic surgery: a propensity score-matched study. J Thorac Cardiovasc Surg 2021; 162: 321–330 e321.

17.

Desai

Liou

Liang

, et al. Availability of integrative medicine therapies at national cancer institute-designated comprehensive cancer centers and community hospitals. J Altern Complement Med 2021; 27: 1011–1013.

18.

Yun

Sun

Mao

. Growth of integrative medicine at leading cancer centers between 2009 and 2016: A systematic analysis of NCI-designated comprehensive cancer center websites. J Natl Cancer Inst Monogr 2017; 2017.

19.

Witt

Balneaves

Cardoso

, et al. A comprehensive definition for integrative oncology. J Natl Cancer Inst Monogr 2017; 2017: lgx012.

20.

Raff

Dorr-Harim

Otto

, et al. Prehabilitation in an integrative medicine day clinic for patients undergoing neoadjuvant treatment: single-center feasibility pilot study. JMIR Res Protoc 2023; 12: e46765.

21.

Ruan

Chen

Tran

BNN

, et al. Integrative medicine in plastic surgery: a systematic review of our literature. Ann Plast Surg 2019; 82: 459–468.

22.

Jessup

. Interdisciplinary versus multidisciplinary care teams: do we understand the difference? Aust Health Rev 2007; 31: 330–331.

23.

Okun

Ramirez-Zamora

Foote

. Neuromedicine service and science hub model. JAMA Neurol 2018; 75: 271–272.

24.

Leech

McHugh

Sullivan

. Evaluation of a method of assessing faecal loading on plain abdominal radiographs in children. Pediatr Radiol 1999; 29: 255–258.

25.

Brown

Oswal

Samra

, et al. Mortality and institutionalization after percutaneous endoscopic gastrostomy in Parkinson's disease and related conditions. Mov Disord Clin Pract 2020; 7: 509–515.

26.

Kim

Jones

Shireman

, et al. Trends and outcomes associated with gastrostomy tube placement in common neurodegenerative disorders. Clin Park Relat Disord 2021; 4: 100088.

27.

Tjaden

. Speech and swallowing in Parkinson's disease. Top Geriatr Rehabil 2008; 24: 115–126.

28.

Quigley

EMM

. Constipation in Parkinson's disease. Semin Neurol 2023; 43: 562–571.

29.

Tucker

Ryan

Hayee

, et al. Distinctive pathophysiology underlying constipation in Parkinson's disease: implications for cognitive inefficiency. J Clin Med 2020; 9: 1916.

30.

Park

Khemani

Nelson

, et al. Rectal gas volume measured by computerized tomography identifies evacuation disorders in patients with constipation. Clin Gastroenterol Hepatol 2017; 15: 543–552 e544.

31.

Rezazadeh

Javaherizadeh

Chahardahcherik

, et al. Reliability of Barr, Leech, and Blethyn Score in using of plain radiography in determining fecal impaction in children with and without constipation. Arq Gastroenterol 2016; 53: 141–145.

32.

Pedrosa Carrasco

Timmermann

Pedrosa

. Management of constipation in patients with Parkinson's disease. NPJ Parkinsons Dis 2018; 4: 6.

33.

Koh

Lee

Kim

, et al. Simple diagnostic approach to childhood fecal retention using the leech score and Bristol stool form scale in medical practice. J Gastroenterol Hepatol 2010; 25: 334–338.

34.

Mehravar

Takakura

Wang

, et al. Symptom profile of patients with intestinal methanogen overgrowth: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. Epub ahead of print August 13, 2024. DOI: 10.1016/j.cgh.2024.07.020.

35.

Beke

Burns

Weir

, et al. Validation of a novel quality of life questionnaire: the digestion-associated quality of life questionnaire (DQLQ). Health Qual Life Outcomes 2022; 20: 53.

36.

Revicki

Wood

Wiklund

, et al. Reliability and validity of the gastrointestinal symptom rating scale in patients with gastroesophageal reflux disease. Qual Life Res 1998; 7: 75–83.

37.

Simren

Palsson

Whitehead

. Update on Rome IV criteria for colorectal disorders: implications for clinical practice. Curr Gastroenterol Rep 2017; 19: 15.

38.

Borghammer

Knudsen

Fedorova

, et al. Imaging Parkinson's disease below the neck. NPJ Parkinsons Dis 2017; 3: 15.

39.

Verbaan

Marinus

Visser

, et al. Patient-reported autonomic symptoms in Parkinson disease. Neurology 2007; 69: 333–341.

40.

Djaldetti

Baron

Ziv

, et al. Gastric emptying in Parkinson's disease. Neurology 1996; 46: 1051–1054.

41.

Evans

Broe

Triggs

, et al. Gastric emptying rate and the systemic availability of levodopa in the elderly parkinsonian patient. Neurology 1981; 31: 1288–1288.

42.

Hardoff

Sula

Tamir

, et al. Gastric emptying time and gastric motility in patients with Parkinson's disease. Mov Disord 2001; 16: 1041–1047.

43.

Trahair

Kimber

Flabouris

, et al. Gastric emptying, postprandial blood pressure, glycaemia and splanchnic flow in Parkinson’s disease. World J Gastroenterol 2016; 22: 4860–4867.

44.

Leopold

Kagel

. Pharyngo-esophageal dysphagia in Parkinson's disease. Dysphagia 1997; 12: 11–18.

45.

Kalf

de Swart

BJM

Bloem

, et al. Prevalence of oropharyngeal dysphagia in Parkinson’s disease: a meta-analysis. Parkinsonism Relat Disord 2012; 18: 311–315.

46.

Noyce

Silveira-Moriyama

Gilpin

, et al. Severe dysphagia as a presentation of Parkinson's disease. Mov Disord 2011; 27: 457–458.

47.

Damian

Adler

Hentz

, et al. Autonomic function, as self-reported on the SCOPA-autonomic questionnaire, is normal in essential tremor but not in Parkinson's disease. Parkinsonism Relat Disord 2012; 18: 1089–1093.

48.

Visser

Marinus

Stiggelbout

, et al. Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA-AUT. Mov Disord 2004; 19: 1306–1312.

49.

Rodriguez-Blazquez

Forjaz

Frades-Payo

, et al. Independent validation of the scales for outcomes in Parkinson’s disease-autonomic (SCOPA-AUT). Eur J Neurol 2010; 17: 194–201.

50.

Edwards

Pfeiffer

Quigley

EMM

, et al. Gastrointestinal symptoms in Parkinson's disease. Mov Disord 2004; 6: 151–156.

51.

Tan

Mahadeva

Thalha

, et al. Small intestinal bacterial overgrowth in Parkinson's disease. Parkinsonism Relat Disord 2014; 20: 535–540.

52.

Dobbs

Charlett

Dobbs

, et al. Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study. Gut Pathogens 2012; 4: 12.

53.

Gabrielli

Bonazzi

Scarpellini

, et al. Prevalence of small intestinal bacterial overgrowth in Parkinson's disease. Mov Disord 2011; 26: 889–892.

54.

Radder

DLM

Nonnekes

van Nimwegen

, et al. Recommendations for the organization of multidisciplinary clinical care teams in Parkinson's disease. J Parkinsons Dis 2020; 10: 1087–1098.

55.

Svedlund

Sjodin

Dotevall

. GSRS–A clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci 1988; 33: 129–134.

56.

Ala

Chen

. Appointment scheduling problem in complexity systems of the healthcare services: a comprehensive review. J Healthc Eng 2022; 2022: 5819813.

57.

Lecky

Hawking

McNulty

, et al. Patients’ perspectives on providing a stool sample to their GP: a qualitative study. Br J Gen Pract 2014; 64: e684–e693.

58.

Butt

Visaggi

Singh

, et al. Lack of awareness of neurogastroenterology and motility within medical education: time to fill the gap. Neurogastroenterol Motil 2023; 35: e14666.

59.

Melchior

Nuzzo

Keszthelyi

. How to raise the interest for neurogastroenterology among young gastroenterologists? United Eur Gastroenterol J 2021; 9: 1193–1196.

60.

Choi

Pak

. A catalog of biases in questionnaires. Prev Chronic Dis 2005; 2: A13.

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