Diagnostic Criteria and Symptom Profiles in Adult Idiopathic Gastroparesis: A Systematic Review

Abstract

Background/Aims

Adult idiopathic gastroparesis, characterized by delayed gastric emptying without mechanical obstruction, presents with symptoms such as nausea, vomiting, early satiety, and postprandial fullness. Diagnostic criteria vary across studies, leading to inconsistencies in diagnosis and management. This systematic review explores the diagnostic criteria and categorization of definite, probable, and possible idiopathic gastroparesis in the literature.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we searched Medline, EMBASE, and Cochrane Library databases for relevant articles published in English up to January 2024. Observational studies (cross-sectional, case-control, and cohort designs) that provided diagnostic criteria for idiopathic gastroparesis were included. Data were extracted on demographics, co-existing conditions, symptoms, and diagnostic approaches. Quality was assessed using Joanna Briggs Institute checklists.

Results

Of 2235 initial results, 11 studies met our inclusion criteria. Most studies were of high quality, exclusively from Western research centers, and had a preponderance of female patients (61.7% to 85.9%) with mean ages ranging from 40.0 years to 58.9 years. Diagnostic variability was noted. A definite diagnosis was most often based on clinical symptoms and positive gastric emptying scintigraphy, while probable gastroparesis was identified by suggestive symptoms with normal upper endoscopy findings. Nausea and upper abdominal pain were frequently reported symptoms. Significant overlaps were observed between idiopathic gastroparesis and functional dyspepsia.

Conclusions

The findings highlight the inherent diagnostic challenges and underscores the need for confirming delayed gastric emptying to clinch an accurate diagnosis of gastroparesis. Future research should focus on developing consistent diagnostic criteria across diverse populations to improve the diagnosis and management of idiopathic gastroparesis.

Introduction

Gastroparesis is an increasingly recognized condition worldwide, with its prevalence rising alongside advancement in diagnosis and heightened medical awareness amongst patients and the healthcare community.^1-3 A large retrospective cross-sectional study in the United States found the overall standardized prevalence of gastroparesis to be 267.7 per 100 000 adults, whereas prevalence of “definite” gastroparesis (individuals diagnosed via gastric emptying scintigraphy with persistent symptoms for more than 3 months) was 21.5 per 100 000.⁴

Several conditions have been thought to result in gastroparesis. Diabetes is the most common underlying cause, followed by post-surgical and drug-induced cases.⁵ However, a significant proportion (approximately one-half of patients) of gastroparesis cases remain idiopathic, that is, no primary underlying abnormality found.⁶ The overlapping symptomatology between gastroparesis and functional dyspepsia further complicates timely and accurate diagnosis, often leading to delays in treatment initiation.^7,8 Gastroparesis is associated with considerable healthcare costs at the systems level, and increased care needs, greater anxiety and impaired quality of life among sufferers,^9,10 which further underscores the need for improved diagnostic criteria and standardized testing.

As highlighted by a recent Rome Foundation and international neurogastroenterology and motility societies’ consensus on idiopathic gastroparesis, although gastroparesis is understood to be a syndrome of objectively delayed gastric emptying in the absence of a mechanical obstruction, significant gaps remain in accurately diagnosing and managing gastroparesis.³ Currently, the ‘gold standard’ for diagnosing gastroparesis is a 4-hour gastric emptying scintigraphy according to the Tougas protocol, which measures the rate of gastric emptying.^11,12 However, this test is costly and invasive.¹³ Alternative tests, such as the gastric emptying breath test, have also been used in some settings.¹⁴ However, there is considerable variability in the diagnostic thresholds and methodologies used across studies and clinical practices, leading to inconsistencies in case identification.^3,13 Additionally, distinctions between “definite,” “probable,” and “possible” gastroparesis are often not consistently applied,¹⁵ further complicating research and clinical decision-making.

This systematic review seeks to address these challenges by examining the diagnostic criteria and classifications of adult idiopathic gastroparesis presented in the literature. Specifically, it compares the definitions of definite, probable, and possible gastroparesis to identify differences in diagnostic approaches, patient demographics, co-existing conditions, and symptoms. In doing so, we aim to highlight the pressing need for consensus on the diagnostic categories and criteria for adult patients with idiopathic gastroparesis.

Methods

Study Design

In terms of the study methodology, this systematic review was performed in accordance with the latest Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines,¹⁶ and the review protocol was registered a priori at PROSPERO (registration number CRD42024531356). In consultation with a medical information specialist, we used combinations of keywords such as “gastroparesis” or “idiopathic gastroparesis” or “primary gastroparesis” or “non-diabetic gastroparesis” and “epidemiologic studies” or “epidemiology” or “prevalence” or “incidence,” and searched Medline, EMBASE, and Cochrane Library databases for relevant articles until end January, 2024. The full search strategy for the various databases is displayed in the Supplementary Material (Supplementary Table 1). We restricted our search to studies published in English. Additional relevant articles were retrieved by screening the reference lists of included studies and consulting a domain expert.

Eligibility and Selection Criteria

Two reviewers (VRZ and YPR) independently reviewed titles and abstracts discovered via electronic searches to select relevant studies. The selected articles were reviewed to determine whether they contained relevant data. Any discrepancy in included studies was resolved by a third author (QXN or KTHS). Inclusion criteria include (1) an adult population of gastroparesis patients, (2) observational studies (cross-sectional, case-control, and cohort studies), and (3) contains information on diagnostic procedure. Exclusion criteria include studies that focused predominantly on (1) pediatric population of gastroparesis patients or (2) non-idiopathic gastroparesis (eg, diabetic gastroparesis and post-surgical gastroparesis), and (3) non-observational studies.

Data Extraction and Outcomes

Following which, a standardized data extraction sheet was created in Microsoft Excel (Redmond, Washington, USA) to report the study characteristics and design, database used, patient demographics and data on gastroparesis. Two of the authors (FS and ASPT) independently extracted data. Extracted data was reviewed by 2 authors (VRZ and YPR) for potential discrepancies and resolved via consensus. The primary outcome of this systematic review is to describe the population demographics of patients with idiopathic gastroparesis and compare the diagnostic criteria used for definite, probable and possible gastroparesis. The secondary outcome is to examine the common symptoms in adult idiopathic gastroparesis.

Quality Assessment and Risk of Bias

The methodological quality of included studies was determined using the Joanna Briggs Institute (JBI) critical appraisal checklist for cohort and cross-sectional studies.¹⁷ We considered a total score of ≥ 8, 4-7, and < 4 and to represent high, moderate and poor quality cohort studies respectively. A total score of ≥ 6, 3-5, and < 3 represent high, moderate and poor quality cross-sectional studies respectively.

Data Synthesis

The data synthesis was performed qualitatively, given the anticipated heterogeneity in the diagnostic criteria, study designs, and reported outcomes across the included studies. Narrative synthesis was used to categorize and compare definitions of idiopathic gastroparesis, including the classifications of definite, probable, and possible gastroparesis. Key study characteristics such as sample size, demographic details, co-existing conditions, and reported symptoms were systematically summarized and tabulated for comparison.

Results

Summary of Included Articles

Initially, 2548 studies were identified by our searches. After removal of 351 duplicates after importing the results into Covidence (Veritas Health Innovation, Australia, https://www.covidence.org), 2197 studies remained. Of these, 2172 studies were excluded due to not meeting the inclusion criteria, or fulfilling exclusion criteria (as illustrated in Figure). Following which, 25 articles were retrieved for full text review, 1 was excluded for being a non-English publication, 4 had the wrong study designs, 6 investigated a pediatric population instead, and 3 did not contain data on idiopathic gastroparesis. Thus, a total of 11 articles were reviewed and their main study characteristics and findings summarized in Table.^4,18-27

Figure.

Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flowchart showing the study search and abstraction process.

Table.

Key Characteristics and Findings for Studies Reviewed (Arranged Alphabetically by First Author’s Last Name)

Author, year	Country	Study Design	Referral/data Source	Study Population (n)a	Definition of Definite Idiopathic Gastroparesis	Definition of Probable Idiopathic Gastroparesis	Definition of Possible Idiopathic Gastroparesis	Common Symptoms	Diagnostic Tool for Gastric Emptying	Cutoff Values
Bielefeldt et al,18 2009	US	Cross-sectional	University of Pittsburgh Medical Center	n = 29; mean age 38.1 ± 2.8 yr; 80.0% females	Symptoms ≥ 6 wk + delayed gastric emptying (scintigraphy, endoscopy, or contrast study)	NS	NS	NS	Scintigraphy, endoscopy	Retained food after 12 hr fasting
Cherian et al,19 2010	US	Cross-sectional	Temple University Hospital	n = 50; mean age 39.5 ± 1.9 yr; 90.0% females	No obstruction + delayed emptying (> 60% retention at 2 hr, > 10% at 4 hr)	NS	NS	Nausea (94%), Pain (90%)	4-hr Scintigraphy	> 60% at 2 hr, > 10% at 4 hr
Huang et al,20 2023	Belgium	Cross-sectional	Leuven Neurogastroenterology and Motility Clinic	n = 238; median age 38 (27.8-49.0) yr; 79.9% females; median BMI 19.9 (15.7-23.1) kg/m2	Symptoms > 6 mo + normal endoscopy + delayed emptying (T1/2 > 95% CI)	Symptoms > 6 mo + normal endoscopy but no delayed emptying	NS	Nausea (100%), fullness (96.2%), bloating (92.4%)	Scintigraphy, breath test	T1/2 >95% CI
Navas et al,21 2021	US	Cohort	Dartmouth-Hitchcock Medical Center	n = 50; mean age 45 ± 15 yr; 80.0% females; BMI 27.1±7.9 kg/m2	ICD diagnosis or related symptoms + scintigraphy confirmation	NS	NS	NS	Scintigraphy	NS
Parkman et al,22 2011a	US	Cohort	Gastroparesis Registry	n = 204; mean age 42.8 ± 13.9 yr; 82.6% females; 53.7% had BMI ≥ 25 kg/m2	Symptoms > 12 wk + no obstruction + delayed emptying (> 60% at 2 hr, > 10% at 4 hr)	NS	NS	NS	4-hr Scintigraphy	> 60% at 2 hr, > 10% at 4 hr
Parkman et al,23 2011b	US	Cohort	Gastroparesis Registry	n = 254; mean age 41.0 ± 14.2 yr; 88.6% females; BMI 25.7 ± 6.9 kg/m2	No gastric surgery, no diabetes, normal HbA1c + delayed emptying	NS	NS	Nausea (84.3%), pain (76%), vomiting (59.8%)	Scintigraphy	NS
Parkman et al,24 2019a	US	Cohort	Gastroparesis Registry	n = 224; mean age 44.3 ± 13.1 yr; 85.0% females	Confirmed by delayed gastric emptying scintigraphy	NS	NS	NS	Scintigraphy	NS
Parkman et al,25 2019b	US	Cohort	Gastroparesis Registry	n = 458; mean age 43.0 ± 13.7 yr; 85.0% females; BMI 27.0 ± 7.5 kg/m2	No gastric surgery, no diabetes, normal HbA1c + delayed emptying	NS	NS	Pain (90.6%)	Scintigraphy	NS
Szeto et al,26 2023	US	Cross-sectional	Temple University Hospital	n = 149; mean age 42.1 ± 17.0 yr; 61.7% females; BMI 25.2 ± 6.8 kg/m2	Delayed emptying (> 60% at 2 hr, > 10% at 4 hr) + no identified cause	NS	NS	NS	Scintigraphy	> 60% at 2 hr, > 10% at 4 hr
Ye et al,4 2022	US	Cross-sectional	Optum Clinformatics Data Mart	n = 8130; mean age 50.7 ± 18.9 yr; 68.7% females	≥ 1 inpatient or ≥ 2 outpatient diagnoses 30 day apart; GES within 90 day; Symptoms (nausea, vomiting, postprandial fullness, early satiety, bloating, epigastric pain) ≥ 90 day before diagnosis	≥ 1 inpatient or ≥ 2 outpatient diagnoses 30 day apart; GES within 90 daysr OR symptoms ≥ 90 day before diagnosis	≥ 1 inpatient or ≥ 2 outpatient diagnoses 30 day apart; no GES within 90 day; no symptoms ≥ 90 day before diagnosis	NS	Scintigraphy	Within 90 days of diagnosis
Yekutiel et al,27 2023	Israel	Cross-sectional	Maccabi Healthcare Services	n = 556; mean age 49.4 ± 16.6 yt; 65.7% females; 22.9% had BMI ≥ 30 kg/m2	Physician diagnosis + gastric emptying test	Physician diagnosis only	NS	NS	Scintigraphy	NS

^an reflects the number of patients with definite/probable/possible idiopathic gastroparesis.

BMI, body mass index; GES, gastric emptying scintigraphy; HbA1c, hemoglobin A1c; ICD, international classification of diseases; NS, not specified.

Risk of Bias Assessment

Majority of the articles (4 of the 5 cohort studies) scored 8 out of 11 points on the JBI checklist, attaining a high overall study quality.^21,23-25 The remaining study scored 7 out of 11 points.²² Similarly, 5 of the 6 cross-sectional studies scored 6 out of 8 points on the JBI checklist,^{18,19,20,26,27} and the remaining study scored 5 out of 8 points.⁴ Detailed breakdown of the ratings can be found in the Supplementary Material (Supplementary Table 2).

Narrative Synthesis of Findings

As detailed in Table, data for 4 (of the 11) studies were sourced from the Gastroparesis Registry, an observational study created by the Gastroparesis Clinical Research Consortium (GpCRC) to enroll a sufficiently large cohort of patients presenting with gastroparesis symptoms of at least 12 weeks duration, delayed gastric emptying on scintigraphy, and no abnormality causing obstruction on upper endoscopy.^22-25 In contrast, 5 articles recruited patients from gastroenterology clinics.^18-21,26 The remaining 2 studies derived their data from locoregional healthcare database or insurance claims, facilitating the calculation of gastroparesis prevalence, which was reported as 0.021% by Yekutiel et al,²⁷ and 0.0215% by Ye et al.⁴ On the whole, the study populations showed a noticeable majority of female patients, with mean ages ranging from 40.0 to 58.9 years across the studies. All included studies were conducted by Western research centers.^4,18-27

Only one study, conducted by Ye et al,⁴ included more than 1000 patients and diagnosed cases of possible idiopathic gastroparesis. Ten of the 11 studies identified patients with definite idiopathic gastroparesis,^18-27 with 3 of these studies also reporting cases of probable idiopathic gastroparesis.^20,27,28

Based on a close examination of the working diagnostic criteria for definite gastroparesis as compared to probable gastroparesis (in Table), 10 of the 11 studies included a gastric emptying scintigraphy as part of their diagnostic approach, with 7 of the studies mandating 100% of patients undergo a gastric emptying scan to confirm a gastroparesis diagnosis.^19,21,22-26 Additional commonly utilized criteria included upper endoscopy to rule out mechanical obstruction, which was employed in 3 studies,^18,20,23 and the presence of persistent gastroparesis symptoms, also reported in 3 studies.^18,20,22 Alternative diagnostic methods to the gastric emptying scan included the gastric emptying breath test,²⁰ and the use of wireless motility capsules and the water load satiety test.²⁵

In contrast to definite gastroparesis, the definition of probable gastroparesis varied more widely across studies, with Yekutiel et al,²⁷ diagnosing it based on physician assessment, while Huang et al,²⁰ identified it in patients with prolonged gastroparesis symptoms but without delayed gastric emptying.

Most patients with definite idiopathic were female, with an average age at presentation ranging from 40 years to 50 years.^19,23 In terms of the symptoms experienced by patients, nausea was most prominent, affecting some 94.0% of patients in the study by Cherian et al.¹⁹ Upper abdominal pain was also commonly reported, with 90.6% of patients in the study by Parkman et al,²⁵ 90.0% in both Cherian’s¹⁹ and Huang’s²⁰ studies and 76.0% in Parkman’s²³ 2011 study. Other frequently reported symptoms include vomiting, post-prandial pain, bloating, regurgitation, early satiety, belching, epigastric burning, diarrhea, constipation, anorexia, and weight changes, etc. These sufferers also reported significant psychological distress (depression and anxiety) and poorer quality of life (36-item Short Form Survey, Patient Assessment of Upper GastroIntestinal Disorders-Quality of Life scores).^18,24

As aforementioned, delayed gastric emptying is a defining feature, often based on 4-hour scintigraphy results (> 10% retention at 4 hours and > 60% at 2 hours).^19,22 Probable and possible gastroparesis patients may thus lack confirmatory gastric emptying testing, leading to diagnostic uncertainty, especially given the overlaps with functional dyspepsia. Two studies studied this overlap and the potential distinguishing features.^19,20 Huang et al,²⁰ noted that 33.2% of gastroparesis-like patients had delayed gastric emptying, whereas only 17.6% of functional dyspepsia patients had delayed gastric emptying. The authors speculated that some functional dyspepsia patients may have mild gastric motility impairments, but not to the degree seen in idiopathic gastroparesis. Cherian et al,¹⁹ reported that abdominal pain (frequently epigastric [43.0%] and triggered by eating [72.0%], with a substantial proportion of patients reporting nocturnal pain [74.0%] that interfered with sleep) was common in idiopathic gastroparesis, similar to nausea and bloating. This suggests that while epigastric pain is often associated with functional dyspepsia, it is not exclusive to it and pain patterns alone are insufficient for distinguishing probable or possible gastroparesis from functional dyspepsia. Gastric motility assessment remains essential.¹⁹

Discussion

This systematic review of 11 studies highlights several key findings related to the diagnosis and symptomatology of idiopathic gastroparesis among adults. Idiopathic gastroparesis has been largely studied in clinical settings rather than in population-based settings, and as such, the exact prevalence, epidemiology and clinical features remain poorly understood. The prevalence estimates of gastroparesis varied across the included studies, with rates ranging from 0.021%²⁷ to 0.0215%⁴ in studies using healthcare databases and insurance claims. These figures likely underestimate the true prevalence of the condition due to the potential for underdiagnosis, a common issue in gastroparesis research. In a 2023 systematic review, the authors reported the standardized prevalence of definite gastroparesis varied significantly across the studies, ranging from 13.8 to 267.7 per 100 000 adults.²⁸ Many of the available studies also relied on broad definitions of gastroparesis, categorizing cases as “probable” or “possible” based solely on diagnosis codes, without objective confirmation of delayed gastric emptying.²⁸ The observed variation in reported prevalence likely also reflects differences in the study populations, with higher rates often observed in specific groups, such as patients with diabetes, compared to the general population.²⁸

In routine practice, it is generally accepted that a diagnosis of gastroparesis requires (1) persistent gastroparetic symptoms, followed by (2) findings of delayed gastric emptying in the (3) absence of mechanical obstruction.^3,5 However, the diagnosis of gastroparesis remains a clinical conundrum. These symptoms have overlapping causes, and although the gastric emptying scintigraphy is recognized as the gold standard, this reliance on gastric emptying scintigraphy for diagnosis is likely to pose a barrier for patients and healthcare providers as it is an expensive test, which involves a small amount of radiation exposure, and is generally available only in specialized centers.¹³ Moreover, the criteria for abnormal scintigraphy results varied across the studies, with some defining delayed gastric emptying as values beyond the 95th percentile in healthy controls, while others used wider thresholds.^19,20,22 It is known that the severity of gastric emptying delay is also weakly correlated with symptom severity and quality of life impairments.²⁹ It is also worth mentioning that previous studies have demonstrated a concerning lack of stability in delayed gastric emptying over time.^30,31 Based on this observation, it has been proposed that studies on gastroparesis recruit only patients with at least 2 abnormal gastric emptying tests to enhance diagnostic accuracy, however, this recommendation is rarely implemented in clinical or research settings.³ This lack of standardization complicates case identification and may contribute to the variability in reported prevalence.

Although 7 of the 11 studies included in this review relied on gastric emptying scintigraphy,^19,21,22-26 alternative assessment methods, such as the gastric emptying breath test and wireless motility capsule, were also employed.^18,20,23 The breath test has been shown to be a reliable method to assess gastric emptying and correlate well with scintigraphy measurements.³² These methods, while promising, have their limitations. For instance, the breath test results may be affected by patients with concomitant liver, lung or malabsorptive diseases.³¹ While the wireless motility capsule may produce inconsistent results due to its reliance on phase III activity of the migrating motor complex,^33,34 which warrants further research into the reliability and validity of this diagnostic tool.

Based on reported cases of definite adult idiopathic gastroparesis across the studies, the symptomatology of gastroparesis encompasses several cardinal symptoms—nausea, vomiting, bloating, and abdominal discomfort.^19,20,23,25 In gastroparesis, nausea often precedes vomiting, which may provide some relief.³⁵ Notably, both nausea and vomiting are cardinal symptoms endorsed by the recently published Rome Foundation and international neurogastroenterology and motility societies’ consensus on idiopathic gastroparesis,³ and they are also validated symptoms in the Gastroparesis Cardinal Symptom Index.³⁶ These symptoms, however, are not distinct and overlap with other gastrointestinal disorders, particularly functional dyspepsia.^7,8,37 A continuum model has been proposed, where functional dyspepsia and gastroparesis exist on a spectrum of gastric sensorimotor dysfunction rather than as entirely separate disorders, particularly when the cause of gastroparesis is unknown.³⁸ This overlap makes it difficult to differentiate between these conditions without objective evidence of delayed gastric emptying; there is a need for objective testing to refine diagnostic classifications, albeit societal guidelines conflict on this.³⁸ In clinical practice, some probable or possible gastroparesis cases may, in fact, be severe forms of functional dyspepsia, particularly if gastric emptying is normal.²⁰ Our review underscores the importance of confirming delayed gastric emptying to achieve an accurate diagnosis of gastroparesis, which should be adopted in clinical guidelines moving forward. This is critical as the prescribed pharmacologic options for idiopathic gastroparesis may be ineffective for functional dyspepsia and vice versa.^37,38 Although nausea emerged as a prominent symptom of idiopathic gastroparesis across the studies,^19,20,23,27 further research is needed to better characterize the full symptom burden in larger and more diverse patient populations.

Study Strengths and Limitations

To the best of our knowledge, this is the first systematic review to focus specifically on the diagnosis of adult idiopathic gastroparesis. However, several limitations of this review should be noted. First, the limited number of included studies, particularly those focusing specifically on idiopathic gastroparesis, restricts the overall strength and generalizability of our findings. Additionally, the small number of cases in some studies, coupled with the potential for underdiagnosis, makes it difficult to establish the true prevalence of idiopathic gastroparesis, although this is outside of the scope of this review. Second, 4 out of 11 reviewed papers came from the same authors and cohort registry (and were published in similar years, 2011 and 2019).^22-25 The patient population among these studies could be largely overlapped and therefore biased the interpretation of this review. Third, the variation in diagnostic criteria across the studies, particularly in the use of gastric emptying scintigraphy and other diagnostic tests, further complicates the comparison of findings and the development of standardized guidelines. Fourth, due to the heterogeneity in study designs, diagnostic criteria, and outcome measures, we were unable to perform a meta-analysis. This inability limits the extent and strength of the quantitative synthesis of results. Last but not least, the available studies were entirely drawn from Western populations, which limits the generalizability of the results to other regions, particularly Asia, where gastroparesis may present differently or be under-researched. This regional disparity in research focus stresses the need for future studies to explore gastroparesis in more diverse populations.

In conclusion, adult idiopathic gastroparesis is characterized by symptoms of delayed gastric emptying without mechanical obstruction, with nausea and upper abdominal pain being prominent symptoms. This systematic review highlights the variability in diagnostic criteria across studies, with a possible diagnosis of idiopathic gastroparesis often based on symptoms alone, a probable diagnosis incorporating symptoms alongside normal findings on upper endoscopy, and a definite diagnosis requiring objective evidence of delayed gastric emptying via gastric scintigraphy or a breath test. However, the inconsistencies in diagnostic criteria complicate case identification and hinder the development of standardized guidelines. There is an urgent need to develop consensus and standardized guidelines on the diagnostic categories of definite, probable, and possible gastroparesis for clinical practice. Future research should focus on developing and validating consistent diagnostic criteria across diverse populations to improve the accuracy and management of idiopathic gastroparesis, particularly in Asian countries where is a dearth of research.

Supplementary Materials

Note: To access the supplementary tables mentioned in this article, visit the online version of Journal of Neurogastroenterology and Motility at http://www.jnmjournal.org/, and at https://doi.org/10.5056/jnm24160.