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Chronic vestibular dysfunction as an unappreciated cause of chronic nausea and vomiting.

Chronic nausea and vomiting can be a challenging symptom complex for both the patient and physician for a variety of reasons, including the large number of potential underlying causes, the difficulty of making a specific diagnosis, and the difficulty of adequately treating symptoms. An accurate history and physical examination are paramount in formulating a diagnostic approach. Once structural lesions are excluded, an underlying motility disorder often is sought (1).

Gastric emptying scintigraphy (GES) is considered to be a critical test when gastroparesis is suspected. A 4-hour, solid-phase gastric emptying study using a standard protocol currently is recommended as the optimal test for evaluation of gastric emptying (2). Despite this recommendation, a variety of less-reliable alternative protocols are still used at some institutions. Emptying also may be altered by concomitant symptoms, such as nausea, or concurrent medications, such as narcotics. Unless the test is done properly, results may be misleading.

Even when the standardized exam is utilized properly, some patients with chronic nausea and vomiting have normal gastric emptying studies. This group of patients has recently been described as having chronic unexplained nausea and vomiting. These patients are clinically indistinguishable from those with delayed emptying in terms of symptom severity and health care utilization (3). The causes for symptoms in these patients are not known.

Patients with chronic nausea and vomiting often are referred to our institution for consideration of placement of gastric electrical stimulators. Many previously were diagnosed with gastroparesis, often on the basis of nonstandard gastric emptying scans. The aim of this retrospective study was to evaluate the diagnoses made in a consecutive series of patients referred for chronic nausea and vomiting and to appraise the GES utilized to assess these patients.


Consecutive patients with chronic nausea and vomiting referred to a single physician at our institution from January 2008 to December 2010 were identified from billing records. Patients with symptoms for over a month were included. Exclusion criteria included age <18 years and pregnancy at the time of referral.

Medical records were reviewed to characterize the evaluation and treatment prior to referral, subsequent investigation and diagnosis, and therapeutic responses when available. This study was approved by the institutional review board in February 2011.

Clinical diagnoses were based on the following criteria:

* Gastroparesis was identified by chronic symptoms of nausea and/or vomiting, typically delayed after eating and accompanied by an abnormal standardized GES (>10% of test meal remaining at 4 hours).

* Suspected chronic vestibular dysfunction (CVD) was defined on the basis of symptoms of nausea and/or vomiting in conjunction with signs of altered vestibular dysfunction on physical examination. This included the presence of nystagmus, a positive Romberg test, or an abnormal modified Fukuda stepping test. We performed the modified Fukuda stepping test by having the patient march in place with eyes shut and ears occluded for 60 seconds. A turn of 90 degrees or more to the right or left was considered abnormal (see supplementary video online).

* Gastroesophageal reflux was defined by symptoms of heartburn and/or regurgitation in association with abnormal duration of reflux on pH-monitoring studies and/or improvement of symptoms with proton pump inhibitor therapy.

* Cyclic vomiting was defined on the basis of Rome III criteria as the presence of three or more discrete stereotypical episodes of vomiting in the prior year with absence of nausea and vomiting between episodes (4).

* Rumination syndrome also was based on Rome III criteria and was considered for those with persistent or recurrent regurgitation of ingested food not preceded by retching with subsequent remastication and swallowing (4).

* Postsurgical nausea and vomiting was characterized by symptoms of nausea and/or vomiting in the setting of prior gastric surgery and absence of delayed emptying.

* Medication-induced nausea and vomiting was distinguished by the resolution of nausea and/or vomiting with medication cessation or recurrence of symptoms upon re-challenge.

Numeric data were expressed as means or medians, and categorical data were expressed as proportions. Between-group comparisons were made using the chi-square or Fisher exact tests where appropriate.


Of 271 patients screened for inclusion, 23 were excluded: 8 had no record identifiable during the data collection period, and 15 were evaluated primarily for other complaints (6 for constipation, 4 for chronic diarrhea, 3 for abdominal pain, 1 for dysphagia, and 1 for allergies); none were pregnant or <18 years. A total of 248 patients were analyzed for the 3-year interval. Baseline characteristics are outlined in Table 1. The typical patient was female, middle aged, and had symptoms of nausea and vomiting for 2 years. Risk factors for delayed gastric emptying were ascertained. The majority had prior diagnostic evaluation that included endoscopy and abdominal imaging. Prior prokinetic medications were tried in 85%.

Of the total cohort, 156 (63%) were referred with a suspected diagnosis of gastroparesis. Of these, 102 (65%) had gastric emptying scan reports available for review, of which 95 (93%) were done with methods other than the 4-hour international standard protocol. Ninety (95%) of these had been interpreted as abnormal. A review of each study protocol revealed that the most common deviation from the international standard was an examination duration less than the recommended 4 hours (found in 43 [45%]). Other deviations included the use of alternative meals (in 7 [7%]), concomitant administration of medications known to alter gastric motility (in 2 [2%]), concurrent symptoms of nausea or abdominal pain during the test (in 2 [2%]), or a combination of these aberrations (in 41 [43%]). Repeat testing using the international standard protocol was done in 36 patients who had a prior abnormal non-standardized GES; 27 (75%) of these repeat studies were normal.

History, examination, and targeted diagnostic evaluation revealed various diagnoses, as outlined in Table 2. Of the entire cohort, gastroparesis was confirmed infrequently despite the frequency with which patients had been referred with that diagnosis. This appeared to be largely the result of using non-standardized GES.

Suspected CVD was the most common specific diagnosis, found in 64 (26%). Findings of altered vestibular function that led to this diagnosis included abnormal modified Fukuda stepping test (in 36 [56%]), presence of nystagmus (in 17 [27%]), and abnormal Romberg test (in 1 [2%]). Ten patients (16%) had a combination of these findings. Forty-three of these patients with CVD (67%) were referred for suspected gastroparesis. Of these, 34 (79%) had previous GES available for review. Thirty-three (97%) were done with nonstandard methods, of which 29 (88%) had been interpreted as abnormal. When a standardized test was repeated in nine of these patients, it was normal in eight.

Compared with patients with other conditions, CVD patients more often presented with nausea alone and tended to have fewer hospitalizations, suggesting less severe symptoms (Table 3). Abdominal discomfort and dizziness were not distinguishing symptoms, and overt vertigo was reported only in a minority of CVD patients (6 [9%]). To assess for possible contributing conditions, various comorbidities were evaluated; only eight CVD patients reported a recognized history of an inner-ear disorder.

Antivertiginous medication trials were administered to 57 of 64 (89%) CVD patients. These typically included scopolamine, meclizine, or benzodiazepines alone or in combination. Follow up was available for 39 of these patients for a median of 5 months. Symptomatic improvement was reported in 25 (64%), while 14 (36%) reported no change in symptoms.


This study has two main conclusions. First, despite the recommendations of experts to use a standardized protocol, most gastric emptying scans available for review were performed with nonstandardized methods. The most common deviation was duration less than the recommended 4-hour timeframe. Tougas et al (5) established a cut-off of >10% isotope retention at 4 hours after ingestion of a standard low-fat meal as indicative of delayed gastric emptying. Despite the validation of this cut-off as the international standard, many institutions still employ a variety of other protocols (6). When standardized exams were repeated at our institution, 75% were normal. Therefore, utilization of nonstandardized GES may lead to a misleading diagnosis of gastroparesis and should be abandoned.

Second, we found that CVD is a noteworthy consideration in patients with chronic nausea and vomiting, and treatments aimed at vestibular dysfunction may mitigate symptoms in some of those patients. CVD is classically characterized by symptoms of vertigo and postural instability but also may manifest with vegetative symptoms such as nausea and vomiting. Examination signs of CVD were found in 26% of our cohort. This is comparable to the 35% of adults over 40 years found to have CVD upon modified Romberg testing in the National Health and Nutrition Examination Survey (7). Although self-reported vertigo in population surveys has an estimated prevalence of 21% to 29% (8-10), the patients in our study presented with complaints of chronic nausea and vomiting and did not frequently report a history of vertigo or a known inner-ear disorder. The mechanisms whereby certain patients with CVD manifest symptoms are incompletely understood but may reflect impaired vestibular compensation to the initial underlying injury (11).

The suspected CVD diagnosis, in this study, was made most commonly on the basis of a positive modified Fukuda stepping examination. With visual, auditory, and proprioceptive inputs eliminated, patients must rely on their vestibular system to maintain orientation. Although the majority of normal subjects maintain orientation with 100 blindfolded steps in a quiet environment, Fukuda in his original experiments described a forward migration up to 1 meter and rotation up to 45 degrees from midline as normal (12). Patients with known vestibular lesions typically demonstrate >90-degree variations from midline (13). Therefore, to increase specificity for CVD, the 90-degree rotation was used as the cut-off in this study. Because advanced vestibular testing was not done as part of the evaluation of these patients, we cannot comment on the accuracy of the modified Fukuda test in this cohort of patients.

Therapy for CVD should ideally be targeted to the underlying lesion if identifiable, and affirmative physical examination signs should prompt referral for specialized confirmatory testing. Initial symptomatic improvement can occur with medications targeted at neurotransmitter targets within the vestibular system, such as antihistamines, anticholinergics, and benzodiazepines. The fact that nausea and vomiting improved with treatments aimed at vestibular dysfunction in many of our patients with suspected CVD supports the notion that CVD may play an important role in the pathogenesis of chronic nausea and vomiting in at least some patients with otherwise idiopathic nausea and vomiting. Future prospective studies should determine the frequency of vestibular dysfunction presenting with chronic nausea and vomiting, the efficacy of therapies such as medications and vestibular rehabilitation, and long-term prognosis.

In addition to CVD, other diagnoses were elicited in our patients suspected of having gastroparesis. These diagnoses included cyclic vomiting, rumination syndrome, gastroesophageal reflux, and postsurgical and medication-induced nausea and vomiting. This reinforces the heterogeneity of potential causes for nausea and vomiting that must be considered in the differential diagnosis. The frequencies of these conditions in our cohort at a tertiary referral center may not be representative of the frequencies in the general community; nevertheless, these are important diagnostic considerations for frontline gastroenterologists, as specific therapies may be more effective than nonspecific symptomatic therapy.

There are limitations to this retrospective study. First, complete prior diagnostic information was not available for review in all patients. Second, patients were not studied prospectively with a uniform diagnostic protocol. Ideally, a prospective study would include standardized GES, advanced vestibular testing, a uniform treatment protocol, and scheduled follow-up. Thus, the data collected are incomplete. Nevertheless, we feel that there are lessons to be learned from our experience.

(1.) Hasler WL, Chey WD. Nausea and vomiting. Gastroenterology 2003;125(6):1860-1867.

(2.) Abell TL, Camilleri M, Donohoe K, Hasler WL, Lin HC, Maurer AH, McCallum RW, Nowak T, Nusynowitz ML, Parkman HP, Shreve P, Szarka LA, Snape WJ Jr, Ziessman HA. Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. Am J Gastroenterol 2008;103(3):753-763.

(3.) Pasricha PJ, Colvin R, Yates K, Hasler WL, Abell TL, Unalp-Arida A, Nguyen L, Farrugia G, Koch KL, Parkman HP, Snape WJ, Lee L, Tonascia J, Hamilton F. Characteristics of patients with chronic unexplained nausea and vomiting and normal gastric emptying. Clin Gastroenterol Hepatol 2011;9(7):567-576.e1-4.

(4.) Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada JR, Stanghellini V. Functional gastroduodenal disorders. Gastroenterology 2006;130(5):1466-1479.

(5.) Tougas G, Eaker EY, Abell TL, Abrahamsson H, Boivin M, Chen J, Hocking MP, Quigley EM, Koch KL, Tokayer AZ, Stanghellini V, Chen Y, Huizinga JD, Ryden J, Bourgeois I, McCallum RW. Assessment of gastric emptying using a low fat meal: establishment of international control values. Am J Gastroenterol 2000;95(6):1456-1462.

(6.) House A, Champion MC, Chamberlain M. National survey of radionuclide gastric emptying studies. Can J Gastroenterol 1997;11(4):317-321.

(7.) Agrawal Y, Carey JP, Della Santina CC, Schubert MC, Minor LB. Disorders of balance and vestibular function in US adults: data from the National Health and Nutrition Examination Survey, 2001-2004. Arch Intern Med 2009;169(10):938-944.

(8.) Havia M, Kentala E, Pyykko I. Prevalence of Meniere's disease in general population of Southern Finland. Otolaryngol Head Neck Surg 2005;133(5):762-768.

(9.) Hannaford PC, Simpson JA, Bisset AF, Davis A, McKerrow W, Mills R. The prevalence of ear, nose and throat problems in the community: results from a national cross-sectional postal survey in Scotland. Fam Pract 2005;22(3):227-233.

(10.) Yardley L, Owen N, Nazareth I, Luxon L. Prevalence and presentation of dizziness in a general practice community sample of working age people. Br J Gen Pract 1998;48(429):1131-1135.

(11.) Lee JH, Ameer AN, Choi MA, Lee MY, Kim MS, Park BR. Recovery of vestibulogastrointestinal symptoms during vestibular compensation after unilateral labyrinthectomy in rats. Otol Neurotol 2010;31(2):241-249.

(12.) Fukuda T. The stepping test: two phases of the labyrinthine reflex. Acta Otolaryngol 1959;50(2):95-108.

(13.) Peitersen E. Vestibulospinal reflexes. VII. Alterations in the stepping test in various disorders of the inner ear and vestibular nerve. Arch Otolaryngol 1964;79:481-486.

Tanya H. Evans, MD, and Lawrence R. Schiller, MD

From the Division of Gastroenterology, Department of Internal Medicine, Baylor University Medical Center at Dallas.

Corresponding author: Tanya H. Evans, MD, Division of Gastroenterology, Baylor University Medical Center, 3600 Gaston Avenue, Suite 260, Dallas, Texas 75246 (e-mail:
Table 1. Baseline characteristics in 248
patients referred for chronic nausea and

Variable                    Value


  Women                   201 (81%)
  Men                      47 (19%)

Age in years              42 (18-78)
(median, range)
Symptom duration          2 (0.2-50)
in years
(median, range)


  Nausea and vomiting     196 (79%)
  Nausea alone             52 (21%)
  Abdominal discomfort    145 (58%)

Prior hospitalization      98 (40%)

Risk factors for

  Diabetes mellitus        63 (25%)
  Prior gastric surgery    29 (12%)
  Medications              91 (37%)

Prior evaluation

  Endoscopy               196 (79%)
  Abdominal imaging       135 (54%)
  Neurologic imaging       34 (14%)

Table 2. Diagnoses in 248 patients referred
for chronic nausea and vomiting

Diagnosis                           n (%)

Chronic vestibular dysfunction    64 (26%)
Gastroparesis                     28 (11%)
Cyclical vomiting syndrome        22 (9%)
Rumination syndrome                3 (1%)
Gastroesophageal reflux disease    5 (2%)
Postsurgical                       6 (2%)
Medication-induced                 3 (1%)
Other miscellaneous               41 (17%)
Unspecified                       76 (31%)

Table 3. Characteristics of patients diagnosed with
chronic vestibular dysfunction versus other diagnoses
among 248 patients referred for chronic nausea and

                      Chronic       Other     P value
                    vestibular    diagnosis
                    dysfunction   (n = 184)
                     (n = 64)


  Men                10 (16%)     37 (20%)     0.42
  Women              54 (84%)     147 (80%)


  Nausea alone       21 (33%)     31 (17%)     <.01
  vs. vomiting
  Abdominal          33 (52%)     112 (61%)     .20
  Dizziness          28 (44%)     69 (38%)      .33
  Vertigo             6 (9%)       2 (1%)      <0.01

Prior                19 (30%)     79 (43%)      .06


  Inner ear           8 (13%)      4 (2%)      <.01
  Diabetes           13 (20%)     50 (27%)      .27
  Prior gastric       4 (6%)      25 (14%)      .17
  Depression         34 (53%)     75 (41%)      .09
  Migraine            5 (8%)      27 (15%)      .15
  Hypertension       15 (23%)     63 (34%)      .11
  Atherosclerosis     5 (8%)       17 (9%)      .76
  Thyroid disease    11 (17%)     24 (13%)      .41
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Author:Evans, Tanya H.; Schiller, Lawrence R.
Publication:Baylor University Medical Center Proceedings
Article Type:Report
Geographic Code:1USA
Date:Jul 1, 2012
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