Autonomic nerve function in adult patients with cyclic vomiting syndrome.

BACKGROUND: Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods. Autonomic dysfunction has been a postulated mechanism for the pathogenesis of this disorder in children but has not been explored in adults. METHODS: Our goals were to investigate autonomic nerve function in adult patients with CVS. The sympathetic nervous system was evaluated through postural changes in heart rate and blood pressure and sympathetic skin response in the hand and foot. The parasympathetic nervous system was tested through heart rate response to deep breathing [expiration/inspiration (E/I)], Valsalva and postural indices (30 : 15 ratio). All patients had a 4-h standard isotope labeled egg beater meal gastric emptying test (GET). KEY RESULTS: Twenty-two adult (18 female), mean age 35 ± 11 (range 19-61 years), who met Rome III criteria for CVS were included. History of migraine headache was reported in three patients. Five (23%) had pediatric onset. Of 21 patients who completed the test, nine patients had 21 abnormalities detected in their autonomic nerve testing profile and the remaining 12 had normal autonomic function results. Orthostatic tachycardia was observed in two (mean heart rate increase 39 beats min(-1)) and a decline in blood pressure (BP) in three patients (mean BP drop 30/14 mmHg). Parasympathetic abnormalities were elicited in six patients with an abnormal response to deep breathing and E/I index <1.25. Sympathetic nerve dysfunction was reported in seven patients with absent sympathetic skin response in the foot and/or hand. Twelve (57%) of CVS group had rapid GET (<50% retention at 1 h). The frequency of abnormal autonomic nerve function was not significantly higher in rapid GET subgroup. CONCLUSIONS & INFERENCES: (i) Autonomic nerve dysfunction is common in adult CVS patients, being observed in 43% of our cohort; (ii) Sympathetic abnormalities dominate; and (iii) Rapid gastric emptying, present in 57% of patients, did not correlate with autonomic testing results. These new data provide more insight into the pathophysiology of CVS in adults and help explain the spectrum of clinical manifestations observed in this entity.

Spectrum of gastric emptying patterns in adult patients with cyclic vomiting syndrome.

BACKGROUND: Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea, vomiting and abdominal pain separated by symptom-free intervals. Both rapid and delayed gastric emptying (GE) have been observed but the reports involved small numbers of CVS patients. METHODS: We performed a retrospective study of 92 adult patients who met Rome Ш diagnostic criteria for CVS between 2003 and 2009 at the Kansas University Medical Center. Gastric emptying was measured by a standardized scintigraphic method involving a low fat (2%) isotope labeled egg white meal of 250 Kcal, with anterior and posterior gastric imaging in the standing position obtained at 0, 1, 2, 4 h after meal ingestion. Rapid GE was defined as <50% isotope retention at 1st h and/or <30% at 2nd h and delayed GE as >10% at 4 h. KEY RESULTS: Ninety two patients were analyzed: 47 males and 45 females mean of age 37 ± 12 years (range: 20-68 years). There were 27 patients with a personal history of migraine headache, 30 with history of marijuana use, 12 had diabetes mellitus (DM) and 10 had irritable bowel syndrome (IBS) as an accompanying diagnosis. Fifty four patients (59%) met criteria for rapid GE, 25 (27%) had normal GE and 13 (14%) had slow GE. Eighty percent of patients with co-existing IBS symptoms were identified as rapid. The subset with delayed emptying was often associated with narcotics use, DM and marijuana use (P < 0.05). CONCLUSIONS & INFERENCES: (i) In adult CVS patients, GE is generally either rapid or normal. (ii) Cyclic vomiting syndrome is an important new etiology to explain the finding of rapid GE on a radionuclide test. (iii) The small subset of CVS patients (14%) whose GE was slow were explained by the role of narcotics and/or marijuana.

Who are the nonresponders to standard treatment with tricyclic antidepressant agents for cyclic vomiting syndrome in adults?

BACKGROUND: Cyclic vomiting syndrome in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods. AIMS: To investigate the demographic and clinical characteristics of adult cyclic vomiting syndrome patients not responding to standard tricyclic antidepressant (TCA) therapy. METHODS: A total of 132 adults (62 men) with cyclic vomiting syndrome were followed for a mean of 1.6 years. Of these, 17 (eight men) patients were identified as nonresponders based on the criteria of unchanged, increased or minimally changed (<25%) frequency/duration of episodes and/or emergency department visits/hospitalizations. Demographic and clinical characteristics at baseline and annually up to 4 years were investigated. RESULTS: The nonresponders were receiving TCAs at an average dose of 90 mg/day compared to a mean dose of 85 mg/day in responders. Compared with the responders, the nonresponders were significantly more likely to have a history of migraine (P < 0.05); co-existing psychological disorders (P < 0.05); chronic marijuana use (P < 0.05) and reliance on narcotics for pain control between cyclic vomiting syndrome episodes (P < 0.05). CONCLUSIONS: (1) Nonresponse to standard therapy in adult cyclic vomiting syndrome patients occurs in approximately 13% and is not explained by under dosing with TCA therapy. (2) The main risk factors for nonresponse are: co-existing migraine headache, psychiatric disorder, chronic narcotic and marijuana use, which should be addressed aggressively when symptom exacerbations continue during attempts to induce remission in cyclic vomiting syndrome with high-dose TCA therapy.

Are pediatric and adult-onset cyclic vomiting syndrome (CVS) biologically different conditions? Relationship of adult-onset CVS with the migraine and pediatric CVS-associated common mtDNA polymorphisms 16519T and 3010A.

Pediatric cyclic vomiting syndrome (CVS) is associated with a high prevalence of co-morbid migraine and other functional disorders, and with two adult migraine-associated mitochondrial DNA (mtDNA) polymorphisms: 16519T and 3010A. These potential associations have not been studied in adult CVS. The objective of this study is to determine the prevalence of 16519T and 3010A mtDNA polymorphisms and other functional disorders in adult CVS patients. Adults with CVS recruited from the University of Kansas meeting Rome III criteria and a population control group completed a self-reported survey that included questions relating to the diagnostic criteria for several functional disorders. DNA was isolated from blood or saliva and genotyping was performed by standard methodologies. Adult CVS subjects, compared to controls, had significantly more symptoms consistent with several other functional disorders. 16519T was present in 22/31 cases (71%) of child-onset (<12 years) and 9/31 (29%) cases of adult-onset (18+ years) CVS (P = 0.01), vs 27% of controls. Among subjects with 16519T, 3010A was present in 30% of child-onset vs 0% of adult-onset CVS (P = 0.05) and 2% of controls. The conclusions drawn were: (i) unlike pediatric CVS, adult CVS is not associated with the 16519T and 3010A mtDNA polymorphisms, suggesting a degree of genetic distinction and (ii) similar to the pediatric setting, adult CVS is associated with a substantial burden of co-morbid functional disorders.