In 1994, the 1st International Symposium on Cyclic Vomiting Syndrome was held. Researchers there proposed relatively strict guidelines for the diagnosis of Cyclic Vomiting:
1. A child has recurrent, severe episodes of vomiting which may last for hours or days but have intervals of complete normal health in between vomiting episodes.
2. No other known cause of the vomiting.
The reason for having these criteria is that there are children who have vomiting for unknown reasons but do not have normal healthy intervals in between episodes. These children may be vomiting every day or every other day as opposed to children with Cyclic Vomiting who tend to go for weeks without vomiting episodes.
This disorder is also known as abdominal migraine. At the 2nd International Scientific Symposium on CVS in 1998, one of the major conclusions of the meeting was the recognition of the close relationship between CVS and migraine. Some children with CVS may evolve to classic migraine.
Stress may be an important precipitant of vomiting for some children and psychological assessment and treatment may be helpful for children and families. During treatment of an acute episode of vomiting, close attention to the amount of fluid that is replaced is important as too much fluid as this may stimulate some of the chemicals which will perpetuate vomiting. It is important to ensure a good supply of sugar during this process.
The treatment is best handled by physicians experienced in managing this problem. A new class of drugs called tachykinin receptor antagonists appear to be extremely potent in preventing vomiting in animals. Australian trials of Ondanestron have shown some promise. One recent article in the gastroenterology literature suggests that tricyclic antidepressants appear to help control symptoms in adults when given in modest doses for a prolonged period, but response to these agents appears to be less satisfactory in adult cyclic vomiting syndrome than in the childhood disorder (Am J Gastroenterol 1996; 91;1923).
The pathogenesis is still unknown with a disorder originating in the central nervous system or gastrointestinal tract as the leading candidates. Adults with this disorder are uncommon and do not have histories extending into childhood. The pathogenesis may be different in adults versus children.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
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Cyclic vomiting and recurrent abdominal pains as migraine or epileptic equivalents.
Lanzi G, Balottin U, Ottolini A, Rosano Burgio F, Fazzi E, Arisi D.
Cephalalgia 1983 Jun;3(2):115-8 Abstract quote
A retrospective method was used to estimate the incidence of recurring motion-sickness, cyclic vomiting and abdominal pain considered as different manifestations of a so-called periodic syndrome in 100 migraine sufferers, 100 epileptics and 100 control subjects in the pediatric age group. Such recurrent symptoms are significantly more frequent in those suffering from migraine than in the other two groups. Examination of subgroups of patients affected by particular forms of migraine (classical and common) and of epilepsy (generalized seizures, simple partial seizures, complex partial seizures) contributed little new to our understanding of the nature of periodic syndrome.
It is concluded that the above symptoms of periodic syndrome should generally be considered as manifestations of a migrainous rather than of an epileptic disorder.
Precipitants and aetiology of cyclic vomiting syndrome.
Withers GD, Silburn SR, Forbes DA.
Princess Margaret Hospital for Children, University of Western Australia, Perth.
Acta Paediatr 1998 Mar;87(3):272-7 Abstract quote
Thirty-two patients aged 2-22 y with cyclic vomiting syndrome (CVS), and 64 age- and gender-matched controls were assessed to determine the nature, severity, precipitants and associated features of attacks and the incidence of potential aetiological factors.
The mean age of onset was 3.5 y. Patients experienced a mean of nine attacks per year, of average duration 2.4 d, and two-thirds missed more than 10 d of school per year. Patients were more likely to have migraine and co-ordination difficulties, a past history of forceps delivery and gastroesophageal reflux than controls.
Compared with controls, subjects had a higher incidence of psychological symptoms (38% compared with 19%) and migraine (37% compared with 9%). CVS is a chronic, disabling condition and is a migraine variant, with attacks usually precipitated by stress and intercurrent infections.
Cyclic vomiting syndrome in South-East Asian children.
Lee WS, Kaur P, Boey CC, Chan KC.
Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
J Paediatr Child Health 1998 Dec;34(6):568-70 Abstract quote
OBJECTIVE: To describe the clinical features, management and outcome of children with cyclic vomiting syndrome (CVS) from South-East Asia.
METHODOLOGY: Retrospective review of all children who fulfilled the diagnostic criteria of CVS and who were seen at Department of Paediatrics, University of Malaya Medical Centre, Kuala Lumpur and Paediatric Unit, Penang Hospital, Penang, Malaysia from 1987 to 1997.
RESULTS: Eight children with CVS were seen at the two units during the study period, five girls and three boys. All had cyclical, self-limited episodes of nausea and vomiting with symptom-free intervals. The mean age of onset was 5.9 years. The clinical features were similar to other series described in the literature. Only two of the eight children were described as 'perfectionist'. Two children identified stress as precipitating factors. Therapy to reduce the number of emeses during acute attacks and to prevent subsequent attacks had been ineffective.
CONCLUSION: There are similarities and differences in CVS from South-East Asian children as compared to those described in the literature.
Psychological and social characteristics and precipitants of vomiting in children with cyclic vomiting syndrome.
Forbes D, Withers G, Silburn S, McKelvey R.
Department of Paediatrics, University of Western Australia, Australia.
Dig Dis Sci 1999 Aug;44(8 Suppl):19S-22S Abstract quote
A psychological etiology or predisposition for cyclic vomiting syndrome (CVS) has long been suspected. Much of the psychiatric literature to date has blamed patients or their families for the problem or focused on psychoanalytic interpretation to account for the syndrome.
Thirty-two patients with CVS were compared with 64 age- and sex-matched controls. The patients had a higher incidence of psychological symptoms and migraine. On the Achenbach Child Behavior Checklist patients had higher internalizing, somatic complaints, and anxiety/depression scores. CVS is a migraine variant, with attacks usually precipitated by stress and intercurrent infections. The psychological characteristics of patients with CVS probably contribute to their vulnerability.
Similarities in cyclic vomiting syndrome across age groups.
Prakash C, Staiano A, Rothbaum RJ, Clouse RE.
Divisions of Gastroenterology and Pediatric Gastroenterology & Nutrition, Washington University School of Medicine, St. Louis, Missouri 63110, USA
Am J Gastroenterol 2001 Mar;96(3):684-8 Abstract quote
OBJECTIVE: Cyclic vomiting syndrome is well recognized in children yet has poorly defined pathogenesis and treatment. Cyclic vomiting syndrome is occasionally diagnosed in older subjects, but little attempt has been made to determine if such cases represent a unique disorder.
METHODS: We reviewed clinical data from 39 patients aged 1.8-75 yr with cyclic vomiting syndrome meeting published criteria for diagnosis. Clinical characteristics were compared between subjects with symptom onset in childhood (<12 yr, n = 18) and subjects with onset at an older age (> or =12 yr, n = 21; mean age at onset 34.8+/-3.8 yr).
RESULTS: All patients had stereotypical episodes of vomiting separated by varying symptom-free intervals. The prevalence rates of prodromal symptoms, triggering events, alleviants, associated symptoms including abdominal pain and diarrhea, and past or family history of migraine were similar in the children and older subjects with the syndrome (p > 0.3 for each). Delay in diagnosis was greater in the older subset (3.1+/-0.8 yr vs 7.9+/-3.1 yr, p < 0.05). Interepisode intervals and total number of hospitalizations did not differ significantly between younger and older patients, but duration of episodes was significantly longer in the older group (2.0+/-0.5 days vs 3.8+/-0.4 days, p < 0.01). When subjects were further substratified by age of illness onset, duration of episodes progressively increased from infant/toddlers (1.8+/-0.4 days) through childhood (2.3+/-0.5 days) and adolescence (2.9+/-1.0 days) and into adulthood (3.9+/-0.5; p < 0.05 across groups). Episode duration did not lengthen further in subgroups >20 yr of age.
CONCLUSIONS: Many characteristics of cyclic vomiting syndrome are similar irrespective of age at disorder onset, suggesting a uniform pathogenesis. Duration of episodes increases with age to age 20 yr. Increased awareness of the condition and a high index of suspicion may help decrease delay in diagnosis after symptom onset.
DISEASE ASSOCIATIONS CHARACTERIZATION
Is cyclic vomiting syndrome related to migraine?
Li BU, Murray RD, Heitlinger LA, Robbins JL, Hayes JR.
Department of Pediatrics, The Ohio State University, Columbus Children's Hospital, Columbus, Ohio, USA.
J Pediatr 1999 May;134(5):567-72 Abstract quote
OBJECTIVE: To examine the overlap between cyclic vomiting syndrome (CVS) and migraine by comparing 2 subsets of children with migraine-associated and non-migraine-associated CVS.
METHODS: We studied all children <18 years of age who met the consensus criteria for CVS after presentation to our pediatric gastroenterology service from 1986 to 1998. The clinical patterns and responses to treatment were obtained from a combination of chart reviews and structured interviews.
RESULTS: Among 214 children identified as having CVS, 82% were classified as having migraine-associated CVS based on 1 of 2 criteria either a family history of migraines or subsequent development of migraine headaches. Compared with the non-migraine CVS subgroup, the migraine subset had milder episodes (20.7 27.3 SD vs 39.5 66.5 emeses/episode, P =.006); more symptoms of abdominal pain (83% vs 66%), headache (41% vs 24%), social withdrawal (40% vs 22%), photophobia (36% vs 16%, all P ^.05); more frequent triggering events (70% vs 49%, P =.013) including psychologic stress (39% vs 22%), physical exhaustion (23% vs 3%), and motion sickness (10% vs 0%); and a higher positive response rate to anti-migraine therapy (79% vs 36%, P =.002).
CONCLUSIONS: The majority of children with CVS were subclassified as having migraine-associated CVS. The migraine-associated subgroup had less severe vomiting, manifested symptoms typical of migraine headaches, and had higher response rates to anti-migraine therapy. These findings strengthen the relationship between migraine and CVS.
Mitochondrial fatty acid oxidation disorders and cyclic vomiting syndrome.
Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA
Dig Dis Sci 1999 Aug;44(8 Suppl):97S-102S Abstract quote
Inherited fatty acid oxidation (FAO) disorders represent a relatively new group of inborn errors of metabolism. Although our understanding of the biochemical and molecular bases of these disorders has improved dramatically in recent years, many patients remain undetected or are given other diagnoses, cyclic vomiting syndrome (CVS) being one of them in a few known cases.
Medium chain acyl-CoA dehydrogenase deficiency and the late-onset form of glutaric acidemia type II have been anecdotally misdiagnosed as CVS. In addition, short chain acyl-CoA dehydrogenase deficiency (either true defects or polymorphism-related phenotypes) and particularly short-chain 3-hydroxy acyl-CoA dehydrogenase deficiency may present with clinical and biochemical features that closely resemble CVS. However, the collective role played by FAO and probably other metabolic disorders among the causes of CVS in unknown.
Guidelines for a diagnostic approach to FAO disorders at the biochemical level are being presented and discussed. Hopefully, a better understanding and an awareness of FAO disorders could improve the diagnostic evaluation of patients with CVS.
Mitochondrial disease and cyclic vomiting syndrome.
Boles RG, Williams JC.
Division of Medical Genetics, Childrens Hospital, Los Angeles, California 90027, USA.
Dig Dis Sci 1999 Aug;44(8 Suppl):103S-107S Abstract quote
Mutations of mitochondrial DNA are being increasingly recognized as a cause of human disease.
Six unrelated children have been evaluated with cyclic vomiting syndrome and a strong maternal family history suggesting a mitochondrial DNA mutation. Manifestations suggestive of migraine were present in each child. Additional clinical findings present in all cases include: developmental delay (3/6 cases), seizures (3/6), and poor growth (3/6). The age of onset for vomiting episodes was < or = 1 year in five cases. An elevated body fluid lactate (lactic acid) was found in 5/6 cases. A mitochondrial DNA mutation was confirmed in one child with the finding of a large rearrangement. These cases suggest that mitochondrial DNA mutations can cause cyclic vomiting syndrome.
Mitochondrial disease should be considered in cases of cyclic vomiting, especially those with additional pathology or possible maternal inheritance. Initial screening should include plasma lactate and urine organic acids obtained during an episode.
Cyclic vomiting syndrome and food allergy/intolerance in seven children: a possible association.
Lucarelli S, Corrado G, Pelliccia A, D'Ambrini G, Cavaliere M, Barbato M, Lendvai D, Frediani T.
Department of Paediatrics, University of Rome La Sapienza, Italy.
Eur J Pediatr 2000 May;159(5):360-3 Abstract quote
Cyclic vomiting syndrome (CVS) is characterized by repeated unpredictable, explosive and unexplained bouts of vomiting. The episodes have a rapid onset, persist over a number of hours or days, and are separated by symptom-free intervals. Despite the recent interest in this disorder, its aetiology, pathogenesis and even its target organ remain unknown.
The purpose of this study is to investigate the role played by food allergy in CVS. The report concerns eight children (five male, three female), mean age 8 years (3-13 years), suffering from CVS for 2 years at least. The diagnosis of CVS was based on characteristic history, normal physical examination and negative laboratory, radiographic, neurological and endoscopic studies. Despite the absence of clinical signs typical of food allergy, skin prick tests were positive in six of the eight patients (75%). Specific IgE were present in 4/8 (50%) of the patients. Skin tests and specific IgE were positive for cow's milk proteins, egg white and soya. IgE levels were higher than the mean + 2SD in 5/8 (63%) of the patients. A double blind placebo controlled food challenge (DBPCFC) was carried out on seven of the eight patients who displayed clinical improvement after an elimination diet for cow's milk (and other foodstuffs indicated by positive skin tests). The DBPCFC was positive in all seven children. Clinical follow-up revealed a state of well-being over the 6 months of observation.
CONCLUSION: It appears reasonable to suggest that food allergy plays a role in cyclic vomiting syndrome.
Idiopathic cyclic nausea and vomiting--a disorder of gastrointestinal motility?
Abell TL, Kim CH, Malagelada JR.
Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905.
Mayo Clin Proc 1988 Dec;63(12):1169-75 Abstract quote
Eight patients (five men and three women) with previously unexplained recurrent cyclic episodes of nausea and vomiting are described.
In these patients, the symptoms developed a mean of once every 3.2 months and persisted a mean of 3.5 days. None of the patients had an identifiable cause of their symptoms on conventional diagnostic tests. A detailed investigation of the gastrointestinal motility during an asymptomatic period revealed abnormal findings in all eight patients. Gastric hypomotility was substantiated in five patients, small bowel dysmotility in six, delayed gastric emptying in two, and gastric dysrhythmia in two.
The data demonstrate that abnormal gastrointestinal motility occurs during an asymptomatic state in patients with cyclic episodes of nausea and vomiting. Because all patients with this syndrome had abnormal gastrointestinal motility but normal results of other gastrointestinal studies, idiopathic cyclic nausea and vomiting may be related to altered gastrointestinal motility.
Cyclic vomiting syndrome: timing, targets, and treatment--a basic science perspective.
Department of Physiology, St. George's Hospital Medical School, London, UK.
Dig Dis Sci 1999 Aug;44(8 Suppl):31S-38S Abstract quote
Nausea and vomiting are both elements of the system that evolved to defend the body against toxins accidentally ingested with the food. When they are induced by an ingested toxin, they are considered to be an appropriate response, but in many clinical settings (eg, anticancer chemotherapy, anesthesia and surgery, raised intracranial pressure) both responses are inappropriate in that the vomiting does not remove the cause and the nausea may lead to aversion to further treatment.
Cyclic vomiting syndrome (CVS) is a particularly intense and prolonged example of inappropriate activation of this protective reflex. This review argues that insights into the pattern of emesis in CVS can be gained by examining the basic unit (quantum) of emesis, the emetic episode usually comprising retches followed by a vomit.
Two (of several) possible mechanisms for the induction of the intense vomiting in CVS are discussed: (1) defects in intrinsic pathways (eg, opioid neurons) that may modulate the brain-stem emetic mechanisms, and (2) defects in the regulation of cellular mechanisms (eg, cAMP, ion channels) in cells at critical locations in the emetic pathway (eg, nucleus tractus solitarius, area postrema).
If it is not possible to identify the causal mechanism of CVS, then will it be possible to treat CVS? This question is discussed in the context of the identification of universal or broad-spectrum antiemetic agents with recent preclinical studies with neurokinin-1 receptor antagonists reviewed to illustrate that such an approach is feasible.
Autonomic function in cyclic vomiting syndrome and classic migraine.
Rashed H, Abell TL, Familoni BO, Cardoso S.
Department of Medicine, University of Tennessee, Memphis 38163, USA.
Dig Dis Sci 1999 Aug;44(8 Suppl):74S-78S Abstract quote
Cyclic vomiting syndrome is an idiopathic disorder characterized by attacks of severe vomiting, interspersed with normal periods, and found in patients with a family history of migraine headaches.
In this report, we investigated the characterization of the autonomic abnormalities in cyclic vomiting syndrome, contrasting them with values in pediatric population, as well as adults with migraine headache.
We studied five groups: 41 normal pediatric controls (NPC), 12 patients with pediatric chronic vomiting (PCV), 15 patients with cyclic vomiting syndrome (CVS), 21 adults patients with migraine headaches (MHA), and 40 normal adult controls (NAC).
We studied the sympathetic and cholinergic functions: two measures of sympathetic adrenergic function-vasoconstriction to cold and postural adjustment ratio; two measures of vagal cholinergic function--Valsalva ratio and ECG R-R interval; and one measure of total autonomic score. Comparisons were performed between and within groups by t tests and reported as mean +/- SEM. Although cholinergic function measures were lower in cyclic vomiting and migraine groups, the most distinct abnormality was low postural adjustment ratio in both cyclic vomiting and migraine groups vs normal pediatric and pediatric chronic vomiting groups. There was also a significant difference between cyclic vomiting and pediatric chronic vomiting groups (P < 0.05 in three other parameters).
Cyclic vomiting syndrome is associated with distinctive adrenergic autonomic abnormalities similar to those in patients with migraine headaches and is usually characterized by a low postural adjustment ratio. These findings may have implications for both confirmation and diagnosis of cyclic vomiting syndrome.
Cyclic vomiting syndrome: the corticotropin-releasing-factor hypothesis.
CURE: Digestive Diseases Research Center, West Los Angeles VA Medical Center, 90073, USA.
Dig Dis Sci 1999 Aug;44(8 Suppl):79S-86S Abstract quote
The characterization of corticotropin-releasing factor (CRF) and CRF receptors and the use of specific CRF antagonists have paved the way to establish a key role of brain CRF in the coding of the stress response. CRF injected into the cerebrospinal fluid or the periphery inhibits gastric emptying in various species. The paraventricular nucleus of the hypothalamus and dorsal vagal complex are brain sites of action for CRF. Endogenous brain CRF plays a role in mediating psychological, physical, somatovisceral, and immunological stress-induced delayed gastric emptying in rats. Postoperative gastric ileus is also prevented by peripheral injection of CRF antagonists.
Cyclic vomiting syndrome (CVS) is precipitated by stimuli or states associated with stimulation of CRF release, and the resulting endocrine, autonomic, and visceral changes are indicative of central CRF activation. Moreover, empiric pharmacotherapy alleviating CVS symptoms are known experimentally to block CRF release or action.
The relevance of central CRF activation in the pathophysiology of CVS deserves further consideration.
Cyclic vomiting syndrome: in vitro nitric oxide and interleukin-6 release by esophageal and gastric mucosa.
Zicari A, Corrado G, Pacchiarotti C, Lucarelli S, Frediani T, Cavaliere M, Porcelli M, Cardi E.
Istituto di Clinica Pediatrica, Departimento di Medicine Sperimentale e Patologia, Universita degli Studi di Roma La Sapienza, Italy.
Dig Dis Sci 2001 Apr;46(4):831-5 Abstract quote
Cyclic vomiting syndrome is a disorder characterized by recurrent episodes of nausea and vomiting with complete resolution of symptoms between attacks. Nitric oxide plays a critical role in regulating several components of gastrointestinal mucosal defense and injury. Interleukin-6 has a wide variety of actions in the gastrointestinal apparatus.
The purpose of this study was to evaluate the synthesis and release of nitric oxide and interleukin-6 by the esophageal and gastric mucosa in 10 children with cyclic vomiting syndrome, during symptom-free periods, and in 10 controls. The nitric oxide and interleukin-6 release by esophageal mucosa cells obtained from cyclic vomiting patients was quite similar to that in controls, but the release of nitric oxide from gastric mucosa cells of patients was significantly higher than that of controls. Conversely, no interleukin-6 was detectable in gastric mucosa cell supernatants in any of the patients.
Further studies are needed to evaluate the relationship between factors triggering cyclic vomiting syndrome and the release of nitric oxide and interleukin-6 by gastric mucosa.
CHARACTERIZATION RADIOLOGIC LABORATORY MARKERS
Neurologic investigations of childhood abdominal migraine: a combined electrophysiologic approach to diagnosis.
Visual Function Department, Birmingham and Midland Eye Hospital, United Kingdom.
J Pediatr Gastroenterol Nutr 1995;21 Suppl 1:S44-8 Abstract quote
Neurologic studies of childhood migraine, including imaging techniques and electrophysiology, have identified a number of abnormalities, but none of high specificity. Therefore, a diagnostic marker for childhood migraine and its equivalents remains elusive.
In this study a combined electrophysiologic approach is assessed, using measurements of visually provoked beta-activity, high-frequency photic following responses, and visually stimulated event-related potentials. Eighteen children younger than 10 years of age with abdominal migraine and/or cyclic vomiting syndrome were investigated with these techniques. They were compared with the responses from a number of control groups, including a group diagnosed as childhood migraine with or without aura. Individually, each investigation yielded high sensitivities but low specificities ( < 50%). However, when these techniques were used in combination the specificity for migraine rose to > 90%. There was no significant difference between abdominal migraineurs and those with migraine with or without aura in any of the parameters studied.
This combined approach is potentially useful in the diagnosis of abdominal migraine and supports the view that abdominal migraine can be classed as a true childhood migraine equivalent.
Electrogastrography in cyclic vomiting syndrome.
Department of Pediatric Gastroenterology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, USA.
Dig Dis Sci 1999 Aug;44(8 Suppl):64S-73S Abstract quote
Children with cyclic vomiting syndrome have a characteristic periodicity, and this could be due to abnormal gastric myoelectrical activity detectable by cutaneous electrogastrography (EGG).
Fifteen children, aged 4-15 years, with CVS (eight symptomatic and seven asymptomatic at the time of study) underwent EGG and were compared to five normal and four disease control children. The relative tachygastria activity (RTA) or power ratio was calculated in each group. Five of the eight symptomatic CVS children showed marked episodes of tachygastria preprandially and all showed tachygastria postprandially. The asymptomatic CVS children showed tachygastria only postprandially after the test meal. RTA index and or power ratio of symptomatic children was significantly different from the asymptomatic CVS children (P = 0.001), normal (P = 0.007) and disease control children (P = 0.006). In a subsequent study, 2-hr gastric emptying 99mTc scintiscans were performed in 28 CVS children and compared to eight healthy control children. Twelve of 16 CVS children (75%) showed abnormal gastric emptying, and 7 of 28 (25%) showed abnormal EGG with significant tachygastria.
The CVS children had significantly higher RTA both preprandially (P < 0.05) and postprandially (P < 0.05). Our results demonstrate that accelerated gastric rhythm was seen during the acute episodes of half of the CVS patients studied. Abnormal EGGs and higher RTA or power ratios were associated with delayed gastric emptying in the CVS children. Abnormal gastric myoelectrical activity may play a role in the pathogenesis of CVS syndrome.
The cyclic vomiting syndrome: a report of 71 cases and literature review.
Fleisher DR, Matar M.
Department of Pediatrics, Cedars-Sinai Medical Center, University of California, Los Angeles.
J Pediatr Gastroenterol Nutr 1993 Nov;17(4):361-9 Abstract quote
This study reviews 71 patients who presented between 1968 and 1988 with recurrent, self-limited episodes of nausea and vomiting separated by symptom-free intervals and were diagnosed with cyclic vomiting syndrome (CVS).
The length and symptomatology of episodes tended to be stereotyped and characteristic for each patient over time. The disorder may persist from months to decades. There is a coincident relationship between CVS, migraine, and irritable bowel syndrome. The differential diagnosis includes many diseases which may mimic CVS.
Management involves a responsive, collaborative doctor-patient relationship, sensitivity to stresses caused by the illness and to feelings and attitudes that may predispose to attacks, use of antiemetic agents to abort or shorten attacks, treatment of complications, and use of prophylactic agents in patients whose episodes are of sufficient frequency and severity to warrant their trial.
Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder.
Li BU, Balint JP.
Ohio State University, USA.
Adv Pediatr 2000;47:117-60 Abstract quote
Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882.
Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children.
Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches.
We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups.
Treatment includes avoidance of triggers, prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
Cyclic vomiting and the slit ventricle syndrome.
Department of Neurology, Loyola University Medical Center, Maywood, Illinois 60153.
Pediatr Neurol 1987 Sep-Oct;3(5):297-9 Abstract quote
Recurrent bouts of vomiting with headache and lethargy occurred in 6 children with ventriculoperitoneal shunts who had small ventricles rather than the expected dilated ones.
Slit ventricle syndrome is not uncommon in children with shunts and its early recognition allows for appropriate surgical treatment.
Differential diagnosis of cyclic vomiting syndrome.
Department of Paediatrics, University of Western Australia, Princess Margaret Hospital for Children, Perth, Australia.
J Pediatr Gastroenterol Nutr 1995;21 Suppl 1:S11-4 Abstract quote
Vomiting is a nonspecific symptom and cyclic vomiting is a symptom complex that may result from a disorder of any major organ system.
Children with cyclic vomiting syndrome (CVS) need careful review and investigation at their earliest presentations to exclude potentially lethal abnormalities such as intestinal volvulus, metabolic disorders, and neurologic space-occupying lesions.
The range of abnormalities that may present with features consistent with CVS includes gastrointestinal obstructive, inflammatory and motility abnormalities, pancreatic disease, metabolic disease (particularly the amino acid-opathies, organic acidurias, fatty acid oxidation defects, and acute intermittent porphyria), renal disease, epilepsy, migraine, and psychiatric disorders.
Careful history taking will usually provide clues to these uncommon problems, but all children should undergo baseline assessment of gastrointestinal morphology and screening tests for renal and metabolic disease.
Heterogeneity of diagnoses presenting as cyclic vomiting.
Li BU, Murray RD, Heitlinger LA, Robbins JL, Hayes JR.
Department of Pediatrics, Ohio State University, Columbus, USA.
Pediatrics 1998 Sep;102(3 Pt 1):583-7 Abstract quote
OBJECTIVE: To establish the diagnostic profile in children who present with cyclic vomiting.
METHODS: We studied 225 children < 18 years of age who presented to our pediatric gastroenterology service from 1986 to 1997 with at least three discrete episodes of vomiting between which they were well. To determine the diagnoses in those presenting with a pattern of cyclic vomiting, the results of diagnostic testing and responses to various treatments were obtained from a combination of chart review and structured telephone interviews.
RESULTS: The largest diagnostic category included idiopathic cyclic vomiting syndrome (88%). Extraintestinal disorders (7%) and gastrointestinal disorders (5%) constituting the probable cause of vomiting were established in those having complete cessation of episodes after therapy. In 12%, serious surgical disorders of the gastrointestinal (malrotation), renal (acute hydronephrosis), and central nervous systems (neoplasm) were found. In 2%, serious endocrine (Addison's disease) and metabolic disorders (disorder of fatty acid oxidation) were found. Among those with idiopathic cyclic vomiting syndrome, 41% had associated disorders (gastroesophageal reflux and chronic sinusitis) that could contribute to the vomiting, but, based on a partial response to therapy, were not deemed to be the main cause. Altogether 49% had an identified disorder that probably caused or could contribute to the vomiting.
CONCLUSIONS: The cyclic pattern of vomiting is a symptom complex that can be induced by heterogeneous disorders that either cause or contribute to the vomiting. Once the cyclic vomiting pattern is identified, systematic diagnostic testing is warranted to look for these underlying disorders.
Cyclic vomiting and elevation of creatine kinase associated with bitemporal hypoperfusion and EEG abnormalities: a migraine equivalent?
Oki J, Miyamoto A, Takahashi S, Itoh J, Sakata Y, Okuno A.
Department of Pediatrics, Asahikawa Medical College, Japan.
Brain Dev 1998 Apr;20(3):186-9 Abstract quote
A 13-year-old mentally retarded boy suffered from repeated vomiting attacks since infancy. Each episode lasted 2 to 10 days, and was precipitated by respiratory infection, exercise or stress.
During an attack he became irritated, agitated and amnesic, but did not have headaches or seizures. Associated findings were transient elevation of serum creatine kinase (CK) (331-3381 IU/l), and of plasma ACTH and cortisol. The raised CK level was the result of muscle hypertonicity. Ictal EEGs showed delta activity in the front-temporal areas, and inter-ictal IMP-SPECT revealed hypoperfusion in both temporal regions. Unlike the periodic ACTH-ADH discharge syndrome, neither hypertension nor depression developed. These attacks were diagnosed as a migraine equivalent and were suppressed with phenytoin. From the EEG and SPECT findings, we concluded that the vomiting and behavioural changes were related to the paroxysmal vascular abnormality in the temporal regions, but it was not easy to make the distinction between migraine and focal epilepsy.
Before a diagnosis of the periodic ACTH-ADH discharge syndrome is made, the possibility of migraine equivalent should be considered.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS TREATMENT
Treatment of cyclic vomiting in childhood with erythromycin.
Vanderhoof JA, Young R, Kaufman SS, Ernst L.
Department of Pediatrics, Creighton University School of Medicine, Omaha, Nebraska.
J Pediatr Gastroenterol Nutr 1993 Nov;17(4):387-91 Abstract quote
Cyclic vomiting syndrome is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful.
We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 20 children (9 boys, 11 girls). Many patients had mild associated abdominal pain with their vomiting. Thirteen patients had previously been given metoclopramide, but none responded. Two patients were mildly developmentally delayed. Twenty patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in 2-4 divided doses for 7 days. This dosage was repeated as needed when symptoms reappeared. Thirteen of 20 patients reported total resolution of symptoms when reevaluated at 2 and 6 months. All males responded, 4 of 13 responders were female, and all seven with partial or no response to therapy were female.
This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of cyclic vomiting syndrome in childhood. As the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in cyclic vomiting syndrome.
Cyclic vomiting: association with multiple homeostatic abnormalities and response to ketorolac.
Pasricha PJ, Schuster MM, Saudek CD, Wand G, Ravich WJ.
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Gastroenterol 1996 Oct;91(10):2228-32 Abstract quote
Cyclic vomiting is a rare syndrome that over the years has variously been ascribed to psychogenic causes, sensory seizures, abdominal migraine, and more recently, to mechanical or electrical disturbances in gastric physiology.
We describe the case of a 65-year-old white diabetic female with a 10-yr history of recurrent episodes of nausea and vomiting, occurring every 10-12 days and lasting approximately 1-3 days at a time. These episodes were accompanied by edema, mild temperature elevations, and remarkable elevations in blood pressure. In between these episodes, the patient remained asymptomatic. Initial screening tests were also negative except for moderate gastroparesis. However, antral motility was found to be normal, as was an electrogastrogram. Detailed neurological and psychiatric evaluations were negative. Trials of erythromycin, metoclopramide, naloxone, ondansetron, and amitryptiline were unsuccessful. Serial endocrinological testing revealed that an episode of vomiting was always preceded by an abnormal elevation in at least one of the following: serum adrenocorticotropic hormone, serum cortisol, or urinary cortisol. In the midst of an episode, all three values were exceedingly high (e.g., > 10-fold increases in 24-hr urinary cortisol levels). Fluctuations of a milder degree, though still abnormally high, were also noted in between cycles at times when the patient was completely asymptomatic. High-dose dexamethasone suppressed these hormonal surges completely but not the clinical symptoms, which continued undisturbed. The patient was finally given a trial of intramuscular ketorolac during one of her episodes, which produced prompt and sustained relief. During the next few weeks, she was given this drug each time her symptoms commenced, and each time it appeared that her cycle had been aborted. She has since been able to terminate her episodes promptly and completely by self-administration of ketorolac.
We speculate that her syndrome is caused by a poorly characterized disorder of endogenous prostaglandin release, resulting not only in derangements in the hypothalamic pituitary system but also in nausea and vomiting.
Effective prophylactic therapy for cyclic vomiting syndrome in children using amitriptyline or cyproheptadine.
Andersen JM, Sugerman KS, Lockhart JR, Weinberg WA.
Department of Pediatrics, University of Texas Southwestern Medical Center and Children's Medical Center, Dallas, Texas, USA.
Pediatrics 1997 Dec;100(6):977-81 Abstract quote
OBJECTIVE: To evaluate our experience using the antimigraine prophylactic drugs, amitriptyline and cyproheptadine, for the prophylactic management of cyclic vomiting syndrome (CVS) in children.
METHODS AND PATIENTS: Twenty-seven patients (16 males) ranging in age from 2 to 16 years at diagnosis, fulfilling the diagnostic criteria for CVS and treated prophylactically with either amitriptyline (22) or/and cyproheptadine (6) were identified through retrospective chart review. Individual patient data were corroborated by the attending physician and/or interviews with patients and families. Minimum follow-up time before entry into the study group was 5 months. Patients were stratified according to three treatment outcomes: 1) complete response-no attacks, 2) partial response-50% or greater reduction in frequency of attacks, and 3) no response-less than 50% decrease in frequency of attacks.
RESULTS: Of the 22 patients treated with amitriptyline, 16 (73%) had a complete response while 4 (18%) had a partial response. Of the 6 patients treated with cyproheptadine, 4 (66%) had a complete response and 1 (17%) had a partial response. Thus, 91% of the amitriptyline group and 83% of the cyproheptadine group had at least a partial response to therapy. No patients experienced significant side effects to either medication.
CONCLUSION: The antimigraine prophylactic drugs, amitriptyline and cyproheptadine, represent effective prophylactic agents for the management of CVS in the vast majority of patients fulfilling the diagnostic criteria for this syndrome.
Cyclic vomiting syndrome in adults: clinical features and response to tricyclic antidepressants.
Prakash C, Clouse RE.
The Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA.
Am J Gastroenterol 1999 Oct;94(10):2855-60 Abstract quote
OBJECTIVE: Cyclic vomiting syndrome (CVS) has been described infrequently in adults, and treatment in both children and adults remains unsatisfactory. We report clinical features of a group of adults with CVS and anecdotal outcome from open-label treatment with tricyclic antidepressants, medications that have some efficacy in other unexplained gastrointestinal disorders.
METHODS: Clinical data were examined from 17 adult patients with CVS seen over a 10-yr period, each having been treated with a tricyclic antidepressant. Outpatient records were reviewed, clinical outcome was extracted using a priori criteria, and findings were compared with 37 patients having usual functional nausea and vomiting who also received tricyclic antidepressant therapy.
RESULTS: Symptoms in CVS began at age 35 yr (range 14-73 yr); the average episode length was 6 days (range 1-21 days) and the symptom-free interval averaged 3.1 months (range 0.5-6 months). Vomiting cycles typically began without warning, and fewer than one-third of the subjects reported a prodrome or potential trigger event, such as menstrual periods, pregnancy, or large meals. Sleep was seemingly beneficial in 23.5%. Tricyclic antidepressant therapy was associated with complete remission in 17.6% and partial response in 58.8%, but was less effective than for functional nausea and vomiting (p = 0.02).
CONCLUSIONS: CVS is a rare diagnosis with distinctive features in adults. Duration of episodes and cycles varies considerably across subjects. In open-label, uncontrolled use, tricyclic antidepressants appear beneficial for some subjects but are less effective in CVS than in chronic, persistent functional nausea and vomiting.
Cyclic Vomiting Syndrome.
Children's Memorial Hospital, Room 729, Nellie A. Black Bldg., 2300 Children's Plaza, Box 57, Chicago, IL 60614-3394, USA
Curr Treat Options Gastroenterol 2000 Oct;3(5):395-402 Abstract quote
For the last century, empiric therapy has been used to treat the relentless vomiting and resulting dehydration associated with cyclic vomiting syndrome. Despite its unknown pathogenesis, in the last decade, uncontrolled trials of various antimigraine and antiemetic agents have demonstrated rates of efficacy of 40% to 90%. Antimigraine agents are used to prevent or abort episodes, whereas antiemetic agents are used to attenuate symptoms during episodes. A positive family history of migraine headaches renders the patient more likely to respond to antimigraine therapy. In addition to antimigraine therapy, antiemetic sedative/anxiolytic, neuroleptic and gastroinestinal prokinetic agents may be useful.
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