Diagnosis and Management of Cyclic Vomiting Syndrome in a Dog: First Report in Veterinary Medicine

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While CVS is well-documented in human medicine, this report details the first diagnosis of CVS in veterinary medicine. Case presentation A 16-year-old neutered male Maltese dog presented with a history of daily vomiting that was unresponsive to standard antiemetic therapies. On physical examination, hematologic tests, radiography, ultrasonography, computed tomography, fluoroscopy, and endoscopy, gastrointestinal and metabolic causes of vomiting were ruled out. In addition, to rule out neurogenic causes of vomiting, magnetic resonance imaging, cerebrospinal fluid analysis, and electroencephalography were performed and showed no remarkable findings. Based on the distinctive vomiting pattern characterized by stress-induced symptoms and association with the circadian rhythm as well as consistency with the clinical criteria used in humans (Rome criteria), the dog was diagnosed with CVS. Therapeutic trials with anticonvulsants, including phenobarbital and levetiracetam, successfully controlled the dog’s clinical signs, which were unresponsive to conventional treatments. Conclusions This case emphasizes the potential for CVS in canine species and highlights the need for further exploration of neurogenic vomiting disorders in dogs. Cyclic vomiting syndrome Dog Neurogenic vomiting Figures Figure 1 Figure 2 Figure 3 Background Cyclic vomiting syndrome (CVS) is known as an idiopathic chronic disorder characterized by recurrent episode of sudden-onset attacks of repetitive vomiting [ 1 ]. In humans, it is relatively a common disorder of childhood with an estimated prevalence of approximately 1.9%, but it has not been reported in veterinary medicine [ 2 ]. The vomiting symptoms are characterized by patterns triggered by psychiatric factors and a circadian vomiting rhythm [ 3 ]. CVS consists of four phases in one cycle including the prodromal, emetic, recovery, and asymptomatic phases. The prodromal phase is characterized by nausea. The emetic phase is characterized by intense nausea and vomiting and lasts from a few seconds to several minutes. After experiencing intense vomiting, the patient goes through the recovery phase, during which vomiting ceases and a normal appetite returns, which leads to the asymptomatic phase. The cycle is defined as a single independent episode, and the interval between cycles can range from several hours to several days or weeks [ 4 , 5 ]. CVS is generally considered to be idiopathic, and there is no specific definitive diagnostic method for CVS. Therefore, the diagnosis of CVS is made based on characteristic clinical criteria. The clinical diagnostic criteria include the Rome criteria, and additional separate guidelines have been provided by multiple associations including the Cyclic Vomiting Syndrome Association [ 1 ]. While these guidelines differ slightly in terms of the defined frequency and duration of episodes, they commonly present the following essential criteria: recurrent and discrete episodes of vomiting, asymptomatic periods between episodes, vomiting lasting from hours to days, and no apparent cause of vomiting. If these criteria are met, CVS can be diagnosed [ 1 , 5 ]. The treatment of CVS involves the use of anticonvulsants, antidepressants, and sedatives as first-line therapies. In addition to pharmacological approaches, multidisciplinary care including stress management may also be necessary [ 5 ]. The aim of this article is to describe the clinical symptoms, diagnostic findings, and outcomes in a dog with presumptive CVS. Case Presentation A 16-year-old neutered male Maltese dog presenting with vomiting that was unresponsive to conventional antiemetic therapy was referred to the veterinary teaching hospital. In terms of patient history, the dog had experienced daily vomiting and snoring symptoms for three weeks with episodes of nausea and vomiting that were triggered by excitement, stress, or separation anxiety in the past. The vomiting typically occurred in the morning after the dog woke up. The only notable medical procedure was a dental scaling that was performed three weeks prior. A physical examination revealed that the dog had a body condition score of 7/9 and a pot-bellied appearance. He had a normal appetite and normal vitality. A neurological examination showed no remarkable findings on the cranial and spinal nerve assessments. During hospitalization, the dog showed signs of nausea, lip smacking, and retching due to stress and discomfort from handling; these symptoms were followed by reverse sneezing and snoring, which continued for a few minutes. Laboratory examinations including a complete blood count revealed mild neutrophilia (18.56 K/µL; reference range, 5.05–16.76 K/µL). Serum biochemistry showed elevated levels of alkaline phosphatase activity (2,513 U/L; reference range, 23–212 U/L) and gamma-glutamyl transferase activity (23 U/L; reference range, 0–11 U/L). C-reactive protein and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase levels were within the normal ranges. An adrenocorticotropic hormone (ACTH) stimulation test showed increased pre-stimulation (13.7 µg/dL; reference range, 2–6 µg/dL) and post-stimulation cortisol levels (23.5 µg/dL; reference range, 6–18 µg/dL). A blood gas analysis showed no remarkable findings. A urinalysis revealed a urine specific gravity of 1.013, and no abnormalities were observed on the dipstick test. Calcium oxalate crystals were detected on the microscopic examination. Respiratory and fecal cytology tests showed no remarkable findings. Diagnostic imaging was also performed, and radiographs of the craniocervical, thorax, and abdomen showed marked hepatomegaly without other remarkable findings. Abdominal ultrasonography showed increased echogenicity of the liver and kidneys and hyperechoic sludge in the gallbladder. The pancreas had normal echogenicity, and both adrenal glands showed no abnormalities in size or shape. Hydrosonography of the gastrointestinal tract revealed no abnormalities. Additional tests were conducted to determine the cause of vomiting. Gastrointestinal contrast studies showed a normal gastric emptying time and motility, fluoroscopy showed no evidence of a swallowing disorder, hiatal hernia, or sliding hernia of the upper gastrointestinal tract. Computed tomography (CT) of the abdomen showed mild thickening of the gastric wall, while the craniocervical and thoracic regions did not display any evidence of major causes of vomiting. To rule out the possibility that imaging studies missed the causes of snoring and vomiting, respiratory and gastrointestinal endoscopy were performed. Rhinoscopy and gastrointestinal endoscopy did not reveal specific abnormalities, except for mild thickening and congestion of the gastric pyloric region (Fig. 1 ). Mildly congested tissue in the nasal choana region was collected through retrograde rhinoscopy, and thickened and congested tissue from the gastric pylorus and body was collected via upper gastrointestinal endoscopy. Histopathology of the nasal tissue was normal, and the gastric tissue showed inflammation without other specific findings. A multiplex polymerase chain reaction (PCR) test was performed to assess for major pathogens such as canine parvovirus, canine coronavirus, canine distemper virus, Clostridium spp., pathogenic Escherichia coli , and Campylobacter spp., that could cause vomiting or respiratory symptoms, and these were all ruled out. Respiratory bacterial culture tests only detected Enterococcus faecalis and Pseudomonas aeruginosa in small amounts. Helicobacter spp. were ruled out through PCR testing and silver staining of the pyloric tissue. The dog was prescribed dietary restrictions, parenteral nutrition, and fluid therapy. Oxygen therapy was administered to reduce respiratory stress. Symptomatic therapy included maropitant (1 mg/kg BW SC SID), ondansetron (1 mg/kg BW IV BID), and metoclopramide (2 mg/kg/day continuous rate infusion). Antibiotics were selected based on the antibiotic sensitivity results of the respiratory tissue culture and included amoxicillin-clavulanate (12.5 mg/kg BW IV BID) and enrofloxacin (5 mg/kg BW SID). Despite symptomatic therapy, the dog’s clinical signs did not improve, and his condition worsened. The vomiting cycle increased in duration and frequency. The dog exhibited more than four vomiting cycles per day without improvement, with a cyclical pattern in the morning (6–10 AM) and evening (4–8 PM). In addition, the vomiting cycle was triggered by handling, postural changes, and respiratory disorder. A tentative diagnosis of neurogenic vomiting was made because no specific findings were observed on the previous tests, and gastrointestinal and metabolic diseases were considered to be completely ruled out. Diagnostic evaluations including magnetic resonance imaging (MRI) cerebrospinal fluid (CSF) examination, and electroencephalography (EEG) were performed to rule out pathophysiologic causes in the central nervous system. However, these examinations also showed no remarkable findings. The dog was diagnosed with CVS based on the Rome criteria because all the following conditions were met: stereotypical episodes of acute vomiting lasting less than a week occurring within the previous three months, at least three episodes in the prior year and two in the past six months occurring at least one week apart, absence of vomiting or nausea symptoms between episodes, and no evidence of organic, systemic, or metabolic diseases on hematologic or radiologic investigations. Therapeutic trials with anticonvulsants were initiated with a loading dose of phenobarbital (12 mg/kg BW IV) administered in three divided doses, each given four hours apart. Low-dose phenobarbital (2.5 mg/kg BW IV BID) led to minor improvement in the vomiting symptoms, but the symptoms were not completely controlled. After increasing the dose of phenobarbital (6 mg/kg BW IV BID), the clinical symptoms were completely resolved within two days (Fig. 2 ). After improvement in the vomiting the symptoms, reverse sneezing and snoring symptoms also resolved completely. The dog was discharged with a prescription including phenobarbital (6 mg/kg BW PO BID), gabapentin (10mg/kg BW PO BID), trazodone (5 mg/kg BW PO BID), and maropitant (2 mg/kg BW PO PRN). Two weeks post-discharge, without any dosage adjustment, the phenobarbital concentration was measured at 43.2 µg/ml. The phenobarbital dosage was subsequently tapered by 1.5 mg/kg (approximately 25% of the original dose) every two weeks, leading to complete discontinuation over eight weeks. During the second tapering cycle, levetiracetam (30 mg/kg BW PO BID) was added. No recurrence of symptoms was observed during the tapering process. The gabapentin and trazodone prescribed as sedatives were replaced and reduced in dosage, respectively, due to the dog experiencing excessive drowsiness as a side effect. The treatment regimen was adjusted to include amitriptyline (2 mg/kg BW PO BID) and trazodone (3 mg/kg BW PO BID). During the hospitalization period, based on the dog’s clinical symptoms and laboratory examinations, he was tentatively diagnosed with concurrent Cushing’s disease, and trilostane (1 mg/kg BW PO BID) was additionally prescribed. A follow-up evaluation for Cushing's disease was performed two weeks after discharge. An ACTH stimulation test revealed pre-stimulation cortisol levels of 4.5 µg/dL (reference range, 2–6 µg/dL) and post-stimulation cortisol levels of 8.0 µg/dL (reference range, 6–18 µg/dL). A blood gas analysis demonstrated no significant abnormalities. Urinalysis showed a urine specific gravity of 1.025, the resolution of polyuria/polydipsia was confirmed, and the cortisol levels were maintained withing target range, leading to the decision to maintain the current dosage of trilostane. There was no recurrence of symptoms or evidence of adverse drug effects during the subsequent follow-up. The vomiting symptoms did not recur for 12 weeks following complete resolution. However, in the 13th week, which was four weeks after the discontinuation of phenobarbital, mild symptoms of nausea and reverse sneezing reappeared, and their frequency and severity gradually increased. Despite increasing the dose of levetiracetam (50 mg/kg BW PO TID), it was difficult to completely control the symptoms. An additional neurologic examination was performed and showed no remarkable findings. An additional EEG examination was conducted during the symptomatic phase, and no specific ictal waves were detected except for a single abnormal waveform (Fig. 3 ). The dog exhibited a cyclic pattern of vomiting from 8–10 AM, 4–6 PM, and 10 PM– 12 AM. Due to potential for recurrent vomiting to lower the vomiting threshold, a long-acting anticonvulsant was re-inducted to quickly suppress the symptoms. The dog was administered phenobarbital (20mg/kg BW PO loading dose, 6 mg/kg BW PO BID), levetiracetam (50 mg/kg BW PO TID), amitriptyline (2 mg/kg BW PO BID), and trazodone (3 mg/kg BW PO BID). In addition, the administration times were adjusted to one hour before the onset of the vomiting cycle. The medications that were prescribed to be administered twice daily were administered in the morning and evening (7 AM, 9 PM), and levetiracetam (50 mg/kg BW) was given only at 3 PM. Complete resolution of symptoms was noted within five days after administration. Two weeks post-discharge, without any dosage adjustments, the phenobarbital concentration was measured at 39.8 µg/ml. The phenobarbital dosage was subsequently tapered by 1.5 mg/kg (approximately 25% of the original dose) every two weeks. The previous prescription is being maintained with only the dosages of phenobarbital (3 mg/kg BW PO BID) and levetiracetam (30 mg/kg PO BID) reduced. The symptoms have not recurred for 13 weeks following complete resolution, and the dog has not experienced any side effects from the medications (Fig. 3 ). Discussion This report describes a case of chronic vomiting due to CVS and examines the novel mechanism of this type of vomiting, which is not well known in veterinary medicine. This syndrome is considered to be activated through pathways different from the common vomiting pathways, which involve stimulation of the vomiting center known as the nucleus tractus solitarius by gastrointestinal vagal afferent fibers, the chemoreceptor trigger zone (area postrema), and vestibular input. Rather, CVS is considered to occur through a “forebrain and limbic pathway”, which is not yet clearly understood [ 6 , 7 , 8 ]. There have been attempts to explain that this pathway is stimulated by “neurocircuit hyperexcitability” caused by congenital or acquired factors, and various experimental results support this hypothesis [ 8 , 9 ]. For this reason, in human medicine, CVS has been referred to as a functional vomiting disorder, idiopathic neurological disorder, or “neurogenic vomiting” [ 4 , 8 ]. This neurogenic vomiting has not been studied in veterinary medicine. However, various idiopathic vomiting disorders suspected to be neurogenic have been documented as case reports. For example, phenobarbital-responsive sialadenosis (PRS) is a relatively well-documented idiopathic neurogenic vomiting disorder in veterinary medicine. Although the precise etiology is not understood, this vomiting disorder requires the exclusion of all other potential causes of vomiting and is recognized as a neurogenic vomiting disorder due to its exclusive response to anticonvulsants [ 10 , 11 ]. There have also been previous reports of vomiting associated with separation anxiety, indicating that cognitive and emotional factors may mediate vomiting in animals [ 12 ]. Such cases indicate that the neuropsychiatric factor-mediated vomiting mechanism, a main hypothesis in CVS, may also operate in dogs. Though limited, these reports suggest the “existence of other unclassified neurogenic vomiting disorders” in veterinary medicine. CVS, as its name suggests, follows a cyclic rhythm of vomiting (particularly in the early morning) and is known to be triggered by stress. In this case, the dog primarily experienced vomiting in the early morning, followed by a pattern of alternating reverse sneezing and vomiting. There was also a history of vomiting triggered by anxiety-inducing situations such as visits from strangers or the owner's absence. These patterns were detected during the dog's hospitalization. The vomiting was induced in stressful situations such as handling for examination, while on days without such procedures, the frequency of vomiting was reduced. CVS is strongly associated with vomiting pathways triggered by emotional and cognitive stimuli within the central nervous system, and changes in neuroendocrine hormones, particularly the activation of corticotropin-releasing factor (CRF), play a crucial role [ 13 ]. In particular, CRF secretion by neurons in the paraventricular nucleus of the hypothalamus increases in the early morning hours [ 14 , 15 ]. Elevated peripheral CRF levels have an inhibitory effect on gastric motility, lowering the threshold for vomiting throughout the day and contributing to its onset [ 16 , 17 ]. The fundamental circadian rhythm and its effects are ultimately influenced by the activity of neurons in the suprachiasmatic nucleus (SCN), and animal studies have already demonstrated changes in SCN neuron activity induced by stress [ 16 ]. It is particularly interesting that the dog exhibited both early-morning-onset and stress-induced vomiting, suggesting that this case aligns with the main etiological aspects of CVS. The dog was also tentatively diagnosed with Cushing's disease based on physical examination, clinical symptoms, elevated cortisol levels, and ACTH stimulation tests. According to the previous reports, similar to this case, patients with CVS have been reported to have significant elevations in ACTH and cortisol levels as well as increased sympathetic nervous system activity [ 16 ]. The dog presented with evidence of a long-term history of Cushing’s disease, including systemic calcium deposits, abdominal distension, polyuria and polydipsia, and bilateral alopecia. Thus, it remains uncertain whether the elevated cortisol levels due to autonomic dysfunction preceded Cushing’s disease, if the latter was the primary condition, or if both factors were contributing. Further research is needed to explore the association between Cushing’s disease and CVS. The exact pathophysiology of CVS is not known; therefore, diagnosis of CVS relies on symptom-based diagnostic criteria including the Rome criteria [ 1 ]. Due to the lack of definitive diagnostic methods, clinicians can make a diagnosis of CVS based on symptom-based diagnostic criteria and the patient's medical history if all other diseases have been completely ruled out. In this case, there was no therapeutic response to conventional antiemetics during the hospitalization period, and no significant or specific findings were identified on any of the diagnostic tests conducted. It was initially suspected that excitement or changes in posture might have caused mechanical problems such as gastrointestinal herniation, leading to vomiting. However, multiple tests completely ruled out this possibility. For this reason, it was suspected that neuropsychiatric factors that were not detectable through standard diagnostic tests were contributing to the vomiting. Unlike other gastrointestinal disorders, CVS is characterized by asymptomatic periods during which the patient exhibits a normal appetite and no clinical symptoms [ 5 ]. Consistent with what has been reported previously, this dog showed a normal appetite during hospitalization, which contrasts with the typical presentation of dogs suffering from more common gastrointestinal disorders. Sometimes, despite thorough diagnostic evaluations, CVS can be misdiagnosed due to the incomplete exclusion of metabolic, endocrine, or mechanical gastrointestinal disorders that could induce vomiting [ 5 ]. It can also be difficult to differentiate CVS from neurogenic vomiting known as ictus emeticus (ictal vomiting), and 4–7% of patients with CVS are later re-diagnosed with ictus emeticus [ 18 , 19 ]. Ictus emeticus presents clinical patterns similar to CVS and can be diagnosed by identifying ictal waves on EEG or detecting structural abnormalities on brain MRI scans as well as through the complete exclusion of other causes of vomiting [ 18 , 20 ]. For this reason, the dog required a detailed physical examination and comprehensive laboratory tests to rule out all disorders that needed to be differentiated from CVS. Notable abnormalities were not detected on any of the tests performed to differentiate the primary cause of vomiting. No structural abnormalities were found in the brain on MRI, and no significant ictal waves were consistently detected on EEG, which tentatively ruled out ictus emeticus. PRS was ruled out due to the absence of salivary gland enlargement or hypersalivation symptoms. Based on this history, a tentative diagnosis of CVS was made. It has been shown that the frequency and severity of CVS episodes can vary depending on the presence of anxiety, and they can be treated with various medical interventions including psychological and pharmacological approaches. Therefore, anxiolytics and tricyclic antidepressants can be utilized [ 21 , 22 ]. Recent research has shown that the clinical patterns of CVS resemble neurological symptoms such as seizures, migraines, and panic disorders. Based on this, a treatment framework known as the 'CVS threshold' has been proposed, and these studies have played a crucial role in forming a consensus on CVS treatment guidelines [ 4 ]. The newly agreed-upon treatment guidelines suggest different therapeutic approaches according to the four main phases of the disorder. During the prodromal, recovery, and asymptomatic phases, preventive treatments such as tricyclic antidepressants, anticonvulsants, and antiemetics as well as good sleep hygiene, stress management, avoidance of fasting and dehydration, and psychotherapy to address psychiatric comorbidities are recommended. During the vomiting phase, it is recommended to use a combination of antiemetics, analgesics, and sedatives, while serotonin antagonists or migraine medications are conditionally recommended. Intravenous fluids are also recommended to prevent complications [ 5 ]. Managing the disorder requires comprehensive multidisciplinary care because CVS is known to be associated with both physical and mental conditions, such as hereditary migraines, malnutrition, psychiatric disorders, and underlying autonomic nervous system disorders, which can contribute to its development [ 23 , 24 , 25 , 26 ]. During treatment, physicians typically address both the physical symptoms and the psychological aspects. It is known that addressing both simultaneously can lead to better outcomes [ 27 ]. There is little long-term follow-up of patients with CVS. In one study with an average follow-up period of 4 years, 86% of patients showed improvement after therapeutic intervention; however, some patients were reported to have worsened [ 2 ]. Based on CVS treatment guidelines and literature reports, a treatment plan was made for the dog. The initial approach was focused on strongly suppressing the symptoms to reduce the frequency of vomiting and increase the seizure threshold. From the early stages of treatment through the long-term monitoring period, observations of the dog’s response to medications revealed that most antiemetics, including maropitant, ondansetron, and metoclopramide, which are known to act on chemoreceptors, did not produce significant clinical improvement. The traditional antiemetics were subsequently discontinued. Instead, anticonvulsants including phenobarbital demonstrated a notable therapeutic effect. It is suspected that the significant therapeutic effect of anticonvulsants in this case may be attributed to the underlying vomiting mechanism being primarily driven by neuronal hyperexcitability. Sedatives and antidepressants were prescribed to alleviate anxiety [ 5 ]. Anticonvulsants with a half-life of 12 hours or more, such as phenobarbital, were selected, and combination therapy with levetiracetam, which has a shorter half-life but fewer side effects, was considered. The timing of administration was determined by identifying the onset time of the symptom cycle and considering the half-life of the drug to set an appropriate dosing schedule. Since the recurrence of symptoms is known to cause significant stress to the patient and lower the threshold for future episodes, any changes in medication dosage were made conservatively [ 28 ]. In addition to pharmacological treatment, attention was required for vomiting caused by separation anxiety observed in the dog. In conclusion, this multidisciplinary treatment strategy proved to be effective for this dog. The symptoms were well-controlled, and the dog has been managed successfully without side effects. Conclusion To the best of our knowledge, CVS has not been previously reported in veterinary medicine, and this case represents the first documentation of diagnosis and management of CVS in a dog. As in this case, when there is no response to standard antiemetic therapies, when diagnostic tests do not differentiate the main cause, and when a history of vomiting triggered by stress and a circadian vomiting pattern are present, CVS can be diagnosed. Sedatives, antidepressants, and anticonvulsants can be used as part of the management of CVS. We hope this report will inspire future research on neurogenic vomiting in veterinary medicine. Abbreviations CVS Cyclic vomiting syndrome ACTH Adrenocorticotropic hormone CT Computed tomography PCR Polymerase chain reaction MRI magnetic resonance imaging CSF Cerebrospinal fluid EEG Electroencephalography BW Body weight IV Intravenous PO Per os PRN Pro re nata CRF Corticotropin-releasing factor SCN Suprachiasmatic nucleus SID Semel in die BID Bis in die TID Ter in die PRS Phenobarbital responsive sialadenosis Declarations Ethics approval and consent to participate This study did not require ethical approval because it did not involve any interventions and utilized previously collected animal tissues obtained as part of diagnostic pathology procedures. Consent for publication Consent was obtained from the present owner of the dog for publication of this case report and any accompanying images. Competing interests The authors declare that they have no competing interests. Funding This work was supported financially by Rural Development Administration (RDA) under grant number RS-2023-00232301 and "Regional Innovation Strategy (RIS) (No.1345370809)" through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE)(2021RIS-002). Author Contribution J.B.J. and K.K. performed and analyzed all the tests conducted in this study. The manuscript was written by J.B.J. and K.K. J.B.J., K.K., W.B.R., and C.M.L. reviewed and edited the manuscript. All authors have read and agreed to the submitted version of the manuscript. Acknowledgements Not applicable. Availability of data and materials No applicable. References Stanghellini V, Chan FKL, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal disorders Gastroenterol. 2016;150(6):1380–e13922. 10.1053/j.gastro.2016.02.011 . Fitzpatrick E, Bourke B, Drumm B, Rowland M. Outcome for children with cyclical vomiting syndrome. Arch Dis Child. 2007;92(11):1001–4. 10.1136/adc.2006.113033 . Taché Y, Bonaz B. Corticotropin-releasing factor receptors and stress-related alterations of gut motor function. J Clin Invest. 2007;117(1):33–40. 10.1172/jci30085 . Levinthal DJ. The cyclic vomiting syndrome threshold: A framework for understanding pathogenesis and predicting successful treatments. Clin Transl Gastroenterol. 2016;7(10):e198. 10.1038/ctg.2016.55 . Venkatesan T, Levinthal DJ, Tarbell SE, Jaradeh SS, Hasler WL, Issenman RM, et al. Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol Motil. 2019;31(Suppl 2):e13604. 10.1111/nmo.13604 . Ellingsen DM, Garcia RG, Lee J, Lin RL, Kim J, Thurler AH, Castel S, Dimisko L, Rosen BR, Hadjikhani N, Kuo B, Napadow V. Cyclic vomiting syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross-comparison with migraine and healthy adults. Neurogastroenterol Motil. 2017;29(6). 10.1111/nmo.13004 . Hornby PJ. Central neurocircuitry associated with emesis. Am J Med. 2001;111(Suppl 8):S106–12. 10.1016/S0002-9343(01)00849-X . Zhong W, Shahbaz O, Teskey G, Beever A, Kachour N, Venketaraman V, et al. Mechanisms of nausea and vomiting: Current knowledge and recent advances in intracellular emetic signaling systems. Int J Mol Sci. 2021;22(11):5797. 10.3390/ijms22115797 . Kenward H, Pelligand L, Savary-Bataille K, Elliott J, Nausea. Current knowledge of mechanisms, measurement and clinical impact. Vet J. 2015;203(1):36–43. 10.1016/j.tvjl.2014.10.007 . Alcoverro E, Tabar MD, Lloret A, Roura X, Pastor J, Planellas M. Phenobarbital-responsive sialadenosis in dogs: Case series. Top Companion Anim Med. 2014;29(4):109–12. 10.1053/j.tcam.2015.01.003 . Stonehewer J, Mackin AJ, Tasker S, Simpson JW, Mayhew IG. Idiopathic phenobarbital-responsive hypersialosis in the dog: An unusual form of limbic epilepsy? J Small Anim Pract. 2000;41(9):416–21. 10.1111/j.1748-5827.2000.tb03236.x . Takeuchi Y, Houpt KA, Scarlett JM. Evaluation of treatments for separation anxiety in dogs. J Am Vet Med Assoc. 2000;217(3):342–5. 10.2460/javma.2000.217.342 . Taché Y, Brunnhuber S. From Hans Selye’s discovery of biological stress to the identification of corticotropin-releasing factor signaling pathways: Implication in stress-related functional bowel diseases. Ann N Y Acad Sci. 2008;1148:29–41. 10.1196/annals.1410.007 . Barretto-de-Souza L, Benini R, Reis-Silva LL, Busnardo C, Crestani CC. Role of corticotropin-releasing factor neurotransmission in the lateral hypothalamus on baroreflex impairment evoked by chronic variable stress in rats. Pflugers Arch. 2024;476(3):351–64. 10.1007/s00424-024-02904-5 . Buckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab. 2005;90(5):3106–14. 10.1210/jc.2004-1056 . Kovacic K, Li BUK. Cyclic vomiting syndrome: A narrative review and guide to management. Headache. 2021;61(2):231–43. 10.1111/head.14073 . Taché Y, Perdue MH. Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function. Neurogastroenterol Motil. 2004;16(Suppl 1):137–42. 10.1111/j.1743-3150.2004.00490.x . Carbonari G, Tonti G, Di Pisa V, Franzoni E, Cordelli DM. Pediatric epilepsies misdiagnosed as gastrointestinal disorders. Epilepsy Behav. 2018;83:137–9. 10.1016/j.yebeh.2018.03.034 . Raucci U, Borrelli O, Di Nardo G, Tambucci R, Pavone P, Salvatore S, et al. Cyclic vomiting syndrome in children. Front Neurol. 2020;11:583425. 10.3389/fneur.2020.583425 . Shuper A, Goldberg-Stern H. Ictus emeticus (ictal vomiting). Pediatr Neurol. 2004;31(4):283–6. 10.1016/j.pediatrneurol.2004.04.013 . Magagna J. Psychophysiologic treatment of cyclic vomiting. J Pediatr Gastroenterol Nutr. 1995;21(Suppl 1):S31–36. 10.1097/00005176-199501001-00010 . Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada JR, Stanghellini V. Functional gastroduodenal disorders. Gastroenterology. 2006;130(5):1466–79. 10.1053/j.gastro.2006.02.011 . Li BUK, Murray RD, Heitlinger LA, Robbins JL, Hayes JR. Is cyclic vomiting syndrome related to migraine? J Pediatr. 1999;134(5):567–72. 10.1016/s0022-3476(99)70242-8 . Sunku B. Cyclic vomiting syndrome: A disorder of all ages. Gastroenterol Hepatol (N Y). 2009;5(7):507–15. Venkatesan T, Prieto T, Barboi A, Li B, Schroeder A, Hogan W, et al. Autonomic nerve function in adults with cyclic vomiting syndrome: a prospective study. Neurogastroenterol Motil. 2010;22(12):1303–e1307339. 10.1111/j.1365-2982.2010.01577.x . Zaki EA, Freilinger T, Klopstock T, Baldwin EE, Heisner KRU, Adams K, et al. Two common mitochondrial DNA polymorphisms are highly associated with migraine headache and cyclic vomiting syndrome. Cephalalgia. 2009;29(7):719–28. 10.1111/j.1468-2982.2008.01793.x . Chow S, Goldman RD. Treating children’s cyclic vomiting. Can Fam Physician. 2007;53(3):417–9. Dehkordi HT, Bijad E, Saghaei E, Korrani MS, Amini-Khoei H. Chronic stress but not acute stress decreases the seizure threshold in PTZ-induced seizure in mice: Role of inflammatory response and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(5):973–82. 10.1007/s00210-022-02364-7 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Dec, 2025 Read the published version in BMC Veterinary Research → Version 1 posted Editorial decision: Revision requested 13 Nov, 2024 Editor assigned by journal 29 Oct, 2024 Submission checks completed at journal 29 Oct, 2024 First submitted to journal 29 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5355999","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":371997191,"identity":"7b002615-3152-4582-8bb5-26e2ca9b9df6","order_by":0,"name":"Jae-Beom Joo","email":"","orcid":"","institution":"Chonnam National University","correspondingAuthor":false,"prefix":"","firstName":"Jae-Beom","middleName":"","lastName":"Joo","suffix":""},{"id":371997192,"identity":"c36a163e-01d2-4471-963f-8148608b8a44","order_by":1,"name":"Keon Kim","email":"","orcid":"","institution":"Chonnam National University","correspondingAuthor":false,"prefix":"","firstName":"Keon","middleName":"","lastName":"Kim","suffix":""},{"id":371997193,"identity":"5fe2edb2-49cc-4795-b87f-d13723ba4f1a","order_by":2,"name":"Woong-Bin Ro","email":"","orcid":"","institution":"Chonnam National University","correspondingAuthor":false,"prefix":"","firstName":"Woong-Bin","middleName":"","lastName":"Ro","suffix":""},{"id":371997194,"identity":"fbcea0df-98ba-4eb3-8ad4-32b208980306","order_by":3,"name":"Chang-Min Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYFAC5gYGBgMJOX72hgSIAA9BLYxALQUWxpI9B0jS8qEiccMNqA6CWvinHWx88MFAgrHh5oNnj3kY7OQZeM4+wKtF4nZis+EMAwlmxtkJ6cY8DMmGDbztBni1GEgntknzGEiwMUsnpEnzMDAnMPCz4XcYUEv77z8GEjxskgdAWuqJ0tLGDAxkCR4JBpCWwwkMvG34tYD8ItljIAG0JyFNco7BccM2nmP4tfDPTj744cefuvr9x8+kSbypqJbn50nDrwUJ8CQA3cnAQMAnKID9AAmKR8EoGAWjYCQBAJ7OOl5qwGtBAAAAAElFTkSuQmCC","orcid":"","institution":"Chonnam National University","correspondingAuthor":true,"prefix":"","firstName":"Chang-Min","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2024-10-29 16:38:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5355999/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5355999/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12917-025-05106-y","type":"published","date":"2025-12-09T15:58:46+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":69911857,"identity":"88388116-0ae6-4e67-947c-059d14522247","added_by":"auto","created_at":"2024-11-26 13:58:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":228567,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUpper gastrointestinal endoscopy findings of the dog in this case\u003c/strong\u003e. Mild thickening and congested mucosa from the gastric fundus (\u003cstrong\u003eA\u003c/strong\u003e) and pylorus (\u003cstrong\u003eB\u003c/strong\u003e), which were considered to be the result of chronic vomiting.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5355999/v1/c81ce8b6ffbc0af1cb04044c.png"},{"id":69911856,"identity":"853f6f63-8436-4ffc-beb3-a3a6b542f66d","added_by":"auto","created_at":"2024-11-26 13:58:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":379307,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIncidence of emetic phases of the dog in this case. \u003c/strong\u003eThis figure shows the timeline of symptom occurrences and the corresponding medications and dosages administered to the dog. The green circles specifically indicate days when vomiting occurred at a consistent time (morning). The red line marks the days when phenobarbital was administered as a loading dose. The criteria for distinguishing the number of vomiting phases are as follows: The end of each phase was defined as a period during which the symptoms ceased for more than one hour. The duration of each phase ranged from a minimum of 10 minutes to more than 30 minutes. The number of phases was calculated based on direct observation, which may have resulted in either underestimation. Despite the patient being under nearly continuous observation, phases were counted even when vomiting episodes were not directly observed but when vomitus was present.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5355999/v1/617863d9f055f4f8b22152b6.png"},{"id":69911858,"identity":"3c0eebda-33ab-4ac8-a1aa-54c49b64b050","added_by":"auto","created_at":"2024-11-26 13:58:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":403633,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUnsedated EEG recording obtained from the dog in this case. \u003c/strong\u003eFor the x-axis, vertical gray lines are at intervals of 1 second. All EEG recordings were made with a digital EEG system that collected synchronized video and EEG traces. Eight EEG channels were recorded in a bipolar montage. The technical recording settings were a 60-Hz notch filter, 10-μv sensitivity, 0.16-second time constant (low-frequency filter), 60-Hz high-frequency filter. The solid vertical lines represent seconds, and the dotted vertical lines represent 200 milliseconds. FP1 = Left prefrontal electrode. FP2 = Right prefrontal electrode. F3 = Left frontal electrode. F4 = Right frontal electrode. O1 = Left occipital electrode. O2 = Right occipital electrode. Pz = Parietal vertex electrode. Cz = Central vertex electrode. T3 = Left temporal electrode. T4 = Right temporal electrode. Significant abnormal waveforms were not observed during both the normal phase and vomiting phase at most observation times. During the observation period on the same day, a single abnormal waveform was detected at the T3 electrode just once as the patient entered the vomiting phase (\u003cstrong\u003eArrow\u003c/strong\u003e), which was considered an artifact caused by the vomiting movement.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5355999/v1/dc53e04cd8058db89c6e75f8.png"},{"id":98243992,"identity":"dc01a3dc-fb30-42a7-b4cc-2e85523c65ad","added_by":"auto","created_at":"2025-12-15 16:12:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1541885,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5355999/v1/84cea7b4-604f-403f-a857-a736edb99d42.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnosis and Management of Cyclic Vomiting Syndrome in a Dog: First Report in Veterinary Medicine","fulltext":[{"header":"Background","content":"\u003cp\u003eCyclic vomiting syndrome (CVS) is known as an idiopathic chronic disorder characterized by recurrent episode of sudden-onset attacks of repetitive vomiting [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In humans, it is relatively a common disorder of childhood with an estimated prevalence of approximately 1.9%, but it has not been reported in veterinary medicine [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The vomiting symptoms are characterized by patterns triggered by psychiatric factors and a circadian vomiting rhythm [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. CVS consists of four phases in one cycle including the prodromal, emetic, recovery, and asymptomatic phases. The prodromal phase is characterized by nausea. The emetic phase is characterized by intense nausea and vomiting and lasts from a few seconds to several minutes. After experiencing intense vomiting, the patient goes through the recovery phase, during which vomiting ceases and a normal appetite returns, which leads to the asymptomatic phase. The cycle is defined as a single independent episode, and the interval between cycles can range from several hours to several days or weeks [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCVS is generally considered to be idiopathic, and there is no specific definitive diagnostic method for CVS. Therefore, the diagnosis of CVS is made based on characteristic clinical criteria. The clinical diagnostic criteria include the Rome criteria, and additional separate guidelines have been provided by multiple associations including the Cyclic Vomiting Syndrome Association [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. While these guidelines differ slightly in terms of the defined frequency and duration of episodes, they commonly present the following essential criteria: recurrent and discrete episodes of vomiting, asymptomatic periods between episodes, vomiting lasting from hours to days, and no apparent cause of vomiting. If these criteria are met, CVS can be diagnosed [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The treatment of CVS involves the use of anticonvulsants, antidepressants, and sedatives as first-line therapies. In addition to pharmacological approaches, multidisciplinary care including stress management may also be necessary [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The aim of this article is to describe the clinical symptoms, diagnostic findings, and outcomes in a dog with presumptive CVS.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 16-year-old neutered male Maltese dog presenting with vomiting that was unresponsive to conventional antiemetic therapy was referred to the veterinary teaching hospital. In terms of patient history, the dog had experienced daily vomiting and snoring symptoms for three weeks with episodes of nausea and vomiting that were triggered by excitement, stress, or separation anxiety in the past. The vomiting typically occurred in the morning after the dog woke up. The only notable medical procedure was a dental scaling that was performed three weeks prior.\u003c/p\u003e \u003cp\u003eA physical examination revealed that the dog had a body condition score of 7/9 and a pot-bellied appearance. He had a normal appetite and normal vitality. A neurological examination showed no remarkable findings on the cranial and spinal nerve assessments. During hospitalization, the dog showed signs of nausea, lip smacking, and retching due to stress and discomfort from handling; these symptoms were followed by reverse sneezing and snoring, which continued for a few minutes.\u003c/p\u003e \u003cp\u003eLaboratory examinations including a complete blood count revealed mild neutrophilia (18.56 K/\u0026micro;L; reference range, 5.05\u0026ndash;16.76 K/\u0026micro;L). Serum biochemistry showed elevated levels of alkaline phosphatase activity (2,513 U/L; reference range, 23\u0026ndash;212 U/L) and gamma-glutamyl transferase activity (23 U/L; reference range, 0\u0026ndash;11 U/L). C-reactive protein and 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase levels were within the normal ranges. An adrenocorticotropic hormone (ACTH) stimulation test showed increased pre-stimulation (13.7 \u0026micro;g/dL; reference range, 2\u0026ndash;6 \u0026micro;g/dL) and post-stimulation cortisol levels (23.5 \u0026micro;g/dL; reference range, 6\u0026ndash;18 \u0026micro;g/dL). A blood gas analysis showed no remarkable findings. A urinalysis revealed a urine specific gravity of 1.013, and no abnormalities were observed on the dipstick test. Calcium oxalate crystals were detected on the microscopic examination. Respiratory and fecal cytology tests showed no remarkable findings.\u003c/p\u003e \u003cp\u003eDiagnostic imaging was also performed, and radiographs of the craniocervical, thorax, and abdomen showed marked hepatomegaly without other remarkable findings. Abdominal ultrasonography showed increased echogenicity of the liver and kidneys and hyperechoic sludge in the gallbladder. The pancreas had normal echogenicity, and both adrenal glands showed no abnormalities in size or shape. Hydrosonography of the gastrointestinal tract revealed no abnormalities. Additional tests were conducted to determine the cause of vomiting. Gastrointestinal contrast studies showed a normal gastric emptying time and motility, fluoroscopy showed no evidence of a swallowing disorder, hiatal hernia, or sliding hernia of the upper gastrointestinal tract. Computed tomography (CT) of the abdomen showed mild thickening of the gastric wall, while the craniocervical and thoracic regions did not display any evidence of major causes of vomiting.\u003c/p\u003e \u003cp\u003eTo rule out the possibility that imaging studies missed the causes of snoring and vomiting, respiratory and gastrointestinal endoscopy were performed. Rhinoscopy and gastrointestinal endoscopy did not reveal specific abnormalities, except for mild thickening and congestion of the gastric pyloric region (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Mildly congested tissue in the nasal choana region was collected through retrograde rhinoscopy, and thickened and congested tissue from the gastric pylorus and body was collected via upper gastrointestinal endoscopy. Histopathology of the nasal tissue was normal, and the gastric tissue showed inflammation without other specific findings. A multiplex polymerase chain reaction (PCR) test was performed to assess for major pathogens such as canine parvovirus, canine coronavirus, canine distemper virus, \u003cem\u003eClostridium\u003c/em\u003e spp., pathogenic \u003cem\u003eEscherichia coli\u003c/em\u003e, and \u003cem\u003eCampylobacter\u003c/em\u003e spp., that could cause vomiting or respiratory symptoms, and these were all ruled out. Respiratory bacterial culture tests only detected \u003cem\u003eEnterococcus faecalis\u003c/em\u003e and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e in small amounts. \u003cem\u003eHelicobacter\u003c/em\u003e spp. were ruled out through PCR testing and silver staining of the pyloric tissue.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe dog was prescribed dietary restrictions, parenteral nutrition, and fluid therapy. Oxygen therapy was administered to reduce respiratory stress. Symptomatic therapy included maropitant (1 mg/kg BW SC SID), ondansetron (1 mg/kg BW IV BID), and metoclopramide (2 mg/kg/day continuous rate infusion). Antibiotics were selected based on the antibiotic sensitivity results of the respiratory tissue culture and included amoxicillin-clavulanate (12.5 mg/kg BW IV BID) and enrofloxacin (5 mg/kg BW SID). Despite symptomatic therapy, the dog\u0026rsquo;s clinical signs did not improve, and his condition worsened. The vomiting cycle increased in duration and frequency. The dog exhibited more than four vomiting cycles per day without improvement, with a cyclical pattern in the morning (6\u0026ndash;10 AM) and evening (4\u0026ndash;8 PM). In addition, the vomiting cycle was triggered by handling, postural changes, and respiratory disorder.\u003c/p\u003e \u003cp\u003eA tentative diagnosis of neurogenic vomiting was made because no specific findings were observed on the previous tests, and gastrointestinal and metabolic diseases were considered to be completely ruled out. Diagnostic evaluations including magnetic resonance imaging (MRI) cerebrospinal fluid (CSF) examination, and electroencephalography (EEG) were performed to rule out pathophysiologic causes in the central nervous system. However, these examinations also showed no remarkable findings.\u003c/p\u003e \u003cp\u003eThe dog was diagnosed with CVS based on the Rome criteria because all the following conditions were met: stereotypical episodes of acute vomiting lasting less than a week occurring within the previous three months, at least three episodes in the prior year and two in the past six months occurring at least one week apart, absence of vomiting or nausea symptoms between episodes, and no evidence of organic, systemic, or metabolic diseases on hematologic or radiologic investigations.\u003c/p\u003e \u003cp\u003eTherapeutic trials with anticonvulsants were initiated with a loading dose of phenobarbital (12 mg/kg BW IV) administered in three divided doses, each given four hours apart. Low-dose phenobarbital (2.5 mg/kg BW IV BID) led to minor improvement in the vomiting symptoms, but the symptoms were not completely controlled. After increasing the dose of phenobarbital (6 mg/kg BW IV BID), the clinical symptoms were completely resolved within two days (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After improvement in the vomiting the symptoms, reverse sneezing and snoring symptoms also resolved completely. The dog was discharged with a prescription including phenobarbital (6 mg/kg BW PO BID), gabapentin (10mg/kg BW PO BID), trazodone (5 mg/kg BW PO BID), and maropitant (2 mg/kg BW PO PRN). Two weeks post-discharge, without any dosage adjustment, the phenobarbital concentration was measured at 43.2 \u0026micro;g/ml. The phenobarbital dosage was subsequently tapered by 1.5 mg/kg (approximately 25% of the original dose) every two weeks, leading to complete discontinuation over eight weeks. During the second tapering cycle, levetiracetam (30 mg/kg BW PO BID) was added. No recurrence of symptoms was observed during the tapering process. The gabapentin and trazodone prescribed as sedatives were replaced and reduced in dosage, respectively, due to the dog experiencing excessive drowsiness as a side effect. The treatment regimen was adjusted to include amitriptyline (2 mg/kg BW PO BID) and trazodone (3 mg/kg BW PO BID).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDuring the hospitalization period, based on the dog\u0026rsquo;s clinical symptoms and laboratory examinations, he was tentatively diagnosed with concurrent Cushing\u0026rsquo;s disease, and trilostane (1 mg/kg BW PO BID) was additionally prescribed. A follow-up evaluation for Cushing's disease was performed two weeks after discharge. An ACTH stimulation test revealed pre-stimulation cortisol levels of 4.5 \u0026micro;g/dL (reference range, 2\u0026ndash;6 \u0026micro;g/dL) and post-stimulation cortisol levels of 8.0 \u0026micro;g/dL (reference range, 6\u0026ndash;18 \u0026micro;g/dL). A blood gas analysis demonstrated no significant abnormalities. Urinalysis showed a urine specific gravity of 1.025, the resolution of polyuria/polydipsia was confirmed, and the cortisol levels were maintained withing target range, leading to the decision to maintain the current dosage of trilostane. There was no recurrence of symptoms or evidence of adverse drug effects during the subsequent follow-up.\u003c/p\u003e \u003cp\u003eThe vomiting symptoms did not recur for 12 weeks following complete resolution. However, in the 13th week, which was four weeks after the discontinuation of phenobarbital, mild symptoms of nausea and reverse sneezing reappeared, and their frequency and severity gradually increased. Despite increasing the dose of levetiracetam (50 mg/kg BW PO TID), it was difficult to completely control the symptoms. An additional neurologic examination was performed and showed no remarkable findings. An additional EEG examination was conducted during the symptomatic phase, and no specific ictal waves were detected except for a single abnormal waveform (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The dog exhibited a cyclic pattern of vomiting from 8\u0026ndash;10 AM, 4\u0026ndash;6 PM, and 10 PM\u0026ndash; 12 AM. Due to potential for recurrent vomiting to lower the vomiting threshold, a long-acting anticonvulsant was re-inducted to quickly suppress the symptoms. The dog was administered phenobarbital (20mg/kg BW PO loading dose, 6 mg/kg BW PO BID), levetiracetam (50 mg/kg BW PO TID), amitriptyline (2 mg/kg BW PO BID), and trazodone (3 mg/kg BW PO BID). In addition, the administration times were adjusted to one hour before the onset of the vomiting cycle. The medications that were prescribed to be administered twice daily were administered in the morning and evening (7 AM, 9 PM), and levetiracetam (50 mg/kg BW) was given only at 3 PM. Complete resolution of symptoms was noted within five days after administration. Two weeks post-discharge, without any dosage adjustments, the phenobarbital concentration was measured at 39.8 \u0026micro;g/ml. The phenobarbital dosage was subsequently tapered by 1.5 mg/kg (approximately 25% of the original dose) every two weeks. The previous prescription is being maintained with only the dosages of phenobarbital (3 mg/kg BW PO BID) and levetiracetam (30 mg/kg PO BID) reduced. The symptoms have not recurred for 13 weeks following complete resolution, and the dog has not experienced any side effects from the medications (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis report describes a case of chronic vomiting due to CVS and examines the novel mechanism of this type of vomiting, which is not well known in veterinary medicine. This syndrome is considered to be activated through pathways different from the common vomiting pathways, which involve stimulation of the vomiting center known as the nucleus tractus solitarius by gastrointestinal vagal afferent fibers, the chemoreceptor trigger zone (area postrema), and vestibular input. Rather, CVS is considered to occur through a \u0026ldquo;forebrain and limbic pathway\u0026rdquo;, which is not yet clearly understood [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. There have been attempts to explain that this pathway is stimulated by \u0026ldquo;neurocircuit hyperexcitability\u0026rdquo; caused by congenital or acquired factors, and various experimental results support this hypothesis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. For this reason, in human medicine, CVS has been referred to as a functional vomiting disorder, idiopathic neurological disorder, or \u0026ldquo;neurogenic vomiting\u0026rdquo; [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis neurogenic vomiting has not been studied in veterinary medicine. However, various idiopathic vomiting disorders suspected to be neurogenic have been documented as case reports. For example, phenobarbital-responsive sialadenosis (PRS) is a relatively well-documented idiopathic neurogenic vomiting disorder in veterinary medicine. Although the precise etiology is not understood, this vomiting disorder requires the exclusion of all other potential causes of vomiting and is recognized as a neurogenic vomiting disorder due to its exclusive response to anticonvulsants [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. There have also been previous reports of vomiting associated with separation anxiety, indicating that cognitive and emotional factors may mediate vomiting in animals [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Such cases indicate that the neuropsychiatric factor-mediated vomiting mechanism, a main hypothesis in CVS, may also operate in dogs. Though limited, these reports suggest the \u0026ldquo;existence of other unclassified neurogenic vomiting disorders\u0026rdquo; in veterinary medicine.\u003c/p\u003e \u003cp\u003eCVS, as its name suggests, follows a cyclic rhythm of vomiting (particularly in the early morning) and is known to be triggered by stress. In this case, the dog primarily experienced vomiting in the early morning, followed by a pattern of alternating reverse sneezing and vomiting. There was also a history of vomiting triggered by anxiety-inducing situations such as visits from strangers or the owner's absence. These patterns were detected during the dog's hospitalization. The vomiting was induced in stressful situations such as handling for examination, while on days without such procedures, the frequency of vomiting was reduced. CVS is strongly associated with vomiting pathways triggered by emotional and cognitive stimuli within the central nervous system, and changes in neuroendocrine hormones, particularly the activation of corticotropin-releasing factor (CRF), play a crucial role [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In particular, CRF secretion by neurons in the paraventricular nucleus of the hypothalamus increases in the early morning hours [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Elevated peripheral CRF levels have an inhibitory effect on gastric motility, lowering the threshold for vomiting throughout the day and contributing to its onset [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The fundamental circadian rhythm and its effects are ultimately influenced by the activity of neurons in the suprachiasmatic nucleus (SCN), and animal studies have already demonstrated changes in SCN neuron activity induced by stress [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It is particularly interesting that the dog exhibited both early-morning-onset and stress-induced vomiting, suggesting that this case aligns with the main etiological aspects of CVS.\u003c/p\u003e \u003cp\u003eThe dog was also tentatively diagnosed with Cushing's disease based on physical examination, clinical symptoms, elevated cortisol levels, and ACTH stimulation tests. According to the previous reports, similar to this case, patients with CVS have been reported to have significant elevations in ACTH and cortisol levels as well as increased sympathetic nervous system activity [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The dog presented with evidence of a long-term history of Cushing\u0026rsquo;s disease, including systemic calcium deposits, abdominal distension, polyuria and polydipsia, and bilateral alopecia. Thus, it remains uncertain whether the elevated cortisol levels due to autonomic dysfunction preceded Cushing\u0026rsquo;s disease, if the latter was the primary condition, or if both factors were contributing. Further research is needed to explore the association between Cushing\u0026rsquo;s disease and CVS.\u003c/p\u003e \u003cp\u003eThe exact pathophysiology of CVS is not known; therefore, diagnosis of CVS relies on symptom-based diagnostic criteria including the Rome criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Due to the lack of definitive diagnostic methods, clinicians can make a diagnosis of CVS based on symptom-based diagnostic criteria and the patient's medical history if all other diseases have been completely ruled out. In this case, there was no therapeutic response to conventional antiemetics during the hospitalization period, and no significant or specific findings were identified on any of the diagnostic tests conducted. It was initially suspected that excitement or changes in posture might have caused mechanical problems such as gastrointestinal herniation, leading to vomiting. However, multiple tests completely ruled out this possibility. For this reason, it was suspected that neuropsychiatric factors that were not detectable through standard diagnostic tests were contributing to the vomiting. Unlike other gastrointestinal disorders, CVS is characterized by asymptomatic periods during which the patient exhibits a normal appetite and no clinical symptoms [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Consistent with what has been reported previously, this dog showed a normal appetite during hospitalization, which contrasts with the typical presentation of dogs suffering from more common gastrointestinal disorders.\u003c/p\u003e \u003cp\u003eSometimes, despite thorough diagnostic evaluations, CVS can be misdiagnosed due to the incomplete exclusion of metabolic, endocrine, or mechanical gastrointestinal disorders that could induce vomiting [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It can also be difficult to differentiate CVS from neurogenic vomiting known as ictus emeticus (ictal vomiting), and 4\u0026ndash;7% of patients with CVS are later re-diagnosed with ictus emeticus [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Ictus emeticus presents clinical patterns similar to CVS and can be diagnosed by identifying ictal waves on EEG or detecting structural abnormalities on brain MRI scans as well as through the complete exclusion of other causes of vomiting [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. For this reason, the dog required a detailed physical examination and comprehensive laboratory tests to rule out all disorders that needed to be differentiated from CVS. Notable abnormalities were not detected on any of the tests performed to differentiate the primary cause of vomiting. No structural abnormalities were found in the brain on MRI, and no significant ictal waves were consistently detected on EEG, which tentatively ruled out ictus emeticus. PRS was ruled out due to the absence of salivary gland enlargement or hypersalivation symptoms. Based on this history, a tentative diagnosis of CVS was made.\u003c/p\u003e \u003cp\u003eIt has been shown that the frequency and severity of CVS episodes can vary depending on the presence of anxiety, and they can be treated with various medical interventions including psychological and pharmacological approaches. Therefore, anxiolytics and tricyclic antidepressants can be utilized [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Recent research has shown that the clinical patterns of CVS resemble neurological symptoms such as seizures, migraines, and panic disorders. Based on this, a treatment framework known as the 'CVS threshold' has been proposed, and these studies have played a crucial role in forming a consensus on CVS treatment guidelines [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The newly agreed-upon treatment guidelines suggest different therapeutic approaches according to the four main phases of the disorder. During the prodromal, recovery, and asymptomatic phases, preventive treatments such as tricyclic antidepressants, anticonvulsants, and antiemetics as well as good sleep hygiene, stress management, avoidance of fasting and dehydration, and psychotherapy to address psychiatric comorbidities are recommended. During the vomiting phase, it is recommended to use a combination of antiemetics, analgesics, and sedatives, while serotonin antagonists or migraine medications are conditionally recommended. Intravenous fluids are also recommended to prevent complications [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Managing the disorder requires comprehensive multidisciplinary care because CVS is known to be associated with both physical and mental conditions, such as hereditary migraines, malnutrition, psychiatric disorders, and underlying autonomic nervous system disorders, which can contribute to its development [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. During treatment, physicians typically address both the physical symptoms and the psychological aspects. It is known that addressing both simultaneously can lead to better outcomes [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. There is little long-term follow-up of patients with CVS. In one study with an average follow-up period of 4 years, 86% of patients showed improvement after therapeutic intervention; however, some patients were reported to have worsened [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBased on CVS treatment guidelines and literature reports, a treatment plan was made for the dog. The initial approach was focused on strongly suppressing the symptoms to reduce the frequency of vomiting and increase the seizure threshold. From the early stages of treatment through the long-term monitoring period, observations of the dog\u0026rsquo;s response to medications revealed that most antiemetics, including maropitant, ondansetron, and metoclopramide, which are known to act on chemoreceptors, did not produce significant clinical improvement. The traditional antiemetics were subsequently discontinued. Instead, anticonvulsants including phenobarbital demonstrated a notable therapeutic effect. It is suspected that the significant therapeutic effect of anticonvulsants in this case may be attributed to the underlying vomiting mechanism being primarily driven by neuronal hyperexcitability. Sedatives and antidepressants were prescribed to alleviate anxiety [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Anticonvulsants with a half-life of 12 hours or more, such as phenobarbital, were selected, and combination therapy with levetiracetam, which has a shorter half-life but fewer side effects, was considered. The timing of administration was determined by identifying the onset time of the symptom cycle and considering the half-life of the drug to set an appropriate dosing schedule. Since the recurrence of symptoms is known to cause significant stress to the patient and lower the threshold for future episodes, any changes in medication dosage were made conservatively [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In addition to pharmacological treatment, attention was required for vomiting caused by separation anxiety observed in the dog. In conclusion, this multidisciplinary treatment strategy proved to be effective for this dog. The symptoms were well-controlled, and the dog has been managed successfully without side effects.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo the best of our knowledge, CVS has not been previously reported in veterinary medicine, and this case represents the first documentation of diagnosis and management of CVS in a dog. As in this case, when there is no response to standard antiemetic therapies, when diagnostic tests do not differentiate the main cause, and when a history of vomiting triggered by stress and a circadian vomiting pattern are present, CVS can be diagnosed. Sedatives, antidepressants, and anticonvulsants can be used as part of the management of CVS. We hope this report will inspire future research on neurogenic vomiting in veterinary medicine.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCVS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCyclic vomiting syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACTH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdrenocorticotropic hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolymerase chain reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCerebrospinal fluid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectroencephalography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody weight\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntravenous\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePer os\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePRN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePro re nata\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCRF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCorticotropin-releasing factor\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSuprachiasmatic nucleus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSID\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSemel in die\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBID\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBis in die\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTID\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTer in die\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePRS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePhenobarbital responsive sialadenosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eThis study did not require ethical approval because it did not involve any interventions and utilized previously collected animal tissues obtained as part of diagnostic pathology procedures.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003e Consent was obtained from the present owner of the dog for publication of this case report and any accompanying images.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003e This work was supported financially by Rural Development Administration (RDA) under grant number RS-2023-00232301 and \"Regional Innovation Strategy (RIS) (No.1345370809)\" through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE)(2021RIS-002).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJ.B.J. and K.K. performed and analyzed all the tests conducted in this study. The manuscript was written by J.B.J. and K.K. J.B.J., K.K., W.B.R., and C.M.L. reviewed and edited the manuscript. All authors have read and agreed to the submitted version of the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eNo applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStanghellini V, Chan FKL, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal disorders Gastroenterol. 2016;150(6):1380\u0026ndash;e13922. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.gastro.2016.02.011\u003c/span\u003e\u003cspan address=\"10.1053/j.gastro.2016.02.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFitzpatrick E, Bourke B, Drumm B, Rowland M. Outcome for children with cyclical vomiting syndrome. Arch Dis Child. 2007;92(11):1001\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/adc.2006.113033\u003c/span\u003e\u003cspan address=\"10.1136/adc.2006.113033\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTach\u0026eacute; Y, Bonaz B. Corticotropin-releasing factor receptors and stress-related alterations of gut motor function. J Clin Invest. 2007;117(1):33\u0026ndash;40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1172/jci30085\u003c/span\u003e\u003cspan address=\"10.1172/jci30085\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLevinthal DJ. The cyclic vomiting syndrome threshold: A framework for understanding pathogenesis and predicting successful treatments. Clin Transl Gastroenterol. 2016;7(10):e198. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/ctg.2016.55\u003c/span\u003e\u003cspan address=\"10.1038/ctg.2016.55\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVenkatesan T, Levinthal DJ, Tarbell SE, Jaradeh SS, Hasler WL, Issenman RM, et al. Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association. Neurogastroenterol Motil. 2019;31(Suppl 2):e13604. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/nmo.13604\u003c/span\u003e\u003cspan address=\"10.1111/nmo.13604\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEllingsen DM, Garcia RG, Lee J, Lin RL, Kim J, Thurler AH, Castel S, Dimisko L, Rosen BR, Hadjikhani N, Kuo B, Napadow V. Cyclic vomiting syndrome is characterized by altered functional brain connectivity of the insular cortex: A cross-comparison with migraine and healthy adults. Neurogastroenterol Motil. 2017;29(6). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/nmo.13004\u003c/span\u003e\u003cspan address=\"10.1111/nmo.13004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHornby PJ. Central neurocircuitry associated with emesis. Am J Med. 2001;111(Suppl 8):S106\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S0002-9343(01)00849-X\u003c/span\u003e\u003cspan address=\"10.1016/S0002-9343(01)00849-X\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhong W, Shahbaz O, Teskey G, Beever A, Kachour N, Venketaraman V, et al. Mechanisms of nausea and vomiting: Current knowledge and recent advances in intracellular emetic signaling systems. Int J Mol Sci. 2021;22(11):5797. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijms22115797\u003c/span\u003e\u003cspan address=\"10.3390/ijms22115797\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKenward H, Pelligand L, Savary-Bataille K, Elliott J, Nausea. Current knowledge of mechanisms, measurement and clinical impact. Vet J. 2015;203(1):36\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.tvjl.2014.10.007\u003c/span\u003e\u003cspan address=\"10.1016/j.tvjl.2014.10.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlcoverro E, Tabar MD, Lloret A, Roura X, Pastor J, Planellas M. Phenobarbital-responsive sialadenosis in dogs: Case series. Top Companion Anim Med. 2014;29(4):109\u0026ndash;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.tcam.2015.01.003\u003c/span\u003e\u003cspan address=\"10.1053/j.tcam.2015.01.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStonehewer J, Mackin AJ, Tasker S, Simpson JW, Mayhew IG. Idiopathic phenobarbital-responsive hypersialosis in the dog: An unusual form of limbic epilepsy? J Small Anim Pract. 2000;41(9):416\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1748-5827.2000.tb03236.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1748-5827.2000.tb03236.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakeuchi Y, Houpt KA, Scarlett JM. Evaluation of treatments for separation anxiety in dogs. J Am Vet Med Assoc. 2000;217(3):342\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2460/javma.2000.217.342\u003c/span\u003e\u003cspan address=\"10.2460/javma.2000.217.342\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTach\u0026eacute; Y, Brunnhuber S. From Hans Selye\u0026rsquo;s discovery of biological stress to the identification of corticotropin-releasing factor signaling pathways: Implication in stress-related functional bowel diseases. Ann N Y Acad Sci. 2008;1148:29\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1196/annals.1410.007\u003c/span\u003e\u003cspan address=\"10.1196/annals.1410.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarretto-de-Souza L, Benini R, Reis-Silva LL, Busnardo C, Crestani CC. Role of corticotropin-releasing factor neurotransmission in the lateral hypothalamus on baroreflex impairment evoked by chronic variable stress in rats. Pflugers Arch. 2024;476(3):351\u0026ndash;64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00424-024-02904-5\u003c/span\u003e\u003cspan address=\"10.1007/s00424-024-02904-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBuckley TM, Schatzberg AF. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab. 2005;90(5):3106\u0026ndash;14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1210/jc.2004-1056\u003c/span\u003e\u003cspan address=\"10.1210/jc.2004-1056\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKovacic K, Li BUK. Cyclic vomiting syndrome: A narrative review and guide to management. Headache. 2021;61(2):231\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/head.14073\u003c/span\u003e\u003cspan address=\"10.1111/head.14073\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTach\u0026eacute; Y, Perdue MH. Role of peripheral CRF signalling pathways in stress-related alterations of gut motility and mucosal function. Neurogastroenterol Motil. 2004;16(Suppl 1):137\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1743-3150.2004.00490.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1743-3150.2004.00490.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarbonari G, Tonti G, Di Pisa V, Franzoni E, Cordelli DM. Pediatric epilepsies misdiagnosed as gastrointestinal disorders. Epilepsy Behav. 2018;83:137\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.yebeh.2018.03.034\u003c/span\u003e\u003cspan address=\"10.1016/j.yebeh.2018.03.034\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaucci U, Borrelli O, Di Nardo G, Tambucci R, Pavone P, Salvatore S, et al. Cyclic vomiting syndrome in children. Front Neurol. 2020;11:583425. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fneur.2020.583425\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2020.583425\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShuper A, Goldberg-Stern H. Ictus emeticus (ictal vomiting). Pediatr Neurol. 2004;31(4):283\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.pediatrneurol.2004.04.013\u003c/span\u003e\u003cspan address=\"10.1016/j.pediatrneurol.2004.04.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMagagna J. Psychophysiologic treatment of cyclic vomiting. J Pediatr Gastroenterol Nutr. 1995;21(Suppl 1):S31\u0026ndash;36. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/00005176-199501001-00010\u003c/span\u003e\u003cspan address=\"10.1097/00005176-199501001-00010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada JR, Stanghellini V. Functional gastroduodenal disorders. Gastroenterology. 2006;130(5):1466\u0026ndash;79. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1053/j.gastro.2006.02.011\u003c/span\u003e\u003cspan address=\"10.1053/j.gastro.2006.02.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi BUK, Murray RD, Heitlinger LA, Robbins JL, Hayes JR. Is cyclic vomiting syndrome related to migraine? J Pediatr. 1999;134(5):567\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0022-3476(99)70242-8\u003c/span\u003e\u003cspan address=\"10.1016/s0022-3476(99)70242-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSunku B. Cyclic vomiting syndrome: A disorder of all ages. Gastroenterol Hepatol (N Y). 2009;5(7):507\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVenkatesan T, Prieto T, Barboi A, Li B, Schroeder A, Hogan W, et al. Autonomic nerve function in adults with cyclic vomiting syndrome: a prospective study. Neurogastroenterol Motil. 2010;22(12):1303\u0026ndash;e1307339. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1365-2982.2010.01577.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1365-2982.2010.01577.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZaki EA, Freilinger T, Klopstock T, Baldwin EE, Heisner KRU, Adams K, et al. Two common mitochondrial DNA polymorphisms are highly associated with migraine headache and cyclic vomiting syndrome. Cephalalgia. 2009;29(7):719\u0026ndash;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1468-2982.2008.01793.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1468-2982.2008.01793.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChow S, Goldman RD. Treating children\u0026rsquo;s cyclic vomiting. Can Fam Physician. 2007;53(3):417\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDehkordi HT, Bijad E, Saghaei E, Korrani MS, Amini-Khoei H. Chronic stress but not acute stress decreases the seizure threshold in PTZ-induced seizure in mice: Role of inflammatory response and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(5):973\u0026ndash;82. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00210-022-02364-7\u003c/span\u003e\u003cspan address=\"10.1007/s00210-022-02364-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-veterinary-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [BMC Veterinary Research](http://bmcvetres.biomedcentral.com/)","snPcode":"12917","submissionUrl":"https://submission.nature.com/new-submission/12917/3?","title":"BMC Veterinary Research","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cyclic vomiting syndrome, Dog, Neurogenic vomiting","lastPublishedDoi":"10.21203/rs.3.rs-5355999/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5355999/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCyclic vomiting syndrome (CVS) is an idiopathic chronic disorder characterized by recurrent episodes of vomiting that are often triggered by psychological stressors and circadian rhythms. While CVS is well-documented in human medicine, this report details the first diagnosis of CVS in veterinary medicine.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003eA 16-year-old neutered male Maltese dog presented with a history of daily vomiting that was unresponsive to standard antiemetic therapies. On physical examination, hematologic tests, radiography, ultrasonography, computed tomography, fluoroscopy, and endoscopy, gastrointestinal and metabolic causes of vomiting were ruled out. In addition, to rule out neurogenic causes of vomiting, magnetic resonance imaging, cerebrospinal fluid analysis, and electroencephalography were performed and showed no remarkable findings. Based on the distinctive vomiting pattern characterized by stress-induced symptoms and association with the circadian rhythm as well as consistency with the clinical criteria used in humans (Rome criteria), the dog was diagnosed with CVS. Therapeutic trials with anticonvulsants, including phenobarbital and levetiracetam, successfully controlled the dog\u0026rsquo;s clinical signs, which were unresponsive to conventional treatments.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis case emphasizes the potential for CVS in canine species and highlights the need for further exploration of neurogenic vomiting disorders in dogs.\u003c/p\u003e","manuscriptTitle":"Diagnosis and Management of Cyclic Vomiting Syndrome in a Dog: First Report in Veterinary Medicine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-26 13:58:23","doi":"10.21203/rs.3.rs-5355999/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-13T11:35:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-30T02:56:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-30T02:55:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Veterinary Research","date":"2024-10-29T16:29:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-veterinary-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [BMC Veterinary Research](http://bmcvetres.biomedcentral.com/)","snPcode":"12917","submissionUrl":"https://submission.nature.com/new-submission/12917/3?","title":"BMC Veterinary Research","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d53dc5e2-b9ab-4698-b373-bfb6a7773be1","owner":[],"postedDate":"November 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T16:04:20+00:00","versionOfRecord":{"articleIdentity":"rs-5355999","link":"https://doi.org/10.1186/s12917-025-05106-y","journal":{"identity":"bmc-veterinary-research","isVorOnly":false,"title":"BMC Veterinary Research"},"publishedOn":"2025-12-09 15:58:46","publishedOnDateReadable":"December 9th, 2025"},"versionCreatedAt":"2024-11-26 13:58:23","video":"","vorDoi":"10.1186/s12917-025-05106-y","vorDoiUrl":"https://doi.org/10.1186/s12917-025-05106-y","workflowStages":[]},"version":"v1","identity":"rs-5355999","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5355999","identity":"rs-5355999","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}