Author's Accepted Manuscript
A CURABLE AND PROBABLY OFTENOVERLOOKED CAUSE OF CYCLIC VOMITING SYNDROME N. Paul Rosman M.D., Monideep Dutt M.D., Hiep T. Nguyen M.D.
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S1071-9091(14)00020-5 http://dx.doi.org/10.1016/j.spen.2014.04.001 YSPEN467
To appear in: Semin Pediatr Neurol
Cite this article as: N. Paul Rosman M.D., Monideep Dutt M.D., Hiep T. Nguyen M.D., A CURABLE AND PROBABLY OFTEN-OVERLOOKED CAUSE OF CYCLIC VOMITING SYNDROME, Semin Pediatr Neurol , http://dx.doi.org/10.1016/j.spen.2014.04.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A CURABLE AND PROBABLY OFTEN-OVERLOOKED CAUSE OF CYCLIC VOMITING SYNDROME
N. Paul Rosman, M.D.1, Monideep Dutt, M.D.1 and Hiep T. Nguyen, M.D.2
Departments of Pediatrics and Neurology Division of Pediatric Neurology Boston University School of Medicine Boston Medical Center Boston, MA 02118-2393
[email protected]; [email protected]; [email protected] 1
Division of Pediatric Neurology, Boston Medical Center, Boston, MA, USA
2
Department of Urology, Children’s Hospital, Boston, MA, USA
Corresponding author: N. Paul Rosman, M.D. Boston Medical Center One Boston Medical Center Place Dowling 3 South Boston, MA 02118-2393 Telephone (617) 414-4589 Fax (617) 414-4502 E-mail: [email protected]
1
Acknowledgement The child’s gastroenterological care was provided by Jenifer R. Lightdale, Children’s Hospital Boston, with whom we had several discussions about the child’s ongoing management.
Author contributions NPR followed the child neurologically throughout his clinical course. He prepared an initial draft of the manuscript after a preliminary literature review and he contributed to all subsequent revisions of the manuscript. MD did an extensive literature review after the initial preliminary one and contributed to all subsequent revisions of the manuscript. HTN followed the child urologically throughout his clinical course, performed the child’s successful surgery, reviewed all of the urological data in the case, and suggested several clarifications.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval No ethical approval was required for this article.
Conflict of Interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this manuscript.
2
Abstract Cyclic vomiting syndrome is a disorder of many causes. The major challenge is to label the disorder as idiopathic or primary only when all possible etiologies, particularly those that can be specifically treated, have been ruled out. In retrospect, our patient had subtle prenatal and early postnatal radiological findings supportive of a urological cause for his symptoms, the importance of which was initially missed. It would probably be wise to include an abdominal ultrasound examination (looking for hydronephrosis) in the “must do” battery of tests for the investigation of all cases of recurrent cyclic vomiting without apparent cause. Otherwise, it seems likely that many cases of ureteropelvic junction obstruction will be missed, cases in which surgical intervention can be curative. Keywords cyclic vomiting syndrome, abdominal migraine, migraine equivalent, ureteropelvic junction obstruction
3
Introduction Cyclic vomiting syndrome is a common disorder with many causes. In most cases, no gastroenterological cause, such as intermittent bowel obstruction, is found. In such cases, the vomiting is often deemed primary or idiopathic and is frequently assumed to be a migraine variant, so-called “abdominal migraine.” Of the many definable causes of cyclic vomiting, whether gastroenterological, neurological, metabolic, mitochondrial or endocrinological, it is particularly important to search for causes that are specifically treatable. Most such secondary cases if specifically treated will usually have a better outcome than those that are primary or idiopathic, where the only intervention is abortive, namely symptomatic treatment of the child’s vomiting and frequently-accompanying abdominal pain. We present a case of refractory cyclic vomiting for which a very extensive investigation initially failed to uncover a specific cause. A misdiagnosis of migraine variant resulted and led to antimigrainous therapy that first was reassuring, for the child appeared to respond. Soon, however, his symptoms returned, further investigative studies were belatedly pursued, the cause of the child’s cyclic vomiting was finally found and definitive treatment led to complete resolution of his symptoms. Case report A 4 year 1 month old boy began to have episodes of recurrent vomiting at age 14 months. The episodes initially occurred only in the evening, between 5-10 p.m. There were no obvious triggers. At onset, the child became quiet, refused to talk and appeared tired. Once his vomiting started, it would continue to recur at 10-15 minute intervals, for durations varying from 3 hours to 2 days. During the episodes, he became pale and clammy, with sunken eyes. The episodes would leave the child dehydrated, sometimes severely so. The vomiting was sometimes accompanied by a low grade fever and occasionally, by diarrhea. Over the next 14 months, the child had a total of 9 episodes of cyclic vomiting, with intervals of 4-8 weeks between attacks. Blood studies, including serum chemistries, liver function tests, serum amylase and lipase and blood ketones were normal. Urinalysis occasionally showed 1+ ketones. With a few of the episodes, the vomiting was bilious and in these cases, abdominal plain radiographs were done and they too were normal, with no evidence of intestinal obstruction. With 8 of the 9 episodes, the child was hospitalized overnight for treatment with IV fluids, ondansetron and lorazepam. The one time he was not hospitalized, he was successfully managed at home with rectal diazepam and rectal ondansetron. The child had been born at term, with a birth weight of about 8 lbs (40 percentile). Prenatal sonogram at 18 weeks showed bilateral hydronephrosis. Follow up ultrasound studies after birth and 4
at 2 weeks showed only mild left hydronephrosis and at age 1 year, the hydronephrosis had cleared. There were no other antenatal concerns or perinatal complications. Developmentally, the child had early mild gross motor delay; for example, he was slow to crawl. Aided by several months of Early Intervention therapy, he quickly caught up. His language development and cognitive skills were at all times normal. Also, between 2 and 6 months, the child had plagiocephaly associated with a left torticollis that resolved quickly with an orthotic helmet. The family history included car sickness in the child’s mother when she was a child, which later resolved. In adulthood, she had longstanding intermittent severe abdominal pain with nausea and vomiting. Her symptoms, initially thought to be “abdominal migraine,” were later determined to be from chronic cholecystitis; all symptoms resolved after a cholecystectomy. The child’s 70-year-old maternal grandmother has a history of car sickness. There was a history of migraine headaches in the child’s paternal great grandmother, paternal grandmother and a paternal aunt. There was no family history of seizures. The child’s past medical history was remarkable for poor appetite and poor weight gain between 6-12 months of age (when his weight percentiles dropped from 25-50% at 4-6 months to 3% by 12 months of age). He had multiple upper respiratory tract and ear infections during that period. Tympanostomy tubes were placed at age 20 months. Because of his poor appetite and poor weight gain, at 14 months of age, he was prescribed a high calorie diet and an appetite stimulant, cyproheptadine, which helped. Two negative sweat chloride tests ruled out cystic fibrosis. The child’s history of recurrent stereotypical episodes of vomiting, with complete resolution of symptoms and return to baseline between episodes, prompted in depth investigations by several specialists to search for an underlying cause. Upper gastrointestinal endoscopy showed only a hiatal hernia. Biopsies from the esophagus, duodenum and stomach were normal. He was placed on lansoprazole, a proton pump inhibitor, but without benefit. Metabolic and mitochondrial laboratory tests showed a normal blood ammonia, carnitine and acylcarnitine profile; plasma amino acids, urine organic acids, blood creatine kinase and serum lactate were normal. Early in his course, during acute presentations of cyclic vomiting at ages 7 months and 14 months, the child had a low blood glucose with 1+ urine ketones, expected in a child with a low glycogen reserve and in a fasting catabolic state, so-called “ketotic hypoglycemia.” Those abnormalities reversed as the child grew older and gained weight. Most of the child’s endocrinologic studies were normal, although he had elevated levels of blood adrenocorticotropic hormone (ACTH 726 pg/ml; normal
A CURABLE AND PROBABLY OFTENOVERLOOKED CAUSE OF CYCLIC VOMITING SYNDROME N. Paul Rosman M.D., Monideep Dutt M.D., Hiep T. Nguyen M.D.
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S1071-9091(14)00020-5 http://dx.doi.org/10.1016/j.spen.2014.04.001 YSPEN467
To appear in: Semin Pediatr Neurol
Cite this article as: N. Paul Rosman M.D., Monideep Dutt M.D., Hiep T. Nguyen M.D., A CURABLE AND PROBABLY OFTEN-OVERLOOKED CAUSE OF CYCLIC VOMITING SYNDROME, Semin Pediatr Neurol , http://dx.doi.org/10.1016/j.spen.2014.04.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A CURABLE AND PROBABLY OFTEN-OVERLOOKED CAUSE OF CYCLIC VOMITING SYNDROME
N. Paul Rosman, M.D.1, Monideep Dutt, M.D.1 and Hiep T. Nguyen, M.D.2
Departments of Pediatrics and Neurology Division of Pediatric Neurology Boston University School of Medicine Boston Medical Center Boston, MA 02118-2393
[email protected]; [email protected]; [email protected] 1
Division of Pediatric Neurology, Boston Medical Center, Boston, MA, USA
2
Department of Urology, Children’s Hospital, Boston, MA, USA
Corresponding author: N. Paul Rosman, M.D. Boston Medical Center One Boston Medical Center Place Dowling 3 South Boston, MA 02118-2393 Telephone (617) 414-4589 Fax (617) 414-4502 E-mail: [email protected]
1
Acknowledgement The child’s gastroenterological care was provided by Jenifer R. Lightdale, Children’s Hospital Boston, with whom we had several discussions about the child’s ongoing management.
Author contributions NPR followed the child neurologically throughout his clinical course. He prepared an initial draft of the manuscript after a preliminary literature review and he contributed to all subsequent revisions of the manuscript. MD did an extensive literature review after the initial preliminary one and contributed to all subsequent revisions of the manuscript. HTN followed the child urologically throughout his clinical course, performed the child’s successful surgery, reviewed all of the urological data in the case, and suggested several clarifications.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval No ethical approval was required for this article.
Conflict of Interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this manuscript.
2
Abstract Cyclic vomiting syndrome is a disorder of many causes. The major challenge is to label the disorder as idiopathic or primary only when all possible etiologies, particularly those that can be specifically treated, have been ruled out. In retrospect, our patient had subtle prenatal and early postnatal radiological findings supportive of a urological cause for his symptoms, the importance of which was initially missed. It would probably be wise to include an abdominal ultrasound examination (looking for hydronephrosis) in the “must do” battery of tests for the investigation of all cases of recurrent cyclic vomiting without apparent cause. Otherwise, it seems likely that many cases of ureteropelvic junction obstruction will be missed, cases in which surgical intervention can be curative. Keywords cyclic vomiting syndrome, abdominal migraine, migraine equivalent, ureteropelvic junction obstruction
3
Introduction Cyclic vomiting syndrome is a common disorder with many causes. In most cases, no gastroenterological cause, such as intermittent bowel obstruction, is found. In such cases, the vomiting is often deemed primary or idiopathic and is frequently assumed to be a migraine variant, so-called “abdominal migraine.” Of the many definable causes of cyclic vomiting, whether gastroenterological, neurological, metabolic, mitochondrial or endocrinological, it is particularly important to search for causes that are specifically treatable. Most such secondary cases if specifically treated will usually have a better outcome than those that are primary or idiopathic, where the only intervention is abortive, namely symptomatic treatment of the child’s vomiting and frequently-accompanying abdominal pain. We present a case of refractory cyclic vomiting for which a very extensive investigation initially failed to uncover a specific cause. A misdiagnosis of migraine variant resulted and led to antimigrainous therapy that first was reassuring, for the child appeared to respond. Soon, however, his symptoms returned, further investigative studies were belatedly pursued, the cause of the child’s cyclic vomiting was finally found and definitive treatment led to complete resolution of his symptoms. Case report A 4 year 1 month old boy began to have episodes of recurrent vomiting at age 14 months. The episodes initially occurred only in the evening, between 5-10 p.m. There were no obvious triggers. At onset, the child became quiet, refused to talk and appeared tired. Once his vomiting started, it would continue to recur at 10-15 minute intervals, for durations varying from 3 hours to 2 days. During the episodes, he became pale and clammy, with sunken eyes. The episodes would leave the child dehydrated, sometimes severely so. The vomiting was sometimes accompanied by a low grade fever and occasionally, by diarrhea. Over the next 14 months, the child had a total of 9 episodes of cyclic vomiting, with intervals of 4-8 weeks between attacks. Blood studies, including serum chemistries, liver function tests, serum amylase and lipase and blood ketones were normal. Urinalysis occasionally showed 1+ ketones. With a few of the episodes, the vomiting was bilious and in these cases, abdominal plain radiographs were done and they too were normal, with no evidence of intestinal obstruction. With 8 of the 9 episodes, the child was hospitalized overnight for treatment with IV fluids, ondansetron and lorazepam. The one time he was not hospitalized, he was successfully managed at home with rectal diazepam and rectal ondansetron. The child had been born at term, with a birth weight of about 8 lbs (40 percentile). Prenatal sonogram at 18 weeks showed bilateral hydronephrosis. Follow up ultrasound studies after birth and 4
at 2 weeks showed only mild left hydronephrosis and at age 1 year, the hydronephrosis had cleared. There were no other antenatal concerns or perinatal complications. Developmentally, the child had early mild gross motor delay; for example, he was slow to crawl. Aided by several months of Early Intervention therapy, he quickly caught up. His language development and cognitive skills were at all times normal. Also, between 2 and 6 months, the child had plagiocephaly associated with a left torticollis that resolved quickly with an orthotic helmet. The family history included car sickness in the child’s mother when she was a child, which later resolved. In adulthood, she had longstanding intermittent severe abdominal pain with nausea and vomiting. Her symptoms, initially thought to be “abdominal migraine,” were later determined to be from chronic cholecystitis; all symptoms resolved after a cholecystectomy. The child’s 70-year-old maternal grandmother has a history of car sickness. There was a history of migraine headaches in the child’s paternal great grandmother, paternal grandmother and a paternal aunt. There was no family history of seizures. The child’s past medical history was remarkable for poor appetite and poor weight gain between 6-12 months of age (when his weight percentiles dropped from 25-50% at 4-6 months to 3% by 12 months of age). He had multiple upper respiratory tract and ear infections during that period. Tympanostomy tubes were placed at age 20 months. Because of his poor appetite and poor weight gain, at 14 months of age, he was prescribed a high calorie diet and an appetite stimulant, cyproheptadine, which helped. Two negative sweat chloride tests ruled out cystic fibrosis. The child’s history of recurrent stereotypical episodes of vomiting, with complete resolution of symptoms and return to baseline between episodes, prompted in depth investigations by several specialists to search for an underlying cause. Upper gastrointestinal endoscopy showed only a hiatal hernia. Biopsies from the esophagus, duodenum and stomach were normal. He was placed on lansoprazole, a proton pump inhibitor, but without benefit. Metabolic and mitochondrial laboratory tests showed a normal blood ammonia, carnitine and acylcarnitine profile; plasma amino acids, urine organic acids, blood creatine kinase and serum lactate were normal. Early in his course, during acute presentations of cyclic vomiting at ages 7 months and 14 months, the child had a low blood glucose with 1+ urine ketones, expected in a child with a low glycogen reserve and in a fasting catabolic state, so-called “ketotic hypoglycemia.” Those abnormalities reversed as the child grew older and gained weight. Most of the child’s endocrinologic studies were normal, although he had elevated levels of blood adrenocorticotropic hormone (ACTH 726 pg/ml; normal
