The salient findings of our study are that both adult- and pediatric-onset CVS patients have a similar demographic profile and disease characteristics except that pediatric-onset patients were more likely to be female and had a higher prevalence of CVS-plus with concomitant neurological disorders. This finding may be explained by the genetic differences that have been elucidated in previous studies [2
]. The pediatric-onset group also had a lower incidence of tobacco and opiate use and a significantly longer delay in diagnosis of CVS. This longer delay in diagnosis is an unexpected finding given that CVS is fairly well-recognized condition in children. It should be noted that though our center attracts both children and adults with CVS, the majority of the patients with pediatric-onset CVS were not transitioned from the Children's Hospital of Wisconsin, which is also a tertiary center for pediatric CVS. Dysautonomia was diagnosed in 64
% of our CVS patients which we recently reported to be a significant problem in this population [17
]. Similar to reported literature, CVS patients in both groups had a strong personal or family history of migraine [18
]. Co-morbid conditions including anxiety, depression and irritable bowel syndrome were seen in both groups and it is unclear if this is related to the lack of receiving a credible diagnosis and the inordinate delay in treatment that these patients experience. In addition, 30
% of patients underwent invasive surgery for CVS symptoms without any benefit. Long delays in diagnosis along with such unnecessary and unhelpful interventions are unacceptable both from a patient standpoint and from an economic perspective.
The majority of our patients (86 %) had either a complete or partial response to prophylactic medications with TCA’s, topiramate and mitochondrial therapy such as carnitine, coenzyme Q-10 and ribofavin. The dose of carnitine used was 1 gram twice daily, co-enzyme Q-10 was 200 mg twice daily and riboflavin 100 mg once daily. On univariate analysis, non-response to therapy was associated with coalescence of symptoms, chronic opiate use and more severe disease as characterized by longer episodes, greater number of ED visits in the year prior to presentation, presence of disability and non-compliance. Compliance was the only significant variable on multivariate analysis that predicted response to therapy. Patients were deemed noncompliant if they continued to use marijuana and it is the practice of the author to advise complete abstinence from marijuana in all patients. We did not routinely check for cessation of marijuana in our patients with toxicology screens. There was no difference in response to therapy between pediatric-onset and adult-onset CVS patients despite recent reports of genetic differences. This may imply that there are other factors involved in the pathogenesis of this disorder aside from mitochondrial abnormalities in adults.
The few patients who were administered TCA’s prior to being seen at our clinic were on a low daily dose of 25 mg that is employed in other functional gastrointestinal disorders. Dose escalation to 1 mg/kg as used in children produced the desired therapeutic effect. However, there was a high incidence of side effects associated with TCA therapy resulting in discontinuation in 26% of patients which limited its use [20
Marijuana use was seen in more than a third of patients with CVS and patients frequently reported using this for alleviation of nausea and as an appetite stimulant. There did not appear to be any clear cause-and-effect or temporal relationship between the use of marijuana and onset of symptoms based on clinical history and these patients were not thought to have symptoms caused by the use of marijuana. Marijuana use has been thought to result in cannabinoid hyperemesis [21
]. Though the patients reported in the literature have not had adequate follow up; this entity as a separate disorder is subject to controversy. This raises questions about whether chronic marijuana use down regulates CB1 receptors and paradoxically causes more nausea and vomiting which will need to be evaluated in the future studies.
We acknowledge that there are several limitations to this study as this was a retrospective analysis though the data was also obtained prospectively with a standardized questionnaire used in clinic. The response to medications has been arbitrary in CVS thus far and there has been no consensus or accepted definitions in adult patients for measures of response to treatment in CVS. ED utilization has been recently studied in CVS patients; we used overall improvement of symptom frequency and severity to assess response to treatment [24
]. We were unable to report on exact numbers of ED visits prior to and after treatment as many patients visited other ED’s for CVS episodes. In addition while other authors have measured ED visits and hospitalizations as outcomes of therapy, some patients with CVS have home intravenous fluid therapy or are seen in infusion clinics as in our practice to help control their symptoms and avoid long waits in the ED and prevent hospitalizations. Our study is one of the largest studies characterizing adult-onset and pediatric-onset CVS patients. This study should pave the way for future prospective evaluation of treatment in patients with CVS and standardized measures of disease outcomes.