Thursday, June 18, 2015

Sicklick vomiting

Title as written in a patient questionnaire.

Lee J, Wong SA, Li BU, Boles RG. NextGen nuclear DNA sequencing in cyclic
vomiting syndrome reveals a significant association with the stress-induced
calcium channel (RYR2). Neurogastroenterol Motil. 2015 Apr 29. doi:
10.1111/nmo.12575. [Epub ahead of print]

Cyclic vomiting syndrome (CVS) is a common, frequently disabling, 'functional' condition characterized by recurring, stereotypical attacks of intense nausea, vomiting, and lethargy, with the essential absence of these symptoms between episodes. Although the pathogenesis of CVS is yet unexplained, evidence has accumulated which suggest pathogenic roles for stress-related, autonomic, neuroendocrine, and mitochondrial factors. The objective of this pilot study was to elucidate mechanism(s) by identifying genes involved in the presumed multifactorial pathogenesis of CVS.
In this pilot study, DNA from 75 unrelated CVS cases and 60 healthy controls were assayed by Courtagen Life Science's next-generation sequencing platform (nucSEEK ), including over 1100 nuclear-encoded genes involved with mitochondria, metabolism, or ion channels. Significant sequence variants were defined as evolutionary conservation at least to Xenopus (frog) per the UCSC Genome Browser.
The RYR2 gene, encoding a stress-induced calcium channel present in many neurons, was the only gene demonstrating a statistically significant difference in the proportion of conserved sequence variants among the groups (18/75 CVS, 24%, vs 3/60 controls, 5%; p = 0.0018, OR = 6.0, 95% CI = 1.7-22).
We propose a mechanism in which RYR2 sequence variants result in aberrant stress-induced calcium release into the mitochondria of autonomic neurons, resulting in an increased risk to develop autonomic/functional disease such as CVS, and related conditions such as migraine and gut dysmotility. This model incorporates the existing hypotheses regarding CVS pathogenesis into a cohesive mechanism, and might have treatment implications.

1 comment:

  1. Kim HS, Anderson JD, Saghafi O, Heard KJ, Monte AA. Cyclic Vomiting
    Presentations Following Marijuana Liberalization in Colorado. Acad Emerg Med.
    2015 Jun;22(6):694-9.

    Case reports have described a syndrome of cyclic vomiting associated with chronic marijuana use, termed cannabinoid hyperemesis syndrome. The primary objective was to determine the prevalence of patients presenting with cyclic vomiting before and after the liberalization of medical marijuana in Colorado in 2009. The secondary objective was to describe the odds of marijuana use among cyclic vomiting visits in these same time periods.
    This was a cross-sectional study of cyclic vomiting visits to the emergency department (ED) before and after marijuana liberalization. ED visits with International Classification of Diseases, ninth revision, coding for cyclic vomiting or that met diagnostic criteria for cyclic vomiting by the Rome III criteria were included.
    The authors reviewed 2,574 visits and identified 36 patients diagnosed with cyclic vomiting over 128 visits. The prevalence of cyclic vomiting visits increased from 41 per 113,262 ED visits to 87 per 125,095 ED visits after marijuana liberalization, corresponding to a prevalence ratio of 1.92 (95% confidence interval [CI] = 1.33 to 2.79). Patients with cyclic vomiting in the postliberalization period were more likely to have marijuana use documented than patients in the preliberalization period (odds ratio = 3.59, 95% CI = 1.44 to 9.00).
    The prevalence of cyclic vomiting presentations nearly doubled after the liberalization of medical marijuana. Patients presenting with cyclic vomiting in the postliberalization period were more likely to endorse marijuana use, although it is unclear whether this was secondary to increased marijuana use, more accurate marijuana reporting, or both.