Gastroparesis is a motility disorder defined by delayed emptying of gastric contents into the duodenum in the absence of an anatomic or mechanical obstruction. The pathophysiology of gastroparesis is not well understood, particularly in children in whom its prevalence rates are unknown. Proposed mechanisms in children range from exaggerated fundic accommodation and relaxation, weak or absent antral contractions, to incomplete relaxation of the pylorus (pylorospasm). Gastroparesis may present with a variety of symptoms in children including vomiting of undigested food, nausea, bloating, early satiety, abdominal discomfort, anorexia, and weight loss. While diagnosis is based primarily on clinical assessment, diagnostic tools such as gastric emptying scintigraphy and antroduodenal manometry provide objective measures of gastric emptying and gastric motor function [15]. For example, the use of antroduodenal manometry may allow differentiation between weak antral contractions (myopathic or neuropathic gastroparesis) versus higher amplitude antral contractions, which may be attributed to incomplete pyloric relaxation or pylorospasm (Fig. 13.1). For the latter, the use of pyloric botulinum toxin (Botox) injection or balloon dilatation may have a role with reported symptom response rates around 51 % for Botox [16].

Nausea is a common symptom with a prevalence of up to 10 % in otherwise healthy adolescents in the community [41]. It is often a difficult symptom to define and locate. It is usually described as a sense of queasiness often perceived in anticipation of imminent vomiting. While patients most notably localize their nausea in the epigastrium, other regions such as the head, throat, or lower abdominal may be considered the predominant site. This heterogeneous presentation underscores the need for a thorough assessment elaborating on the quality, duration, location, and associated symptoms related to the nausea.

When nausea is chronic and unexplained, the patient’s and family’s daily activities are often profoundly disrupted with loss in quality of life. The origin of nausea is often difficult to define objectively due to multifactorial causes with precipitating triggers and mechanisms not well described. Thus, it is imperative for the general clinician as well as for specialists to take a comprehensive history and perform a detailed examination for considerations both within and outside the GI tract. Oftentimes, when routine diagnostic testing fails to identify a cause for the nausea, patients are generally treated with empiric therapy in an attempt to alleviate their symptoms.

There are no specific diagnostic criteria for chronic idiopathic nausea in children, necessitating the use of adult criteria as defined by the Rome III definitions of functional gastrointestinal disorders. Chronic idiopathic nausea is diagnosed when there is a report of bothersome nausea, occurring at least several times per week, not typically associated with vomiting, in the absence of medical abnormalities that would explain the nausea (e.g., peptic ulcer disease, gastritis, celiac disease, delayed gastric emptying). These criteria need to be fulfilled for the past 3 months, with symptom onset at least 6 months prior to diagnosis [40]. This condition has received little attention in pediatrics until recently. Kovacic et al. [42] compared medical records of children seen in a pediatric GI clinic that had nausea as a primary complaint to youth with functional abdominal pain and associated nausea. The former group was significantly more likely to be Caucasian adolescent females with severe daily nausea that peaks in the morning. The nausea was of sufficient intensity to interfere with daily activities, including school.

The medical comorbidities in youth with chronic nausea are diverse once again supporting the complex nature of the mechanisms underlying these symptoms. Common comorbidities include migraines (62 %), family history of migraines (71 %), postural orthostatic tachycardia syndrome (36 %), and cyclic vomiting syndrome (27 %) [42]. Children presenting with chronic nausea as a primary complaint compared to those with abdominal pain and nausea, have been found to have more comorbid symptoms such as anxiety, dizziness, and fatigue [42]. Chronic nausea has also been found in youth with orthostatic intolerance (i.e., symptoms made worse upon standing and improve with recumbence) [43–45].

There is limited literature on psychiatric comorbidity in children with nausea. Pediatric subjects presenting with chronic nausea as a primary complaint, compared to those with abdominal pain and nausea, have been found to have more symptoms of anxiety and to have greater functional disability [42]. Nausea is also a common symptom in pediatric patients with POTS, CVS, Systemic exertional intolerance disease (SEID) (formally Known as myalgic encephalomyelitis/chronic fatigue syndrome), and functional abdominal pain [6, 20, 46], and these youth are reported to have an increased prevalence of anxiety symptoms. [29, 47–50]. Furthermore, in adolescents with orthostatic intolerance, nausea has been found to be significantly associated with both state and trait anxiety symptoms [43]. Explanations for the relationships among anxiety and nausea symptoms have not been established in these conditions, although there is preliminary research suggesting that the perception of intense nausea leads to activation of brain areas involved in the processing of fear conditioning [51]. Napadow et al. also found that increases in nausea were associated with enhanced interoceptive awareness of the stomach, and it is known that individuals with anxiety are hypervigilant of and differentially attend to interoceptive sensory information [52]. Nausea is also one of the most common symptoms of panic disorder in adolescents [53]. Panic is the only anxiety disorder to include nausea as a diagnostic criterion [54]. Although the presence of nausea is clinically observed in children and adolescents with generalized anxiety and fear-based anxiety disorders such as phobias and social anxiety, there is no mention of nausea as a comorbidity or as a diagnostic criterion for other anxiety disorders.

Dysautonomia manifesting as orthostatic intolerance is found in nearly 500,000 Americans with approximately 15 % of all children experiencing syncope before the end of adolescence [41, 55]. There is increasing recognition that autonomic disorders such as POTS are frequently associated with GI complaints including nausea, abdominal pain, and constipation [56]. For example, in subjects with functional dyspepsia, increased sympathetic nervous system reactivity was associated with higher nausea scores, and those with decreased parasympathetic flexibility demonstrated a higher incidence of tachygastria on electrogastrogram (EGG) [57]. In pediatric patients with POTS, abnormal gastric myoelectrical activity has been observed during head-upright tilt (HUT) table testing compared to those without POTS [58]. In addition, for pediatric subjects with chronic upper GI complaints and reported orthostatic symptoms such as dizziness, 42 % exhibited reproducible GI systems when challenged with HUT [59].

In one pediatric study, diagnostic workup for chronic idiopathic nausea revealed underlying cardiovascular instability manifesting primarily as postural orthostatic tachycardia syndrome (POTS) in 68 % of subjects [45]. When a similar cohort of subjects was treated with fludrocortisone for their orthostatic symptoms, nausea, abdominal pain, and dizziness improved by over 30 %, and school attendance improved by 44 % [44]. Despite the close link between the autonomic nervous system and gastrointestinal symptoms and motility, determining the presence of dysautonomia symptoms is not part of routine GI clinical assessment.