Gary N. McAbee DO, JD, Anne Marie Morse DO, Ward Cook DO, Vivian Tang MD and Yuri Brosgol MD. Neurologic etiologies and pathophysiology of cyclic vomiting syndrome. Pediatric Neurology. In press.
Cyclic vomiting syndrome (CVS) is an idiopathic chronic periodic disorder of childhood, which may persist into the adult years. Although cyclic vomiting syndrome is considered a central nervous system (CNS) disorder, it is often managed by a pediatric gastroenterologist. The practitioner should not assume a gastrointestinal or non-neurological cause of symptoms especially if there are co-existing neurological symptoms and signs or if vomiting does not bring relief. This suggests a possible CNS cause which may necessitate a pediatric neurology consultation. Examples of CNS causes of CVS which can have subjective and objective neurologic findings include abdominal migraine, certain types of epilepsy, structural lesions (tumors, Arnold Chiari malformation, demyelinating disease), mitochondrial disease, autonomic disorders, fatty acid/ organic acid disorders, urea cycle defects and cannabinoid hyperemesis syndrome. Improved familiarity with CVS and its mimics may improve time to appropriate diagnosis and may reduce morbidity related to CVS.
From the manuscript
Coexisting neurologic findings of developmental delay, seizures, hypotonia with or without neuromuscular disease manifestations, cognitive impairment, myopathy and cranial nerve dysfunction have been found in up to 25% of CVS patients. CVS with these additional neurologic findings has been referred to as CVS plus (CVS+)….
A feature that distinguishes abdominal migraine(AM) from CVS is the predominant symptom of pain with less prominent vomiting with abdominal migraine, versus the predominant symptom of nausea and vomiting in CVS. The transition into more typical migraine is not a diagnostic clue as it occurs with both AM and CVS . Positive family migraine history occurs in CVS but is more common in AM. Others suggest that certain pain characteristics are less likely to be present in AM: pain that is burning, non-midline, mild and not interfering in daily activities, and duration of less than one hour. AM and CVS can co-exist in the same child, and there are therapeutic, genetic and electrophysiological associations shared by migraine and CVS. Similar therapeutic responses can be seen with pharmaceutical treatment in migraine and CVS. For instance, valproic acid, propranolol, amitriptyline, cyproheptadine, flunarizine and sumatriptan have been reported to possibly be effective for both AM and CVS although evidence-based efficacy is lacking. Genetically, there are two common genetic mitochondrial DNA (mtDNA) polymorphisms that have been reported in migraine as well as CVS (16519C>T, 6 times more common than in controls, and 3010G>A, 17 times more common than in controls). Neurophysiologic abnormalities detected on visual evoked potentials have been detected in both AM and CVS. ..
Stress, anxiety, infections, physical exhaustion, sleep deprivation and fasting are known triggers of CVS. These may also produce symptoms of mitochondrial dysfunction because of their effects on cellular metabolism. Boles et al. proposed that many of their patients with “cyclic vomiting plus” had mitochondrial dysfunction. In a retrospective study of 106 children with CVS, 38% had biochemical evidence of a mitochondrial disorder. Although these children were not definitively diagnosed with mitochondrial disorders and the results should be reviewed with caution, elevations in alanine with or without elevations in glycine or proline in plasma amino acid screening and elevations in lactate, methyl-glutaconate or Krebs cycle intermediaries in urine organic acid screening were reported. These tests may be normal when the child is well, but become abnormal during episodes of cyclic vomiting. ..
Cyclic vomiting has been described as the most common gastrointestinal symptom in MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) This disorder should be considered if other associated features are present, such as stroke-like episodes, elevated blood and CSF lactic acid, short stature or other organ system involvement (e.g. hearing loss and cardiac conduction abnormalities). Radiologic tests may be helpful and genetic tests for MELAS are available. 46 Muscle biopsy may be needed for diagnosis. Cyclic vomiting has also been reported in Kearns-Sayre syndrome which is associated with ptosis, external ophthalmoplegia, ataxia, muscle weakness and cognitive impairment. ...
CVS is not a rare disorder and there are many neurologic and non-neurologic conditions in which vomiting may be the primary symptom or chief complaint and thus mistaken for CVS, particularly in the pediatric population.
Moreover studies have suggested neurologic, endocrine, and metabolic components which may contribute or be co-morbid associations with this disorder. It is important for the clinician, when suspecting a diagnosis of CVS to screen for these other associated conditions for appropriate and effective treatment.
As discussed in this review, many of these “CVS mimics” carry with them additional symptomatology or may not follow the typical pattern of periodic emesis with an interval return to baseline as is seen with “typical” CVS. Furthermore, there are comorbid associations and clinical overlap with CVS and these other conditions, making the diagnosis an even more difficult challenge for the clinician.
It is prudent for the practitioner to obtain a detailed history and have a general understanding of these conditions in order to appropriately evaluate and treat the patient.