Cyclic Vomiting Syndrome
Cyclic vomiting syndrome (CVS) is a condition characterised by recurrent bouts of nausea and vomiting, without the cause being a diagnosable gastrointestinal disorder.
The pathway to diagnosis for parents and their children alike is often a frustrating one with years often passing and many different doctor visits and investigations from onset of symptoms to diagnosis, as initial episodes are passed off to food poisoning, motion sickness, stress, and viral illnesses. It’s usually the parents that pick up patterns:
- similar times of the day or week, or with similar spacing (e.g. wake at 6am every 2 months)
- consistent but seemingly unrelated triggers (car travel, anticipatory anxiety – pre-birthday party/Xmas/big event etc, over/under sleep, stress, hot car)
- No-one else at home or school ever gets this ‘virus’
CVS (like tension-type headache) has struggled to be taken seriously. First described in 1882 1 it was seen as an outward expression of an anxiety disorder and an illness, of
‘highly strung, fidgety, nervous children of slight build’ 2
Far from a ‘nervous disorder’ CVS is more similar to migraine than it is to other gastrointestinal disorders, in that it is a primary disorder of an irritated nervous system, which is just as prevalent and significantly under-diagnosed in adults.
CVS and migraine have a number of similar traits:
- Conditions of periodic and recurrent episodes
- Primary or functional diagnosis – exclusion of ‘medical or pathological’ causes
- They respond to similar medications (serotonin agonists, SNRI’s)
- Up to 80% of childhood CVS sufferers will go on to develop migraine as adults.
- Nausea and/or vomiting is one of the key defining features of migraine. So much so that back in the early 1900’s migraine was often referred to as ‘sick or bilious’ headache. It is commonly thought that nausea and/or vomiting is the natural result of strong pain, but in fact this isn’t the case. Cluster headache sufferers have the most severe pain we are aware of, yet nausea is rarely part of the presentation. Up to 1 in 4 migraineurs will experience nausea as a premonitory symptom – i.e. well before the headaches starts and sometimes up to 2-3 days before pain.
The ‘Nausea’ Centre in the Brainstem
Nausea is controlled by a key area in the dorsal vagal complex of the brainstem named the Solitary nucleus. The lower part of this nucleus receives the vagus nerve impulses coming up from the internal organs, and is involved in control of heart rate, blood pressure and the stomach (i.e. detecting problems). When activated this nucleus can do many different things, including generate the sensation of nausea. If the nausea signals build to a certain threshold we reach the ‘point of no return’ where the solitary nucleus signals a range of other control centres – referred to as ‘central pattern generation’ producing the familiar premonitory symptoms of vomiting – increased heart rate, sweating, swallowing/gulping and then relaxation of the opening (sphincter) of the stomach and abdominal wall contractions to produce emesis (vomiting).
What is interesting is that migraineurs who get nausea in their premonitory phase (i.e. before onset of headache) hav increased activation in the solitary nucleus. Even more interesting is that the small muscles from the top of the neck have the ability to excite (increase activity) or inhibit (decrease activity) of the solitary nucleus. While this seems odd at first, it forms a vital part of our blood pressure control to the head. Engagement of the neck muscles in particular patters tells the brain we are moving against gravity, and this provides a boost (when getting up) or drop (when lowering down) before the baroreceptors in our arteries kick in, to help maintain adequate blood flow to the head. It is possible that in the face of this increased activity, the brain is receiving conflicting information – instead of changing blood pressure it ‘shunts it off’ to an adjacent area – and nausea is the result.
Whatever the exact mechanism proves to be – one thing is clear. The small muscles under the base of the skull are capable of being responsible in part or wholly for recurrent nausea and vomiting disorders.
watson headache® approach
Regardless of age, severity or the length of time you or your child has been suffering, the Watson Headache® Approach can provide rapid and sustained relief from CVS and its more persistent variant, chronic nausea and vomiting syndrome (CNVS). Treatment is very well tolerated by all ages including children, with the youngest client with CVS being 3 years old – having suffered since 9 months old, every 2 months. On last report she was a healthy, happy 11 year old. As headache isn’t usually part of the problem, there is often no need for deep pressure on the neck which can be painful. The structure we need to push on is quit superficial, and often treatment will only go for a few weeks.
While it doesn’t offer a solution for everyone, getting it checked and treated comes with no side effects (maybe a little tenderness on the point of pressure), but offers the potential for rapid (sometimes immediate) and sustained relief.
Diagnosis & Symptoms
Diagnosis of nausea and vomiting disorders is interesting because problems related to the gastrointestinal system are not typically the realm of neurologists. We therefore have two classifications from two different specialties.
Gastroenterologists are developing a classification system for gastrointestinal disorders, and created the Rome guidelines, which is a consensus statement from experts in the field. In its fourth version, ROME IV describes functional gastrointestinal disorders, and under category B, wherein we find:
B3. Nausea and Vomiting disorders
- Chronic nausea and vomiting syndrome (CNVS)
- Cyclic vomiting syndrome (CVS)
- Cannabinoid hyperemesis syndrome (CHS) (not described here)
Chronic nausea and vomiting syndrome (CNVS)
Must include all of the following:
- Bothersome (i.e. severe enough to impact on usual activities) nausea, occurring at least 1 day per week and/or 1 or more vomiting episodes per week.
- Self-induced vomiting, eating disorders, regurgitation, or rumination are excluded.
- No evidence of organic, systemic, or metabolic diseases that is likely to explain the symptoms on routine investigations (including upper endoscopy)
Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis.
Cyclic Vomiting Syndrome (CVS)
Must include all of the following:
- Stereotypical episodes of vomiting regarding onset (acute) and duration (less than 1 week). Episodes abrupt in onset and occurring at least 1 week apart.
- At least 3 discrete episodes in the prior year and 2 episodes in the past 6 months, occurring at least 1 week apart.
- Absence of vomiting between episodes, but other milder symptoms can be present between cycles.
Supportive remarks: History or family history of migraine headaches.
Neurologists have the International Headache Society (IHS) definition3 according to the most recent classification – International Classification of Headache Disorders (ICHD-3) (as cyclical rather than cyclic) under migraine:
Section 1.6 – Episodic syndromes that may be associated with migraine:
1.6.1 Recurrent gastrointestinal disturbance
22.214.171.124 Cyclical vomiting syndrome:
Recurrent episodic attacks of intense nausea and vomiting, usually stereotypical in the individual and with predictable timing of episodes. Attacks may be associated with pallor and lethargy. There is complete resolution of symptoms between attacks.
A. At least 5 attacks of intense nausea and vomiting, fulfilling criteria B and C
B. Stereotypical in the individual patient and recurring with predictable periodicity
C. All of the following:
- nausea and vomiting occur at least 4 times per hour
- attacks last for > 1 hour, up to 10 days
- attacks occur > 1 week apart
D. Complete freedom from symptoms between attacks
E. Not attributed to another disorder
0%of child CVS sufferers develop migraine
0%are accurately diagnosed
Several studies have been performed to elucidate the prevalence of CVS in children. The first of these in the 1960’s in Western Australia found a prevalence of 2.3% (2.0% for girls and 2.5% for boys).
Similar rates were noted in a 1995 study in Scotland and 2006 study in Turkey both finding a prevalence of 1.9% though with differing gender ratio’s (Turkish girls 2:1, Scottish 1:1).
More recently studies in children used the ROME III criteria to classify sufferers. In 2015 children in the USA and Puerto Rico reported a higher prevalence of 3.4% in the age groups 1-4yrs and in 2016 children in Colombia reported 3.8% in ages 1-12yrs with adolescents to adults (13-48 yrs) reporting 6.1%.
In 2019 an epidemiological study using the latest ROME IV criteria assessed the prevalence of functional nausea and vomiting disorders (FNVD’s) in adults in the United States, Canada and the United Kingdom.
2.2% of the population fulfilled the criteria for functional nausea and vomiting disorders (FNVD’s) with 3% in the USA, 1.9% in Canada and 1.8% in the U.K.
The prevalence of CNVS (Chronic Nausea and Vomiting Syndrome) was similar across the three countries, with the different in prevalence being accounted for by a significantly higher proportion of CVS in the USA (2%) compared with Canada (0.7%) and the U.K. (1%)
Once investigations of the gastroenterological system have excluded structural causes, the management becomes pharmacological. Acute management relies on the sufferer identifying their prodromal phase and acting before the nausea escalates. Unfortunately, like primary headache disorders, there is then little thought given to the parts of the brain that are causing the problem and where to look for the irritation. That’s where we excel.
The non-drug answer and treatment for many sufferers of cyclic vomiting syndrome lies in the close connection between the ‘headache centre’ in the brainstem and one of the key controls in the brainstem for nausea and vomiting.
Acute episodes are typically managed with serotonin agonists to ease the nausea and try and prevent vomiting:
Triptans – such as sumatriptan (Imigran) which is a first line migraine abortive medication.
Ondansetron (Zofran) – commonly prescribed for the nausea and vomiting associated with chemotherapy or radiotherapy for cancer treatment, or surgery. If episodes are typically triggered by motion this may not work as Ondansetron is ineffective for nausea caused by motion sickness.
Benzodiazepines (Lorazepam) – sleeping tablets/relaxants, and central nervous system depressants.
Prophylaxis/Preventive medications may be recommended if the condition is considered moderate to severe (more than 4 episodes per year), severe nausea and vomiting, recurrent hospital ED visits and inability to maintain normal activities of daily living.
Amitriptyline (Endep) – a tricyclic antidepressant
Zonisamide, Levetiracetam, Topiramate (topomax) – anticonvulsants (epileptic) drug
Aprepitant (Emend) – binds to receptors in the Nucleus Tractus Solitarius that mediate the emetic motor reflex – interestingly in one trial a patient had a severe migraine triggered by this drug. Commonly prescribed for post surgical and chemotherapy induced nausea.
Mitochondrial supplements (CoQ10, L-carnitine, riboflavin) conditionally recommended as alternate prophylactic medications.
Screening for co-morbid conditions (anxiety, depression, migraine headache, autonomic dysfunction, sleep disorders, and substance abuse).
Alternate techniques like meditation, relaxation, and biofeedback may be offered to improve overall wellbeing and patient care outcomes but research is needed to indicate efficacy.
Nausea has many different causes from a variety of sources, such as the stomach (vagus nerve), neuroendocrine (morning sickness), cortex and limbic (anxiety), vestibular (motion sickness) and chemical filters of the blood (CRTZ – chemotherapy, hormones, drugs). All these different inputs converge in a part of the brainstem called the nucleus tractus solitarius or NTS. Once the NTS reaches a certain threshold it will then signal multiple centres predominantly in the hypothalamus at once – a central pattern generator which begins the emetic cascade – and vomiting occurs.
Nausea and/or vomiting is a key diagnostic pillar of migraine but until recently it was not understood what the connection was. Many believed, simply because intense nausea and vomiting often occur as episodes escalate in intensity that the nausea is due to pain intensity, however sufferers of Cluster Headache (the most intense headache pain we know of) rarely report nausea or vomiting. However researchers found that migraineurs who suffer nausea during their prodrome or premonitory phase have increased activity in the NTS. What then is causing this increased signalling?
In migraine we have evidence that the trigeminal nucleus is in a state of constant irritation.
Critical information from imaging studies that shows us that increased hypothalamus activity (responsible for premonitory symptoms or the prodrome occur in response to trigeminal nucleus activity.
There are direct connections from the trigeminal nucleus to the NTS.
Putting all these pieces together then:
- Trigeminal nucleus on constant state of irritation
- Hypothalamus and NTS become irritated during prodrome causing nausea, lethargy, yawning, cravings etc
- NTS trips threshold into emetic phase
This brings the neck right into the main suspect list, as the nerves from the top of the neck feed directly into the trigeminal nucleus. Small faults at the top of the neck can cause a major disruption in the trigeminal nucleus. Correction of these faults is often all that is required for successful management of CVS (as well as migraine and other related disorders).
The ROME IV diagnostic criteria for CVS and CNVS include the exclusion of eating disorders, regurgitation, or rumination and no evidence of organic, systemic, or metabolic diseases that are likely to explain the symptoms.
Such diseases include:
- MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)
- Peptic ulcer disease
- Intermittent small bowel obstruction
- Biliary tract dysmotility
- Renal colic
- Urea cycle defects (UCD)
- fatty acid oxidation disorders
- organic acidurias
- Acute intermittent porphyria,
- Adrenal insufficiency
- Central Nervous system disorders (hydrocephalus among others)
- Chronic Vestibular Dysfunction
A careful history by a Gastroenterologist and minimal testing should be enough to exclude these in most cases. Indications for further metabolic testing:
- There is any degree of abnormality between attacks – children with ‘migrainous’ CVS are completely normal between attacks. Poor growth and developmental delay require more extensive investigation
- Presence of encephalopathy – presenting as an altered mental state (beyond lethargy and flat mood). This may include combative behaviour as seen in cases of urea cycle defect
- Attacks are precipitated by illness, high fat or high protein meals (UCD).
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