Zespół wymiotów cyklicznych – Patofizjologia i mechanizm

Zespół wymiotów cyklicznych
Patofizjologia i mechanizm

Zespół wymiotów cyklicznych (ZWC) to funkcjonalne zaburzenie charakteryzujące się nawracającymi epizodami intensywnych wymiotów, z przerwami względnego zdrowia. Patogeneza ZWC jest wieloczynnikowa i obejmuje dysfunkcję mitochondrialną (polimorfizmy mtDNA 16519T i 3010A, zwiększające ryzyko nawet 17-krotnie), dysregulację układu autonomicznego (90% dorosłych pacjentów wykazuje upośledzenie funkcji współczulnego układu nerwowego), zaburzenia osi podwzgórze-przysadka-nadnercza (rola CRF), nadpobudliwość neuronalną oraz powiązania z migreną (40-46% pacjentów z ZWC ma migrenę). Układ endokannabinoidowy również odgrywa istotną rolę, zwłaszcza w kontekście zespołu hiperemesis kannabinoidowej (CHS). Czynniki wyzwalające epizody to m.in. stres, czynniki pokarmowe, ekspozycja na zimno, menstruacja, używanie marihuany oraz wyczerpanie fizyczne. Dysfunkcje kanałów jonowych (mutacje w genie RYR2) i zaburzenia osi mózg-jelito także uczestniczą w patogenezie.

Zespół wymiotów cyklicznych – Patogeneza

Zespół wymiotów cyklicznych (ZWC), po angielsku Cyclic Vomiting Syndrome (CVS), to funkcjonalne schorzenie charakteryzujące się nawracającymi, stereotypowymi epizodami intensywnych wymiotów, przedzielonymi okresami względnego zdrowia. Pomimo wieloletnich badań dokładna patogeneza tego schorzenia pozostaje nieznana, jednak współczesne badania wskazują na wieloczynnikowe podłoże zaburzenia, obejmujące interakcje między układem nerwowym, autonomicznym, endokrynnym oraz czynnikami genetycznymi¹².

Związek z migreną

Jedną z najsilniej udokumentowanych powiązań patogenetycznych jest związek ZWC z migreną. Zwraca uwagę wysoka częstość występowania migreny zarówno u pacjentów z ZWC (40-46%), jak i w ich rodzinach (28-82%), co sugeruje wspólny mechanizm patofizjologiczny¹². Podobieństwo ZWC do innych okresowych zaburzeń neurologicznych, takich jak migrena czy padaczka, dostarcza istotnych wskazówek dotyczących potencjalnych fenotypów prowadzących do rozwoju tego schorzenia¹. Wielu badaczy uważa ZWC za wariant migreny, w którym ból głowy może nie występować, ale może poprzedzać go aura podobna do migrenowej¹.

Dysfunkcja mitochondrialna

Istotną rolę w patogenezie ZWC przypisuje się dysfunkcji mitochondrialnej. Badania wskazują na występowanie mutacji i polimorfizmów mitochondrialnego DNA (mtDNA), które mogą predysponować do rozwoju ZWC¹. Polimorfizm 16519T występuje 6 razy częściej u pediatrycznych pacjentów z ZWC niż w populacji kontrolnej. Polimorfizm 3010A zwiększa prawdopodobieństwo wystąpienia ZWC u osób z 16519T nawet 17-krotnie¹. Zaburzenia funkcji mitochondriów mogą prowadzić do deficytów w produkcji energii komórkowej, co może mieć szczególne znaczenie w komórkach nerwowych układu autonomicznego, które kontrolują funkcje przewodu pokarmowego¹.

Na związek między ZWC a dysfunkcją mitochondrialną wskazuje również matrylinearny wzorzec dziedziczenia oraz skuteczność terapeutyczna koenzymu Q10, kofaktora mitochondrialnego łańcucha transportu elektronów¹. Koenzym Q10, stosowany w dawce 10-15 mg/kg/dobę, wykazuje znaczącą skuteczność w zmniejszaniu częstości epizodów ZWC, z medianą wskaźnika odpowiedzi na poziomie 78,85%¹.

Dysfunkcja układu autonomicznego

Badania wykazały istotną rolę dysfunkcji układu autonomicznego w patogenezie ZWC. U przeważającej większości (90%) dorosłych pacjentów z ZWC stwierdza się upośledzenie funkcji współczulnego układu nerwowego (naczyniowo-ruchowego i gruczołów potowych), przy zachowanej prawidłowej funkcji układu przywspółczulnego¹. Nadreaktywność współczulna i dysfunkcja autonomiczna przyczyniają się do patogenezy ZWC, co przejawia się podczas epizodów tachykardią, zawrotami głowy, nadmiernym ślinotokiem i bladością skóry¹².

Układ autonomiczny odgrywa kluczową rolę w regulacji odruchu wymiotnego. Obserwowana dysregulacja układu autonomicznego ma implikacje terapeutyczne, takie jak zastosowanie neuromodulacji nerwu błędnego za pomocą przezskórnej stymulacji elektrycznej pola nerwowego, która poprawia objawy poprzez modulację funkcji nerwu błędnego u pacjentów z zaburzeniami osi mózgowo-jelitowej i ZWC¹.

Rola osi podwzgórze-przysadka-nadnercza

Reakcja stresowa, zapośredniczona przez oś podwzgórze-przysadka-nadnercza (HPA), może potencjalnie indukować epizody ZWC¹. Sugeruje się, że czynnik uwalniający kortykotropinę (CRF) może być mediatorem na osi mózg-jelito w ZWC, bezpośrednio łączącym stres z wymiotami². Sugeruje się, że zmieniona sygnalizacja za pośrednictwem receptorów CRF jest kluczowym czynnikiem powodującym wymioty u pacjentów z ZWC¹.

Badania z użyciem metod obrazowania funkcjonalnego u ludzi zaczynają wyjaśniać specyficzne obwody neuronalne odpowiadające za nudności i wymioty w wyższych ośrodkach mózgu. Możliwe, że nadpobudliwość neuronalna i obniżony próg wyzwalania specyficznych wzorców aktywności neuronalnej w obwodach korowych i podkorowych są cechami patogenetycznymi ZWC¹.

Nadpobudliwość neuronalna

Nadpobudliwość neuronalna może stanowić wspólne ogniwo między ZWC a innymi epizodycznymi zaburzeniami ośrodkowego układu nerwowego¹². Uwrażliwiony pień mózgu może odbierać niegroźne bodźce, takie jak spożywanie określonych pokarmów, i wywoływać objawy wymiotne. Ta nadpobudliwość objawów ZWC wynika ze zwiększonego pobudzenia i wrażliwości pnia mózgu. Uwrażliwiony pień mózgu przekazuje informacje sensoryczne do mózgu, ale wzmacnia sygnał odczucia, przez co mózg odbiera informacje jako bolesne¹.

W migrenie istnieją dowody na to, że jądro nerwu trójdzielnego znajduje się w stanie ciągłego podrażnienia. Wnosi to szyję na listę głównych podejrzanych, ponieważ nerwy z górnej części szyi zasilają bezpośrednio jądro nerwu trójdzielnego. Niewielkie wady w górnej części szyi mogą powodować poważne zakłócenia w jądrze nerwu trójdzielnego. Korekcja tych wad często jest wszystkim, co jest wymagane do skutecznego leczenia ZWC (a także migreny i innych pokrewnych zaburzeń)¹.

Rola układu endokannabinoidowego

Układ sygnalizacji endokannabinoidowej odgrywa istotną rolę w ZWC¹. Związek między przewlekłym używaniem marihuany a zespołem podobnym do cyklicznych wymiotów (zespół hiperemesis kannabinoidowej, CHS) rodzi pytanie o rolę endogennego układu kannabinoidowego¹.

Rola konopi w patogenezie objawów w ZWC jest kontrowersyjna. Kilka badań wykazało, że 40%-80% pacjentów z ZWC używa konopi¹. CHS ma cechy kliniczne nieodróżnialne od ZWC, z wyjątkiem przewlekłego, intensywnego używania konopi. Opisano swoiste zachowanie związane z kąpielą, zwane „kompulsywną kąpielą w gorącej wodzie”, które uważano za patognomoniczne dla użycia konopi. Jednak badania pokazują, że to zachowanie związane z gorącą kąpielą występuje również u około 50% pacjentów z ZWC, którzy nie używają konopi².

Autorzy sugerują, że patogeneza wymiotów może być podobna w różnych punktach spektrum używania konopi, przy czym szlak sygnałowy eCB/CB1R odgrywa rolę w wymiotach i istotnie przyczynia się do terapeutycznego efektu kąpieli w gorącej wodzie¹.

Inne czynniki

Wśród innych czynników potencjalnie zaangażowanych w patogenezę ZWC wymienia się:

Dysfunkcję kanałów jonowych – badania genomiczne nowej generacji wykazały istotnie związaną mutację w genie RYR2 u pacjentów z ZWC w porównaniu z grupą kontrolną¹
Zaburzenia osi mózg-jelito – ZWC wydaje się obejmować dysregulowane centralne obwody neuronalne i mediatory neuroendokrynne¹
Rolę układu endokrynnego w patogenezie ZWC, która może być związana z cyklem menstruacyjnym²
Alergie pokarmowe – sugerowane jako możliwa patogeneza ZWC, jednak kwestia ta pozostaje kontrowersyjna z powodu braku dalszych badań nad związkiem między ZWC a alergią pokarmową¹

Wieloczynnikowy model patogenezy

Wiarygodny model ZWC musi uwzględniać różnorodność czynników wyzwalających atak i szeroki zakres objawów prodromalnych występujących na początku epizodów ZWC¹. Patogenezę tego schorzenia warto konceptualizować jako wynik skumulowanej interakcji unikalnych kombinacji szeregu odrębnych procesów fenotypowych i chorób współistniejących prowadzących do cyklicznych wymiotów².

Patogeneza ZWC jest prawdopodobnie wieloczynnikowa, z udziałem wielu czynników genetycznych, autonomicznych, centralnych i środowiskowych². Aby lepiej opracować metody leczenia oparte na mechanizmach, konieczne jest wyjaśnienie patogenezy, cech klinicznych i powiązań chorobowych w ZWC³.

Mechanizmy wyzwalające epizody ZWC

Epizody ZWC mogą być wyzwalane przez różnorodne czynniki, co odzwierciedla złożoność patogenezy tego schorzenia¹. Wśród najczęściej identyfikowanych czynników wyzwalających wymienia się:

Stres emocjonalny i lęk antycypacyjny – stres psychologiczny i lęk antycypacyjny mogą wyzwalać epizody¹
Czynniki pokarmowe – niektóre pokarmy, takie jak czekolada czy ser, mogą działać jako czynniki wyzwalające¹
Ekspozycja na zimno – narażenie na zimno może wyzwalać ataki u predysponowanych osób²
Alergie i problemy z zatokami – mogą stanowić czynnik wyzwalający epizody ZWC³
Intensywne emocje lub ekscytacja – silne emocje mogą prowokować wystąpienie epizodu⁴
Wyczerpanie fizyczne – nadmierne zmęczenie organizmu może być czynnikiem wyzwalającym⁵
Menstruacja – u kobiet cykl menstruacyjny może wyzwalać epizody ZWC⁶
Choroba lokomocyjna – podatność na chorobę lokomocyjną może korelować z występowaniem ZWC⁷
Używanie marihuany – zarówno używanie, jak i zaprzestanie używania konopi indyjskich może wyzwalać epizody u niektórych pacjentów²

Identyfikacja czynników wyzwalających epizody może pomóc w zarządzaniu zespołem wymiotów cyklicznych¹. Kluczem do opracowania skutecznych, spersonalizowanych metod leczenia ZWC jest rozpoznanie czynników wyzwalających i mechanizmów oraz podniesienie indywidualnego progu rozwoju objawów¹.

Implikacje dla terapii wynikające z patogenezy

Zrozumienie złożonej patogenezy ZWC ma kluczowe znaczenie dla opracowania ukierunkowanych strategii terapeutycznych¹. Aktualna wiedza na temat mechanizmów choroby przekłada się na następujące podejścia terapeutyczne:

Leczenie ukierunkowane na dysfunkcję mitochondrialną

W oparciu o teorię dysfunkcji mitochondrialnej, koenzym Q10, jako kofaktor mitochondrialny, wykazuje znaczącą skuteczność w leczeniu ZWC¹. Działając jako nośnik wysokoenergetycznych elektronów z kompleksu I i II do kompleksu III, CoQ10 może poprawiać funkcję mitochondriów i zmniejszać częstość epizodów ZWC². Przy stosowaniu w monoterapii, w dawce 10-15 mg/kg/dobę, CoQ10 wykazuje wskaźnik odpowiedzi na poziomie 83% przy redukcji objawów o ponad 50%¹.

Biorąc pod uwagę poziom skuteczności i doskonały profil bezpieczeństwa, CoQ10 powinien być lekiem pierwszego wyboru u pacjentów, u których wstępna ocena nie wykazała lęku ani wyraźnych objawów dysautonomicznych².

Modulacja układu autonomicznego

Dysregulacja układu autonomicznego w ZWC sugeruje potencjalne korzyści z terapii modulujących aktywność tego układu. Neuromodulacja nerwu błędnego za pomocą przezskórnej stymulacji elektrycznej pola nerwowego może poprawiać objawy poprzez modulację funkcji nerwu błędnego u pacjentów z zaburzeniami osi mózgowo-jelitowej i ZWC¹.

Leczenie oparte na pokrewieństwie z migreną

Ze względu na podobieństwa między ZWC a migreną, pacjenci z ZWC mogą odnieść korzyść z prób terapii obecnie dostępnych w leczeniu migren, napadów padaczkowych lub zaburzeń lękowych z napadami paniki¹. Leki przeciwmigrenowe mogą być skuteczne w leczeniu ZWC, co dodatkowo potwierdza wspólną patofizjologię tych zaburzeń¹.

Rola leków przeciwpsychotycznych

Chociaż dopamina jest ważnym neuroprzekaźnikiem w leczeniu wymiotów i ZWC, opcje leczenia farmakologicznego lekami przeciwpsychotycznymi są rzadko wymieniane w literaturze¹. Risperidon, w swojej unikalnej kombinacji z amitryptyliną, może być ważną alternatywą dla osiągnięcia zadowalającego wyniku leczenia w przypadkach opornych².

Mechanizm neurobiologiczny amisulprydu w ZWC pozostaje nieznany. Jego właściwości przeciwwymiotne mogą być jednym z takich mechanizmów¹. Przeciwwymiotne działanie amisulprydu wydaje się być zapośredniczone przez jego silną aktywność antagonistyczną wobec receptora D3². Niska dawka amisulprydu może być podejściem terapeutycznym pozwalającym uniknąć objawów epizodów u kobiet z ZWC związanym z menstruacją³.

Przyszłe kierunki badań

Aby opracować ukierunkowane terapie ZWC, przyszłe badania muszą zdefiniować podtypy ZWC w oparciu o definicje mechanistyczne, a nie wyłącznie kryteria objawowe². Rola czynników genetycznych, takich jak mitochondrialne DNA, kanały jonowe, funkcja neurohumoralna (układ endokannabinoidowy i oś podwzgórze-przysadka-nadnercza) oraz czynniki neurogenne w rozwoju ZWC wymaga systematycznego badania¹.

W przyszłości badania mutacji mitochondrialnego DNA, defektów kanałów jonowych, czynnika uwalniającego kortykotropinę oraz fizjologii i farmakologii receptorów serotoniny i tachykininy mogą pomóc odkryć etiologię i patogenezę tego zaburzenia¹.

Kompleksowe rozumienie patogenezy ZWC

Zespół wymiotów cyklicznych jest złożonym, wieloczynnikowym zaburzeniem osi mózg-jelito o nadal nie w pełni wyjaśnionej patogenezie¹. Aktualne dane sugerują, że ZWC wynika z kombinacji czynników genetycznych i osobniczych, które prowadzą do wymiotów¹.

Główne proponowane mechanizmy patofizjologiczne obejmują:

Dysfunkcję mitochondrialną z mutacjami i polimorfizmami mtDNA¹
Dysfunkcję układu autonomicznego, szczególnie nadreaktywność współczulną¹
Zaburzenia osi podwzgórze-przysadka-nadnercza i rola czynnika uwalniającego kortykotropinę¹
Nadpobudliwość neuronalną jako wspólne ogniwo między ZWC a innymi epizodycznymi zaburzeniami OUN¹
Związek z migreną, sugerujący wspólny proces patofizjologiczny¹
Rolę układu endokannabinoidowego w regulacji odruchu wymiotnego¹

Coraz lepsze zrozumienie patofizjologii ZWC przyniosło postępy w jego leczeniu¹. ZWC jest podatny na leczenie u większości pacjentów lekami, które są szeroko dostępne i znane z dobrej tolerancji¹. Dostępne są wytyczne, które pomagają lekarzom niespecjalistom wychwycić i leczyć pacjentów z ZWC, którzy dobrze reagują na standardowe leczenie².

Ta kompleksowa baza informacji dotyczących patofizjologii ZWC i CHS może wskazać nowe kierunki w leczeniu tych trudnych stanów¹. Przyszłość pozostaje obiecująca mimo trwających wyzwań związanych z zarządzaniem tym schorzeniem¹.

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Materiały źródłowe

#1 Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions
https://pmc.ncbi.nlm.nih.gov/articles/PMC6899706/
Cyclic vomiting syndrome is, by definition, a syndrome with episodic bouts of uncontrollable vomiting, separated by periods of relative wellness. […] To better design mechanism-driven management approaches, it is essential that we elucidate the pathogenesis, clinical features, and disease associations in CVS. […] A viable CVS model must consider the diversity of attack triggers and the breadth of prodromal symptoms experienced at the onset of CVS episodes. […] It is useful to conceptualize its pathogenesis as resulting from the cumulative interaction of unique combinations of a number of distinct phenotypic processes and comorbid conditions leading to cyclical emesis. […] The similarity of CVS to other periodic disorders such as migraine and epilepsy offers clues about potential phenotypes that may lead to the development of CVS in adults.
#1 Cyclic vomiting syndrome | MedLink Neurology
https://www.medlink.com/articles/cyclic-vomiting-syndrome
Cyclic vomiting syndrome is considered one of the disorders of gut-brain interaction and migraine variants. […] Its pathophysiology is still not well understood; however, identification of autonomic and mitochondrial dysfunction has helped towards a better understanding. […] The pathophysiology of cyclic vomiting syndrome is unclear. Given the link between migraine and cyclic vomiting it is assumed that there are similarities in underlying cause. […] The initial link between migraine and cyclic vomiting syndrome was because of the high rates of personal (40% to 46%) and family history (28% to 82%) of migraine in those with cyclic vomiting syndrome. […] There also seems to be some overlap in the presumed mechanisms behind migraine and cyclic vomiting syndrome including mitochondrial dysfunction and autonomic dysfunction.
#1 Cyclic vomiting syndrome: diagnostic approach and current management s | CEG
https://www.dovepress.com/cyclic-vomiting-syndrome-diagnostic-approach-and-current-management-st-peer-reviewed-fulltext-article-CEG
Cyclic vomiting syndrome (CVS) is a disorder characterized by episodes of nausea and vomiting lasting for 15 days followed by asymptomatic periods. […] Various hypotheses of CVS pathogenesis are cited in the literature. Proposed mechanisms for CVS include psychological or physical stress resulting in activation of the hypothalamic-pituitary-adrenal axis, abnormal gastric emptying (eg, irritable bowel syndrome), dysfunction in the autonomic nervous system, mitochondrial dysfunction, elevated levels of ghrelin, and food allergies. […] Studies show a close association of CVS and migraine headaches, especially in pediatric patients. […] Though not fully understood, this association suggests a common pathophysiological mechanism with a diverse array of symptoms caused by a more generalized underlying central nervous system disorder. […] This hypothesis describes CVS as a variant of migraine in which headache may not be present, but may have an aura prior to acute phase. […] CVS is an uncommon diagnosis with an unknown etiology and pathophysiology.
#1 Cyclic Vomiting Syndrome: Practice Essentials, Pathophysiology and Etiology, Epidemiology
https://emedicine.medscape.com/article/933135-overview
Cyclic vomiting syndrome (CVS), first described in children by Samuel Gee in 1882, is a chronic functional disorder of unknown etiology that is characterized by paroxysmal, recurrent episodes of vomiting. […] The pathophysiology is unknown, but data suggest a strong genetic component in children with CVS, with evidence of mitochondrial heteroplasmies that predispose to CVS and other related disorders (eg, migraine and chronic fatigue syndrome). […] Other theories include autonomic dysfunction and, possibly, corticotropin-releasing factor (CRF) because stress is known to be a trigger for these episodes. […] Mitochondrial DNA (mtDNA) mutations may be involved in the pathogenesis of CVS. […] The 16519T polymorphism is 6 times more common in pediatric CVS patients than in control populations.
#1 Cyclic Vomiting Syndrome: Practice Essentials, Pathophysiology and Etiology, Epidemiology
https://emedicine.medscape.com/article/933135-overview
The 3010A polymorphism increases the likelihood of CVS in subjects with 16519T by as much as 17 times. […] Sympathetic hyperresponsiveness and autonomic dysfunction also appear to contribute to the pathogenesis of CVS. […] The stress response, mediated by the hypothalamic-pituitary-adrenal (HPA) axis, can also potentially induce episodes of CVS. […] Therefore, CRF may be a brain-gut mediator of CVS that directly connects stress and vomiting. […] In conclusion, the pathogenesis of CVS is likely to be multifactorial, with multiple genetic, autonomic, central, and environmental factors playing a role. Further studies are needed to elucidate the exact mechanisms underlying this disorder.
#1 Cyclic vomiting syndrome: MedlinePlus GeneticsLock
https://medlineplus.gov/genetics/condition/cyclic-vomiting-syndrome/
Some cases of cyclic vomiting syndrome, particularly those that begin in childhood, may be related to changes in mitochondrial DNA. […] Several changes in mitochondrial DNA have been associated with cyclic vomiting syndrome. Some of these changes alter single DNA building blocks (nucleotides), whereas others rearrange larger segments of mitochondrial DNA. […] Researchers speculate that the impaired mitochondria may cause certain cells of the autonomic nervous system to malfunction, which could affect the digestive system. However, it remains unclear how changes in mitochondrial function could cause episodes of nausea, vomiting, and lethargy; abdominal pain; or migraines in people with this condition.
#1 Efficacy of Coenzyme Q10 in the Treatment of Cyclic Vomiting Syndrome in Children
https://austinpublishinggroup.com/pediatrics-child-health-care/fulltext/jpchc-v6-id1038.php
Cyclic Vomiting Syndrome (CVS) is a chronic functional gastrointestinal disorder related to migraine, characterized by episodic nausea and vomiting. […] As mitochondriopathy has been involved in the pathophysiology of CVS, Coenzyme Q10 (CoQ10), a mitochondrial cofactor, has been used as the third line treatment in CVS. […] The rational for the efficacy of CoQ10 in CVS is based on the potential relations between CVS and mitochondrial disease and the link between migraine syndromes and mitochondrial abnormality is supported by multiple facts. […] CoQ10 is a mitochondrial electron-transport chain cofactor acting as a carrier of high-energy electrons from complex I and II to complex III. […] This could be the mechanism by which exogenous intake of CoQ10 can improve symptoms in mitochondrial myopathies or cardiomyopathies.
#1 Efficacy of Coenzyme Q10 in the Treatment of Cyclic Vomiting Syndrome in Children
https://austinpublishinggroup.com/pediatrics-child-health-care/fulltext/jpchc-v6-id1038.php
Our study demonstrates that CoQ10, used in monotherapy, can be efficient at a posology of 10-15mg/kg/day with a significant decrease of CVS episodes per year under treatment by CoQ10 with a median response rate of 78.85%. […] Considering the potential difficulty to give the treatment during the school time in children, some of our patients were taking CoQ10 bid during the school days and tid the other days. […] In our study, CoQ10 has 83% of response rate over 50% and 74% obtained a reduction of 70% and more. […] This means that CoQ10 is, at least, as efficient as most standard treatments with a much better safety profile. […] Mitochondriopathy cannot resume the pathophysiology of CVS, in our study, 2 patients were completely unresponsive, both of them have an important anxious personality and amitriptyline has been prescribed at the end of the study and was very efficient in these two cases. […] We think that, considering the level of efficacy associated to the excellent safety profile, CoQ10 should be the first line treatment in patients in whom the initial evaluation did not find anxiety or clear dysautonomic signs.
#1 :: PGHN :: Pediatric Gastroenterology, Hepatology & Nutrition
https://pghn.org/DOIx.php?id=10.5223/pghn.2015.18.4.224
Cyclic vomiting syndrome (CVS) is a functional disorder characterized by stereotypical episodes of intense vomiting separated by weeks to months. […] The precise pathophysiology of CVS is not known but a strong association with migraine headaches, in the patient as well as the mother indicates that it may represent a mitochondriopathy. […] Studies have also suggested the role of an underlying autonomic neuropathy involving the sympathetic nervous system in its pathogenesis. […] The syndrome is a complex, multifactorial disorder of the brain-gut axis of as yet unclear pathogenesis, often associated with other episodic conditions like migraine headaches and abdominal migraine. […] An underlying autonomic neuropathy in CVS has been suggested based on an overwhelming majority (90%) of adult patients who have impairment of the sympathetic nervous system (vasomotor and sudomotor) but a normal parasympathetic nerve function.
#1 Cyclic Vomiting Syndrome: Recognition and Guidelines for Treatment | UPMC Physician Resources
https://www.upmcphysicianresources.com/news/011822-cyclic-vomiting-syndrome
CVS is characterized by four phases. […] Sympathetic nervous system activation likely contributes to CVS pathogenesis, and CVS episodes are typically accompanied by tachycardia, dizziness, salivation, and paleness of the skin. […] These similarities suggest a common neurogenic etiology and, moreover, suggest that patients with CVS could benefit from trials of therapies that are currently available for the treatment of migraines, seizures, or panic disorder. […] The guidelines are a fundamentally important tool for the recognition of CVS by primary care and emergency medicine physicians and for getting patients the diagnosis and treatment required to mitigate CVS. […] CVS is treatable in most patients with drugs that are widely available and known to be well-tolerated. Guidelines are available to help non specialists catch and care for patients with CVS who respond readily to standard treatments.
#1 Cyclic vomiting syndrome: From pathophysiology to treatment | Revista de GastroenterologÃa de MÃ©xico
https://www.revistagastroenterologiamexico.org/en-cyclic-vomiting-syndrome-from-pathophysiology-articulo-S2255534X24000616
The autonomous nervous system plays an outstanding role in emesis. […] This observed dysregulation of the autonomous nervous system has implications in the treatment of CVS, such as vagal neuromodulation with percutaneous electrical nerve field stimulation, which improves symptoms, modulating the vagal function in patients with gut-brain axis gastrointestinal disorders and those with CVS. […] The fact that vomiting and retching during the emetic phase of CVS are mainly produced when the stomach is empty, implies that the allostatic feedback mechanisms are disordered, which could give rise to a reduced threshold for vomiting and retching, regardless of physiologic necessity or peripheral information. […] Neuronal hyperexcitability can be a common link between CVS and other central nervous system (CNS) disorders. […] The increasing understanding of the pathophysiology of CVS has brought about advances in its treatment.
#1 Cyclic vomiting syndrome responding to amisulpride â A case report – Indian Journal of Physiology and Pharmacology
https://ijpp.com/cyclic-vomiting-syndrome-responding-to-amisulpride-a-case-report/
Cyclic vomiting syndrome (CVS) is a functional illness with unknown cause defined by stereotyped repeated episodes of vomiting of acute onset and length (1 week) with three or more separate vomiting episodes in the previous year and absence of nausea and vomiting between episodes. […] In the afferent and efferent brain-gut axis of nausea and vomiting, CVS appears to involve dysregulated central neuronal circuits and neuroendocrine mediators. Autonomic, GI, central neuroendocrine and mitochondrial metabolic variables have been suggested to have additional pathogenic roles. […] The role of the endocrine system in the pathogenesis of CVS could be linked to the menstrual cycle. […] Tache believes that altered CRF receptor-mediated signalling is a crucial factor in causing emesis in CVS patients.
#1 Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions
https://pmc.ncbi.nlm.nih.gov/articles/PMC6899706/
The key to developing effective, personalized treatments for CVS hinges on recognizing disease triggers and mechanisms and raising the individual threshold for developing symptoms. […] In order to develop targeted CVS therapies, future research needs to define CVS subtypes based on mechanistic definitions, rather than solely on symptom criteria. […] Neuronal hyperexcitability may represent a common link between CVS and other episodic CNS disorders. […] The specific neural circuits for nausea and vomiting within higher centers of the brain are beginning to be elucidated using functional imaging methods in human subjects. […] It is possible that neuronal hyperexcitability and a lowered threshold to trigger specific patterns of neural activity within these cortical and subcortical circuits are pathogenic features of CVS.
#1 Cyclical Vomiting Syndrome Treatment | Zetland, Sydney
https://sydneymigraine.com.au/cyclical-vomiting-syndrome-treatment/
Cyclical Vomiting Syndrome (CVS) can be defined as episodes of severe vomiting followed by mostly complete symptom-free periods, hence the cyclical nature of the disorder. However, occasionally sufferers may experience mild symptoms between episodes. The episodes can last from one hour up to ten days. […] The exact mechanism of Cyclical Vomiting Syndrome is currently not known, however, some theories have proposed that chemicals like histamine and serotonin that are produced by the body have a role to play. Other possible causes include hormonal imbalances or genetic differences. […] A sensitised brainstem can perceive non-threatening stimuli such as consuming certain foods and create vomiting symptoms, where the sensory information was originally detected. This hyper-excitability of CVS symptoms is due to the heightened arousal and sensitive brainstem. A brainstem that is sensitised will relay the sensory information to the brain, but will heighten the signal of the sensation so that the brain perceives the information as painful.
#1 Cyclic Vomiting Syndrome | Melbourne Headache Centre
https://melbourneheadachecentre.com.au/conditions/cyclic-vomiting-syndrome/
In migraine we have evidence that the trigeminal nucleus is in a state of constant irritation. […] 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).
#1 Cyclic vomiting syndrome: From pathophysiology to treatment | Revista de GastroenterologÃa de MÃ©xico
https://www.revistagastroenterologiamexico.org/en-cyclic-vomiting-syndrome-from-pathophysiology-articulo-S2255534X24000616
Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent and unpredictable episodes of intense vomiting, interspersed with periods of apparent wellbeing. […] The aim of the present review is to examine the most important aspects of the epidemiology, pathophysiology, subtypes, diagnostic criteria, and current management of CVS. Even though the exact etiology remains unknown, genetic factors (polymorphisms), nervous system alterations and autonomic dysregulation, and environmental factors (use and abuse of cannabinoids) are postulated as possible triggers. […] The proposed pathophysiologic mechanisms of CVS are (Fig. 1): Possible pathophysiologic mechanisms of CVS. Current data suggest that CVS is explained by a combination of genetic and host factors that lead to emesis. […] The endocannabinoid signaling system plays an important role in CVS.
#1 Cyclic vomiting syndrome | MedLink Neurology
https://www.medlink.com/articles/cyclic-vomiting-syndrome
A review of a small number of adult and pediatric patients with cyclic vomiting syndrome noted that clinically the circadian nature of attacks, autonomic dysfunction, as well as objective findings on PET imaging implicate the hypothalamus as well as the insula. […] The connection between chronic marijuana use and a cyclic vomiting-like syndrome (cannabinoid hyperemesis syndrome) has also raised a question about the role of the endogenous cannabinoid system.
#1 Cyclic vomiting syndrome: A GI primer | MDedge
https://www.mdedge.com/gihepnews/article/221281/mixed-topics/cyclic-vomiting-syndrome-gi-primer/page/0/1
The role of cannabis in the pathogenesis of symptoms in CVS is controversial. […] The use of cannabis has increased over the past decade with increasing legalization. […] Several studies have shown that 40%-80% of patients with CVS use cannabis. […] Following this, cannabinoid hyperemesis syndrome (CHS) was coined as a separate entity based on this statistical association, though there are no data to support the notion that cannabis causes vomiting. […] CHS has clinical features that are indistinguishable from CVS except for the chronic heavy cannabis use. […] A peculiar bathing behavior called âcompulsive hot-water bathingâ has been described and was thought to be pathognomonic of cannabis use. […] A small number of patients may sustain burns from the hot-water bathing. […] However, studies show that this hot-water bathing behavior also is seen in about 50% of patents with CVS who do not use cannabis.
#1
https://link.springer.com/article/10.1007/s10620-020-06448-3
Cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS) are two related disorders with incompletely understood pathogenesis. […] The authors hypothesize that the improvement in symptoms may be mediated by increased release of endocannabinoids acting on the CB1 subtype of cannabinoid receptors. […] Regardless of the distinction between CVS and CHS, by showing that hot water bathing can be therapeutic for vomiting symptoms in patients with varying levels of cannabis use, the authors suggest the pathogenesis of vomiting may be similar at various different points along the cannabis use spectrum, with the eCB/CB1R signaling pathway playing a role in vomiting, and importantly contributing to the therapeutic effect of hot water bathing. […] This important study has shown that hot water bathing temporary relieves multiple symptoms during both the prodromal and emetic phases of CVS in a population of individuals with varying levels of marijuana use. In so doing, it provides further insight into the pathogenesis of CVS, raising important questions about whether similar treatments can be utilized throughout the CVS/CHS spectrum.
#1 Cyclic vomiting syndrome | MedLink Neurology
https://www.medlink.com/articles/cyclic-vomiting-syndrome
Mitochondrial dysfunction was initially implicated in the pathophysiology of cyclic vomiting syndrome because of the maternal inheritance pattern and abnormalities seen in laboratory studies performed during attacks, including lactic acidosis and urine organic acid patterns consistent with energy failure. […] The autonomic nervous system dysfunction in cyclic vomiting syndrome has been noted since the late 1990s when two groups of investigators noted increased sympathetic cardiovascular tone in patients with cyclic vomiting syndrome. […] It is thought that hypersensitivity of the autonomic nervous system to emetic signals is what predisposes some to such abnormal vomiting reaction. […] Seventy-five patients with cyclic vomiting syndrome were compared to controls with next-generation genomic sequencing and there was a significantly associated mutation in the RYR2 gene.
#1 Recent Concepts on Cyclic Vomiting Syndrome in Children
https://www.jnmjournal.org/journal/view.html?uid=135&vmd=Full
Genetic association including A3243G mitochondrial DNA mutation was also suggested as the possible cause of CVS. […] Food allergy was also suggested as a possible pathogenesis of CVS by Lucarelli et al. in 2000. However, there have been no more studies on the relationship between CVS and food allergy; it is yet controversial.
#1 :: PGHN :: Pediatric Gastroenterology, Hepatology & Nutrition
https://pghn.org/DOIx.php?id=10.5223/pghn.2015.18.4.224
It has been hypothesised that central corticotrophin-releasing factor activation may play a role which may be involved in endocrine autonomic and visceral changes seen in these patients. […] Gene studies have shown association with two single nucleotide polymorphism (SNP) of mitochondrial DNA (mtDNA): 16519T and 3010A that adversely affect energy metabolism. […] Psychologically, emotional stress and anticipatory anxiety may trigger an episode. […] Triggering factors that may precipitate an episode include exposure to cold, allergies, sinus problems, emotional stress or excitement, anxiety or panic attack, intake of foods like chocolate or cheese, overeating, going to bed immediately after a meal, hot weather, physical exhaustion, menstruation or motion sickness.
#1 An Unusual Case: Cyclic Vomiting Syndrome (CVS) » in-Training, the online peer-reviewed publication for medical students
https://in-training.org/an-unusual-case-cyclic-vomiting-syndrome-cvs-875
The pathogenesis is unknown but some possible associations are present. Some patients may have a cycle of vomiting, abdominal pain and migraines. Some think that the vomiting leads to abdominal pain, which then leads to migraines, but this is not always present. […] Certain foods, such as chocolate and cheese, are inciting factors, as is cannabis use. Cessation of cannabis usually causes an episode of CVS to resolve. However, CVS is distinct from cannabis-induced emesis. In CVS, the patient has episodic vomiting, which may or may not be induced by smoking cannabis, and is symptom free between these episodes. In cannabis-induced emesis, the patient has daily emesis due to smoking cannabis.
#1 Cyclic vomiting syndrome – Symptoms & causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/cyclic-vomiting-syndrome/symptoms-causes/syc-20352161
Cyclic vomiting syndrome is characterized by episodes of severe vomiting that have no apparent cause. Episodes can last for hours or days and alternate with symptom-free periods. Episodes are similar, meaning that they tend to start at the same time of day, last the same length of time, and occur with the same symptoms and intensity. […] The underlying cause of cyclic vomiting syndrome is unknown. Some possible causes include genes, digestive difficulties, nervous system problems and hormone imbalances. Specific bouts of vomiting may be triggered by: […] Identifying the triggers for vomiting episodes may help with managing cyclic vomiting syndrome.
#1 Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) | Italian Journal of Pediatri
https://ijponline.biomedcentral.com/articles/10.1186/s13052-022-01346-y
Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder characterized by stereotypical and repetitive episodes of vomiting and intense nausea lasting between few hours and several days. […] Although our understanding of the pathogenesis of childhood CVS is still limited, several mechanisms have been postulated, including hypothalamic-pituitary-adrenal activation, autonomic dysfunction, polymorphisms of mitochondrial DNA, genetic abnormalities, neuronal hyperexcitability, and gastric dysmotility. […] Noteworthy, the high prevalence of both personal and family history of migraine, the effectiveness of anti-migraine therapy, the presence of mitochondrial DNA polymorphisms and the frequent developmental progression from CVS to migraine later in life suggest a common pathophysiologic process and, in turn, to consider CVS as a migraine-related or migraine-equivalent disorder.
#1 Cyclic Vomiting Syndrome: An Update Illustrated by a Case Report
https://www.psychiatrist.com/pcc/cyclic-vomiting-syndrome/
Cyclic vomiting syndrome is a disorder characterized by episodes of idiopathic vomiting alternated with periods of no symptoms. […] While the exact pathogenesis remains unknown, there seems to be an association between cyclic vomiting syndrome and migraine headaches and abdominal migraine. […] An underlying autonomic neuropathy (impairment of the sympathetic nervous system) has been suggested. […] Although dopamine is an important neurotransmitter in the treatment of vomiting and cyclic vomiting syndrome, pharmacologic treatment options with antipsychotics are hardly mentioned in the literature. […] Risperidone, in its unique combination with amitriptyline, might be an important alternative to achieve a satisfactory treatment result in refractory cases.
#1 Cyclic vomiting syndrome responding to amisulpride â A case report – Indian Journal of Physiology and Pharmacology
https://ijpp.com/cyclic-vomiting-syndrome-responding-to-amisulpride-a-case-report/
Amisulpride neurobiological mechanism in CVS remains unknown. Its antiemetic property could be one such mechanism. […] Amisulpride antiemetic action appears to be mediated by its potent D3 receptor antagonistic activity. […] Low dose of amisulpride may be a therapeutic approach for avoiding symptom of episodes in women with menstruation-related CVS.
#1 Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions
https://pmc.ncbi.nlm.nih.gov/articles/PMC6899706/
The role of genetic factors such as mitochondrial DNA, ion channels, neurohumoral function (endocannabinoid system and the hypothalamic-pituitary-adrenal axis), and neurogenic contributors in CVS development needs to be studied systematically. […] This comprehensive information base relating to CVS and CHS pathophysiology may identify new directions to pursue in treating these challenging conditions.
#1 Cyclic Vomiting Syndrome: Evolution in Our Understanding of a Brain-Gut Disorder
https://www.periodicos.capes.gov.br/index.php/acervo/buscador.html?task=detalhes&id=W3017225772
Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. […] Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. […] In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder.
#1
https://link.springer.com/article/10.1007/s00431-018-3218-7
Cyclic vomiting syndrome (CVS) in children is characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. […] The pathophysiology appears to involve aberrant brain-gut and cellular pathways including migraine pathways, autonomic and hypothalamic-pituitary-adrenal axis hyperreactivity, and mitochondrial dysfunction. […] This review extends the NASPGHAN Consensus Statement by reviewing recent literature and combining it with extensive clinical experience (1200 patients). […] The most prevalent comorbidity is anxiety that affects 47% of (59% of school-aged) children with CVS. […] Once viewed as simply a repetitive vomiting disorder, CVS appears to be associated with several comorbid symptoms and conditions, 3.1 per child. […] The concept of underlying mitochondrial dysfunction originates from findings of a strong matrilineal history of migraine, two highly associated mitochondrial single nucleotide polymorphisms (SNPs), and evidence of efficacy of coenzyme Q10. […] The future remains promising despite the ongoing challenges of management.
#2 Cyclic Vomiting Syndrome: Practice Essentials, Pathophysiology and Etiology, Epidemiology
https://emedicine.medscape.com/article/933135-overview
Cyclic vomiting syndrome (CVS), first described in children by Samuel Gee in 1882, is a chronic functional disorder of unknown etiology that is characterized by paroxysmal, recurrent episodes of vomiting. […] The pathophysiology is unknown, but data suggest a strong genetic component in children with CVS, with evidence of mitochondrial heteroplasmies that predispose to CVS and other related disorders (eg, migraine and chronic fatigue syndrome). […] Other theories include autonomic dysfunction and, possibly, corticotropin-releasing factor (CRF) because stress is known to be a trigger for these episodes. […] Mitochondrial DNA (mtDNA) mutations may be involved in the pathogenesis of CVS. […] The 16519T polymorphism is 6 times more common in pediatric CVS patients than in control populations.
#2 Cyclic vomiting syndrome: From pathophysiology to treatment | Revista de GastroenterologÃa de MÃ©xico
https://www.revistagastroenterologiamexico.org/en-cyclic-vomiting-syndrome-from-pathophysiology-articulo-S2255534X24000616
Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent and unpredictable episodes of intense vomiting, interspersed with periods of apparent wellbeing. […] The aim of the present review is to examine the most important aspects of the epidemiology, pathophysiology, subtypes, diagnostic criteria, and current management of CVS. Even though the exact etiology remains unknown, genetic factors (polymorphisms), nervous system alterations and autonomic dysregulation, and environmental factors (use and abuse of cannabinoids) are postulated as possible triggers. […] The proposed pathophysiologic mechanisms of CVS are (Fig. 1): Possible pathophysiologic mechanisms of CVS. Current data suggest that CVS is explained by a combination of genetic and host factors that lead to emesis. […] The endocannabinoid signaling system plays an important role in CVS.
#2 Cyclic Vomiting Syndrome: Practice Essentials, Pathophysiology and Etiology, Epidemiology
https://emedicine.medscape.com/article/933135-overview
The 3010A polymorphism increases the likelihood of CVS in subjects with 16519T by as much as 17 times. […] Sympathetic hyperresponsiveness and autonomic dysfunction also appear to contribute to the pathogenesis of CVS. […] The stress response, mediated by the hypothalamic-pituitary-adrenal (HPA) axis, can also potentially induce episodes of CVS. […] Therefore, CRF may be a brain-gut mediator of CVS that directly connects stress and vomiting. […] In conclusion, the pathogenesis of CVS is likely to be multifactorial, with multiple genetic, autonomic, central, and environmental factors playing a role. Further studies are needed to elucidate the exact mechanisms underlying this disorder.
#2 Cyclic vomiting syndrome: From pathophysiology to treatment | Revista de GastroenterologÃa de MÃ©xico
https://www.revistagastroenterologiamexico.org/en-cyclic-vomiting-syndrome-from-pathophysiology-articulo-S2255534X24000616
The autonomous nervous system plays an outstanding role in emesis. […] This observed dysregulation of the autonomous nervous system has implications in the treatment of CVS, such as vagal neuromodulation with percutaneous electrical nerve field stimulation, which improves symptoms, modulating the vagal function in patients with gut-brain axis gastrointestinal disorders and those with CVS. […] The fact that vomiting and retching during the emetic phase of CVS are mainly produced when the stomach is empty, implies that the allostatic feedback mechanisms are disordered, which could give rise to a reduced threshold for vomiting and retching, regardless of physiologic necessity or peripheral information. […] Neuronal hyperexcitability can be a common link between CVS and other central nervous system (CNS) disorders. […] The increasing understanding of the pathophysiology of CVS has brought about advances in its treatment.
#2 Cyclic vomiting syndrome: A GI primer | MDedge
https://www.mdedge.com/gihepnews/article/221281/mixed-topics/cyclic-vomiting-syndrome-gi-primer/page/0/1
The role of cannabis in the pathogenesis of symptoms in CVS is controversial. […] The use of cannabis has increased over the past decade with increasing legalization. […] Several studies have shown that 40%-80% of patients with CVS use cannabis. […] Following this, cannabinoid hyperemesis syndrome (CHS) was coined as a separate entity based on this statistical association, though there are no data to support the notion that cannabis causes vomiting. […] CHS has clinical features that are indistinguishable from CVS except for the chronic heavy cannabis use. […] A peculiar bathing behavior called âcompulsive hot-water bathingâ has been described and was thought to be pathognomonic of cannabis use. […] A small number of patients may sustain burns from the hot-water bathing. […] However, studies show that this hot-water bathing behavior also is seen in about 50% of patents with CVS who do not use cannabis.
#2 Cyclic vomiting syndrome responding to amisulpride â A case report – Indian Journal of Physiology and Pharmacology
https://ijpp.com/cyclic-vomiting-syndrome-responding-to-amisulpride-a-case-report/
Cyclic vomiting syndrome (CVS) is a functional illness with unknown cause defined by stereotyped repeated episodes of vomiting of acute onset and length (1 week) with three or more separate vomiting episodes in the previous year and absence of nausea and vomiting between episodes. […] In the afferent and efferent brain-gut axis of nausea and vomiting, CVS appears to involve dysregulated central neuronal circuits and neuroendocrine mediators. Autonomic, GI, central neuroendocrine and mitochondrial metabolic variables have been suggested to have additional pathogenic roles. […] The role of the endocrine system in the pathogenesis of CVS could be linked to the menstrual cycle. […] Tache believes that altered CRF receptor-mediated signalling is a crucial factor in causing emesis in CVS patients.
#2 Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions
https://pmc.ncbi.nlm.nih.gov/articles/PMC6899706/
Cyclic vomiting syndrome is, by definition, a syndrome with episodic bouts of uncontrollable vomiting, separated by periods of relative wellness. […] To better design mechanism-driven management approaches, it is essential that we elucidate the pathogenesis, clinical features, and disease associations in CVS. […] A viable CVS model must consider the diversity of attack triggers and the breadth of prodromal symptoms experienced at the onset of CVS episodes. […] It is useful to conceptualize its pathogenesis as resulting from the cumulative interaction of unique combinations of a number of distinct phenotypic processes and comorbid conditions leading to cyclical emesis. […] The similarity of CVS to other periodic disorders such as migraine and epilepsy offers clues about potential phenotypes that may lead to the development of CVS in adults.
#2 :: PGHN :: Pediatric Gastroenterology, Hepatology & Nutrition
https://pghn.org/DOIx.php?id=10.5223/pghn.2015.18.4.224
It has been hypothesised that central corticotrophin-releasing factor activation may play a role which may be involved in endocrine autonomic and visceral changes seen in these patients. […] Gene studies have shown association with two single nucleotide polymorphism (SNP) of mitochondrial DNA (mtDNA): 16519T and 3010A that adversely affect energy metabolism. […] Psychologically, emotional stress and anticipatory anxiety may trigger an episode. […] Triggering factors that may precipitate an episode include exposure to cold, allergies, sinus problems, emotional stress or excitement, anxiety or panic attack, intake of foods like chocolate or cheese, overeating, going to bed immediately after a meal, hot weather, physical exhaustion, menstruation or motion sickness.
#2 An Unusual Case: Cyclic Vomiting Syndrome (CVS) » in-Training, the online peer-reviewed publication for medical students
https://in-training.org/an-unusual-case-cyclic-vomiting-syndrome-cvs-875
The pathogenesis is unknown but some possible associations are present. Some patients may have a cycle of vomiting, abdominal pain and migraines. Some think that the vomiting leads to abdominal pain, which then leads to migraines, but this is not always present. […] Certain foods, such as chocolate and cheese, are inciting factors, as is cannabis use. Cessation of cannabis usually causes an episode of CVS to resolve. However, CVS is distinct from cannabis-induced emesis. In CVS, the patient has episodic vomiting, which may or may not be induced by smoking cannabis, and is symptom free between these episodes. In cannabis-induced emesis, the patient has daily emesis due to smoking cannabis.
#2 Efficacy of Coenzyme Q10 in the Treatment of Cyclic Vomiting Syndrome in Children
https://austinpublishinggroup.com/pediatrics-child-health-care/fulltext/jpchc-v6-id1038.php
Cyclic Vomiting Syndrome (CVS) is a chronic functional gastrointestinal disorder related to migraine, characterized by episodic nausea and vomiting. […] As mitochondriopathy has been involved in the pathophysiology of CVS, Coenzyme Q10 (CoQ10), a mitochondrial cofactor, has been used as the third line treatment in CVS. […] The rational for the efficacy of CoQ10 in CVS is based on the potential relations between CVS and mitochondrial disease and the link between migraine syndromes and mitochondrial abnormality is supported by multiple facts. […] CoQ10 is a mitochondrial electron-transport chain cofactor acting as a carrier of high-energy electrons from complex I and II to complex III. […] This could be the mechanism by which exogenous intake of CoQ10 can improve symptoms in mitochondrial myopathies or cardiomyopathies.
#2 Efficacy of Coenzyme Q10 in the Treatment of Cyclic Vomiting Syndrome in Children
https://austinpublishinggroup.com/pediatrics-child-health-care/fulltext/jpchc-v6-id1038.php
Our study demonstrates that CoQ10, used in monotherapy, can be efficient at a posology of 10-15mg/kg/day with a significant decrease of CVS episodes per year under treatment by CoQ10 with a median response rate of 78.85%. […] Considering the potential difficulty to give the treatment during the school time in children, some of our patients were taking CoQ10 bid during the school days and tid the other days. […] In our study, CoQ10 has 83% of response rate over 50% and 74% obtained a reduction of 70% and more. […] This means that CoQ10 is, at least, as efficient as most standard treatments with a much better safety profile. […] Mitochondriopathy cannot resume the pathophysiology of CVS, in our study, 2 patients were completely unresponsive, both of them have an important anxious personality and amitriptyline has been prescribed at the end of the study and was very efficient in these two cases. […] We think that, considering the level of efficacy associated to the excellent safety profile, CoQ10 should be the first line treatment in patients in whom the initial evaluation did not find anxiety or clear dysautonomic signs.
#2 Cyclic Vomiting Syndrome: An Update Illustrated by a Case Report
https://www.psychiatrist.com/pcc/cyclic-vomiting-syndrome/
Cyclic vomiting syndrome is a disorder characterized by episodes of idiopathic vomiting alternated with periods of no symptoms. […] While the exact pathogenesis remains unknown, there seems to be an association between cyclic vomiting syndrome and migraine headaches and abdominal migraine. […] An underlying autonomic neuropathy (impairment of the sympathetic nervous system) has been suggested. […] Although dopamine is an important neurotransmitter in the treatment of vomiting and cyclic vomiting syndrome, pharmacologic treatment options with antipsychotics are hardly mentioned in the literature. […] Risperidone, in its unique combination with amitriptyline, might be an important alternative to achieve a satisfactory treatment result in refractory cases.
#2 Cyclic vomiting syndrome responding to amisulpride â A case report – Indian Journal of Physiology and Pharmacology
https://ijpp.com/cyclic-vomiting-syndrome-responding-to-amisulpride-a-case-report/
Amisulpride neurobiological mechanism in CVS remains unknown. Its antiemetic property could be one such mechanism. […] Amisulpride antiemetic action appears to be mediated by its potent D3 receptor antagonistic activity. […] Low dose of amisulpride may be a therapeutic approach for avoiding symptom of episodes in women with menstruation-related CVS.
#2 Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions
https://pmc.ncbi.nlm.nih.gov/articles/PMC6899706/
The key to developing effective, personalized treatments for CVS hinges on recognizing disease triggers and mechanisms and raising the individual threshold for developing symptoms. […] In order to develop targeted CVS therapies, future research needs to define CVS subtypes based on mechanistic definitions, rather than solely on symptom criteria. […] Neuronal hyperexcitability may represent a common link between CVS and other episodic CNS disorders. […] The specific neural circuits for nausea and vomiting within higher centers of the brain are beginning to be elucidated using functional imaging methods in human subjects. […] It is possible that neuronal hyperexcitability and a lowered threshold to trigger specific patterns of neural activity within these cortical and subcortical circuits are pathogenic features of CVS.
#2 Cyclic Vomiting Syndrome: Recognition and Guidelines for Treatment | UPMC Physician Resources
https://www.upmcphysicianresources.com/news/011822-cyclic-vomiting-syndrome
CVS is characterized by four phases. […] Sympathetic nervous system activation likely contributes to CVS pathogenesis, and CVS episodes are typically accompanied by tachycardia, dizziness, salivation, and paleness of the skin. […] These similarities suggest a common neurogenic etiology and, moreover, suggest that patients with CVS could benefit from trials of therapies that are currently available for the treatment of migraines, seizures, or panic disorder. […] The guidelines are a fundamentally important tool for the recognition of CVS by primary care and emergency medicine physicians and for getting patients the diagnosis and treatment required to mitigate CVS. […] CVS is treatable in most patients with drugs that are widely available and known to be well-tolerated. Guidelines are available to help non specialists catch and care for patients with CVS who respond readily to standard treatments.
#3 Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions
https://pmc.ncbi.nlm.nih.gov/articles/PMC6899706/
Cyclic vomiting syndrome is, by definition, a syndrome with episodic bouts of uncontrollable vomiting, separated by periods of relative wellness. […] To better design mechanism-driven management approaches, it is essential that we elucidate the pathogenesis, clinical features, and disease associations in CVS. […] A viable CVS model must consider the diversity of attack triggers and the breadth of prodromal symptoms experienced at the onset of CVS episodes. […] It is useful to conceptualize its pathogenesis as resulting from the cumulative interaction of unique combinations of a number of distinct phenotypic processes and comorbid conditions leading to cyclical emesis. […] The similarity of CVS to other periodic disorders such as migraine and epilepsy offers clues about potential phenotypes that may lead to the development of CVS in adults.
#3 :: PGHN :: Pediatric Gastroenterology, Hepatology & Nutrition
https://pghn.org/DOIx.php?id=10.5223/pghn.2015.18.4.224
It has been hypothesised that central corticotrophin-releasing factor activation may play a role which may be involved in endocrine autonomic and visceral changes seen in these patients. […] Gene studies have shown association with two single nucleotide polymorphism (SNP) of mitochondrial DNA (mtDNA): 16519T and 3010A that adversely affect energy metabolism. […] Psychologically, emotional stress and anticipatory anxiety may trigger an episode. […] Triggering factors that may precipitate an episode include exposure to cold, allergies, sinus problems, emotional stress or excitement, anxiety or panic attack, intake of foods like chocolate or cheese, overeating, going to bed immediately after a meal, hot weather, physical exhaustion, menstruation or motion sickness.
#3 Cyclic vomiting syndrome responding to amisulpride â A case report – Indian Journal of Physiology and Pharmacology
https://ijpp.com/cyclic-vomiting-syndrome-responding-to-amisulpride-a-case-report/
Amisulpride neurobiological mechanism in CVS remains unknown. Its antiemetic property could be one such mechanism. […] Amisulpride antiemetic action appears to be mediated by its potent D3 receptor antagonistic activity. […] Low dose of amisulpride may be a therapeutic approach for avoiding symptom of episodes in women with menstruation-related CVS.
#4 :: PGHN :: Pediatric Gastroenterology, Hepatology & Nutrition
https://pghn.org/DOIx.php?id=10.5223/pghn.2015.18.4.224
It has been hypothesised that central corticotrophin-releasing factor activation may play a role which may be involved in endocrine autonomic and visceral changes seen in these patients. […] Gene studies have shown association with two single nucleotide polymorphism (SNP) of mitochondrial DNA (mtDNA): 16519T and 3010A that adversely affect energy metabolism. […] Psychologically, emotional stress and anticipatory anxiety may trigger an episode. […] Triggering factors that may precipitate an episode include exposure to cold, allergies, sinus problems, emotional stress or excitement, anxiety or panic attack, intake of foods like chocolate or cheese, overeating, going to bed immediately after a meal, hot weather, physical exhaustion, menstruation or motion sickness.
#5 :: PGHN :: Pediatric Gastroenterology, Hepatology & Nutrition
https://pghn.org/DOIx.php?id=10.5223/pghn.2015.18.4.224
It has been hypothesised that central corticotrophin-releasing factor activation may play a role which may be involved in endocrine autonomic and visceral changes seen in these patients. […] Gene studies have shown association with two single nucleotide polymorphism (SNP) of mitochondrial DNA (mtDNA): 16519T and 3010A that adversely affect energy metabolism. […] Psychologically, emotional stress and anticipatory anxiety may trigger an episode. […] Triggering factors that may precipitate an episode include exposure to cold, allergies, sinus problems, emotional stress or excitement, anxiety or panic attack, intake of foods like chocolate or cheese, overeating, going to bed immediately after a meal, hot weather, physical exhaustion, menstruation or motion sickness.
#6 :: PGHN :: Pediatric Gastroenterology, Hepatology & Nutrition
https://pghn.org/DOIx.php?id=10.5223/pghn.2015.18.4.224
It has been hypothesised that central corticotrophin-releasing factor activation may play a role which may be involved in endocrine autonomic and visceral changes seen in these patients. […] Gene studies have shown association with two single nucleotide polymorphism (SNP) of mitochondrial DNA (mtDNA): 16519T and 3010A that adversely affect energy metabolism. […] Psychologically, emotional stress and anticipatory anxiety may trigger an episode. […] Triggering factors that may precipitate an episode include exposure to cold, allergies, sinus problems, emotional stress or excitement, anxiety or panic attack, intake of foods like chocolate or cheese, overeating, going to bed immediately after a meal, hot weather, physical exhaustion, menstruation or motion sickness.
#7 :: PGHN :: Pediatric Gastroenterology, Hepatology & Nutrition
https://pghn.org/DOIx.php?id=10.5223/pghn.2015.18.4.224
It has been hypothesised that central corticotrophin-releasing factor activation may play a role which may be involved in endocrine autonomic and visceral changes seen in these patients. […] Gene studies have shown association with two single nucleotide polymorphism (SNP) of mitochondrial DNA (mtDNA): 16519T and 3010A that adversely affect energy metabolism. […] Psychologically, emotional stress and anticipatory anxiety may trigger an episode. […] Triggering factors that may precipitate an episode include exposure to cold, allergies, sinus problems, emotional stress or excitement, anxiety or panic attack, intake of foods like chocolate or cheese, overeating, going to bed immediately after a meal, hot weather, physical exhaustion, menstruation or motion sickness.