Cluster Headache_ Background, Pathophysiology, Etiology

10/7/2015 ClusterHeadache:Background,Pathophysiology,Etiology

http://emedicine.medscape.com/article/1142459overview#showall 1/5

ClusterHeadacheAuthor:MichelleBlanda,MDChiefEditor:TarakadSRamachandran,MBBS,FRCP,FRCPCmore...

Updated:Apr08,2014

BackgroundClusterheadache(CH),alsoknownashistamineheadache,isaprimaryneurovascularprimaryheadachedisorder,thepathophysiologyandetiologyofwhicharenotwellunderstood.[1]Asthenamesuggests,CHinvolvesagroupingofheadaches,usuallyoveraperiodofseveralweeks.AccordingtothediagnosticcriteriadevelopedbytheInternationalHeadacheSociety(IHS),CHhasthefollowingcharacteristics[2,3]:

Thepatientexperiencesattacksofsevereorverysevere,strictlyunilateralpain(orbital,supraorbital,ortemporalpain)thatlast15180minutesandoccurfromonceeveryotherdayto8timesadayTheattacksareassociatedwith1ormoreofthefollowing(allipsilateral):conjunctivalinjection,lacrimation,nasalcongestion,rhinorrhea,foreheadandfacialsweating,miosis,ptosis,oreyelidedema

CHmaybeusefullyclassifiedinto2mainformsasfollows:

EpisodicCH,inwhichatleast2clusterphaseslasting7daysto1yearareseparatedbyaclusterfreeintervalof1monthorlongerChronicCH,inwhichtheclustersoccurmorethanonceayearwithoutremissionortheclusterfreeintervalisshorterthan1month

Pathophysiology

TheunderlyingpathophysiologyofCHisincompletelyunderstood.[4,5]Theperiodicityoftheattackssuggeststheinvolvementofabiologicclockwithinthehypothalamus(whichcontrolscircadianrhythms),withcentraldisinhibitionofthenociceptiveandautonomicpathwaysspecifically,thetrigeminalnociceptivepathways.Positronemissiontomography(PET)andvoxelbasedmorphometryhaveidentifiedtheposteriorhypothalamicgraymatterasthekeyareaforthebasicdefectinCH.[1]Seetheimagesbelow.

Clusterheadache:Functionalimagingshowsactivationofspecificbrainareasduringpain.CourtesyofWikipediaCommons.



Clusterheadache(CH):Voxelbasedmorphometry(VBM)structuralimagingshowsspecificbrainareaofCHpatients'(hypothalamus)beingdifferenttononCHpatients'brains.CourtesyofWikipediaCommons.

Alteredhabituationpatternsandchangeshavebeenobservedwithinthetrigeminalfacialneuronalcircuitrysecondarytocentralsensitization,inadditiontodysfunctionoftheserotonergicraphenucleihypothalamicpathways(thoughthelatterisnotasstrikingasinmigraine).FunctionalhypothalamicdysfunctionhasbeenconfirmedbyabnormalmetabolismbasedontheNacetylaspartateneuronalmarkerinmagneticresonancespectroscopy.[6]

SubstancePneuronscarrysensoryandmotorimpulsesinthemaxillaryandophthalmicdivisionsofthetrigeminalnerve.Theseconnectwiththesphenopalatineganglionandinteriorcarotidperivascularsympatheticplexus.SomatostatininhibitssubstancePandreducesthedurationandintensityofCH.

VasculardilatationmayplayaroleinthepathogenesisofCH,butbloodflowstudiesareinconsistent.Extracranialbloodflow(hyperthermiaandincreasedtemporalarterybloodflow)increases,butonlyaftertheonsetofpain.Vascularchangeisconsideredsecondarytoprimaryneuronaldischarge.

Althoughtheevidencesupportingacausativeroleforhistamineisinconsistent,clusterheadachesmaybeprecipitatedwithsmallamountsofhistamine.Antihistaminesdonotabortclusterheadaches.Increasednumbersofmastcellshavebeenfoundintheskinofpainfulareasofsomepatients,butthisfindingisinconsistent.

EtiologyTheexactcauseofCHisunknown.Thedisorderissporadic,thoughrarecasesofanautosomaldominantpatternwithinasinglefamilyhavebeenreported.

SeveralfactorshavebeenshowntoprovokeCHattacks.Subcutaneousinjectionofhistamineprovokesattacksin69%ofpatients.Stress,allergens,seasonalchanges,ornitroglycerinmaytriggerattacksinsomepatients.Alcoholinducesattacksduringaclusterbutnotduringremission.About80%ofCHpatientsareheavysmokers,and50%haveahistoryofheavyethanoluse.

RiskfactorsforCHincludethefollowing:

MalesexAgeolderthan30yearsSmallamountsofvasodilators(eg,alcohol)Previousheadtraumaorsurgery(occasionally)

EpidemiologyTheexactprevalenceofCHintheUnitedStatesisunknownKudrowestimatedittobe0.4%inmenand0.08%inwomen.[7]Comparedwithclassicmigraine,CHisrelativelyuncommon,withanincidenceequivalenttoonly29%ofthatofmigraine.Prevalenceinmalesis0.41%.Inanextensivestudyof100,000inhabitantsoftherepublicofSanMarino,theprevalencewas0.07%.TheincidenceofCHintheUnitedKingdomisequivalenttothatofmultiplesclerosis.

Age,sex,andracerelateddemographics

CHusuallybeginsinmiddleadultlife(eg,inthe30s)however,ithasbeenreportedinpatientsasyoungas1yearandasoldas79years.

CHismorecommoninmalesthaninfemalesthemaletofemaleratiowas6:1inthe1960sbutisnowcloserto2:1.Presentationsinfemalesmaydifferfromthoseinmales,accordingtodatafromtheUnitedStatesClusterHeadacheSurvey.[8]Forexample,womentendtodevelopCHatanearlierageandarealsomorelikelytoexhibitasecondpeakofCHincidenceaftertheageof50.

Racialandethnicdifferenceshavenotbeenwellstudied,butCHmaybeslightlymoreprevalentinAfricanAmericansandmaybeunderdiagnosedinblackwomen.

PrognosisGenerally,CHisalifelongproblem.Potentialoutcomesincludethefollowing:



RecurrentattacksProlongedremissionsPossibilityoftransformationofanepisodicclustertoachronicclusterandviceversa

About80%ofpatientswithepisodicCHmaintaintheepisodicformofthedisorder.In413%,episodicCHeventuallytransformsintochronicCH.Intermediate(mixed)formsmayalsodevelop.Prolonged,spontaneousremissionsoccurinasmanyas12%ofpatients,particularlyinthosewithepisodicCH.ChronicCHismorerelentlessandmaypersistinthisforminasmanyas55%ofcases.Lessfrequently,chronicCHmayremitintoanepisodicform.

NoreportedmortalityisdirectlyassociatedwithCH.However,patientswithCHareatincreasedriskforselfinjuryduringattacks,suicideattempts,alcoholuse(andotherformsofsubstanceabuse),cigarettesmoking,andpepticulcerdisease.Suicideshavebeenreportedincaseswhereattacksarefrequentandsevere.TheintensityoftheattacksoftenleadsCHpatientstomisstimefromactivitiessuchasworkorschool.Medicationsusedmayhavesideeffects,includingtheunmaskingofcoronaryarterydisease.

PharmacologicinterventionmayplayapartinthetransformationofchronicCHintotheepisodicformotherwise,itdoesnotinfluenceoutcome.Lateonsetofthedisorder,malesex,andpreviousepisodicCHallpredictalessfavorablecourse.

PatientEducationPatientsshouldbeeducatedregardingtheneedtoavoidknownprecipitantsofCH.Inaddition,theyshouldbeinstructedtoavoidhighaltitudes.

Forpatienteducationresources,seetheHeadacheCenter,aswellasCausesandTreatmentsofMigraineandRelatedHeadaches,ClusterHeadache,AlternativeandComplementaryApproachestoMigraineandClusterHeadaches,ClusterHeadacheFAQs,andUnderstandingMigraineandClusterHeadacheMedications.

ClinicalPresentation

ContributorInformationandDisclosuresAuthorMichelleBlanda,MDChairEmeritus,DepartmentofEmergencyMedicine,SummaHealthSystemAkronCity/StThomasHospitalProfessorofEmergencyMedicine,NortheasternOhioUniversitiesCollegeofMedicine

MichelleBlanda,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofEmergencyPhysicians,SocietyforAcademicEmergencyMedicine

Disclosure:Nothingtodisclose.

Coauthor(s)RimaMDafer,MD,MPH,FAHAAssociateProfessor,DepartmentofNeurologyandNeurologicalSurgery,LoyolaUniversity,ChicagoStritchSchoolofMedicine

RimaMDafer,MD,MPH,FAHAisamemberofthefollowingmedicalsocieties:AmericanAcademyofNeurology,AmericanHeartAssociation,AmericanHeadacheSociety


ChiefEditorTarakadSRamachandran,MBBS,FRCP,FRCPCProfessorEmeritusofNeurologyandPsychiatry,ClinicalProfessorofMedicine,ClinicalProfessorofFamilyMedicine,ClinicalProfessorofNeurosurgery,StateUniversityofNewYorkUpstateMedicalUniversityNeuroscienceDirector,DepartmentofNeurology,CrouseIrvingMemorialHospital

TarakadSRamachandran,MBBS,FRCP,FRCPCisamemberofthefollowingmedicalsocieties:AmericanCollegeofInternationalPhysicians,AmericanHeartAssociation,AmericanStrokeAssociation,AmericanAcademyofNeurology,AmericanAcademyofPainMedicine,AmericanCollegeofForensicExaminersInstitute,NationalAssociationofManagedCarePhysicians,AmericanCollegeofPhysicians,RoyalCollegeofPhysicians,RoyalCollegeofPhysiciansandSurgeonsofCanada,RoyalCollegeofSurgeonsofEngland,RoyalSocietyofMedicine


AcknowledgementsJosephCarcioneJr,DO,MBAConsultantinNeurologyandMedicalAcupuncture,MedicalManagementandOrganizationalConsulting,CentralWestchesterNeuromuscularCare,PCMedicalDirector,OxfordHealthPlans

JosephCarcioneJr,DO,MBAisamemberofthefollowingmedicalsocieties:AmericanAcademyofNeurology


StevenCDronen,MD,FAAEMChair,DepartmentofEmergencyMedicine,LeConteMedicalCenter

StevenCDronen,MD,FAAEMisamemberofthefollowingmedicalsocieties:AmericanAcademyofEmergencyMedicineandSocietyforAcademicEmergencyMedicine


RagasriKumar,DOResidentPhysician,DepartmentofNeurology,LoyolaUniversityMedicalCenter


EdwardAMichelson,MDAssociateProfessor,ProgramDirector,DepartmentofEmergencyMedicine,UniversityHospitalHealthSystemsinCleveland

EdwardAMichelson,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofEmergencyPhysicians,NationalAssociationofEMSPhysicians,andSocietyforAcademicEmergencyMedicine




LoriKSargeant,MDConsultingStaff,SummaEmergencyAssociates,Inc

LoriKSargeant,MDisamemberofthefollowingmedicalsocieties:AlphaOmegaAlpha,AmericanCollegeofEmergencyPhysicians,andOhioStateMedicalAssociation


FranciscoTalavera,PharmD,PhDAdjunctAssistantProfessor,UniversityofNebraskaMedicalCenterCollegeofPharmacyEditorinChief,MedscapeDrugReference

Disclosure:MedscapeSalaryEmployment

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Cluster Headache_ Background, Pathophysiology, Etiology

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