Review
Epilepsy
and
physical
exercise
Jose´ Pimentel
a,*
,
Raquel
Tojal
b,
Joana
Morgado
caLaboratoryofNeuropathology,Epilepsy,Clinic,DepartmentofNeurology,FacultyofMedicineoftheUniversityofLisbon,HospitaldeSantaMaria,Lisbon,
Portugal
bDepartmentofNeurology,HospitalProf.Dr.FernandoFonseca,Amadora,Portugal c
DepartmentofNeurology,HospitaldosCapuchos,CentroHospitalardeLisboaCentral,Lisbon,Portugal
1. Introduction
The practice of physical exercise by persons with epilepsy (PWE)hasbeenamatterofdebateforhealthprofessionalsdealing withthisdisease,andofconcernforthepatientsthemselvesand familiesandcaregivers.Aquestionfrequentlyaskedisifexercise could result in an increase of the seizures. As physicians themselveswereunabletoproperlycounselPWE,theyhavebeen discouragedfromparticipatinginphysicalactivitiesorsports.PWE mustdealwithmanysocialandculturalstigmas,sothatrestricting physicalactivitycontributestofurtherlimitationstoanormaland healthylife.
SomesurveysperformedinthelastdecadeshowedthatPWE perceivetheirhealthaspoorandexerciselessthanthepopulation withoutepilepsy.1–3Additionally,asampleof176PWEfollowed
forameanof35 yearspresenteda significantlypoorerphysical fitnessthanmatchedcontrols,eveniftheyhadafeelingofgood personalhealth.4Guidelinestophysicalactivityissuedbymedical
organizationsarescarceandgeneral,althoughthereappearstobe a recent shift toward encouraging rather than restricting participation.Finally,articlesinneuroscienceoreveninepilepsy journalsaremainlybasedonsmallgroupsandsometimestheyfail toprovideadequateandupdatedinformationtothoseinchargeof takingcareofthispopulation.
This article presentsand discusses someof themain issues relatedtophysicalexerciseandepilepsyaimingtoproviderecent informationtoenableguidanceofPWEonthissubject.
2. Generalaspectsofepilepsy
Currently, epilepsy is defined as a disorder of the brain characterizedbyanenduringpredispositiontogenerateepileptic seizures, and by neurobiological, cognitive, psychological, and socialconsequencesofthiscondition.5Thenon-clinicalpartofthis
definitionshouldbekeptinmind.Stigmahasbeendescribedas‘‘a distinguishingmarkof disgrace’’or‘‘an attributethat is deeply discrediting’’, and PWE still carry the burden of psychosocial stigmatization, in both developed and developing countries.6
Thesemayincludelowerincome,poorerqualityoflife,lowratesof marriage and of employment, and, for children, lower school
ARTICLE INFO
Articlehistory: Received29June2014
Receivedinrevisedform24September2014 Accepted26September2014 Keywords: Epilepsy Physicalexercise Risks Benefits Comorbidities ABSTRACT
Epilepsyisoneofthecommonestneurologicdiseasesandhasalwaysbeenassociatedwithstigma.Inthe interestofsafety,theactivitiesofpersonswithepilepsy(PWE)areoftenrestricted.Inkeepingwiththis, physicalexercisehasoftenbeendiscouraged.Theprecisenatureofaperson’sseizures(orwhether seizureswereprovokedorunprovoked)maynothavebeenconsidered.Althoughtherehasbeena changeinattitudeoverthelastfewdecades,theexactroleofexerciseininducingseizuresoraggravating epilepsystillremainsamatterofdiscussionamongexpertsinthefield.Basedmainlyonretrospective, butalsoonprospective,populationandanimal-basedresearch,thehypothesisthatphysicalexerciseis prejudicialhasbeenslowlyreplacedbytherealizationthatphysicalexercisemightactuallybebeneficial forPWE.Thebenefitsarerelatedtoimprovementofphysicalandmentalhealthparametersandsocial integrationandreductioninmarkersofstress,epileptiformactivityandthenumberofseizures.
Nowadays,thegeneralconsensusisthatthereshouldbenorestrictionstothepracticeofphysical exerciseinpeoplewithcontrolledepilepsy,exceptforscubadiving,skydivingandothersportsat heights. Whilst broader restrictionsapply forpatients with uncontrolled epilepsy, individual risk assessmentstakingintoaccounttheseizuretypes,frequency,patternsortriggersmayallowPWEto enjoyawiderangeofphysicalactivities.
ß2014BritishEpilepsyAssociation.PublishedbyElsevierLtd.Allrightsreserved.
* Correspondingauthor.Tel.:+351217959329. E-mailaddress:josepimentel@fm.ul.pt(J.Pimentel).
ContentslistsavailableatScienceDirect
Seizure
j o urn a lhom e pa g e :ww w . e l se v i e r. c om / l oca t e / y se i z
http://dx.doi.org/10.1016/j.seizure.2014.09.015
attendanceandpoorperformance,amongmanyothers.6–8Another
importantissueisthecomorbidconditions,ofwhichpsychiatric and behavioral problems are the most frequent (2–60%).7 In
addition,approximately40% of children and adolescentssuffer fromcognitivedelay,speech/languagedisabilitiesorotherspecific learning disabilities, eitherdue tothe primary disease causing epilepsyortotheassociatedtreatment.
Despitethesehandicaps,moreandmorePWEallovertheworld arechoosing to carry out physical activity or practicesport. It should also be remembered that children have compulsory physical education in school and therefore limiting them to practicesportswillreducetheirself-esteemandsocialintegration.
3. Doesphysicalactivityworsenepilepsy?
DiscouragingphysicalactivityinPWEhasbeenthenormuntil themidseventies. TheAmericanMedicalAssociation (AMA),in 1968,recommended restricting the activity of PWE for fear of injuryorofinducingseizureactivity.9Duetoraisedcontroversy,
AMA,in1974,permittedtheparticipationincontactsportsif‘‘to dosoisconsidered a majoramelioratingfactor inthepatient’s adjustmenttoschool,associates,andtheseizuredisorder’’.10
ItisofimportancetodistinguishbetweenthosePWEexercising aspartof a healthy lifestyle from those whomake sport their profession. The number and the intensity of eventual seizure precipitatingfactorsinvolvedinbothsituationsvaryandthismust betakenintoaccountwhencounseling.
3.1. Precipitatingfactors
Potentially,manyseizureprecipitatingfactorsexistinrelation tophysicalexercise, fatigue,stress,repeatedheadinjuryduring contact sports, excessive aerobic exercise, hyperventilation, changes in the metabolism of antiepileptic drugs (AEDs), and ionic/metabolic disturbances.8,11,12 In general, seizures seem to
rarelybetriggeredbyphysicalactivity.Inastudyencompassing 400 PWE,onlytwo wereable toidentifyphysical activityas a precipitant.13Nolinkhasbeenestablishedbetweenpostexercise
fatigueandincreasedseizurefrequency.8Stresshasbeenidentified
as a seizure trigger in a considerable number of patients, suggesting that intense athletic activity may increase sei-zures.8,11,13Inaddition,physicalstressandneurosteroidsappear
tobelinkedinepilepsy.Inresponsetostressinducedbyphysical exercise,it hasbeen demonstrated,both in humanand animal models,thattheactivationofthehypothalamic–pituitary–adrenal axisaffectsadrenalsteroidsandneurosteroidsandincreasesthe seizure susceptibility.13 However, the same stress may also activate hypothalamiccorticotrophin-releasing hormone, which inturnstimulatesdeoxycorticosteroneproductionintheadrenal gland. Increased levels of allotetrahydrodeoxycorticosterone synthesizedintheliverandbrainbycirculating deoxycorticoster-one activates GABAA receptors in certain brain regions, with
decreasedseizuresusceptibility.13Furtherstudiesareneededto
elucidate theexact roleof thephysical stress inthe controlof seizures.
Itiswellknownthathyperventilationatresttriggersabsence seizures;thereforeonemightassumethatthesamewouldapply duringexercise.Howeverduring exercise, hyperventilationis a physiological response to an increased metabolic demand, a compensatory response to prevent hypercapnia. On the other hand,restinghyperventilationleadstohypocapniaand vasocon-striction.Furthermore, exercise-inducedhyperventilation, as an adaptivereactiontoacidosis, mayevenproducesuppressionof interictal abnormalities.11,12 Therefore, hyperventilation during
exerciseappearstodeterseizureonset.
Exerciseisthoughttoincreaseliver-enzymemetabolismandso couldalsoincreasethemetabolismofseveralAEDs,particularly the‘‘oldgeneration’’ones.14Greaterdrugclearanceand
competi-tion for protein (albumin) binding sites are factors that may accountforadecreaseintheirserumlevels.11Aprospectivestudy ontheeffectofphysicaltrainingonserumlevelsofAEDs,however, failedtoshowanycorrespondentdecreaseorabnormalityofthe metabolismrate.15Anotherstudyshowedonlyslightvariationsin
serum levels, especially for phenytoin (small decrease) and valproic acid and phenobarbital (small increase) between the exerciseand pre-exerciseperiods, not statistically relevantand withnorepercussiononseizurefrequency,asitwasasmallsample conclusionsmustbedrawnwithcaution.14Despitethis
contra-dictory evidence, we would only recommend checking serum levelsofAEDsinPWEpracticingsportswhenclinicallyindicated. Finally, hypoxia (mainly altitude-related), hyperhydration, hyperthermia, hypoglycemia and hyponatremia are all distur-banceslinkedtophysicalactivityandknowntotriggerseizures, although, at least some of them, may correspond to acute symptomatic seizures.12 There are no studies showing a link
between thesemetabolic disturbancesand theincrease of true epilepticseizures,northatPWEaremoresusceptibletothemthan athleteswithoutepilepsy.8 However, it is alsotrue that robust
studieshavenotyetbeencarriedout.
3.2. Influenceofthetypeofphysicalexercise
There is no evidence in literature that minor head trauma exacerbatesseizures,implyingthatcontactsportsarenotharmful forPWE.11,16Onlyafewcasesofseizuresoccurringduringfootball
have been identified, perhaps wrongly attributed to excessive physicalactivity,althoughonereporthaslinkedseizurestoblows totheheadandmostoftheheadinjuriessufferedduringphysical exerciseare somild that it is highly unlikely that theyinduce epilepsy.11,16
Althoughaerobicexercisehasbeenreportedtotriggerseizures, thishasnothadasignificantimpactbecausepatientsthemselves aresoonabletorecognizetheassociationandavoidtheactivityif necessary.11,17A small studysubmittedpatients withtemporal
lobe epilepsy tomaximal/exhaustive exerciseand showedthat none experiencedseizures during or after exercise.18 Interictal epileptiformactivitiesusuallyremainunchangedorevendecrease duringorimmediatelyafterexercise,eveninthosepatientswith exercise-related seizures.15 There areother clinical and animal reports pointing to thebenefit of aerobic exercise in reducing seizure frequency.14,19,21,22 This reduction both in number of
seizuresandepileptiformdischargesduringexercise(aerobicand anaerobic)isthoughttobedue,amongotherfactors,toamental activationthatsuppressestheepileptiformactivity.23
ANorwegianstudywasdevisedtocomparetheexercisehabits in asample of204outpatientswithepilepsy(bettercontrolled epilepsy than inpatients) with those of age and sex matched controlsinthegeneralpopulation,andtostudyphysicalexercise asaseizureprecipitantandtheriskofsustainingseizure-related injurieswhileexercising.24PWEwithanyneurologicimpairment
or disability were excluded. In accordance with the general impression, the proportion of individuals not exercising was significantlyhigherinthepatientgroup.Ofthosewhodidexercise, thepatternofexercisewassimilartothecontrols.Abouthalfofthe patientshadneverexperiencedseizureswhileexercising.Among those who did experience seizures, about 10% claimed to experiencethem inmorethan10%ofthetrainingsessions,but only 2% of these had ‘‘genuine’’ exercise-induced seizures (arbitrarilydefined ashavingseizuresin morethan 50%of the training sessions). In addition, structural epilepsies (with no preferentiallocalization)predominatedinthegrouppronetohave
exercise-inducedseizures,themajoritycomplexpartialseizures withorwithoutsecondarygeneralization.Mostoftheseseizures occurred during strenuous exercise (ball games, jogging and hiking),neverthelessthismaybeduetothefactthatthesearethe mostpopularsports in Norway. Hence,for themajority of the patients,physicalactivityhadnoadverseeffects,anda consider-able proportion (36%) claimed to experience better epilepsy controlwithregularexercise.However,itmustbekeptinmind thattheconclusionswerebasedonaself-reportedquestionnaire andtheanswersmaynotreflectthepatientstrueactivitiesand experiences.
Therefore,itseemsthataerobicexercisecanberecommended, for the majority of PWE, if each individuals experience and limitationsaretakeninaccount.
4. Risksassociatedwithphysicalexercise
Themainconcernsregardingepilepsyandphysicalexerciseare theinductionofseizuresandinjuriessecondarytothemduring physicalactivity.25
Basedonprospectiveandretrospectivestudies,itisconsidered thatpersonswithepilepsyhaveahigherriskofinjuries.26These
can be of various types, the most common being minor head injuries generally derived from a seizure; minor head injuries themselvesdonotprovokeepilepsy.Inthepreviouslymentioned Norwegianstudyofthe45%whoreportedinjuriesassociatedwith seizuresduring exercisemost(94%) hadminorinjuries (mainly soft tissue injuries). In a prospective study by Nakken and Lossius,27with 62 PWE withsevere therapy-resistant epilepsy,
only1.2%ofseizuresprovokedinjuries,themostcommonbeing headtrauma,submersioninjuries,burnsandfractures,thelastalso assumedtobeaconsequenceofmineralizationlosssecondaryto certainAEDs(inparticularcytochromep450inducers).26Although
thesestudiesdidnotspecificallyaddressinjuriesoccurringduring physical exercise, they concluded that PWE should not be forbiddenfrom participatinginsports simply toavoid possible injuries,andshouldinsteadbestimulatedtodoso.26
Te´llez-Zenteno et al.28 performed a population based study
comparingtheoccurrenceofinjuriessevereenoughtointerferein normalactivitiesinadolescentsandadultswithepilepsyandthe generalpopulationandthesituationsweretheseoccurred.There was no statistical difference between the number of injuries reportedinbothgroupsand theonlydifferencefoundwasthat amongthegeneralpopulationtheinjuriesoccurredmoreduring sportsactivitiescomparedtoPWE.Forbothgroupsmostinjuries occurredathome,andforPWEcommercialareasfollowedit.Soin thisstudytheideathatPWEareathigherriskofinjuriesduring sports seenin many studies that are basedon morerestricted epilepsypopulationswasnotconfirmed.28
Itgoeswithoutsayingthattheriskofseizuresandassociated injuriesisratherelevatedinpatientswithuncontrolledepilepsy with primarily or secondarily generalized seizures and high seizurefrequencyaswellasinthosewithmulti-handicapsand mentalretardation.26Inthesecases,thereisahigherriskofhaving
aseizureduringeithernormaldailyactivitiesorphysicalexercise, howeverasconcludedinmoststudiesthemostcommontypeof injuryrelatedtoseizuresaresoft-tissueinjuries.26Some factors precludealowerriskofinjuriesduringactivitiesasseizuresthat occurmainlyatnightandthosewithpreviousaura.26
Thetype of seizures is alsoimportant when recommending physicalexerciseandtherisksassociatedwithit.Sometypesof seizures preclude a higher risk of injury then others. Namely generalized tonic-clonic and atonic seizures that can induce unprotected falls. In the case of seizures with disturbance of consciousness(absenceandcomplexpartialseizures)thepatient losesawarenessofthesurroundingsandmightbyattheriskof
losingbalanceorbeinghitbyaballorothersportsparticipants. Simplepartialseizuresaretheoneslesslikelytoinduceinjurydue totheretainedconsciousnessandbriefduration.11
5. Factorsthatinfluencephysicalexerciseadherence
Ina selectedgroupofin-patientswithuncontrolledepilepsy althoughaccesstosportsfacilitieswasnota problemthegreat majorityleadasedentarylifestyleandthereasonsgivenforthat werelackofinterestin physicalexercise,fatigueresultingfrom medication,fearofseizures/injuries,lackofinstructorsandlackof driverslicense.Howevertheauthorsconsiderthatthisgroupmay notberepresentativeofthegeneralPWEpopulation.30
InasmallCanadianstudywhichcomparedthesedentaryand sportsactivitiesbetweenchildren/teenswithepilepsy(cognitively normal)andtheirsiblingswithoutepilepsy(similarages)basedon parentalandchildren/teens appliedqualitative questionnairesa statistically significant difference between teens (not children) withepilepsyandtheirsiblingswasfound,havingthefirstalesser amountoftimespentintotalsportsandingroupsportsactivities. Onlyatrendwasfoundconcerninghigherseizurefrequency(at least one seizure every three months) and decreased total participationin sports. Theteens(withepilepsy) lesseractivity didnotseemtocorrelatewithparentalrestrictionsbutratherto lack ofinterestor laziness.No differenceswerefoundbetween physicalactivitylevelsbetweenchildrenwithepilepsyregarding presenceofgeneralizedtonic-clonicseizuresintheprecedingyear ortheetiologyofepilepsy.31
Anotherstudy,32basedonaself-reportquestionnaire,triedto
determine the adherence to exercise in an adult, cognitively normal cohort ofPWE and tofindout thebarrierstoexercise. Seventy-eightpercentoftheparticipants(totalof193)reported havingsomekindofphysicalactivity,mainlywalking.However, duetothefrequency,durationandintensitythemajoritydidnot qualify ashaving anactive lifestyle. A small percentage(15%) thoughtofincreasedseizuresinrelationtoexercise.Thebarriersto exercisedetermined,beyondtheonesalsopresentinthegeneral population (lack of motivation, time), were personal safety concerns (19%), fear of seizures (19%) and access to facilities (18%). Worth mentioning was also the fact that most of the participantswereunemployedorretiredandhadlowerincomes which might influence adherence to more structured physical activities.
A third study33 alsousing questionnaires but additionallya clinicalevaluation selected136outpatientsandcomparedtheir habitsandviewsaboutexercisewithcontrols.Thisstudydiffered fromthepreviousinthenumberofsubjectsbutalsointhefactthat morethanhalfofthemhadcontrolledepilepsy.Theresultsshowed thatbothgroupsthoughtthatsportswerepositiveandsuitablefor PWE butonly 25% ofthepatients in comparisonto42% ofthe controlsperformedsportsregularly,andsurprisinglymostofthe patients preferred swimming and bicycling. The most frequent reason for inactivity wasthediseaseitself, however in a more recentstudythediseasewasconsideredasphysicallylimitingby only twopercent ofthepatients but 68%of thesesubjectshad discontinuedAEDsandwereseizurefree.4Althoughnopatienthad
beenadvisedagainstthepracticeofsportsbyteachersorsports instructorsandonlysixhadbeenforbiddenofexercisingbytheir doctorsorrelatives.However41%ofthepatientsfearedhavinga seizure during sports and 40% were afraid of seizure related injuries. Worth noticing was the fact that around 45% of the patientshadnevertalkedwiththeirdoctorsaboutthepracticeof sportsandrecommendations.33Aridaetal.34studiedtheexercise habitsofBrazilianpatientsandfoundsimilarresults.For84%(of 100patients)noseizureshadoccurredduringphysicalactivities, and 85% did not believe that exercise precipitated seizures.
However,45%wereafraidofhavingseizuresduringexerciseand makingfoolsoutof themselves,15% werenotallowedby their physicianstoengageinphysicalactivities,andrelativesorfriends discourageditin14%.Mostofthepatientspreferredengagingin individualphysicalactivities.
A Canadian study that assessed the exercise habits of individuals12–39 yearsold foundthat therewasno difference betweenPWEandpersonswithoutepilepsyinthemonthlyleisure exercise frequency. However, the exercise profiles did differ, walkingbeingthemostcommonamongPWE.35
6. RecommendationsregardingsportsparticipationforPWE
In1997,andforthelasttime,theILAECommissionReport36 changeditspreviouspolicyonexerciseandchildrenwithepilepsy. It was considered difficult to determine guidelines regarding exerciseforallchildrenwithepilepsy,thereforerisksandbenefits wouldhavetobeweighedseparatelyineachcase.Nevertheless,it was deliberated that most of these children should only have restrictionsiftheyhadpoorlycontrolledepilepsy,inthefirst2–3 monthsafterafirstuntreatedseizure,andduringthefirstmonths afterAEDswereinitiatedordiscontinued.Sportslikescubadiving and skydivingwerethe onlyones that shouldbeavoided, and others such as horseback riding, motor sports, and sports performedat heights werepermittedwithcaution, considering thepotential risk to thepatients themselves and to others. In general,webelievethattherestrictionsandassessmentsproposed forchildrencanbeextrapolatedforolderPWE.
TheAmericanAcademyofPediatrics(AAP)publishedapolicy statementin 2008,reviewing previous statements, in which it deliberatedthatchildrenwithcertainmedicalconditionsshould havelimitationsinsportingactivities.Forchildrenwithepilepsy withcontrolledseizurestherewereno limitationsandforthose withpoorlycontrolledseizuresanindividualassessmentshouldbe made in order to protect them from self-injury or injury to others.37
7. Higherrisksports
Throughouttheliterature,sportsthatinvolvemotorvehicles, heights(includingskydiving)andscubadivingduetothereknown associatedrisksarenotadvisedforpeoplewithepilepsy.8Thelegal
considerationsineachcountryconcerningdrivingalsohavetobe takenintoaccountinrelationtomotorsports.
Recommendations to avoid water sports are due to the associatedriskofdrowningduringaseizure.Theconclusionsof thestudiesonthissubjectvaryowingtodifferentpopulationsand different methodologies of analysis. The determined risk of drowningrangesfromthatofthegeneralpopulation toaround 4timesorhigherindifferentstudies.Diekemaetal.38underwenta
population-basedcohort studythat analyzed epilepsyas a risk factorforsubmersionanddrowningdeathamongchildren.Based on 336 non-intentional submersion incidents they found that children with epilepsy (CWE) had a relative risk of 13.9 for submersion and 13.8 for drowning compared to non-epileptic children.Bathtubswerethefirstandswimmingpoolsthesecond mostcommonsiteofsubmersion.Nodifferencebetweenthetwo groupswasfoundforotherbodiesofwaterandtheriskwasalways higherforCWEfiveyearsofageorolder.Accordingtothisstudy, and removing the CWE with additional handicap, the risk of submersion and drowning of CWE was approximately 10-fold, especially in older children and when there was no direct supervisionofCWEeveninsupervisedpools.Theyconsiderthat theirdatasupportstheconclusionthatCWEcanswimsafelywith constant supervision, because although submersion accidents occur in a greater proportion,death and major injuries canbe
prevented.38Therecommendationremainsthatswimmingshould
take place in supervised facilities, in which supervisors are informed that the swimmer has epilepsy and supervise PWE constantly,sothatin theeventofsubmersionaccident prompt cardioresuscitationinterventionispossible.24,25,39,40
In2008ameta-analysisontheriskofdrowninginPWEwas published. According to the 51 cohorts analyzed, death by drowning constituted 5% of all deaths in the studies and the calculated standardized mortalityratio was18.7,theratio was higherforPWEwithlearningdisabilities,peopleininstitutionsfor epilepsyandaftertemporallobeexcision.Basedontheirdatathey consideredthattheyshowedthatPWEhada15–19foldincreased risk of death due to drowning compared with the general population, beingthis risk lowerin children, probably because theyaremoresupervised.Howeverthismeta-analysisevaluates articlesthatapproachthegeneralcausesofdeathinPWEandnot exclusively deaths due to drowning occurring during water physical activities, so it is not possible to transport these observationstothepracticeofsports.Neverthelessone assump-tionisuseful,thefactthatPWEshouldbeunderdirectsupervision when bathing or swimming because in these cases death is avoidablewhenthenecessaryprecautionsaretaken.41
Aridaetal.12consideredthatactivitiestobeavoidedinpeople
withepilepsywerescubadiving,motorracing,varioussportsat heights(parachuting,high-altitudeclimbing,gliding,handgliding) andaviation.Also,whendecidingwhetherornottopracticesports thecrucialfactorwasthebalancebetweenitspotentialrisksand benefitstoeachpatient,becausegeneralizationsinthisgroupof patientsaredifficulttocreate.
In 2007, a review on thecontraindication of scuba diving42
focusedonthepossiblephysiologicalalterationsthatcouldoccur inthissetting(decompressionsickness,oxygentoxicity,nitrogen narcosis),andon thepossiblerisktothepatientandthediving buddy(whocouldsufferfromdecompressionsicknessintheneed of rapid ascent). It concluded that, although the risk of death associated withdivingwasgreater in theseindividuals, ifthey wereseizurefreeforaminimumof4years,theriskofhavinga seizurewhiledivingwasminimal.However,thiswasanempirical conclusion with no substantial studies backingit up. Notwith-standing,takingintoaccountthepossiblesedativeeffectofsome antiepilepticmedication,peoplewhoreporthavingsedation,asa sideeffectshouldnotdivebecauseitcouldincreasethepossibility ofnitrogennarcosis.Thus,itremainsanindividualdecision,and thephysicianshouldexplainthepossiblerisksevenifthepatientis seizurefreeforfouryearsormore,astherealwaysremainsthe possibility of havinga seizure. In general, scuba diving is still contraindicatedbyepilepsyandsports committees/associations. For example,accordingtothedivingmedicalcommittee ofthe UnitedKingdomSports,apersonwithepilepsyispermittedtodive whenhereachesa periodoffiveyearsseizurefreeandwithout medication;iftheseizuresareduringthenightonly,athree-year periodisrequired.43
Besides the risk of seizures during sports in persons with diagnosed epilepsy, there is also the questionwhether certain sports associated injuries can induce epilepsy. In the case of boxing, studies of amateur boxers demonstrated that head concussionswereminorand didnotresultin neurophysiologic or clinical signs of epilepsy. A sports practitioner can have a concussiveconvulsionasaresultofaminorconcussionbutthisisa limitedeventintimeanddoesnotprovokeepilepsy.11
8. Doesphysicalactivitybenefitepilepsy?
Overtheyears,manybasicandclinicalinvestigationshavebeen developedtostudythebenefitsofphysicalactivityonepilepsy. Theseinvestigationsencompasstheinfluenceofphysicalactivity
inpreventingandcontrollingepilepsyandreducingcomorbidities directlylinkedtothispathology.
8.1. Theroleinepilepsyprevention
Positive results have been found in basic research about physicalactivityasaprimarypreventiontothedevelopmentof epilepsy.Exercisecanreducebraincelllossorneuronaldamage secondarytobraininsultsinanimal studies.20Onestudyabout
physical exercise during post-natal brain development in rats showedthatwhentheyweresubmittedtodailyexerciseforforty daystheypresenteda delayedonset andareduced intensityof pilocarpine-induced motor symptoms during midlife.44 The
kindling modelof epilepsyinduced by repeatedadministration of a subconvulsive stimulus into a limbic structure has been frequentlyusedinanimalstudiesofphysicalexercise.12Theeffect
of acute and chronic physical exercise was evaluated on the developmentofamygdalakindling,showingthatmorestimulus werenecessarytoprovokeseizuresinratssubmittedtoexercise thancontrols.12Neurotransmittersplayanimportantrolehereas
they are influenced by exercise. Noradrenaline appears to be increasedinratssubmittedtophysicaltraining,ithasaninhibitory effectonthedevelopmentofkindling,anditsdepletionfacilitates thepropagationofepileptiformactivityofhippocampalkindling.12
The possible preventive effects of exercise on epilepsy in humansarestilluncertain.ThereisonlyonestudyinaSwedish population-basedcohortof6796individualsfollowedthrougha periodof40 years examiningthisissue.47Itwasobservedthat subjectswho presentedlowcardiovascularfitnessattheageof 18hadanincreasedriskofbeingdiagnosedwithepilepsylaterin life, and this association remained after adjusting for several potential confounders. However, other variables that could influence this association were not analyzed, and the sample was only made up of males. Despite its limitations, thestudy suggests that physical exercise at an early age may have a protectiveeffectonthelaterdevelopmentofepilepsybybuilding neuralreserves,butmoreepidemiologicandprospectivestudies areneededtoconfirmthishypothesis.
8.2. Theinfluenceinseizureinductionandcontrol
Thepilocarpinemodelofepilepsyisanexperimentalmodelin ratsoftemporallobeepilepsyinhumans.Ratswith pilocarpine-induced epilepsy submitted to a physical training program presented a lower frequency of spontaneous seizures than controls.19,20,46,48,49 A very low probability of exercise-induced
seizures was found and no sudden death occurred while exercising.Evenstrengthtraining(climbingserieswith progres-sivelyheavierload)improvedseizurefrequency.50Otheranimal
modelsofepilepsy(penicillin,pentylenetetrazol,kainicacid)have shownsimilarpositiveresults.51–53Althoughthesestudiesreveal
importantdata,theycannotbetranslatedreadilytohumans. PWEwhopracticeregularlyphysical exercisetendtoreport fewerseizuresthaninactiveones.25Nevertheless,clinical
investi-gation presentsseveral limitations, such as lackof appropriate controlsandthepresenceofpotentialconfounders,like compli-ance tophysical exercise and toAEDs therapy.48 Some human researcheshavebeenmoresuccessfulthanothers.Nakkenetal.14
studied twenty-one patients with uncontrolled epilepsy submitted to aerobic physical exercise for four weeks, and no differencebetweenseizurefrequencytwoweeksbefore,during,or twoweeksaftertheexerciseprogramwasfound.Hence,physical activityseemednottorepresentanimportantseizure-inducing factor, a fact also demonstrated in a randomized controlled studywithtwenty-threepatients duringatwelveweekaerobic exercise program.54 Another study with fifteen women with
pharmacologically intractable epilepsy submitted to aerobic activityforfifteenweekspresentedadecreaseinseizurefrequency duringtheexerciseperiod.55Inadditiontoaerobicexercise,the
effectofmaximalphysicaleffortwasalsostudied.Inasampleof sixteen patients withtemporallobe epilepsy, no onepresented seizuresafteranexhaustivephysicalexercise.18Similarfindings
wereobservedinnineteenPWEsubmittedtoacardiopulmonary exercise test where a decrease in the number of epileptiform dischargeswasseenbetweentherestandtheexercisestateand betweentherestandrecoverystate.56Arelatedstudyinjuvenile
myoclonicepilepsyfoundasignificantreductioninthenumberof epileptiformdischargesduringrecoverystatecomparedwiththe restingone.57
Ingeneral,andaccordingtoAridaetal.inarecentreviewof antiepileptogenicandneuroprotectiveeffectsofexerciseinclinical andexperimentalmodelsofepilepsy,physicalactivityseemsnot tobe a seizure-inducingfactor but indeedprovidebenefit asa complementarytherapyforepilepsy.20,21
8.3. Theeffectinepilepsycomorbidities
Theeffectofphysicalexerciseinreducingcomorbiditiesrelated toepilepsyisnotascontroversial.Nevertheless,wehavetokeepin mindthatthesecomorbiditiesareinterconnectedtoeachother.
MentalhealthdisordersaremorefrequentlyfoundinPWEthan in general population, and they include psychoses, mood and personality disorders, and behavioral problems.58–60 A higher
prevalence of suicidal ideation in PWEwas reported aswell.59 WithinthepsychiatriccomorbiditiesinPWE,depressionseemsto bethemostfrequentone,butotherpsychologicalproblemssuch asanxietyandstressarealsofrequentlyreported.58,61–63Mental health disorders in epilepsy result from the interplay of neurobiologic,iatrogenic (AEDsor epilepsysurgeryeffects) and psychosocialmechanisms.64Inaneurobiologicview,itisknown
that both epilepsy and mood disorders share dysfunctions in neurotransmitter systems (serotonin, noradrenaline, dopamine, glutamateandGABA),whichmightcontributetotheircoexistence and bidirectional relationship.22,65,66 It seems important to
managethesedisordersinadditiontoseizuremanagementwhen treating PWE.64,65 Research on physically healthy adults has
consistentlyshownanemotionalwellbeingassociatedtoaregular exerciseprogram.25Thetherapeuticeffectofexercisetrainingon
depressioninPWEhasbeenstudiedwithpromisingresults.Some explanations for that consist in the increase and regulation of neurotransmittersystemsinvolvedindepressionphysiopathology andothercomorbiditiesimprovementthatcaninfluence depres-sion.22 PWE who practice exercise present lower levels of depressionindependentlyofotherfactorslikeage,gender,seizure frequency or stressful life experience.25,55,60 Nakken et al.14
recordedabeneficialeffectinmentalstate,self-esteemandsocial integrationafterfourweeksofintensivephysicaltrainingprogram. Eriksen et al. showed that women with intractable epilepsy exposedtoexercise(aerobicdancingwithstrengthtraining and stretching)forfifteenweeksdidnotpresentsignificantchangesin anxietyanddepressionscales.However, therewasasignificant reduction in overall health complaints, like fatigue and sleep problems.55 A randomized controlled study for twelve weeks documentedanimprovementintheexercisearmformood, self-esteem and quality of life measured by self-administered questionnaires.54Depressionseemsto mediatetherelationship between stress and anxietyand tochangeseizure frequency.65
Thereisevidencethatpeoplehavingregularphysicalactivitycope better with stressful situations, thus minimizing the seizures inducedbypsychologicalstress.13Hence,it seemsimportantto
proposearegularandappropriateprogramofexercisetoPWEin ordertoavoidortreatdepressionassociatedwithepilepsy.
StudiesofmentalhealthdisordersinPWEcanbeconfounded by multiple factors, like AEDs therapy, psychosocial, familial, socioeconomicandintellectualeffects.67
Obesity is another common comorbidity found in PWE associatedtolowself-confidenceandthatcanbeimprovedwith physicaltraining.1–3,68,69Animalandhumanstudiesshowedthat
animalsandPWEpresentahigherbodymassindexthanhealthy ones.34,69 Overweight is frequently associated to AEDs and
sedentarybecauseofthefear ofexerciseinduce-seizures.22,32,70
Generalizedepilepsy,idiopathicsyndromeand familyhistoryof epilepsyseemtorepresentsomefactorsassociatedwithobesityin thesepatients.68Likeinhealthypeople,PWEcanbenefitofweight
andbodyfatreductionwithphysicaltraining,aswellasriskfactors reductionfordiabetes,hypertension,obesityandcoronaryheart disease.12,14,71
Vitamin D metabolism is another factor affected by AEDs leadingtoareducedbonedensity.22,72,73Indeed,PWEpresenta
biggerpredispositiontofracturesthanthegeneralpopulation.58,74 TheexactmechanismsbywhichAEDsaffectbonearchitectureare notfullyunderstood.72Abonemineraldensityscreeningaswellas
anosteoprotectivebehaviorisbeingpromotedinPWEthroughan individualbasis.75Nutritionalsupplementation,dietandphysical
exercisearesomeofthemethodstopreventosteoporosis.Inthe generalpopulation,itiswellknownthatphysicalactivityinduces osteoprotection.Indeed,itwillincreasebonegrowthinwidthand mineral content in girls and female adolescents, but also in postmenopausalwomen,carriedoutinvolumesandatintensities seeninathletes,withagreathormonalinfluenceandaccompanied byadequatecaloricandcalciumintakes.22,76,77Themainsports
associatedtothisissuearethosethatinvolverunningandjumping (likesoccer,basketball,volleyball,tennis,running,weightlifting, gymnastic).76InPWE,experimentaldataaboutexercisetoprevent
and treat bone loss are still lacking.22 Nevertheless, it is
recommendedtopatientsofallagesasabonehealthprotector. In summary, even though the role of physical activity in preventingandcontrollingepilepsyand itscomorbiditiesisnot always clear, exercise programs should be encouraged as a complementarytherapyforPWEduetoitsprovenbenefits.
9. Recommendations
Some onlinesitescounselingPWEproviderecommendations regardingdifferentsportactivities,andmostarequiteliberalinthe
sportsrecommended.EspeciallyforPWEwithcontrolledepilepsy, however,thereisstillsomeconflictingopinionsregardingmore controversial physical activities, like sky diving, scuba diving, waterskiing,climbing,handgliding,orboxingandothercontact sports.
Mostconsiderthatwatersportsshouldalwaysbeperformed underatrainedsupervisor,withalifejacket,andthatswimming shouldbedoneinsupervisedpools.78
Some consider that restrictions for persons with complex partialortonic-clonicseizuresareneededevenwhenpreceded bywarningsforsportslikeskydivingandscubadiving.Amore radicalpositionisthe onenot recommendingitin generalfor PWE because they are life-threatening in case of a seizure occurrence.79–83Whilesomedonotlimitparticipation,othersdo
not recommend orcounselcaution for thepracticeof combat sportslikeboxingormartialartsthatmayinvolveblowstothe head. Nevertheless,asseen intheliterature fromstudieswith boxersandothersportsthatmightinvolveconcussions,mostof thesearemildanddonotprecludethedevelopmentofepilepsy nor do theyaggravate a preexistingepilepsy.79–83 Takinginto
account the articles reviewed, there seems to be currently a general consensus thatsports andphysical activity, excluding scuba diving, skydiving and solo hand gliding, should be encouraged to all PWE with controlled epilepsy (seizure free for more thanone year). Forhigher risksports like climbing, cycling,horseback-riding,watersportsandswimming, snorkel-ing, among others, PWE should practice them with a friend/ relative,orunderclosesurveillanceofsomeonewhoknowsthat thepersonhasepilepsyandhowtodealwiththeoccurrenceofa seizure. For those not well controlled, limitations should be appliedaccordingtotheseizuretypeandtheparticularsportor physical activity to beperformed, alwaysafter discussing the risks,benefitsandsportspossibilities,andtheneedforsuitable protectiveequipmentwiththeassistantphysicianandwiththe sportsprofessional.
Thepracticeofsportsisstillanindividualchoiceanddecision becausenoguidelinesareavailableaccordingtoeach particular frequencyortypeofseizuresandAEDsintake.However,thosethat continuehavingseizuresonlyatnight,oralwaysprecededbyan auraallowingtheactivityarrestshouldhavelesslimitationsthan thosewithmyoclonic,atonic,absence,complexpartialor tonic-clonic seizures. Rice and the Council of Sports Medicine and Fitness37elaboratedguidanceforclinicians,includingthosewho
Table 1
Sportrecommendations.8,11,36,37,84
Swimmingandwatersports Alwaysswiminsupervisedpoolswithdirectsupervisionoftrainedprofessionals(cardiopulmonaryresuscitationtraining)thatare awareoftheconditionofthesportspractitioner.
Donotswiminunsupervisedopenwaters.
Alwayswearalife-vestwheninaboat,whenwater-skiingoranyothersimilarsport(sportsnottobeundertakenalone),avoid thesesportsinuncontrolledepilepsy.
Scubadivingisgenerallynotrecommended.
Sportsatheights Hand-gliding,parachuting,sky-divingarenotrecommended;horseback-ridingpermittedifundersupervisionastherapy;therisk forcertainsports(bicycling,gymnasticsatparallelbarsorinvolvingacrobaticactivities,rockclimbing)shouldbeassessedforthose withcontrolledepilepsya
andtherecommendationistoperformthemwiththenecessarysafetyequipmentandnotalone.For cyclingavoidanceofbusyroadsisalsorecommended.
Notrecommendedforthosewithuncontrolledepilepsy. Motorsports Noformalrestrictionsifepilepsyiscontrolleda
andaccordingtothedrivingregulationsofeachcountry,howeverthesafetyof othersandnotonlyofthePWEshouldbeaccountedfor.
Notrecommendedforthosewithuncontrolledepilepsy.
Shootingsports ForPWEwithcontrolledepilepsythetypeofseizuresandtypeofweaponshouldbeevaluated. Notrecommendedforthosewithuncontrolledepilepsy.
Contactsports Generallyrecommendedwiththeexceptionofboxing,asportforwhichnogeneralconsensushasbeenreachedonwhetheritis harmfulornottoPWE.
Aerobicsports(e.g.:running, basketball,stationarybike, aerobics,gymnasticsnot involvingheights)
Norestrictionswiththeuseofappropriatesafetyequipmentwhenadvised.
a
treatCWE, andtheydo notrecommendspecial precautionsfor those withcontrolled epilepsy. For theones withuncontrolled seizures,anindividualassessmentforcollision,contactor limited-contactsports,andavoidanceofarchery,swimming,weightlifting, powerlifting,strengthtraining andsportsinvolvingheightsare recommend.
ForPWEtherearegeneralrecommendationsforeachtypeof sports(Table1),whichshouldbeusefulwhenassessingindividual patients.
10. Conclusions
People with chronic diseases including epilepsy, should be encouraged to exercise, as should the general population. The mentalandphysicaladvantagesofregularexerciseareregardedas highlybeneficialtoagroupthatisnormallysedentary,overweight andwithhigherratesofdepression.Sportsmedicineprofessionals shouldhave an understanding of epilepsy syndromes,types of seizures,medications,whattodowhena seizureoccursduring sports practice,the effectof physical exerciseon seizures, and whenrestrictionsareappliedtothepracticeofsports.
However,literatureonthissubjectisstillscarceandmostofthe studiespresentedinthisreviewwerebasedonasmallnumberof patients.Furthermore,agoodproportionofthedatacollectedand analyzedwasbasedonquestionnairesconstructedbytheauthors withqualitative measurementsand relying onlyon patients or relative’sreports,thoughwithoutclinicalconfirmationorbasedon clinicalreports collected retrospectively.Therefore,other,more robust,controlled,randomizedstudiesonepilepsyandphysical exercisearedeemedinordertoprovidebasisforphysicianstogive informedcounselingonthissubject.
General physicians, neurologists and pediatricians should support the practice of regular physical exercise and inform patientsandcaregiversaboutthebenefitsassociatedwithphysical activityand thenecessaryprecautions,like protectivegear.For handicappedpatients,betteraccesstoexercisefacilities andan appropriate exercise program ought to be provided. An effort shouldbemadetoreducethestigmaassociatedwithepilepsy,so thatqualityoflifeofpeoplewithepilepsycancontinueimproving.
Conflictofinterests
Noneoftheauthorshasanyconflictofinteresttodisclose.
Acknowledgements
TheauthorswanttothankDr.MrinaliHonavarforhertechnical assistanceinwritingthemanuscript.
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