Prolonged Atrial Fibrillation Precipitated by New-Onset Seizures and Marijuana Abuse

abstractWe report a case of prolonged atrial fibrillation (AF) precipitated bynew-onset generalized tonic–clonic convulsions and marijuana abusein a developmentally normal 18-year-old adolescent with a structurallynormal heart. Our case highlights an interesting association anda unique pathophysiology between generalized tonic–clonic convul-sions, marijuana abuse, and AF. We suggest that seizures and mari-juana abuse should be considered in the differential diagnosis of theetiology of AF in children. Pediatrics 2014;133:e443–e446

AUTHORS: Dinesh Singh, MBBS, MD, DCH, MargaretHuntwork, MD, Varun Shetty, Gina Sequeira, andOlugbenga Akingbola, MD

Division of Pediatric Critical Care, Department of Pediatrics,Tulane University School of Medicine, New Orleans, Louisiana

KEY WORDSPICU, adolescents, seizures, arrhythmia, drug abuse

ABBREVIATIONSAF—atrial fibrillationED—emergency departmentGTCC—generalized tonic–clonic convulsion

Drs Singh and Huntwork conceptualized and designed the study,drafted the initial manuscript, and reviewed and revised themanuscript; Dr Akingbola carried out the initial analyses; MrShetty, Ms Sequeira, and Dr Huntwork coordinated andsupervised data collection and critically reviewed themanuscript; and all authors approved the final manuscript assubmitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2013-1831

doi:10.1542/peds.2013-1831

Accepted for publication Aug 29, 2013

Address correspondence to Dinesh Singh, MBBS, MD, DCH,Division of Pediatric Critical Care, Department of Pediatrics,Tulane University School of Medicine, New Orleans, LA 70112.E-mail: dsingh@tulane.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2014 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicatedthey have no potential conflicts of interest to disclose.

PEDIATRICS Volume 133, Number 2, February 2014 e443

CASE REPORT

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Marijuana is one of themost commonlyabused illicit drugs among young peo-ple in the United States, and it accountsfor 61% of admissions for drug abusetreatment under age 15 years and for56% between 15 and 19 years of age.Research shows that ∼9%, or ∼1 in 11,of those who use marijuana at leastonce will become addicted. This rateis 16%, or ∼1 in 6, in those who startusing the drug in their teenage years.The addiction rate is 25% to 50% amongdaily users.1 Marijuana use has beenassociated with serious cardiovascu-lar complications, including acute an-gina, myocardial infarction, ventriculararrhythmias, and a few cases of atrialfibrillation (AF) in young adults.2,3

Similarly, peri-ictal cardiac rhythm ab-normalities are common and mostlyinclude sinus tachycardia or occasion-ally bradycardia. Rarely, lethal rhythmabnormalities such as ventriculartachycardia, prolonged QT abnormali-ties, and asystole can occur, leading toserious consequences including sud-den unexplained death in epilepsy.4–6

Although a few cases of hemodynamically

stable AF have been reported as a resultof generalized tonic–clonic convulsions(GTCCs) in adults with structurally nor-mal hearts, there are no such data in thepediatric or adolescent age group. Wereport a hemodynamically stable ado-lescent with a structurally normal heartwho developed AF in the setting of GTCCsand marijuana abuse.

CASE REPORT

An 18-year-old previously healthy youngman presented to the emergency de-partment (ED)with 2 new-onset, afebrileGTCCs. The 2 seizures occurred 21 hoursapart, both early in the morning whilethe patient was sleeping. Both seizureswere witnessed, each lasting for ∼10minutes, and each time, the patient felloff the couch on which he was sleeping.

The patient stated that his “heart beganfeeling weak” after the first seizure. Henoted transient left leg numbness and1 episode of emesis after the secondseizure. He denied aura, palpitations,and bladder and bowel incontinence. Hedenied any history of seizures or syn-cope and stated that he had been in his

usual state of health with the exceptionof a mild cough for the past 2 weeks.

According to the emergency responseteam, thepatientwaspostictal, afebrile,and hemodynamically stable at homeandon arrival at the ED. Hewas noted tohave an irregular heart rate of 85 to 96beatsperminute,with abloodpressureof 115/80 mm Hg and an oxygen satu-ration of 99% on room air. Otherwise,his physical examination was benign,and a thorough review of systems wasnegative. He had no significant pastmedical history. Family history wasnoncontributory. He also admitted tonightly marijuana use the week beforethe seizures and occasional alcoholand cigarette use.

A 12-lead electrocardiogram was per-formed that confirmed AF (Fig 1), anda loading dose of anticonvulsant ther-apy with levetiracetam was given in theED. He was transferred to the PICU withthe diagnoses of new-onset GTCC, mar-ijuana abuse, and AF.

Laboratory studies including completeblood count, complete metabolic panel,serummagnesium, phosphate, troponin

FIGURE 1Electrocardiogram before cardioversion.

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I, thyroid studies, coagulation profile,lipid panel, antistreptolysin O titers, se-rum alcohol levels, viral studies, cul-tures, and basic autoimmune workupwere within normal limits. Urine drugscreen was positive for marijuana.Myoglobin and creatinine kinase weremildly elevated secondary to seizures.Urine mass spectroscopy was negative.Arterial blood gas was within normallimits, with pH = 7.42, PaO2 = 100, PaCO2 =38, bicarbonate = 22, and Base DeficitBD20.5.

A transesophageal echocardiogram id-entified no anatomic abnormalities orthrombi. The size of the right ventriclewas reported to be 1.5 cm, and the es-timated right ventricle systolic pressurewas 32mm Hg.MRI of the brain revealeda 1.73 1.0 cm nonenhancing abnormalintensity in the subcortical left frontalgray matter suggestive of heterotopicgray matter possibly mild cortical dys-plasia. (Figs 2 and 3). EEG demonstratedno evidence of seizure activity.

The patient remained in documented AFfor at least 6 hours before admission tothe PICU. Electrical cardioversion wasperformed, which resulted in normalsinus rhythm. Maintenance anticonvul-sant therapy with levetiracetam wasinitiated. There was no recurrence ofeither seizures or AF during the patient’sstay in the PICU. However, the patient leftagainst medical advice after 24 hours ofPICU stay and did not attend scheduledfollow-up appointments.

DISCUSSION

AF in a child with a structurally normalheart is extremely rare. A large Aus-tralian pediatric ED study over 6.5 yearsshowed that the incidence of pediatricarrhythmias was 11.5 in 10 000 ED vis-its, and more than half of them weresupraventricular tachycardias, whichoccurred with an incidence of 6.5 in10 000 ED visits. AF occurred in 0.2 in10 000 ED visits, and all these childrenhad structural heart disease.7 Common

and uncommon causes of AF are listedin Table 1.

On the other hand, seizures are the mostcommon pediatric neurologic disorder,with ∼150 000 children presenting witha first-time, unprovoked seizure eachyear.8 Depending on the duration and thefrequency, the seizures can be associatedwith various complications that includehypoxemia, hypercapnia, hypotension orhypertension, acidosis, rhabdomyolysis,acute renal failure, apnea, brady-tachyarrhythmias, and death.9

AF secondary toGTCC iswell recognized inadults, but the data in the pediatric pop-ulation are sparse. The exact mechanism

ofAFsecondary toseizures isnotclearlyunderstood. The possible mechanismsmay include a sudden catecholaminesurge and simultaneous sympatheticand parasympathetic (sympathovagal)discharge.10,11 Prolonged GTCC and toa lesser extent complex partial seizuresresult in a sudden surge in circulatingplasma norepinephrine and epineph-rine levels by 12 and 40 times, respec-tively. Factors such as hypoxia furtherincrease these levels.12

The heart is richly innervated by boththe extrinsic (sympathovagal) and theintrinsic cardiac nervous system (in-tracardiac specialized ganglia), par-ticularly around the pulmonary veins,and these areas are thought to be thefoci of AF in structurally normal hearts.Imbalances in the sympathovagal dis-charges greatly influence the atrialelectrophysiological properties actingvia these specialized ganglia. Thus, AFappears to be vagally mediated inyoung patients without structuralheart disease and sympatheticallymediated in subjects with structuralheart disease.10,13 At the cellular level,

FIGURE 2MRI (brain) showing a 1.7 3 1.0 cm non-enhancing abnormal intensity in the subcorticalleft frontal gray matter, suggestive of hetero-topic gray matter.

FIGURE 3MRI (brain) coronal fluid attenuated inversionrecovery.

TABLE 1 Causes of AF

Structural heart diseaseMitral valve diseaseHypertrophic cardiomyopathyDilated cardiomyopathyRestrictive cardiomyopathyMyocarditisPericarditisHypertensionSevere pulmonary hypertensionWolff–Parkinson–White syndromeExcessive alcohol intakeOpen heart or thoracic surgeryPulmonary embolismHyperthyroidismMetabolic syndromeObesityObstructive sleep apneaExerciseAnger and hostilityHornet stingDengue hemorrhagic feverElectrical shockSubclinical atherosclerosis and geneticpredisposition

Cardiac tumors

CASE REPORT

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tachycardia associated with simulta-neous sympathovagal discharge resultsin accumulation of intracellular calciumand significant shortening of actionpotential duration. High intracellularcalcium then causes activation of thesodium–calcium exchanger, which re-sults in triggered activity and rapidheart rate, culminating in rhythm ab-normalities including AF.14

We think that frequentmarijuana abuseand GTCC probably increased the riskof AF in our patient. The consequencesof marijuana abuse on the cardiovas-cular system are caused primarily byD9-tetrahydrocannabinol mediated viacannabinoid CB1 and CB2 receptors.These effects vary depending on theroute of administration, the prepara-tion of cannabis, and the D9-tetrahy-drocannabinol content. High-doseD9-tetrahydrocannabinol results in amarked increase in heart rate, postural hy-potension, and serum carboxyhemoglobinlevels. This results in decreased oxygen-carrying capacity and increased myo-cardial oxygen demand, leading to acutecoronary ischemia. This ischemic insultin the presence of sympathovagal im-balance acts as a substrate for vari-ous types of arrhythmias, including

AF.15 Our patient had normal troponin Ilevels and echocardiogram. There-fore, we postulate that the significantsympathovagal imbalance resultingfrom both the GTCC and the marijuanaabuse might have led to an additiveeffect, which in the presence of ictal orpostictal tachycardia might have trig-gered the AF.

Factors such as vomiting, hypoxia, hy-percapnia, acidosis, and electrolyteabnormalities commonly seen duringGTCC are proarrhythmogenic and havebeen implicated in causing AF. Thesefactors are less likely to be responsiblefor the initiation of AF in our patientbecause the arterial blood gas andserum electrolytes were completelynormal. Severe hemodynamic com-promise leading to hypoxemic ischemicinjury to the brain and ischemic strokecaused by thromboembolic phenome-non secondary to atrial dilatation mayalso lead to seizures, but in our casethese 2 possibilities were ruled out byimaging. However, the etiology of theabnormal heterotopic focus on the MRI(brain) could not be ascertained be-cause of the lack of follow-up by thepatient, and it probably representscortical dysplasia. We also postulate

that our patient might have developedAF after the first seizure (when his“heart began feeling weak”), whichwouldmean that the duration of AF wasmore than 24 hours, but the docu-mented AF was only for 6 hours.

CONCLUSIONS

Our case is unique in that 2 commonconditions, GTCC and marijuana abuse,resulted in AF, a rare condition in anadolescent with a structurally normalheart. We suggest that seizures andmarijuana abuse, occurring both in-dividually or in combination, should beconsidered in the differential diagnosisof the etiology of AF in a patient witha structurally normal heart. Consider-ing the heterogeneity of AF, we suggestthat the goals of treatment should beindividualized according to the riskfactors. We recommend close moni-toring of cardiac function in patientswithmarijuana abuse and GTCC, whichmay reduce subsequent morbidityand mortality. We anticipate thatfuture studies involving genetic, met-abolic, and neurohumoral mecha-nisms, at both the macroscopic andmicroscopic levels, will increase ourknowledge.

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DOI: 10.1542/peds.2013-1831 originally published online January 13, 2014; 2014;133;e443Pediatrics 

AkingbolaDinesh Singh, Margaret Huntwork, Varun Shetty, Gina Sequeira and Olugbenga

AbuseProlonged Atrial Fibrillation Precipitated by New-Onset Seizures and Marijuana

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DOI: 10.1542/peds.2013-1831 originally published online January 13, 2014; 2014;133;e443Pediatrics 

AkingbolaDinesh Singh, Margaret Huntwork, Varun Shetty, Gina Sequeira and Olugbenga

AbuseProlonged Atrial Fibrillation Precipitated by New-Onset Seizures and Marijuana

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