Long QT Syndrome Presenting as a Seizure LINDA L. HERMAN, MD, MARGIE STOSHAK, TIMOTHY J. RITTENBERRY, A 2%year-old woman was brought to the emergency department after being found unconscious in a hotel lobby. On presentation, she was awake but confused. The initial evaluation revealed no evidence of trauma, metabolic abnormality, drug ingestion, or intracranial process. The only abnormality noted was electrocardiographic, and included a long QT intenral as well as occasional atrial and junctional beats within a normal sinus rfrythm. While in the department the patient developed tonic-clonic activity and was concurrently noted to have developed ventricular tachycardia. A precordial thump was given with the simultaneous cessation of the arrythmia and the seizure. After definitive electrophysiologic study, the diagnosis of long QT syndrome was made. Treatment consisting of p blockade and pacemaker insertion prevented further arrythmia or seizure activity. long QT syndrome should be considered a possible etiology in any patient presenting with new onset seizures, especially in the young. (Am J Emerg Mad 1992;10:435-438. Copyright 0 1992 by W.8. Saunders Company)
Long QT syndrome (LQTS) may first manifest as syncopal episodes or seizures, most frequently in children and young adults. However, of the various causes of seizures in this population, such a cardiac etiology is relatively uncommon. We report a case of a young woman who presented to the emergency department in a postictal state who further demonstrated seizure activity and concurrent ventricular tachycardia that directly resulted from LQTS. Failure to identify this uncommon syndrome on inspection of the emergency department electrocardiogram can prove fatal. The hereditary and idiopathic forms of LQTS are reviewed with attention to pathophysiology, the ECG, and the factors associated with life-threatening ventricular arrhythmias. CASE REPORT A 2i-year-old woman was transported to the emergency department after a suspected syncopal episode. The patient was found unconscious on the floor of a hotel lobby by bystanders. Upon arrival of the paramedics, the patient was awake but confused. There were no signs of trauma. An intravenous line was established with normal saline, oxygen was administered, and the patient was placed on a cardiac monitor showing normal sinus rhythm. Her blood pressure was 112/68 mm Hg; pulse 78 beats per minute; respirations 20 breaths per minute. She was then transported to the emergency department. Upon arrival the patient was indeed disoriented, preventing an adequate historical interview. The patient’s husband was present
From the Department of Emergency Medicine, University of Illinois College of Medicine Emergency Medicine Residency, IIlinois Masonic Medical Center, Chicago, IL. Manuscript received February 19, 1992; revision accepted April 17, 1992. Address reprint requests to Dr Herman, Department of Emergency Medicine, Illinois Masonic Medical Center, 838 W Wellington, Chicago, IL 80857. Kev Words: Lonq QT syndrome, sudden death, ventricular arrhythmias, seizure, LQTS as seizure. Copyright 0 1992 by W.B. Saunders Company 0735-8757/92/l 005-0009$5.00/0
MD, MD
but unaware of any pertinent past medical history aside from a recent uncomplicated pregnancy resulting in the birth of a healthy girl 1 month earlier. He could provide no history concerning seizures, or any other cardiac or neurologic disease. Cardiac monitoring and intravenous access were maintained while a rapid glucose determination of a fingerstick blood sample was done, revealing a glucose level of 120 mg/dL. Physical examination revealed a thin female, initially thrashing about upon the cart, verbalizing in a confused manner, oblivious to surroundings. In undressing the patient, recent urinary incontinence was noted. Her blood pressure was 1lo/70 mmHg; pulse 74 beats per minute; respirations 20 breaths per minute; and tympanic temperature 37.W. Dermatologic examination was negative for rashes, cyanosis, or ecchymosis. There was no evidence of trauma to the head. Pupils were equal, round, and reactive to light. No nystagmus was noted. Fundi had sharp disk margins and no hemorrhages or papilledema were seen. The tympanic membranes were normal in appearance. The oropharynx was without lesion and a gag reflex was present. The neck was supple, without masses or thyromegaly. The lungs were clear and breath sound were equal bilaterally. The apical pulse was regular with normal first and second heart sounds. A grade III/VI blowing systolic murmur was noted, loudest at the second left intercostal space near the sternal border. The abdomen was benign. The extremities were without deformities and had strong, symmetric pulses. Although the patient was confused on arrival, her level of consciousness slowly improved enough to allow a detailed neurologic examination. All cranial nerve functions were intact. Motor strength in the extremities was strong and symmetrical. There were no deficits appreciated on testing the deep tendon reflexes, and there were no pathologic reflexes elicited. Initially, she was unable to adequately follow commands to fully assess cerebellar function, but when the examination was repeated she could follow all commands, demonstrating good coordination. After approximately 1 hour in the emergency department, the patient’s mental status had sufficiently improved to allow for obtaining a more detailed and dependable history. She did not recall any events beyond her entering the hotel lobby. She stated that she had two previous syncopal episodes, one at the age of 12 and another at age 13. She had no recent symptoms of palpitations, chest pains, or headache. She denied any history of rheumatic heart disease or seizures, and did not use drugs, alcohol, or tobacco. She had no allergies and took no medications. Her family history was significant for the sudden death of her mother at a young age, who had collapsed and died without apparent cause. The electrocardiogram (ECG) demonstrated sinus rhythm at a rate of 60 with occasional premature atria1 and junctional contractions (Figure 1). The QT interval was noted to be 0.52 seconds and abnormally long (normal .42-.45 seconds; Figure 2). A chest radiograph was normal. Arterial blood gas on room air revealed a pH 7.41, Pco, 38, and PO, of 91 mm Hg. Other laboratory results included hemoglobin of 10.8 g/dL, hematocrit 32.3%. leukocyte count 7,4Wmm3, serum sodium 142 mEq/L, potassium 3.2 mEq/L, chloride 105 mEq/L, carbon dioxide 22 mm Hg, glucose 166 mg/dL, blood urea nitrogen 11 mg/dL, creatinine 0.8 mg%, magnesium 1.5 mg/dL, and calcium 8.8 mg/dL. A urine screen for drugs of abuse was negative. Computed tomographic scan of the brain without contrast showed no evidence of a mass, bleeding, or edema. Prior to transport from the emergency department to an inpatient bed, the patient concurrently developed generalized tonic-clonic seizure ac435
436
FIGURE 1.
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Initial ECG showing sinus rhythm with occasional premature atria1 and junctional beats with prolonged QT interval as noted.
tivity and ventricular tachycardia. The patient was immediately given a precordial thump with simultaneous cessation of the arrythmia and her seizure activity. Lidocaine was then administered prophylactically and the patient remained in normal sinus rhythm. The patient was admitted to the coronary intensive care unit where she was further evaluated by the cardiology service. An exhaustive work-up included a 24-hour Hoher monitor which revealed sinus rhythm with an average rate of 57 beats per minute. No arrhythmias were seen in the 24-hour period. Findings on an echocardiogram were consistent with a patent ductus arteriosus which was later confirmed by cardiac catheterization. Wall motion, ejection fraction, and other anatomy were all normal. Upon electrophysiologic study she was found to have a normal HV interval, and no sustained supraventricular or ventricular arrhythmias could be induced. A di-
FIGURE 2.
agnosis of congenital LQTS was consistent with the patient’s history, ECG abnormalities, family history, and the electrophysiologic findings. The patient’s daughter was examined by a pediatric cardiologist and was also found to have a long QT interval on ECG. The patient was then placed on a long acting 6 blocker and discharged home. She later required multiple admissions for similar events and was eventually managed successfully with the insertion of a permanent pacemaker in addition to 6 blockade therapy.
DISCUSSION There are two major etiologies for LQTS, congenital and acquired. Congenital LQTS was first described by Jervell and Lange-Nielsen in 1957 in a group of four siblings with
Sinus rhythm with prolonged QT interval.
HERMAN
ET AL W LQTS AS SEIZURE
sensorineural deafness, a long QT interval on ECG, and sudden death.’ Independently, Roman0 et al in 1963* and Ward in 19643 reported families having members with long QT intervals who had convulsions and sudden death without sensorineural hearing loss. The Lange-Nielsen syndrome is an autosomal recessive disorder while the Romano-Ward syndrome is an autosomal dominant disorder with variable expression. Since then, cases of LQTS have been reported without any evidence of familial involvement.4 Acquired LQTS has been noted as a side effect of drugs such as quinidine, procainamide, the phenothiazines, disopyramide, flecanide, amiodarone the tricyclic antidepressants, sotalol, prabacol, and encainide. It is also seen with electrolyte disturbances such as hypocalcemia, hypokalemia, and hypomagnesemia. It has been noted with hypothermia, cerebrovascular disease, atrioventricular block, ischemit heart disease, and after various operations involving the neck. Although once thought to be more prevalent in females with mitral valve prolapse, this hypothesis has been studied and disproven.’ The mortality rate for individuals with LQTS is 1.3% per year, with an average age at demise of 24 years, as determined through an international registry begun in 1974 by Schwartz and colleagues6 The rate of syncopal episodes is approximately 8.6% per year. Of those with congenital LQTS the independent risk factors for sudden death or syncope were found to be congenital deafness, history of syncope, and female sex with relative risk being 9.9,4.5, and 2.2 times more frequent, respectively. These data for sudden death and syncopal episodes differ somewhat from Schwartz’s original work in 1975 when he estimated the risk of sudden death at 5% per year. The lower mortality rate of his later work is apparently due to increased recognition and earlier treatment of patients with LQTS. There are multiple reports of children diagnosed with seizures or syncope who are found to have congenital LQTS on further investigation. ‘-lo The decreased perfusion to the brain during ventricular tachycardia is the presumed cause of the syncope or seizure. Long QT syndrome is typically discovered in childhood or the early teens, but true diagnosis is elusive until young adulthood in 25% of the cases. A case of LQTS has also been reported in which a 21-year-old female presented with left hemiplegia without seizure or syncope.” Clues to the possibility of LQTS are the onset of syncope, seizures, and/or focal neurologic deficit in the childhood and teenage years, a family history significant for syncope, seizures, or sudden death, a normal electroencephalogram, and a long QT interval on the ECG. Other abnormalities have been noted on the ECG of individuals with congenital LQTS. The duration of the T wave may be prolonged and its morphology unusual with biphasic, bitid, or notched configurations.‘* Patients with LQTS have been observed to have low resting heart rates which do not increase appropriately with exercise.13 Atria1 and ventricular rhythms alike have been noted but sinus rhythm is the most frequent presenting cardiac rhythm.‘*3*8-12*14Mongkolsmai reported a case of a 26-month-old male who presented with a junctional rhythm, a long QT interval, and a history of seizure activity.’ This is unusual because an escape A-V junctional rhythm is more dependent upon adrenergic control, and frequently a junctional escape rhythm is unpredict-
437
able or fails to emerge. I5 This may have been a component in this case as our patient did have frequent premature atrial and junctional beats. The seizures or syncope of congenital LQTS are frequently preceded by emotional outbursts or loud noises. An increase in sympathetic activity leading to the induction of ventricular tachycardia has been proposed in these patients, and multiple studies have been done attempting to substantiate this theory. Left ganglia stellectomy or blockade has been shown to decrease the ventricular threshold and may offer a protective effect.i4 Solti and colleagues studied the effects of l3 blocker administration and found that propran0101 significantly shortened QT interval in the presence of LQTS but had no effect in the control population studied. l5 This further supports the theory of sympathetic hyperactivity. Still, there is evidence that this may not be the only underlying pathophysiologic process. Bharati and associates performed postmortem examinations of the cardiac conduction system in four patients with the Romano-Ward syndrome and one patient with Jervall-Lange-Nielsen syndrome. Four patients had a lobulated atrioventricular (AV) bundle. Four also had fibrosis of the AV bundle and bundle branches. In all, the ventricular myocardium was chronically inflamed.16 Other investigators have discovered pathologic abnormalities of the conduction system such as neuritis and degeneration of the neural elements of the sinus node, AV node, His bundle, and ventricular myocardium.‘7~‘9 It is possible that these anatomic abnormalities might lead to a delay in repolarization in a prolonged QT interval. The pathophysiology of acquired LQTS, however, seems very different from the congenital syndrome in that the ventricular arrhythmias are typically pause-dependent (following a long ventricular cycle or pause). Ventricular arrhythmias are not related to exercise or stress as in the congenital form. Repolarization changes often are seen in the ST segment, T wave, and QT interval. A slow wave known as the TU wave which usually appears hours to days before the onset of ventricular tachycardia may be seen in the acquired form. The most frequent pattern preceding ventricular tachycardia is a ventricular extrasystole followed by a normal QRS complex with a pause, leading into a bizarre postpause TU complex and subsequent ventricular tachycardia.*’ In contrast, those with congenital LQTS do not have ventricular tachycardia that is pause-dependent, and the slow wave changes and abnormal T waves appear during regular sinus rhythm. In 1985, Bhandari and associates per> formed electrophysiologic studies on 15 patients with LQTS. He was not able to induce sustained ventricular tachycardia in any patient. Although he was able to induce nonsustained ventricular tachycardia in six patients, it was of no prognostic value. They also found no prognostic value in the failure to suppress episodes of induced ventricular tachycardia by B blocker therapy.” Treatment for acquired LQTS consists of correcting any electrolyte imbalance and/or discontinuing any offending medication. During the period of correction, cardiac pacing at an increased rate may be of benefit. Medications such as atropine or isoproterenol that increase the rate are also helpful in terminating the ventricular tachycardia and may be instituted while a pacemaker is being inserted. Interestingly, lidocaine as well as phenytoin are ineffective in preventing
436
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or treating ventricular arrhythmias due to the acquired form of LQTS.** Data from Tzivoni and coworkers suggest that magnesium sulfate, 1 to 2 g intravenously, may be successful in suppressing drug-induced torsades de points in normomagnesemic patients.23 In congenital LQTS, treatment consists of B blockade. p Blockers provide a chemical means of providing antiadrenergic activity and protect the heart from sympathetic discharge. Propranolol has been used most successfully at an initial dose of 2 mg/kg orally, increasing the dose as necessary to control arrhythmias. The relative risk with such treatment falls to .41.‘* Unfortunately, not all patients with LQTS respond to B blockers. If l3 blocker therapy fails, high thoracic left sympathectomy may be used. The relative risk of syncope or sudden death after this procedure decreases to 0.25.‘* As discussed earlier, there may be diverse etiologies for LQTS and thoracic left sympathectomy is also known to be ineffective in some patients. These nonresponders have been placed on B blockers again after surgery with some success, but this has not been well studied. Calcium channel blockers have also been used sporadically, with success reported in at least one case.24 Recently, permanent pacemaker insertion has been attempted to decrease the high morbidity and mortality in a patient with LQTS. Eldar and associates inserted pacemakers in eight patients with LQTS. Five of these patients were refractory or intolerant to B blocker therapy, and three had unsuccessful left cardiothoracic sympathectomies. Although different pacemakers were used, a heart rate which provided maximal shortening of the QT interval was chosen as an endpoint in all patients. Survival was 100% at the end of 35 months.*’ Pacing may provide protection for those with LQTS that do not respond to standard medical treatment. CONCLUSION This article reviews the case of a young woman whose emergency department evaluation for seizure led to the discovery of episodic ventricular tachycardia due to an underlying congenital cardiac conduction abnormality-LQTS. The high rate of morbidity and mortality associated with LQTS underscores the importance of its consideration in the evaluation of seizures, especially those in children and young adults. The ECG changes which help identify patients with LQTS are discussed. The diagnosis is dependent upon supporting and/or family history, the findings of long QT interval on ECG, and the demonstration of ventricular tachycardia or dysrhythmia. This diagnosis can be made in the absence of electrophysiologic studies. Treatment consists of B blockade, thoracic left sympathectomy, or cardiac pacing in those with the congenital LQTS. Removal of the offending agent or correction of electrolyte abnormalities are necessary in treating acquired LQTS. The authors wish to acknowledge the assistance of Mary Richardson, and Rose Sturghill-Bradford for their diligent work in the preparation of this manuscript.
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REFERENCES 1. Jervell A, Lange-Nielsen F: Congenital deaf mutism, functional heart disease with prolongation of the QT interval and sudden death. Am Heart J 1957;54:59-68 2. Roman0 C, Gemme G, Ponsiglione R: Artimie Cardiache Rare Deil Ete Pediatria. Clin Paediatr 1963;45:656-683 3. Ward OC: A new familial cardiac syndrome in children. J Irish Med Assoc 1964;54:103-106 4. Schwartz PJ: Delayed repolarization (QT or QTU prolongation) and malignant ventricular arrhythmias. Mod Cone Cardiovasc Dis 1982;51:85 5. Cowan MD, Fye WB: Prevalence of QTC prolongation in women with mitral valve prolapse. Am J Cardiol 1989;63:133-134 6. Moss AJ, Schwartz PJ, Crampton RS: The long QT syndrome: A prospective international study. Circulation 1965;71: 17-21 7. Mongkolsmai C: The long QT syndrome: Syncope versus seizure. IMJ 1963;167:451-453 8. Horn CA, Beekman RH, Macdonald D, et al: The congenital long QT syndrome. Am J Dis Child 1986;140:659-661 9. Ballardie FW, Murphy RP, Davis J: Epilepsy: A presentation of the Romano-Ward syndrome. Br Med J 1983;267:896-897 10. Bricker JT, Garson A, Gilette PC: A family history of seizures associated cardiac death. Am J Dis Child 1984;136:866868 1 I. Frank E, Tew JM, Pagani L: The prolonged QT syndrome presenting as a focal neurological lesion. Surg Neurol 1981;16: 333-335 12. Schwartz PJ: Idiopathic long QT syndrome: Prooress and questions. Am Heart J i985;109:399-411. 13. Schwartz PJ. Periti M. Malliani A: The lona_ QT svndrome. , Am Heart J 1975;69:378-396 14. Pandey RC, Svivastava RD, Bhatnagar VM: Effects of unilateral stellate ganglion blockade and stimulation on experimental arrhythmias. J Physiol Pharmacol 1975;23:305-311 15. Solti F, Szatmary L, Vecsey T, et al: The effect of sympathetic and parasympathetic activity on QT duration. Cor Vasa 1969;31:9-15 16. Bharati S, Dreifus L, Bucheleres G, et al: The conduction system in patients with a prolonged QT interval. J Am Coll Cardiol 1965;6:1110-1119 17. James TN, Froggatt P, Atkinson WJ, et al: Observations on the pathophysiology of the long QT syndrome with special reference to the neuropathology of the heart. Circulation 1976;57: 1221-1231 16. Phillips J, lchinose H: Clinical and pathological studies in the hereditary syndrome of long QT interval, syncopal attacks and sudden death. Chest 1976;58:236-243 19. Hashibu K: Hereditary Q-T prolongation syndrome in Japan: Genetic analysis and pathological findings of the conduction system. Jpn Circ J 1978;42:1133-1150 _ 20. Jackman WM. Clark M. Fridav K. et al: Ventricular tachvarrhythmias in the long QT syndromes.‘Med Clin North Am 1984; 68:1079-1109 21. Bhandari AK, Shapiro WA, Morady F: Electrophysiologic testing in patients with the long QT syndrome. Circulation 1985; 71:63-71 22. Kahn MM, Logan KR, McComb JM, et al: Management of recurrent ventricular tachyarrhythmias with AT prolongation. Am J Cardiol 1961;47:1301-1306 23. Tzivoni D, Keren A, Cohen AM, et al: Magnesium therapy for torsades de points. Am J Cardiol 1984;53:528-530 24. Schechter E, Freeman CC, Lazzara R: After depolarization as a mechanism for the long QT syndrome: electrophysiologic studies of a case. J Am Coll Cardiol 1984;3:1556. 25. Eldar M, Griffin JC, Abbott JA: Permanent cardiac pacing in patients with the long QT syndrome. J Am Coll Cardiol 1987; 10:600-807
Long QT syndrome (LQTS) may first manifest as syncopal episodes or seizures, most frequently in children and young adults. However, of the various causes of seizures in this population, such a cardiac etiology is relatively uncommon. We report a case of a young woman who presented to the emergency department in a postictal state who further demonstrated seizure activity and concurrent ventricular tachycardia that directly resulted from LQTS. Failure to identify this uncommon syndrome on inspection of the emergency department electrocardiogram can prove fatal. The hereditary and idiopathic forms of LQTS are reviewed with attention to pathophysiology, the ECG, and the factors associated with life-threatening ventricular arrhythmias. CASE REPORT A 2i-year-old woman was transported to the emergency department after a suspected syncopal episode. The patient was found unconscious on the floor of a hotel lobby by bystanders. Upon arrival of the paramedics, the patient was awake but confused. There were no signs of trauma. An intravenous line was established with normal saline, oxygen was administered, and the patient was placed on a cardiac monitor showing normal sinus rhythm. Her blood pressure was 112/68 mm Hg; pulse 78 beats per minute; respirations 20 breaths per minute. She was then transported to the emergency department. Upon arrival the patient was indeed disoriented, preventing an adequate historical interview. The patient’s husband was present
From the Department of Emergency Medicine, University of Illinois College of Medicine Emergency Medicine Residency, IIlinois Masonic Medical Center, Chicago, IL. Manuscript received February 19, 1992; revision accepted April 17, 1992. Address reprint requests to Dr Herman, Department of Emergency Medicine, Illinois Masonic Medical Center, 838 W Wellington, Chicago, IL 80857. Kev Words: Lonq QT syndrome, sudden death, ventricular arrhythmias, seizure, LQTS as seizure. Copyright 0 1992 by W.B. Saunders Company 0735-8757/92/l 005-0009$5.00/0
MD, MD
but unaware of any pertinent past medical history aside from a recent uncomplicated pregnancy resulting in the birth of a healthy girl 1 month earlier. He could provide no history concerning seizures, or any other cardiac or neurologic disease. Cardiac monitoring and intravenous access were maintained while a rapid glucose determination of a fingerstick blood sample was done, revealing a glucose level of 120 mg/dL. Physical examination revealed a thin female, initially thrashing about upon the cart, verbalizing in a confused manner, oblivious to surroundings. In undressing the patient, recent urinary incontinence was noted. Her blood pressure was 1lo/70 mmHg; pulse 74 beats per minute; respirations 20 breaths per minute; and tympanic temperature 37.W. Dermatologic examination was negative for rashes, cyanosis, or ecchymosis. There was no evidence of trauma to the head. Pupils were equal, round, and reactive to light. No nystagmus was noted. Fundi had sharp disk margins and no hemorrhages or papilledema were seen. The tympanic membranes were normal in appearance. The oropharynx was without lesion and a gag reflex was present. The neck was supple, without masses or thyromegaly. The lungs were clear and breath sound were equal bilaterally. The apical pulse was regular with normal first and second heart sounds. A grade III/VI blowing systolic murmur was noted, loudest at the second left intercostal space near the sternal border. The abdomen was benign. The extremities were without deformities and had strong, symmetric pulses. Although the patient was confused on arrival, her level of consciousness slowly improved enough to allow a detailed neurologic examination. All cranial nerve functions were intact. Motor strength in the extremities was strong and symmetrical. There were no deficits appreciated on testing the deep tendon reflexes, and there were no pathologic reflexes elicited. Initially, she was unable to adequately follow commands to fully assess cerebellar function, but when the examination was repeated she could follow all commands, demonstrating good coordination. After approximately 1 hour in the emergency department, the patient’s mental status had sufficiently improved to allow for obtaining a more detailed and dependable history. She did not recall any events beyond her entering the hotel lobby. She stated that she had two previous syncopal episodes, one at the age of 12 and another at age 13. She had no recent symptoms of palpitations, chest pains, or headache. She denied any history of rheumatic heart disease or seizures, and did not use drugs, alcohol, or tobacco. She had no allergies and took no medications. Her family history was significant for the sudden death of her mother at a young age, who had collapsed and died without apparent cause. The electrocardiogram (ECG) demonstrated sinus rhythm at a rate of 60 with occasional premature atria1 and junctional contractions (Figure 1). The QT interval was noted to be 0.52 seconds and abnormally long (normal .42-.45 seconds; Figure 2). A chest radiograph was normal. Arterial blood gas on room air revealed a pH 7.41, Pco, 38, and PO, of 91 mm Hg. Other laboratory results included hemoglobin of 10.8 g/dL, hematocrit 32.3%. leukocyte count 7,4Wmm3, serum sodium 142 mEq/L, potassium 3.2 mEq/L, chloride 105 mEq/L, carbon dioxide 22 mm Hg, glucose 166 mg/dL, blood urea nitrogen 11 mg/dL, creatinine 0.8 mg%, magnesium 1.5 mg/dL, and calcium 8.8 mg/dL. A urine screen for drugs of abuse was negative. Computed tomographic scan of the brain without contrast showed no evidence of a mass, bleeding, or edema. Prior to transport from the emergency department to an inpatient bed, the patient concurrently developed generalized tonic-clonic seizure ac435
436
FIGURE 1.
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1992
Initial ECG showing sinus rhythm with occasional premature atria1 and junctional beats with prolonged QT interval as noted.
tivity and ventricular tachycardia. The patient was immediately given a precordial thump with simultaneous cessation of the arrythmia and her seizure activity. Lidocaine was then administered prophylactically and the patient remained in normal sinus rhythm. The patient was admitted to the coronary intensive care unit where she was further evaluated by the cardiology service. An exhaustive work-up included a 24-hour Hoher monitor which revealed sinus rhythm with an average rate of 57 beats per minute. No arrhythmias were seen in the 24-hour period. Findings on an echocardiogram were consistent with a patent ductus arteriosus which was later confirmed by cardiac catheterization. Wall motion, ejection fraction, and other anatomy were all normal. Upon electrophysiologic study she was found to have a normal HV interval, and no sustained supraventricular or ventricular arrhythmias could be induced. A di-
FIGURE 2.
agnosis of congenital LQTS was consistent with the patient’s history, ECG abnormalities, family history, and the electrophysiologic findings. The patient’s daughter was examined by a pediatric cardiologist and was also found to have a long QT interval on ECG. The patient was then placed on a long acting 6 blocker and discharged home. She later required multiple admissions for similar events and was eventually managed successfully with the insertion of a permanent pacemaker in addition to 6 blockade therapy.
DISCUSSION There are two major etiologies for LQTS, congenital and acquired. Congenital LQTS was first described by Jervell and Lange-Nielsen in 1957 in a group of four siblings with
Sinus rhythm with prolonged QT interval.
HERMAN
ET AL W LQTS AS SEIZURE
sensorineural deafness, a long QT interval on ECG, and sudden death.’ Independently, Roman0 et al in 1963* and Ward in 19643 reported families having members with long QT intervals who had convulsions and sudden death without sensorineural hearing loss. The Lange-Nielsen syndrome is an autosomal recessive disorder while the Romano-Ward syndrome is an autosomal dominant disorder with variable expression. Since then, cases of LQTS have been reported without any evidence of familial involvement.4 Acquired LQTS has been noted as a side effect of drugs such as quinidine, procainamide, the phenothiazines, disopyramide, flecanide, amiodarone the tricyclic antidepressants, sotalol, prabacol, and encainide. It is also seen with electrolyte disturbances such as hypocalcemia, hypokalemia, and hypomagnesemia. It has been noted with hypothermia, cerebrovascular disease, atrioventricular block, ischemit heart disease, and after various operations involving the neck. Although once thought to be more prevalent in females with mitral valve prolapse, this hypothesis has been studied and disproven.’ The mortality rate for individuals with LQTS is 1.3% per year, with an average age at demise of 24 years, as determined through an international registry begun in 1974 by Schwartz and colleagues6 The rate of syncopal episodes is approximately 8.6% per year. Of those with congenital LQTS the independent risk factors for sudden death or syncope were found to be congenital deafness, history of syncope, and female sex with relative risk being 9.9,4.5, and 2.2 times more frequent, respectively. These data for sudden death and syncopal episodes differ somewhat from Schwartz’s original work in 1975 when he estimated the risk of sudden death at 5% per year. The lower mortality rate of his later work is apparently due to increased recognition and earlier treatment of patients with LQTS. There are multiple reports of children diagnosed with seizures or syncope who are found to have congenital LQTS on further investigation. ‘-lo The decreased perfusion to the brain during ventricular tachycardia is the presumed cause of the syncope or seizure. Long QT syndrome is typically discovered in childhood or the early teens, but true diagnosis is elusive until young adulthood in 25% of the cases. A case of LQTS has also been reported in which a 21-year-old female presented with left hemiplegia without seizure or syncope.” Clues to the possibility of LQTS are the onset of syncope, seizures, and/or focal neurologic deficit in the childhood and teenage years, a family history significant for syncope, seizures, or sudden death, a normal electroencephalogram, and a long QT interval on the ECG. Other abnormalities have been noted on the ECG of individuals with congenital LQTS. The duration of the T wave may be prolonged and its morphology unusual with biphasic, bitid, or notched configurations.‘* Patients with LQTS have been observed to have low resting heart rates which do not increase appropriately with exercise.13 Atria1 and ventricular rhythms alike have been noted but sinus rhythm is the most frequent presenting cardiac rhythm.‘*3*8-12*14Mongkolsmai reported a case of a 26-month-old male who presented with a junctional rhythm, a long QT interval, and a history of seizure activity.’ This is unusual because an escape A-V junctional rhythm is more dependent upon adrenergic control, and frequently a junctional escape rhythm is unpredict-
437
able or fails to emerge. I5 This may have been a component in this case as our patient did have frequent premature atrial and junctional beats. The seizures or syncope of congenital LQTS are frequently preceded by emotional outbursts or loud noises. An increase in sympathetic activity leading to the induction of ventricular tachycardia has been proposed in these patients, and multiple studies have been done attempting to substantiate this theory. Left ganglia stellectomy or blockade has been shown to decrease the ventricular threshold and may offer a protective effect.i4 Solti and colleagues studied the effects of l3 blocker administration and found that propran0101 significantly shortened QT interval in the presence of LQTS but had no effect in the control population studied. l5 This further supports the theory of sympathetic hyperactivity. Still, there is evidence that this may not be the only underlying pathophysiologic process. Bharati and associates performed postmortem examinations of the cardiac conduction system in four patients with the Romano-Ward syndrome and one patient with Jervall-Lange-Nielsen syndrome. Four patients had a lobulated atrioventricular (AV) bundle. Four also had fibrosis of the AV bundle and bundle branches. In all, the ventricular myocardium was chronically inflamed.16 Other investigators have discovered pathologic abnormalities of the conduction system such as neuritis and degeneration of the neural elements of the sinus node, AV node, His bundle, and ventricular myocardium.‘7~‘9 It is possible that these anatomic abnormalities might lead to a delay in repolarization in a prolonged QT interval. The pathophysiology of acquired LQTS, however, seems very different from the congenital syndrome in that the ventricular arrhythmias are typically pause-dependent (following a long ventricular cycle or pause). Ventricular arrhythmias are not related to exercise or stress as in the congenital form. Repolarization changes often are seen in the ST segment, T wave, and QT interval. A slow wave known as the TU wave which usually appears hours to days before the onset of ventricular tachycardia may be seen in the acquired form. The most frequent pattern preceding ventricular tachycardia is a ventricular extrasystole followed by a normal QRS complex with a pause, leading into a bizarre postpause TU complex and subsequent ventricular tachycardia.*’ In contrast, those with congenital LQTS do not have ventricular tachycardia that is pause-dependent, and the slow wave changes and abnormal T waves appear during regular sinus rhythm. In 1985, Bhandari and associates per> formed electrophysiologic studies on 15 patients with LQTS. He was not able to induce sustained ventricular tachycardia in any patient. Although he was able to induce nonsustained ventricular tachycardia in six patients, it was of no prognostic value. They also found no prognostic value in the failure to suppress episodes of induced ventricular tachycardia by B blocker therapy.” Treatment for acquired LQTS consists of correcting any electrolyte imbalance and/or discontinuing any offending medication. During the period of correction, cardiac pacing at an increased rate may be of benefit. Medications such as atropine or isoproterenol that increase the rate are also helpful in terminating the ventricular tachycardia and may be instituted while a pacemaker is being inserted. Interestingly, lidocaine as well as phenytoin are ineffective in preventing
436
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OF EMERGENCY
or treating ventricular arrhythmias due to the acquired form of LQTS.** Data from Tzivoni and coworkers suggest that magnesium sulfate, 1 to 2 g intravenously, may be successful in suppressing drug-induced torsades de points in normomagnesemic patients.23 In congenital LQTS, treatment consists of B blockade. p Blockers provide a chemical means of providing antiadrenergic activity and protect the heart from sympathetic discharge. Propranolol has been used most successfully at an initial dose of 2 mg/kg orally, increasing the dose as necessary to control arrhythmias. The relative risk with such treatment falls to .41.‘* Unfortunately, not all patients with LQTS respond to B blockers. If l3 blocker therapy fails, high thoracic left sympathectomy may be used. The relative risk of syncope or sudden death after this procedure decreases to 0.25.‘* As discussed earlier, there may be diverse etiologies for LQTS and thoracic left sympathectomy is also known to be ineffective in some patients. These nonresponders have been placed on B blockers again after surgery with some success, but this has not been well studied. Calcium channel blockers have also been used sporadically, with success reported in at least one case.24 Recently, permanent pacemaker insertion has been attempted to decrease the high morbidity and mortality in a patient with LQTS. Eldar and associates inserted pacemakers in eight patients with LQTS. Five of these patients were refractory or intolerant to B blocker therapy, and three had unsuccessful left cardiothoracic sympathectomies. Although different pacemakers were used, a heart rate which provided maximal shortening of the QT interval was chosen as an endpoint in all patients. Survival was 100% at the end of 35 months.*’ Pacing may provide protection for those with LQTS that do not respond to standard medical treatment. CONCLUSION This article reviews the case of a young woman whose emergency department evaluation for seizure led to the discovery of episodic ventricular tachycardia due to an underlying congenital cardiac conduction abnormality-LQTS. The high rate of morbidity and mortality associated with LQTS underscores the importance of its consideration in the evaluation of seizures, especially those in children and young adults. The ECG changes which help identify patients with LQTS are discussed. The diagnosis is dependent upon supporting and/or family history, the findings of long QT interval on ECG, and the demonstration of ventricular tachycardia or dysrhythmia. This diagnosis can be made in the absence of electrophysiologic studies. Treatment consists of B blockade, thoracic left sympathectomy, or cardiac pacing in those with the congenital LQTS. Removal of the offending agent or correction of electrolyte abnormalities are necessary in treating acquired LQTS. The authors wish to acknowledge the assistance of Mary Richardson, and Rose Sturghill-Bradford for their diligent work in the preparation of this manuscript.
MEDICINE
W Volume
10, Number
5 n September
1992
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