Information for pediatric neurologists-

Evaluating the child with syncope or first seizure for Long QT syndrome by measuring the corrected QT interval on EEG

Background

Long QT syndrome (LQTS) causes sudden death in seemingly healthy children. Two forms were originally described based on the inheritance pattern and the presence of deafness. Jervell and Lange-Nielsen in 1957 described an autosomal recessive form of sudden death in children associated with a prolonged QT interval and deafness (1). In 1963, Romano and Ward independently described a dominant inheritance pattern of prolonged QT interval and sudden death in children (2,3). Although originally felt to be separate conditions, these two forms have recently been shown to be caused by mutations in either one (dominant LQTS) or both (recessive LQTS) alleles of two different cardiac ion channel genes. This information is the result of the recent flurry of interest in the disorder that followed the identification of the genetic basis of the condition (4). Between 1995 and the present, the molecular basis of LQTS has been determined for many families with this disorder. Although physiologically elegant, the discoveries have proved that LQTS is a genetically complex condition. Five of the responsible genes code for cardiac ion channels that underlie the cardiac myocyte action potential and prolong its repolarization phase thus prolonging the QT interval (5-8). However, multiple mutations are present in each of the known genes, and other genes are expected to be involved as well. In addition, genotype-phenotype correlation has shown that a clearly prolonged QT interval is not present in up to one-third of affected individuals (4). Thus, the diagnosis of LQTS remains a problem and depends on a high index of suspicion and measurement of the rate corrected QT interval (QTc).

The natural history of this condition shows that children are more likely to die from cardiac arrhythmia than adults with the condition. Symptomatic children are at highest risk and 10-30% die of ventricular fibrillation. Syncope is the major symptom preceding sudden death in individuals with LQTS. It should suggest the diagnosis especially when associated with exertion or emotional upset. However, its association with LQTS is easily overlooked since syncope is common and usually not caused by LQTS. If LQTS could be recognized, treatment with a beta-blocker is effective in preventing death due to ventricular fibrillation in most cases (9,10). Thus, identifying individuals with this condition is important since it is serious and there is a simple and potentially life-saving intervention.
 

Role of the pediatric neurologist

Pediatric neurologists are often the first specialtist consulted after a child has an episode of syncope or a first seizure. Even when the neurologist is not asked to see the child directly, the electroencephalography laboratory may be utilized in the assessment of these children. Many laboratories routinely monitor the ECG during EEG recordings. This has proved useful in detecting cardiac rhythm disorders which may or may not account for the child's symptoms but which should result in referral to a pediatric cardiologist. Until recently, assessment of the QTc has been difficult and rarely performed by electroencephaolographers. After a series of papers (11-13) by a fellow pediatric neurologist, Sidney M. Gospe, MD, PhD, this measurement can now be made quickly and easily. This is thanks to a nomogram available from Grass Instruments, a division of Astro-Med, Inc., designed with Dr. Gospe's input. If the end of a representative T-wave falls in the shaded area of the nomogram (below) it indicates the child has a QTc of 0.44 or greater and should be referred for 12-lead ECG and pediatric cardiology consultation to rule-out LQTS.








This nomogram is available by contacting your Grass-Telefactor sales representative or at Grass-Telefactor online and is found on the page: http://www.grass-telefactor.com/knowledgebase/educational.html. It is accompanied by a booklet that describes Long QT syndrome and its symptoms especially as may be encountered by the pediatric neurologist. 

[see below if you use digital EEG] 

~ Walter C. Allan, MD

References

1. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval, and sudden death. Am Heart J 1957;54:59-68.
2. Romano C, Gemme G, Pongigilione R. Aritmie cardiache rare dellietai-pediatrica. II. Accessi sincopali per fibrillazione ventriculare parossistica. Clin Pediatr (Bologna) 1963;45:656-683.
3. Ward OC. A new familial cardiac syndrome in children. J Irish Med Assoc 1964;54:103-106.
4. Vincent GM, Timothy KW, Leppert M, Keating M. The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. New Engl J Med 1992;327:846-852.
5. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 1995;80:795-803.
6. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT. SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell 1995;80:805-811.
7. Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Shen J, Timothy KW, Vincent GM, de Jager T, Schwartz PJ, Towbin JA, Moss AJ, Atkinson DL, Landes GM, Connors TD, Keating MT Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nature Genet 1996;12:17-23.
8. Zareba W, Moss AJ, Schwartz PJ, Vincent GM, Robinson JL, Priori SG, Benhorin J, Locati EH, Towbin JA, Keating MT, Lehmann MH, Hall WJ, for the International Long-QT Syndrome Registry Research Group. Influence of the genotype on the clinical course of the long-QT syndrome. New Engl J Med 1998;339:960-965.
9. Vincent GM, Fox J, Zhang L, Timothy KW.  Beta-blockers markedly reduce risk and syncope in KVLQT1 long QT patients.  Circulation 1996;94(Suppl.  1) I-204.
10. Schwartz PJ, Locati EH, Napolitano C, Priori SG.  The long QT syndrome.  In Cardiac Electrophysiology: From cell to bedside, ed.  DP Zipes, J Jalife, pp 788-811.  Philadelphia:Saunders, 2nd ed.
11. Gospe SM Jr, Choy M. Hereditary long Q-T syndrome presenting as epilepsy: electroencephalography laboratory diagnosis. Ann Neurol 1989;25:514-516.
12. Gospe SM Jr, Gabor AJ. Electroencephalography laboratory diagnosis of prolonged QT interval. Ann Neurol 1990;28:387-390.
13. Gospe, SM Jr:  Routine monitoring of the electrocardiogram Q-T inteval in the EEG laboratory. Am. J. EEG Technol. 1992;32:58-64.
 


 

Problems presented by digitial EEG

Digital EEG recordings can not be evaluated with the nomogram without a further step. Possible approaches are listed.
  1. The technician can print out representative samples of EEG with ECG at 30mm/sec on routine EEG paper and the nomogram can be applied. The results of this approach would be analyzed as discussed above.
  2. Measurement of the R-R interval and following QT interval can be made on the monitor screen using the time and amplitude scaler. This would produce measurements in seconds. The QTc can be calculated using Bazett's formula:
 
 

QTc Nomogram for routine ECG

(25mm/sec paper speed)


The QTc can be analyzed by using the ECG nomogram below (intended for use with a routine ECG recorded at 25 mm/second). That is, the QT and RR interval in seconds determined by measurement on the monitor can be looked up using the ECG nomogram rather than calculating the QTc by Bazett's formula...