Abstract
Objectives: Disorders of cardiovascular and other autonomic nervous system functions are often found in patients with temporal lobe epilepsy (TLE). Cardiovascular dysregulation in TLE has previously been quantified assessing traditional time and frequency domain measures of heart rate (HR) variability from short term ECG recordings. However, new complexity and fractal measures of HR variability based on non-linear dynamics and fractals ("chaos theory") may disclose certain patterns of HR dynamics that cannot be detected using only conventional measures.
Methods: In addition to the traditional spectral and non-spectral components of HR variability, fractal correlation properties, approximate entropy (ApEn) of RR interval dynamics, and the slope of the power law relation were measured from 24 hour ambulatory ECG recordings to evaluate interictal autonomic cardiovascular regulatory function in 19 patients with refractory TLE, 25 patients with well controlled TLE, and in 34 healthy age and sex matched control subjects.
Results: The traditional time and frequency domain measures were lower in patients with TLE than in controls (p<0.05). In addition, the power law slope (p<0.005) and ApEn (p<0.05) were also reduced in TLE patients. Furthermore, ApEn was smaller in patients with refractory TLE than in patients with well-controlled TLE ( p<0.01), whereas the long term fractal correlation value α2 was lower in patients with well controlled TLE (p<0.05). An altered HR variation was not associated with any particular AED regimen.
Conclusions: In addition to reduced overall HR variability, the long term fractal organisation and complexity of HR dynamics seem to be altered in TLE. These abnormalities in HR behaviour may partly contribute to the occurrence of adverse cardiovascular events, such as life threatening arrhythmias in patients with TLE.
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Selected References
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- Ansakorpi H., Korpelainen J. T., Suominen K., Tolonen U., Myllylä V. V., Isojärvi J. I. Interictal cardiovascular autonomic responses in patients with temporal lobe epilepsy. Epilepsia. 2000 Jan;41(1):42–47. doi: 10.1111/j.1528-1157.2000.tb01503.x. [DOI] [PubMed] [Google Scholar]
- Bigger J. T., Jr, Steinman R. C., Rolnitzky L. M., Fleiss J. L., Albrecht P., Cohen R. J. Power law behavior of RR-interval variability in healthy middle-aged persons, patients with recent acute myocardial infarction, and patients with heart transplants. Circulation. 1996 Jun 15;93(12):2142–2151. doi: 10.1161/01.cir.93.12.2142. [DOI] [PubMed] [Google Scholar]
- Brouwer J., van Veldhuisen D. J., Man in 't Veld A. J., Haaksma J., Dijk W. A., Visser K. R., Boomsma F., Dunselman P. H. Prognostic value of heart rate variability during long-term follow-up in patients with mild to moderate heart failure. The Dutch Ibopamine Multicenter Trial Study Group. J Am Coll Cardiol. 1996 Nov 1;28(5):1183–1189. doi: 10.1016/s0735-1097(96)00279-3. [DOI] [PubMed] [Google Scholar]
- Denton T. A., Diamond G. A., Helfant R. H., Khan S., Karagueuzian H. Fascinating rhythm: a primer on chaos theory and its application to cardiology. Am Heart J. 1990 Dec;120(6 Pt 1):1419–1440. doi: 10.1016/0002-8703(90)90258-y. [DOI] [PubMed] [Google Scholar]
- Devinsky O., Perrine K., Theodore W. H. Interictal autonomic nervous system function in patients with epilepsy. Epilepsia. 1994 Jan-Feb;35(1):199–204. doi: 10.1111/j.1528-1157.1994.tb02933.x. [DOI] [PubMed] [Google Scholar]
- Fleisher L. A., Pincus S. M., Rosenbaum S. H. Approximate entropy of heart rate as a correlate of postoperative ventricular dysfunction. Anesthesiology. 1993 Apr;78(4):683–692. doi: 10.1097/00000542-199304000-00011. [DOI] [PubMed] [Google Scholar]
- Frysinger R. C., Engel J., Harper R. M. Interictal heart rate patterns in partial seizure disorders. Neurology. 1993 Oct;43(10):2136–2139. doi: 10.1212/wnl.43.10.2136. [DOI] [PubMed] [Google Scholar]
- Goldberger A. L. Non-linear dynamics for clinicians: chaos theory, fractals, and complexity at the bedside. Lancet. 1996 May 11;347(9011):1312–1314. doi: 10.1016/s0140-6736(96)90948-4. [DOI] [PubMed] [Google Scholar]
- Ho K. K., Moody G. B., Peng C. K., Mietus J. E., Larson M. G., Levy D., Goldberger A. L. Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics. Circulation. 1997 Aug 5;96(3):842–848. doi: 10.1161/01.cir.96.3.842. [DOI] [PubMed] [Google Scholar]
- Ho K. K., Moody G. B., Peng C. K., Mietus J. E., Larson M. G., Levy D., Goldberger A. L. Predicting survival in heart failure case and control subjects by use of fully automated methods for deriving nonlinear and conventional indices of heart rate dynamics. Circulation. 1997 Aug 5;96(3):842–848. doi: 10.1161/01.cir.96.3.842. [DOI] [PubMed] [Google Scholar]
- Huikuri H. V. Heart rate variability in coronary artery disease. J Intern Med. 1995 Apr;237(4):349–357. doi: 10.1111/j.1365-2796.1995.tb01186.x. [DOI] [PubMed] [Google Scholar]
- Huikuri H. V., Niemelä M. J., Ojala S., Rantala A., Ikäheimo M. J., Airaksinen K. E. Circadian rhythms of frequency domain measures of heart rate variability in healthy subjects and patients with coronary artery disease. Effects of arousal and upright posture. Circulation. 1994 Jul;90(1):121–126. doi: 10.1161/01.cir.90.1.121. [DOI] [PubMed] [Google Scholar]
- Huikuri H. V., Seppänen T., Koistinen M. J., Airaksinen J., Ikäheimo M. J., Castellanos A., Myerburg R. J. Abnormalities in beat-to-beat dynamics of heart rate before the spontaneous onset of life-threatening ventricular tachyarrhythmias in patients with prior myocardial infarction. Circulation. 1996 May 15;93(10):1836–1844. doi: 10.1161/01.cir.93.10.1836. [DOI] [PubMed] [Google Scholar]
- Huikuri H. V., Valkama J. O., Airaksinen K. E., Seppänen T., Kessler K. M., Takkunen J. T., Myerburg R. J. Frequency domain measures of heart rate variability before the onset of nonsustained and sustained ventricular tachycardia in patients with coronary artery disease. Circulation. 1993 Apr;87(4):1220–1228. doi: 10.1161/01.cir.87.4.1220. [DOI] [PubMed] [Google Scholar]
- Isojärvi J. I., Ansakorpi H., Suominen K., Tolonen U., Repo M., Myllylä V. V. Interictal cardiovascular autonomic responses in patients with epilepsy. Epilepsia. 1998 Apr;39(4):420–426. doi: 10.1111/j.1528-1157.1998.tb01394.x. [DOI] [PubMed] [Google Scholar]
- Iyengar N., Peng C. K., Morin R., Goldberger A. L., Lipsitz L. A. Age-related alterations in the fractal scaling of cardiac interbeat interval dynamics. Am J Physiol. 1996 Oct;271(4 Pt 2):R1078–R1084. doi: 10.1152/ajpregu.1996.271.4.R1078. [DOI] [PubMed] [Google Scholar]
- Johnston S. C., Horn J. K., Valente J., Simon R. P. The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol. 1995 Apr;37(4):531–537. doi: 10.1002/ana.410370416. [DOI] [PubMed] [Google Scholar]
- Johnston S. C., Siedenberg R., Min J. K., Jerome E. H., Laxer K. D. Central apnea and acute cardiac ischemia in a sheep model of epileptic sudden death. Ann Neurol. 1997 Oct;42(4):588–594. doi: 10.1002/ana.410420409. [DOI] [PubMed] [Google Scholar]
- Leestma J. E., Annegers J. F., Brodie M. J., Brown S., Schraeder P., Siscovick D., Wannamaker B. B., Tennis P. S., Cierpial M. A., Earl N. L. Sudden unexplained death in epilepsy: observations from a large clinical development program. Epilepsia. 1997 Jan;38(1):47–55. doi: 10.1111/j.1528-1157.1997.tb01076.x. [DOI] [PubMed] [Google Scholar]
- Massetani R., Strata G., Galli R., Gori S., Gneri C., Limbruno U., Di Santo D., Mariani M., Murri L. Alteration of cardiac function in patients with temporal lobe epilepsy: different roles of EEG-ECG monitoring and spectral analysis of RR variability. Epilepsia. 1997 Mar;38(3):363–369. doi: 10.1111/j.1528-1157.1997.tb01129.x. [DOI] [PubMed] [Google Scholar]
- Mäkikallio T. H., Seppänen T., Airaksinen K. E., Koistinen J., Tulppo M. P., Peng C. K., Goldberger A. L., Huikuri H. V. Dynamic analysis of heart rate may predict subsequent ventricular tachycardia after myocardial infarction. Am J Cardiol. 1997 Sep 15;80(6):779–783. doi: 10.1016/s0002-9149(97)00516-x. [DOI] [PubMed] [Google Scholar]
- Mäkikallio T. H., Seppänen T., Niemelä M., Airaksinen K. E., Tulppo M., Huikuri H. V. Abnormalities in beat to beat complexity of heart rate dynamics in patients with a previous myocardial infarction. J Am Coll Cardiol. 1996 Oct;28(4):1005–1011. doi: 10.1016/s0735-1097(96)00243-4. [DOI] [PubMed] [Google Scholar]
- Nashef L., Garner S., Sander J. W., Fish D. R., Shorvon S. D. Circumstances of death in sudden death in epilepsy: interviews of bereaved relatives. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):349–352. doi: 10.1136/jnnp.64.3.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nashef L., Walker F., Allen P., Sander J. W., Shorvon S. D., Fish D. R. Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry. 1996 Mar;60(3):297–300. doi: 10.1136/jnnp.60.3.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nilsson L., Farahmand B. Y., Persson P. G., Thiblin I., Tomson T. Risk factors for sudden unexpected death in epilepsy: a case-control study. Lancet. 1999 Mar 13;353(9156):888–893. doi: 10.1016/s0140-6736(98)05114-9. [DOI] [PubMed] [Google Scholar]
- Oppenheimer S. The anatomy and physiology of cortical mechanisms of cardiac control. Stroke. 1993 Dec;24(12 Suppl):I3–I5. [PubMed] [Google Scholar]
- Peng C. K., Havlin S., Stanley H. E., Goldberger A. L. Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos. 1995;5(1):82–87. doi: 10.1063/1.166141. [DOI] [PubMed] [Google Scholar]
- Pincus S. M. Approximate entropy as a measure of system complexity. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2297–2301. doi: 10.1073/pnas.88.6.2297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pincus S. M., Goldberger A. L. Physiological time-series analysis: what does regularity quantify? Am J Physiol. 1994 Apr;266(4 Pt 2):H1643–H1656. doi: 10.1152/ajpheart.1994.266.4.H1643. [DOI] [PubMed] [Google Scholar]
- Pincus S. M., Viscarello R. R. Approximate entropy: a regularity measure for fetal heart rate analysis. Obstet Gynecol. 1992 Feb;79(2):249–255. [PubMed] [Google Scholar]
- Schraeder P. L., Lathers C. M. Paroxysmal autonomic dysfunction, epileptogenic activity and sudden death. Epilepsy Res. 1989 Jan-Feb;3(1):55–62. doi: 10.1016/0920-1211(89)90068-5. [DOI] [PubMed] [Google Scholar]
- Sperling M. R., Feldman H., Kinman J., Liporace J. D., O'Connor M. J. Seizure control and mortality in epilepsy. Ann Neurol. 1999 Jul;46(1):45–50. doi: 10.1002/1531-8249(199907)46:1<45::aid-ana8>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
- Tennis P., Cole T. B., Annegers J. F., Leestma J. E., McNutt M., Rajput A. Cohort study of incidence of sudden unexplained death in persons with seizure disorder treated with antiepileptic drugs in Saskatchewan, Canada. Epilepsia. 1995 Jan;36(1):29–36. doi: 10.1111/j.1528-1157.1995.tb01661.x. [DOI] [PubMed] [Google Scholar]
- Timmings P. L. Sudden unexpected death in epilepsy: is carbamazepine implicated? Seizure. 1998 Aug;7(4):289–291. doi: 10.1016/s1059-1311(98)80020-4. [DOI] [PubMed] [Google Scholar]
- Tomson T., Ericson M., Ihrman C., Lindblad L. E. Heart rate variability in patients with epilepsy. Epilepsy Res. 1998 Mar;30(1):77–83. doi: 10.1016/s0920-1211(97)00094-6. [DOI] [PubMed] [Google Scholar]
- Vikman S., Mäkikallio T. H., Yli-Mäyry S., Pikkujämsä S., Koivisto A. M., Reinikainen P., Airaksinen K. E., Huikuri H. V. Altered complexity and correlation properties of R-R interval dynamics before the spontaneous onset of paroxysmal atrial fibrillation. Circulation. 1999 Nov 16;100(20):2079–2084. doi: 10.1161/01.cir.100.20.2079. [DOI] [PubMed] [Google Scholar]
- Wannamaker B. B. Autonomic nervous system and epilepsy. Epilepsia. 1985;26 (Suppl 1):S31–S39. doi: 10.1111/j.1528-1157.1985.tb05722.x. [DOI] [PubMed] [Google Scholar]
- Woo M. A., Stevenson W. G., Moser D. K., Middlekauff H. R. Complex heart rate variability and serum norepinephrine levels in patients with advanced heart failure. J Am Coll Cardiol. 1994 Mar 1;23(3):565–569. doi: 10.1016/0735-1097(94)90737-4. [DOI] [PubMed] [Google Scholar]
- XXI Congress of the European Society of Cardiology. Barcelona, Spain, August 28-September 1, 1999. Abstracts. Eur Heart J. 1999 Aug;20(ABSTR):1–753. [PubMed] [Google Scholar]