2007 Heart-Brain summit proceedings

Imad Najm, MD, Director

Epilepsy Center,
Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, S51,
Cleveland, OH 44195

najmi@ccf.org

Lara Jehi, MD

Epilepsy Center, Neurological Institute,
Cleveland Clinic,
Cleveland, OH

Click here for Full Article PDF (Sudden unexpected death in epilepsy: Impact, mechanisms, and prevention)

Click here for the abstract

Back to 2007 Proceedings Contents

ABSTRACT

Patients with refractory epilepsy face an elevated risk of sudden death, with rates as high as 1% per year. This phenomenon, known as sudden unexpected death in epilepsy (SUDEP), is believed to be a seizure-related occurrence, but the exact underlying mechanisms are uncertain. Both pulmonary and cardiac pathophysiologies have been proposed. The cardiac mechanism of greatest interest is the precipitation of arrhythmias by seizure discharges via the autonomic nervous system. SUDEP prevention has centered on effective seizure control, and epilepsy surgery has reduced SUDEP incidence in a number of studies. Additional prophylaxis methods are needed, however, for the large number of patients with treatment-refractory epilepsy. Future research should aim to clarify whether the association between seizures and autonomic dysfunction and cardiac arrhythmias extends to a demonstrable cardiac mechanism for SUDEP.

CITATIONS

1. Nilsson L, Farahmand BY, Persson PG, Thiblin I, Tomson T.
   Risk factors for sudden unexpected death in epilepsy: a case-control study. Lancet 1999; 353:888–893.
   http://www.ncbi.nlm.nih.gov/pubmed/10093982
   
   
   FIGURE 3. Electroencephalographic and electrocardiographic tracings from a patient with ictal bradycardia (A) and then asystole (B) during a right temporal lobe seizure.
   Fp1–F7
   F7–SP1
   SP1–T7
   T7–P7
   P7–O1
   Fp2–F8
   F8–SP2
   SP2–T8
   T8–P8
   P8–O2
   SP1–SP2
   TP9–TP10
   Fp1–F3
   F3–C3
   C3–P3
   P3–O1
   Fp2–F4
   F4–C4
   C4–P4
   P4–O2
   EKG1–EKG2
   200 _V
   Fp1–F7
   F7–SP1
   SP1–T7
   T7–P7
   P7–O1
   Fp2–F8
   F8–SP2
   EKG1–EKG2
   200 _V
   P3–O1
   Fp2–F4
   F4–C4
   C4–P4
   P4–O2
   EKG1–EKG2
   200 _V
   50 _V
   100 _V
   A B
2. Tennis P, Cole TB, Annegers JF, Leestma JE, 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; 36:29–36.
   http://www.ncbi.nlm.nih.gov/pubmed/8001505
3. Dasheiff RM.
   Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and speculation on the relationship to sudden cardiac death. J Clin Neurophysiol 1991; 8:216–222.
   http://www.ncbi.nlm.nih.gov/pubmed/2050822
4. Leestma JE, Annegers JF, Brodie MJ, et al.
   Sudden unexplained death in epilepsy: observations from a large clinical development program. Epilepsia 1997; 38:47–55.
   http://www.ncbi.nlm.nih.gov/pubmed/9024183
5. Sperling MR, Feldman H, Kinman J, Liporace JD, O’Connor MJ.
   Seizure control and mortality in epilepsy. Ann Neurol 1999; 46:45–50.
   http://www.ncbi.nlm.nih.gov/pubmed/10401779
6. Ficker DM.
   Sudden unexplained death and injury in epilepsy. Epilepsia 2000; 41(Suppl 2):S7–S12.
   http://www.ncbi.nlm.nih.gov/pubmed/10885735
7. Pedley TA, Hauser WA.
   Sudden death in epilepsy: a wake-up call for management. Lancet 2002; 359:1790–1791.
   http://www.ncbi.nlm.nih.gov/pubmed/12044369
8. Ficker DM, So EL, Shen WK, et al.
   Population-based study of the incidence of sudden unexplained death in epilepsy. Neurology 1998; 51:1270–1274.
   http://www.ncbi.nlm.nih.gov/pubmed/9818844
9. Monté CP, Arends JB, Tan IY, Aldenkamp AP, Limburg M, de Krom MC.
   Sudden unexpected death in epilepsy patients: risk factors. A systematic review. Seizure 2007; 16:1–7.
   http://www.ncbi.nlm.nih.gov/pubmed/17134918
10. Nashef L, Walker F, Allen P, Sander JW, Shorvon SD, Fish DR.
    Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry 1996; 60:297–300.
    http://www.ncbi.nlm.nih.gov/pubmed/8609507
11. So EL, Sam MC, Lagerlund TL.
    Postictal central apnea as a cause of SUDEP: evidence from near-SUDEP incident. Epilepsia 2000; 41:1494–1497.
    http://www.ncbi.nlm.nih.gov/pubmed/11077466
12. Terrence CF, Rao GR, Perper JA.
    Neurogenic pulmonary edema in unexpected, unexplained death of epileptic patients. Ann Neurol 1981; 9:458–464.
    http://www.ncbi.nlm.nih.gov/pubmed/7271241
13. Johnston SC, Horn JK, Valente J, Simon RP.
    The role of hypoventilation in a sheep model of epileptic sudden death. Ann Neurol 1995; 37:531–537.
    http://www.ncbi.nlm.nih.gov/pubmed/7717690
14. Blumhardt LD, Smith PE, Owen L.
    Electrocardiographic accompaniments of temporal lobe epileptic seizures. Lancet 1986; 1:1051–1056.
    http://www.ncbi.nlm.nih.gov/pubmed/2871334
15. Nei M, Ho RT, Abou-Khalil BW, et al.
    EEG and ECG in sudden unexplained death in epilepsy. Epilepsia 2004; 45:338–345.
    http://www.ncbi.nlm.nih.gov/pubmed/15030496
16. Nei M, Ho RT, Sperling MR.
    EKG abnormalities during partial seizures in refractory epilepsy. Epilepsia 2000; 41:542–548.
    http://www.ncbi.nlm.nih.gov/pubmed/10802759
17. Opherk C, Coromilas J, Hirsch LJ.
    Heart rate and EKG changes in 102 seizures: analysis of influencing factors. Epilepsy Res 2002; 52:117–127.
    http://www.ncbi.nlm.nih.gov/pubmed/12458028
18. Tigaran S, Mølgaard H, McClelland R, Dam M, Jaffe AS.
    Evidence of cardiac ischemia during seizures in drug refractory epilepsy patients. Neurology 2003; 60:492–495.
    http://www.ncbi.nlm.nih.gov/pubmed/12578934
19. Leung H, Kwan P, Elger CE.
    Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy. Epilepsy Behav 2006; 9:19–30.
    http://www.ncbi.nlm.nih.gov/pubmed/16809068
20. Yasui Y, Breder CD, Saper CB, Cechetto DF.
    Autonomic responses and efferent pathways from the insular cortex in the rat. J Comp Neurol 1991; 303:355–374.
    http://www.ncbi.nlm.nih.gov/pubmed/2007654
21. Jokeit H, Noerpel I, Herbord E, Ebner A.
    Heart rate does not decrease after right hemispheric amobarbital injection. Neurology 2000; 54:2347–2348.
    http://www.ncbi.nlm.nih.gov/pubmed/10881273
22. Zamrini EY, Meador KJ, Loring DW, et al.
    Unilateral cerebral inactivation produces differential left/right heart rate responses. Neurology 1990; 40:1408–1411.
    http://www.ncbi.nlm.nih.gov/pubmed/2392227
23. Yoon BW, Morillo CA, Cechetto DF, Hachinski V.
    Cerebral hemispheric lateralization in cardiac autonomic control. Arch Neurol 1997; 54:741–744.
    http://www.ncbi.nlm.nih.gov/pubmed/9193209
24. Keilson MJ, Hauser WA, Magrill JP.
    Electrocardiographic changes during electrographic seizures. Arch Neurol 1989; 46:1169–1170.
    http://www.ncbi.nlm.nih.gov/pubmed/2818251
25. Keilson MJ, Hauser WA, Magrill JP, Goldman M.
    ECG abnormalities in patients with epilepsy. Neurology 1987; 37:1624–1626.
    http://www.ncbi.nlm.nih.gov/pubmed/3658168
26. Galimberti CA, Marchioni E, Barzizza F, Manni R, Sartori I, Tartara A.
    Partial epileptic seizures of different origin variably affect cardiac rhythm. Epilepsia 1996; 37:742–747.
    http://www.ncbi.nlm.nih.gov/pubmed/8764812
27. Liedholm LJ, Gudjonsson O.
    Cardiac arrest due to partial epileptic seizures. Neurology 1992; 42:824–829.
    http://www.ncbi.nlm.nih.gov/pubmed/1565237
28. Leung H, Schindler K, Kwan P, Elger C.
    Asystole induced by electrical stimulation of the left cingulate gyrus. Epileptic Disord 2007; 9:77–81.
    http://www.ncbi.nlm.nih.gov/pubmed/17307716
29. Blum AS, Ives JR, Goldberger AL, et al.
    Oxygen desaturations triggered by partial seizures: implications for cardiopulmonary instability in epilepsy. Epilepsia 2000; 41:536–541.
    http://www.ncbi.nlm.nih.gov/pubmed/10802758
30. Langan Y, Nashef L, Sander JW.
    Case-control study of SUDEP. Neurology 2005; 64:1131–1133.
    http://www.ncbi.nlm.nih.gov/pubmed/15824334
31. Hennessy MJ, Langan Y, Elwes RD, Binnie CD, Polkey CE, Nashef L.
    A study of mortality after temporal lobe epilepsy surgery. Neurology 1999; 53:1276–1283.
    http://www.ncbi.nlm.nih.gov/pubmed/10522885
32. Nilsson L, Ahlbom A, Farahmand BY, Tomson T.
    Mortality in a population-based cohort of epilepsy surgery patients. Epilepsia 2003; 44:575–581.
    http://www.ncbi.nlm.nih.gov/pubmed/12681008
33. Sperling MR, Harris A, Nei M, Liporace JD, O’Connor MJ.
    Mortality after epilepsy surgery. Epilepsia 2005; 46(Suppl 11):49–53.
    http://www.ncbi.nlm.nih.gov/pubmed/16393181
34. Jeha LE, Najm I, Bingaman W, Dinner D, Widdess-Walsh P, Lüders H.
    Surgical outcome and prognostic factors of frontal lobe epilepsy surgery. Brain 2007; 130:574–584.
    http://www.ncbi.nlm.nih.gov/pubmed/17209228
35. Jeha LE, Najm IM, Bingaman WE, et al.
    Predictors of outcome after temporal lobectomy for the treatment of intractable epilepsy. Neurology 2006; 66:1938–1940.
    http://www.ncbi.nlm.nih.gov/pubmed/16801667