Could sudden cardiac death in epilepsy be related to the occurrence of thalamic dysfunction or anatomic change?

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1. Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol 2003;16:165-170.

2. Annegers JF. Epidemiology of epilepsy. In: Wyllie E (ed). The treat-ment of epilepsy: principles and practice. 2nd ed. Baltimore: Williams & Wilkins, 1997:165-172.

3. Begley CE, Annegers JF, Lairson LB, Reynolds TF. Epilepsy incidence, prognosis, and use of medical care in Houston, Texas, and Rochester, Minnesota. Epilepsia 1998;39:222.

<XHQ$:6DQGHU-:,VRPHJDIDWW\DFLGGHÀFLHQF\DIDFWRUFRQ

-tributing to refractory seizures and SUDEP? A hypothesis. Seizure 2004;13:104-107.

5. Sander JW. Some aspects of prognosis in the epilepsies: a review. Epi-lepsia 1993;34:1007-1016.

6. Kwan P, Sander JW. The natural history of epilepsy: an epidemiologi-cal view. J Neurol Neurosurg Psychiatry 2004;75:1376-1381. 7. Halatchev VN. Epidemiology of epilepsy-recent achievements and

fu-ture. Folia Medica 2000;42:17-22.

8. Duncan JS, Sander JW, Sisodiya SM, Walker MC. Adult epilepsy. Lan-cet 2006;367:1087-1100.

9. Nashef L. Sudden unexpected death in epilepsy: terminology and def-initions. Epilepsia 1997;38:S6-8.

10. Tomson T, Walczak T, Sillanpaa M, Sander JW. Sudden unexpected death in epilepsy: a review of incidence and risk factors. Epilepsia 2005;46:54-61.

11. 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.

12. Tennis P, Cole TB, Annegers JF, Leestma JE, McNutt M, Rajput A. Co-hort study of incidence of sudden unexplained death in persons with seizure disorder treated with antiepileptic drugs in Saskatchewan, Can-ada. Epilepsia 1995;36:29-36.

13. Nashef L, Fish DR, Sander JW, Shorvon SD. Incidence of sudden unex-pected death in an adult outpatient cohort with epilepsy at a tertiary referral centre. J Neurol Neurosurg Psychiatry 1995;58:462-464. 14. Ficker DM, So EL, Shen WK, et al. Population-based study of the

incidence of sudden unexplained death in epilepsy. Neurology 1998;515:1270-1274.

15. Lhatoo SD, Johnson AL, Goodridge DM, MacDonald BK, Sander JW,

=`^*%>iXg_`Zi\gi\j\ekXk`fef]k_\ZldlcXk`m\]i\hl\eZpf]jgfekX$ e\fljj\`qli\jg\in\\b[\k\Zk\[`ej_XdXe[\og\i`d\ekXc^iflgj# Y\]fi\Xe[X]k\ijXc`e\fi`Yfk\e`ZXZ`[`ea\Zk`fej`ekfcXk\iXcgfjk\i`$ fik_XcXd`ZelZc\`CG %;XkXXi\\ogi\jj\[Xjd\XepJ;%!g'%',%

(+*

6KRUYRQ6'0RUWDOLW\LQHSLOHSV\LQWKHÀUVWWR\HDUVDIWHUGLDJ

-nosis: multivariate analysis of a long-term, prospective, population-based cohort. Ann Neurol 2001;49:336-344.

16. Medical Research Council. Antiepileptic Drug Withdrawal Study Group. Randomised study of antiepileptic drug withdrawal in patients in remission. Lancet 1991;337:1175-1180.

17. 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.

18. Walczak TS, Leppik IE, D’Amelio M et al. Incidence and risk factors in sudden unexpected death in epilepsy: a prospective cohort study. Neu-rology 2001;56:519-525.

19. Sperling MR, Feldman H, Kinman J, Liporace JD, O’Connor MJ. Sei-zure control and mortality in epilepsy. Ann Neurol 1999;46:45-50. 20. Langan Y, Nashef L, Sander JW. Case-control study of SUDEP.

Neurol-ogy 2005;64:1131-1133.

21. Kloster R, Engelskjon T. Sudden unexpected death in epilepsy (SUDEP): a clinical perspective and a search for risk factors. J Neurol Neurosurg Psychiatry 1999;67:439-444.

22. Nilsson L, Bergman U, Diwan V, Farahmand BY, Persson PG, Tomson T. Antiepileptic drug therapy and its management in sudden unexpect-ed death in epilepsy: a case-control study. Epilepsia 2001;42:667-673. 23. Scorza FA, de Albuquerque M, Arida RM, Cavalheiro EA. Sudden

un-expected death in epilepsy: are winter temperatures a new potential risk factor? Epilepsy Behav 2007;10:509-510.

6WROOEHUJHU&)LQVWHUHU-&DUGLRUHVSLUDWRU\ÀQGLQJVLQVXGGHQXQ

-explained/unexpected death in epilepsy (SUDEP). Epilepsy Res 2004;59:51-60.

25. Wang GH. Johann Paul Karplus (1866-1936) and Alois Kreidl (1864-1928): two pioneers in the study of central mechanisms of vegetative function. Buu Hist Med 1965;39:529-539.

26. Burdenko N, Mogilnitzki BZ. Zur pathogenese einiger Formen dês Runden-Magen-Darm geschwürs. Ztschr ges Neurol Psychiat 1926;103:42.

27. Selye H. The chemical prevention of cardiac necrosis. New York. Ron-ald Press, 1958.

28. Delgado JM. Circulatory effects of cortical stimulation. Physiol Rev 1960;4:146-178.

29. Melville KI, Garvey HL, Shister HE, Knaack J. Central nervous system stimulation and cardiac ischemic changes in monkeys. Ann N Y Acad Sci 1969;156:241-260.

30. Kisin IE, Sinitsyn LN. Prevention of disorders of myocardial blood sup-ply, caused by the stimulation of the cerebral cortex by pharmacologic agents. Vestn Akad Med Nauk 1963;18:18-23.

31. Raab W, Chaplin Jp, Bajusz E. Myocardial necroses produced in domes-ticated rats and in wild rats by sensory and emotional stresses. Proc Soc Exp Biol Med 1964;116:665-669.

32. Smookler HH, Severs WB, Kinnard WJ, Buckley JP. Centrally medi-ated cardiovascular effects of angiotensin II. J Pharmacol Exp Ther 1966;153:485-494.

33. Severs WB, Daniels AE, Smookler HH, Kinnard WJ, Buckley JP. Inter-relationship between angiotensin II and the sympathetic nervous sys-tem. J Pharmacol Exp Ther 1966;153:530-537.

34. Carroll MN Jr, Golinko RJ, Lyon AF, Dunst M, Rene HF Jr, Ford DH. CNS-evoked coronary changes and cardiac arrhythmias-anti-ar-rhythmic properties of mebutamate. Arch Int Pharmacodyn Ther 1968;171:462-474.

35. Klouda MA, Brynjolfsson G. Cardiotoxic effects of electrical stimula-tion of the stellate ganglia. Ann N Y Acad Sci 1969;156:271-280.

36. Powell DA, Milligan WL, Mull P. Lateral septal lesions enhance condi-tioned bradycardia in the rabbit. J Comp Physiol Psychol 1982;96:742-754. 37. Powell DA, Buchanan S, Hernandez L. Electrical stimulation of insular cortex elicits cardiac inhibition but insular lesions do not abolish con-ditioned bradycardia in rabbits. Behav Brain Res 1985;17:125-144. 38. Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular

ef-fects of human insular cortex stimulation. Neurology 1992;42:1727-1732. 39. Sampaio KN, Mauad H, Biancardi VC, et al. Cardiovascular changes following acute and chronic chemical lesions of the dorsal periaque-ductal gray in conscious rats. J Auton Nerv Syst 1999;76:99-107. 40. Pedrino GR, Nakagawa Sera CT, Cravo SL, Colombari DS.

Anteroven-tral third ventricle lesions impair cardiovascular responses to intrave-nous hypertonic saline infusion. Auton Neurosci 2005;117:9-16. 41. Leestma JE, Walczak T, Hughes JR, Kalelkar MB, Teas SS. A prospective

study on sudden unexpected death in epilepsy. Ann Neurol 1989;26: 195-203.

42. Devinsky O, Pacia S, Tatambhotla G. Bradycardia and asystole in-duced by partial seizures: a case report and literature review. Neurol-ogy 1997;48:1712-1714.

43. Norden AD, Blumenfeld H. The role of subcortical structures in human epilepsy. Epilepsy Behav 2002;3:219-231.

44. Jasper HH, Droogleever-Fortuyn J. Experimental studies on the func-tional anatomy of pett mal epilepsy. Res Publ Ass Nerv Ment Dis 1947;26:272-298.

45. Macchi G, Bentivoglio M, Minciacchi D, Molinari. Trends in the

anatom-LFDORUJDQL]DWLRQDQGIXQFWLRQDOVLJQLÀFDQFHRIWKHPDPPDOLDQWKDOD

-mus. Ital J Neurol Sci 1996;17:105-129.

46. Faull RLM, Mehler WR. Thalamus. In: Paxinos G (ed.). The rat nervous system. Vol 1: Forebrain and midbrain. Sydney: Academic Press Aus-tralia, 1985:129-168.

47. Bonilha L, Kobayashi E, Rorden C, Cendes F, Li LM. Medial tempo-ral lobe atrophy in patients with refractory tempotempo-ral lobe epilepsy. J Neurol Neurosurg Psychiatry 2003;74:1627-1630.

48. Bonilha L, Kobayashi E, Cendes F, Min Li L. Protocol for volumetric segmentation of medial temporal structures using high-resolution 3-D magnetic resonance imaging. Hum Brain Mapp 2004;22:145-154. 49. Bernasconi N, Bernasconi A, Caramanos Z, Andermann F, Dubeau F,

Arnold DL. Morphometric MRI analysis of the parahippocampal re-gion in temporal lobe epilepsy. Ann N Y Acad Sci 2000;911:495-500. 50. Bonilha L, Rorden C, Castellano G, Cendes F, Li LM. Voxel-based

mor-phometry of the thalamus in patients with refractory medial temporal lobe epilepsy. Neuroimage 2005;25:1016-1021.

51. Scorza FA, Sanabria ERG, Calderazzo L, Cavalheiro EA. Glucose utili-zation during interictal intervals in an epilepsy model induced by pilo-carpine: a qualitative study. Epilepsia 1998;39:1041-1045.

52. Scorza FA, Arida RM, Priel M, Calderazzo L, Cavalheiro EA. The con-tribution of the lateral posterior and anteroventral thalamic nuclei on spontaneous recurrent seizures in the pilocarpine model of epilepsy. Arq Neuropsiquiatr 2002;60:572-575.

53. Betting LE, Mory SB, Li LM, Lopes-Cendes I, Guerreiro MM, Guerreiro CA, Cendes F. Voxel-based morphometry in patients with idiopathic generalized epilepsies. Neuroimage 2006;32:498-502.

54. Betting LE, Mory SB, Lopes-Cendes I, Li LM, Guerreiro MM, Guerreiro CA, Cendes F. MRI volumetry shows increased anterior thalamic vol-umes in patients with absence seizures. Epilepsy Behav 2006;8:575-580. 55. Boyko WJ, Galabru CK, McGeer EG, McGeer PL. Thalamic injections

of kainic acid produce myocardial necrosis. Life Sci 1979;25:87-98. 56. Colugnati DB, Gomes PA, Arida RM, et al. Analysis of cardiac