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Febrile Seizures: Current Views and Investigations

Published online by Cambridge University Press:  02 December 2014

Aylin Y. Reid
Affiliation:
Epilepsy & Brain Circuits Program and Hotchkiss Brain Institute, Departments of Neuroscience, University of Calgary, Calgary, Alberta, Canada Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada
Michael A. Galic
Affiliation:
Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada
G. Campbell Teskey
Affiliation:
Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada
Quentin J. Pittman
Affiliation:
Physiology & Pharmacology, University of Calgary, Calgary, Alberta, Canada
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Abstract

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Febrile seizures (FSs) are seizures that occur during fever, usually at the time of a cold or flu, and represent the most common cause of seizures in the pediatric population. Up to 5% of children between the ages of six months and five years-of-age will experience a FS. Clinically these seizures are categorized as benign events with little impact on the growth and development of the child. However, studies have linked the occurrence of FSs to an increased risk of developing adult epileptic disorders. There are many unanswered questions about FSs, such as the mechanism of their generation, the long-term effects of these seizures, and their role in epileptogenesis. Answers are beginning to emerge based on results from animal studies. This review summarizes the current literature on animal models of FSs, mechanisms underlying the seizures, and functional, structural, and molecular changes that may result from them.

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Other
Copyright
Copyright © The Canadian Journal of Neurological 2009

References

1.Berg, AT, Shinnar, S, Hauser, WA, Alemany, M, Shapiro, ED, Salomon, ME, et al.A prospective study of recurrent febrile seizures. N Engl J Med. 1992; 327:11227.CrossRefGoogle ScholarPubMed
2.Verity, CM, Golding, J.Risk of epilepsy after febrile convulsions: a national cohort study. BMJ. 1991; 303:13736.Google Scholar
3.Hauser, WA.The prevalence and incidence of convulsive disorders in children. Epilepsia. 1994; 35 Suppl 2:S16.Google Scholar
4.Nelson, KB, Ellenberg, JH.Prognosis in children with febrile seizures. Pediatrics. 1978; 61:7207.Google Scholar
5.Annegers, JF, Hauser, WA, Shirts, SB, Kurland, LT.Factors prognostic of unprovoked seizures after febrile convulsions. N Engl J Med. 1987; 316:4938.Google Scholar
6.Frantzen, E, Lennox-Buchthal, M, Nygaard, A.Longitudinal EEG and clinical study of children with febrile convulsions. Electroencephalogr Clin Neurophysiol. 1968; 24:197212.Google Scholar
7.Falconer, MA, Taylor, DC.Surgical treatment of drug-resistant epilepsy due to mesial temporal sclerosis. Etiology and significance. Arch Neurol. 1968; 19:3531.Google Scholar
8.Lewis, DV.Febrile convulsions and mesial temporal sclerosis. Curr Opin Neurol. 1999; 12:197201.Google Scholar
9.Avishai-Eliner, S, Brunson, KL, Sandman, CA, Baram, TZ.Stressed-out, or in (utero)? Trends Neurosci. 2002; 25:51824.Google Scholar
10.Verity, CM, Greenwood, R, Golding, J.Long-term intellectual and behavioral outcomes of children with febrile convulsions. N Engl J Med. 1998; 338:17238.Google Scholar
11.Chang, YC, Guo, NW, Wang, ST, Huang, CC, Tsai, JJ.Working memory of school-aged children with a history of febrile convulsions: a population study. Neurology. 2001; 57:3742.CrossRefGoogle ScholarPubMed
12.Baram, TZ, Gerth, A, Schultz, L.Febrile seizures: an appropriate-aged model suitable for long-term studies. Brain Res Dev Brain Res. 1997; 98:26570.CrossRefGoogle ScholarPubMed
13.Holtzman, D, Obana, K, Olson, J.Hyperthermia-induced seizures in the rat pup: a model for febrile convulsions in children. Science. 1981; 213:10346.CrossRefGoogle Scholar
14.Lennox, MA, Sibley, WA, Zimmerman, HM.Fever and febrile convulsions in kittens: a clinical, electroencephalographic, and histopathologic study. J Pediatr. 1954; 45:17990.Google Scholar
15.Baram, TZ, Shinnar, S.Febrile seizures. Elsevier. San Diego: Academic Press; 2002.Google Scholar
16.Hjeresen, DL, Diaz, J.Ontogeny of susceptibility to experimental febrile seizures in rats. Dev Psychobiol. 1988; 21:26175.Google Scholar
17.Jiang, W, Duong, TM, de Lanerolle, NC.The neuropathology of hyperthermic seizures in the rat. Epilepsia. 1999; 40:519.CrossRefGoogle ScholarPubMed
18.Berg, AT.Are febrile seizures provoked by a rapid rise in temperature? Am J Dis Child. 1993; 147:11013.Google Scholar
19.Ostberg, JR, Taylor, SL, Baumann, H, Repasky, EA.Regulatory effects of fever-range whole-body hyperthermia on the LPS-induced acute inflammatory response. J Leukoc Biol. 2000; 68:81520.CrossRefGoogle ScholarPubMed
20.Elmquist, JK, Scammell, TE, Saper, CB.Mechanisms of CNS response to systemic immune challenge: the febrile response. Trends Neurosci. 1997; 20:56570.Google Scholar
21.Saper, CB.Neurobiological basis of fever. Ann N Y Acad Sci. 1998; 856:904.Google Scholar
22.van Dam, AM, Poole, S, Schultzberg, M, Zavala, F, Tilders, FJ.Effects of peripheral administration of LPS on the expression of immunoreactive interleukin-1 alpha, beta, and receptor antagonist in rat brain. Ann N Y Acad Sci. 1998; 840:12838.Google Scholar
23.Roth, J, Rummel, C, Barth, SW, Gerstberger, R, Hübschle, T.Molecular aspects of fever and hyperthermia. Neurol Clin. 2006; 24:42139.Google Scholar
24.Dubé, CM, Brewster, AL, Baram, TZ.Febrile seizures: mechanisms and relationship to epilepsy. Brain Dev. 2009; 31:36671.Google Scholar
25.Heida, JG, Boissé, L, Pittman, QJ.Lipopolysaccharide-induced febrile convulsions in the rat: short-term sequelae. Epilepsia. 2004; 45:131729.Google Scholar
26.Heida, JG, Teskey, GC, Pittman, QJ.Febrile convulsions induced by the combination of lipopolysaccharide and low-dose kainic acid enhance seizure susceptibility, not epileptogenesis, in rats. Epilepsia. 2005; 46:1898905.Google Scholar
27.Heida, JG, Pittman, QJ.Causal links between brain cytokines and experimental febrile convulsions in the rat. Epilepsia. 2005; 46:190613.Google Scholar
28.Dubé, C, Chen, K, Eghbal-Ahmadi, M, Brunson, K, Soltesz, I, Baram, TZ.Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term. Ann Neurol. 2000; 47:33644.Google Scholar
29.Dubé, C, Richichi, C, Bender, RA, Chung, G, Litt, B, Baram, TZ.Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis. Brain. 2006; 129:91122.Google Scholar
30.McCaughran, JA, Schechter, N.Experimental febrile convulsions: long-term effects of hyperthermia-induced convulsions in the developing rat. Epilepsia. 1982; 23:17383.Google Scholar
31.El Radhi, AS, Withana, K, Banajeh, S.Recurrence rate of febrile convulsion related to the degree of pyrexia during the first attack. Clin Pediatr (Phila). 1986; 25:3113.Google Scholar
32.El Radhi, AS.Lower degree of fever at the initial febrile convulsion is associated with increased risk of subsequent convulsions. Eur J Paediatr Neurol. 1998; 2:916.Google Scholar
33.Gordon, KE, Dooley, JM, Wood, EP, Bethune, P.Is temperature regulation different in children susceptible to febrile seizures? Can J Neurol Sci. 2009; 36:1925.Google Scholar
34.Tsuboi, T.Epidemiology of febrile and afebrile convulsions in children in Japan. Neurology. 1984; 34:17581.Google Scholar
35.al-Eissa, YA.Febrile seizures: rate and risk factors of recurrence. J Child Neurol. 1995; 10:3159.Google Scholar
36.Armstrong, LE, Casa, DJ, Millard-Stafford, M, Moran, DS, Pyne, SW, Roberts, WO.American College of Sports Medicine position stand. Exertional heat illness during training and competition. Med Sci Sports Exerc. 2007; 39:55672.Google Scholar
37.Qu, L, Liu, X, Wu, C, Leung, LS.Hyperthermia decreases GABAergic synaptic transmission in hippocampal neurons of immature rats. Neurobiol Dis. 2007; 27:3207.Google Scholar
38.Qu, L, Leung, LS.Mechanisms of hyperthermia-induced depression of GABAergic synaptic transmission in the immature rat hippocampus. J Neurochem. 2008; 106:215869.Google Scholar
39.Dubé, C, Brunson, KL, Eghbal-Ahmadi, M, Gonzalez-Vega, R, Baram, TZ.Endogenous neuropeptide Y prevents recurrence of experimental febrile seizures by increasing seizure threshold. J Mol Neurosci. 2005; 25:27584.Google Scholar
40.Pittman, QJ, Naylor, A, Poulin, P, Disturnal, J, Veale, WL, Martin, SM, et al.The role of vasopressin as an antipyretic in the ventral septal area and its possible involvement in convulsive disorders. Brain Res Bull. 1988: 20:88792.Google Scholar
41.Allan, SM, Parker, LC, Collins, B, Davies, R, Luheshi, GN, Rothwell, NJ.Cortical cell death induced by IL-1 is mediated via actions in the hypothalamus of the rat. Proc Natl Acad Sci USA. 2000; 97:55805.Google Scholar
42.Allan, SM, Rothwell, NJ.Cytokines and acute neurodegeneration. Nat Rev Neurosci. 2001; 2:73444.Google Scholar
43.De Simoni, MG, Perego, C, Ravizza, T, Moneta, D, Conti, M, Marchesi, F, et al.Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci. 2000; 12:262333.Google Scholar
44.Eriksson, C, Tehranian, R, Iverfeldt, K, Winblad, B, Schultzberg, M.Increased expression of mRNA encoding interleukin-1beta and caspase-1, and the secreted isoform of interleukin-1 receptor antagonist in the rat brain following systemic kainic acid administration. J Neurosci Res. 2000; 60:26679.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
45.Jankowsky, JL, Patterson, PH.The role of cytokines and growth factors in seizures and their sequelae. Prog Neurobiol. 2001; 63:12549.Google Scholar
46.Lehtimaki, KA, Peltola, J, Koskikallio, E, Keranen, T, Honkaniemi, J.Expression of cytokines and cytokine receptors in the rat brain after kainic acid-induced seizures. Brain Res Mol Brain Res. 2003; 110:25360.Google Scholar
47.Ichiyama, T, Nishikawa, M, Yoshitomi, T, Hayashi, T, Furukawa, S.Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures. Comparison with acute encephalitis/encephalopathy. Neurology. 1998; 50:40711.Google Scholar
48.Lynch, AM, Walsh, C, Delaney, A, Nolan, Y, Campbell, VA, Lynch, MA.Lipopolysaccharide-induced increase in signalling in hippocampus is abrogated by IL-10-a role for IL-1 beta? J Neurochem. 2004; 88:63546.Google Scholar
49.Viviani, B, Bartesaghi, S, Gardoni, F, Vezzani, A, Behrens, MM, Bartfai, T, et al.Interleukin-1beta enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci. 2003; 23:8692700.Google Scholar
50.Hu, S, Sheng, WS, Ehrlich, LC, Peterson, PK, Chao, CC.Cytokine effects on glutamate uptake by human astrocytes. Neuroimmunomodulation. 2000; 7:1539.Google Scholar
51.Bezzi, P, Domercq, M, Brambilla, L, Galli, R, Schols, D, De Clercq, E, et al.CXCR4-activated astrocyte glutamate release via TNFalpha: amplification by microglia triggers neurotoxicity. Nat Neurosci. 2001; 4:70210.Google Scholar
52.Casamenti, F, Prosperi, C, Scali, C, Giovannelli, L, Colivicchi, MA, Faussone-Pellegrini, MS, et al.Interleukin-1beta activates forebrain glial cells and increases nitric oxide production and cortical glutamate and GABA release in vivo: implications for Alzheimer’s disease. Neuroscience. 1999; 91:83142.Google Scholar
53.Wang, S, Cheng, Q, Malik, S, Yang, J.Interleukin-1beta inhibits gamma-aminobutyric acid type A (GABA(A)) receptor current in cultured hippocampal neurons. J Pharmacol Exp Ther. 2000; 292:497504.Google Scholar
54.Helminen, M, Vesikari, T.Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions. Acta Paediatr Scand. 1990; 79:8106.Google Scholar
55.Matsuo, M, Sasaki, K, Ichimaru, T, Nakazato, S, Hamasaki, Y.Increased IL-1beta production from dsRNA-stimulated leukocytes in febrile seizures. Pediatr Neurol. 2006; 35:1026.Google Scholar
56.Pociot, F, Mølvig, J, Wogensen, L, Worsaae, H, Nerup, J.A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest. 1992; 22:396402.Google Scholar
57.Kira, R, Torisu, H, Takemoto, M, Nomura, A, Sakai, Y, Sanefuji, M, et al.Genetic susceptibility to simple febrile seizures: interleukin-1beta promoter polymorphisms are associated with sporadic cases. Neurosci Lett. 2005; 384:23944.Google Scholar
58.Virta, M, Hurme, M, Helminen, M.Increased frequency of interleukin-1beta (-511) allele 2 in febrile seizures. Pediatr Neurol. 2002; 26:1925.Google Scholar
59.Kanemoto, K, Kawasaki, J, Yuasa, S, Kumaki, T, Tomohiro, O, Kaji, R, et al.Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion. Epilepsia. 2003; 44:7969.Google Scholar
60.Serdaroğlu, G, Alpman, A, Tosun, A, Pehlivan, S, Ozkinay, F, Tekgül, H, Gökben, S.Febrile seizures: interleukin 1beta and interleukin-1 receptor antagonist polymorphisms. Pediatr Neurol. 2009; 40:1136.Google Scholar
61.Lahat, E, Livne, M, Barr, J, Katz, Y.Interleukin-1beta levels in serum and cerebrospinal fluid of children with febrile seizures. Pediatr Neurol. 1997; 17:346.Google Scholar
62.Tomoum, HY, Badawy, NM, Mostafa, AA, Harb, MY.Plasma interleukin-1beta levels in children with febrile seizures. J Child Neurol. 2007; 22:68992.CrossRefGoogle ScholarPubMed
63.Haspolat, S, Anlar, B, Köse, G, Coskun, M, Yegin, O.Interleukin-1beta, interleukin-1 receptor antagonist levels in patients with subacute sclerosing panencephalitis and the effects of different treatment protocols. J Child Neurol. 2001; 16:41720.Google Scholar
64.Riazi, K, Galic, MA, Kuzmiski, JB, Ho, W, Sharkey, KA, Pittman, QJ.Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation. Proc Natl Acad Sci USA. 2008; 105:171516.Google Scholar
65.Konsman, JP, Veeneman, J, Combe, C, Poole, S, Luheshi, GN, Dantzer, R.Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide. Eur J Neurosci. 2008; 28:2499510.Google Scholar
66.Rummel, C, Inoue, W, Sachot, C, Poole, S, Hübschle, T, Luheshi, GN.Selective contribution of interleukin-6 and leptin to brain inflammatory signals induced by systemic LPS injection in mice. J Comp Neurol. 2008; 511:37395.Google Scholar
67.Hart, Y.Rasmussen’s encephalitis. Epileptic Disord. 2004; 6:13344.Google Scholar
68.Hart, YM, Cortez, M, Andermann, F, Hwang, P, Fish, DR, Dulac, O, et al.Medical treatment of Rasmussen’s syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients. Neurology 1994; 44:10306.Google Scholar
69.Walter, GF, Renella, RR.Epstein-Barr virus in brain and Rasmussen’s encephalitis. Lancet. 1989; 1:27980.Google Scholar
70.Power, C, Poland, SD, Blume, WT, Girvin, JP, Rice, GP.Cytomegalo-virus and Rasmussen’s encephalitis. Lancet. 1990; 336:12824.Google Scholar
71.Farrell, MA, DeRosa, MJ, Curran, JG, Secor, DL, Cornford, ME, Comair, YG, et al.Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy. Acta Neuropathol. 1992; 83: 24659.Google Scholar
72.O’Meara, M, Ouvrier, R.Viral encephalitis in children. Curr Opin Pediatr. 1996; 8: 115.Google Scholar
73.Panayiotopoulos, CP, Michael, M, Sanders, S, Valeta, T, Koutroumanidis, M.Benign childhood focal epilepsies: assessment of established and newly recognized syndromes. Brain. 2008; 131:226486.Google Scholar
74.Scheffer, IE, Harkin, LA, Grinton, BE, Dibbens, LM, Turner, SJ, Zielinski, MA, et al.Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. Brain. 2007; 130:1009.Google Scholar
75.Harkin, LA, McMahon, JM, Iona, X, Dibbens, L, Pelekanos, JT, Zuberi, SM, et al.The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain. 2007; 130:84352.Google Scholar
76.Dubé, C, Vezzani, A, Behrens, M, Bartfai, T, Baram, TZ.Interleukin-1beta contributes to the generation of experimental febrile seizures. Ann Neurol. 2005; 57:1525.Google Scholar
77.Gadomski, AM, Permutt, T, Stanton, B.Correcting respiratory rate for the presence of fever. J Clin Epidemiol. 1994; 47:10439.Google Scholar
78.Taylor, JA, Del Beccaro, M, Done, S, Winters, W.Establishing clinically relevant standards for tachypnea in febrile children younger than 2 years. Arch Pediatr Adolesc Med. 1995; 149: 2837.CrossRefGoogle Scholar
79.Kaila, K, Ransom, B. 1998. Concept of pH and its importance in neurobiology. In: pH and Brain Function. Kaila, K, Ransom, B, editors. New York: Wiley-Liss; 1998. p. 310.Google Scholar
80.Jarolimek, W, Misgeld, U, Lux, HD.Activity dependent alkaline and acid transients in guinea pig hippocampal slices. Brain Res. 1989; 505:22532.Google Scholar
81.Schuchmann, S, Vanhatalo, S, Kaila, K.Neurobiological and physiological mechanisms of fever-related epileptiform syndromes. Brain Dev. 2009; 31:37882.Google Scholar
82.Schuchmann, S, Schmitz, D, Rivera, C, Vanhatalo, S, Salmen, B, Mackie, K, et al.Experimental febrile seizures are precipitated by a hyperthermia-induced respiratory alkalosis. Nat Med. 2006; 12:81723.Google Scholar
83.Schuchmann, S, Tolner, EA, Marshall, P, Vanhatalo, S, Kaila, K.Pronounced increase in breathing rate in the “hair dryer model” of experimental febrile seizures. Epilepsia. 2008; 49:9268.Google Scholar
84.Bocti, C, Robitaille, Y, Diadori, P, Lortie, A, Mercier, C, Bouthillier, A, et al.The pathological basis of temporal lobe epilepsy in childhood. Neurology. 2003; 60:1915.Google Scholar
85.Germano, IM, Zhang, YF, Sperber, EF, Moshé, SL.Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats. Epilepsia. 1996; 37:90210.Google Scholar
86.Scantlebury, MH, Ouellet, PL, Psarropoulou, C, Carmant, L.Freeze lesion-induced focal cortical dysplasia predisposes to atypical hyperthermic seizures in the immature rat. Epilepsia. 2004; 45: 592600.Google Scholar
87.Scantlebury, MH, Gibbs, SA, Foadjo, B, Lema, P, Psarropoulou, C, Carmant, L.Febrile seizures in the predisposed brain: a new model of temporal lobe epilepsy. Ann Neurol. 2005; 58:419.Google Scholar
88.Gibbs, SA, Scantlebury, MH, Awad, P, Lema, P, Essouma, JB, Parent, M, et al.Hippocampal atrophy and abnormal brain development following a prolonged hyperthermic seizure in the immature rat with a focal neocortical lesion. Neurobiol Dis. 2008; 32:17682.Google Scholar
89.Vestergaard, M, Pedersen, CB, Sidenius, P, Olsen, J, Christensen, J.The long-term risk of epilepsy after febrile seizures in susceptible subgroups. Am J Epidemiol. 2007; 165:9118.Google Scholar
90.Camfield, P, Camfield, C, Gordon, K, Dooley, J.What types of epilepsy are preceded by febrile seizures? A population-based study of children. Dev Med Child Neurol. 1994; 36:88792.Google Scholar
91.Tarkka, R, Pääkkö, E, Pyhtinen, J, Uhari, M, Rantala, H.Febrile seizures and mesial temporal sclerosis: no association in a long-term follow-up study. Neurology. 2003; 60:2158.Google Scholar
92.Pittau, F, Bisulli, F, Mai, R, Fares, JE, Vignatelli, L, Labate, A, et al.Prognostic factors in patients with mesial temporal lobe epilepsy. Epilepsia. 2009; 50 Suppl 1:414.Google Scholar
93.Kanemoto, K, Takuji, N, Kawasaki, J, Kawai, I.Characteristics and treatment of temporal lobe epilepsy with a history of complicated febrile convulsion. J Neurol Neurosurg Psychiatry. 1998; 64:2458.Google Scholar
94.Schmidt, D, Tsai, JJ, Janz, D.Febrile seizures in patients with complex partial seizures. Acta Neurol Scand. 1985; 72:6871.Google Scholar
95.Janszky, J, Schulz, R, Ebner, A.Clinical features and surgical outcome of medial temporal lobe epilepsy with a history of complex febrile convulsions. Epilepsy Res. 2003; 55:18.Google Scholar
96.Abou-Khalil, B, Andermann, E, Andermann, F, Olivier, A, Quesney, LF.Temporal lobe epilepsy after prolonged febrile convulsions: excellent outcome after surgical treatment. Epilepsia. 1993; 34:87883.Google Scholar
97.Kwak, SE, Kim, JE, Kim, SC, Kwon, OS, Choi, SY, Kang, TC.Hyperthermic seizure induces persistent alteration in excitability of the dentate gyrus in immature rats. Brain Res. 2008; 1216: 115.Google Scholar
98.Ateş, N, Akman, O, Karson, A.The effects of the immature rat model of febrile seizures on the occurrence of later generalized tonicclonic and absence epilepsy. Brain Res Dev Brain Res. 2005; 154:13740.Google Scholar
99.Theodore, WH, DeCarli, C, Gaillard, WD.Total cerebral volume is reduced in patients with localization-related epilepsy and a history of complex febrile seizures. Arch Neurol. 2003; 60: 2502.Google Scholar
100.Ellenberg, JH, Nelson, KB.Febrile seizures and later intellectual performance. Arch Neurol. 1978; 35:1721.Google Scholar
101.Chang, YC, Guo, NW, Huang, CC, Wang, ST, Tsai, JJ.Neurocognitive attention and behavior outcome of school-age children with a history of febrile convulsions: a population study. Epilepsia. 2000; 41:41220.Google Scholar
102.Mesquita, AR, Tavares, HB, Silva, R, Sousa, N.Febrile convulsions in developing rats induce a hyperanxious phenotype later in life. Epilepsy Behav. 2006; 9:4016.Google Scholar
103.Werboff, J, Havlena, J.Febrile convulsions in infant rats, and later behavior. Science. 1963; 142:6845.Google Scholar
104.Kornelsen, RA, Boon, F, Leung, LS, Cain, DP.The effects of a single neonatally induced convulsion on spatial navigation, locomotor activity and convulsion susceptibility in the adult rat. Brain Res. 1996; 706:1559.Google Scholar
105.Lemmens, EM, Aendekerk, B, Schijns, OE, Blokland, A, Beuls, EA, Hoogland, G.Long-term behavioral outcome after early-life hyperthermia-induced seizures. Epilepsy Behav. 2009; 14: 30915.Google Scholar
106.Nealis, JG, Rosman, NP, De Piero, TJ, Ouellette, EM.Neurologic sequelae of experimental febrile convulsions. Neurology. 1978; 28:24650.Google Scholar
107.Chang, YC, Huang, AM, Kuo, YM, Wang, ST, Chang, YY, Huang, CC.Febrile seizures impair memory and cAMP response-element binding protein activation. Ann Neurol. 2003; 54:70618.Google Scholar
108.Provenzale, JM, Barboriak, DP, VanLandingham, K, MacFall, J, Delong, D, Lewis, DV.Hippocampal MRI signal hyperintensity after febrile status epilepticus is predictive of subsequent mesial temporal sclerosis. AJR Am J Roentgenol. 2008; 190:97683.Google Scholar
109.Hesdorffer, DC, Chan, S, Tian, H, Allen Hauser, W, Dayan, P, Leary, LD, et al.Are MRI-detected brain abnormalities associated with febrile seizure type? Epilepsia. 2008; 49:76571.Google Scholar
110.Natsume, J, Bernasconi, N, Miyauchi, M, Naiki, M, Yokotsuka, T, Sofue, A, et al.Hippocampal volumes and diffusion-weighted image findings in children with prolonged febrile seizures. Acta Neurol Scand Suppl. 2007; 186:258.Google Scholar
111.Scott, RC, King, MD, Gadian, DG, Neville, BG, Connelly, A.Hippocampal abnormalities after prolonged febrile convulsion: a longitudinal MRI study. Brain. 2003; 126:25517.Google Scholar
112.Auer, T, Barsi, P, Bone, B, Angyalosi, A, Aradi, M, Szalay, C, et al.History of simple febrile seizures is associated with hippocampal abnormalities in adults. Epilepsia. 2008; 49:15629.Google Scholar
113.Dubé, C, Yu, H, Nalcioglu, O, Baram, TZ.Serial MRI after experimental febrile seizures: altered T2 signal without neuronal death. Ann Neurol. 2004; 56:70914.Google Scholar
114.Bender, RA, Dubé, C, Gonzalez-Vega, R, Mina, EW, Baram, TZ.Mossy fiber plasticity and enhanced hippocampal excitability, without hippocampal cell loss or altered neurogenesis, in an animal model of prolonged febrile seizures. Hippocampus. 2003; 13:399412.Google Scholar
115.Toth, Z, Yan, XX, Haftoglou, S, Ribak, CE, Baram, TZ.Seizure-induced neuronal injury: vulnerability to febrile seizures in an immature rat model. J Neurosci. 1998; 18:428594.Google Scholar
116.Sendrowski, K, Sobaniec, W, Sobaniec-Lotowska, ME, Artemowicz, B.Topiramate as a neuroprotectant in the experimental model of febrile seizures. Adv Med Sci. 2007; 52 Suppl 1:1615.Google Scholar
117.Lemmens, EM, Lubbers, T, Schijns, OE, Beuls, EA, Hoogland, G.Gender differences in febrile seizure-induced proliferation and survival in the rat dentate gyrus. Epilepsia. 2005; 46:160312.Google Scholar
118.Lemmens, EM, Schijns, OE, Beuls, EA, Hoogland, G.Cytogenesis in the dentate gyrus after neonatal hyperthermia-induced seizures: what becomes of surviving cells? Epilepsia. 2008; 49:85360.Google Scholar
119.Pape, HC.Queer current and pacemaker: the hyperpolarization-activated cation current in neurons. Annu Rev Physiol. 1996; 58: 299327.Google Scholar
120.Siegelbaum, SA.Presynaptic facilitation by hyperpolarization-activated pacemaker channels. Nat Neurosci. 2000; 3:1012.Google Scholar
121.Chen, K, Aradi, I, Thon, N, Eghbal-Ahmadi, M, Baram, TZ, Soltesz, I.Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability. Nat Med. 2001; 7:3317.Google Scholar
122.Brewster, A, Bender, RA, Chen, Y, Dubé, C, Eghbal-Ahmadi, M, Baram, TZ.Developmental febrile seizures modulate hippocampal gene expression of hyperpolarization-activated channels in an isoform- and cell-specific manner. J Neurosci. 2002; 22:45919.Google Scholar
123.Brewster, AL, Bernard, JA, Gall, CM, Baram, TZ.Formation of heteromeric hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the hippocampus is regulated by developmental seizures. Neurobiol Dis. 2005; 19:2007.Google Scholar
124.Kamal, A, Notenboom, RG, de Graan, PN, Ramakers, GM.Persistent changes in action potential broadening and the slow afterhyperpolarization in rat CA1 pyramidal cells after febrile seizures. Eur J Neurosci. 2006; 23:22304.Google Scholar
125.Richichi, C, Brewster, AL, Bender, RA, Simeone, TA, Zha, Q, Yin, HZ, et al.Mechanisms of seizure-induced ‘transcriptional channelopathy’ of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Neurobiol Dis. 2008; 29:297305.Google Scholar
126.Chen, K, Baram, TZ, Soltesz, I.Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nat Med. 1999; 5:88894.Google Scholar
127.Chen, K, Ratzliff, A, Hilgenberg, L, Gulyás, A, Freund, TF, Smith, M, et al.Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures. Neuron. 2003; 39:599611.Google Scholar
128.González Ramírez, M, Orozco Suárez, S, Salgado Ceballos, H, Feria Velasco, A, Rocha, L.Hyperthermia-induced seizures modify the GABA(A) and benzodiazepine receptor binding in immature rat brain. Cell Mol Neurobiol. 2007; 27:21127.Google Scholar
129.Han, Y, Qin, J, Bu, DF, Chang, XZ, Yang, ZX.Successive alterations of hippocampal gamma-aminobutyric acid B receptor subunits in a rat model of febrile seizure. Life Sci. 2006; 78:294452.Google Scholar
130.Tsai, ML, Leung, LS.Decrease of hippocampal GABA B receptor-mediated inhibition after hyperthermia-induced seizures in immature rats. Epilepsia. 2006; 47:27787.Google Scholar