The main focus of a nation's health system revolves around the development of
effective strategies and new options of treatment, with the aim of preventing or even
reversing human diseases (11. Scorza FA, Yacubian EM, Calderazzo L, Scorza CA, Albuquerque Md,
Cavalheiro EA. Training and workforce: an expert panel presents a new approach
to epilepsy in the tropics. Clinics. 2013;68(2):127-8,
http://dx.doi.org/10.6061/clinics/2013(02)OA01.
http://dx.doi.org/10.6061/clinics/2013(0...
). The spectrum of
disorders of the brain, part of the central nervous system (CNS), is large, covering
hundreds of disorders that are listed in either the mental or the neurological disorder
chapters of established international diagnostic classification systems. Brain disorders
account for the majority of short- and long-term impairments and disabilities (22. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J,
Beghi E, et al. Eur Neuropsychopharmacol. 2011;21(10):718-79.). As such, the best available estimates of the
prevalence and cost per person for 19 groups of brain disorders in Europe have been
reported (22. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J,
Beghi E, et al. Eur Neuropsychopharmacol. 2011;21(10):718-79.). In brief, the total cost of brain
disorders is estimated at €798 billion (22. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J,
Beghi E, et al. Eur Neuropsychopharmacol. 2011;21(10):718-79.). Furthermore, the European per capita cost of brain disorders is €1550
on average but varies by country (22. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J,
Beghi E, et al. Eur Neuropsychopharmacol. 2011;21(10):718-79.). The costs
(in billion €PPP 2010) of the included brain disorders are as follows: mood
disorders €113.4; dementia: €105.2; psychotic disorders: €93.9;
anxiety disorders: €74.4; addiction: €65.7; stroke: €64.1;
headache: €43.5; mental retardation: €43.3; sleep disorders: €35.4;
traumatic brain injury: €33.0; personality disorders: €27.3;
child/adolescent disorders: €21.3; somatoform disorder: €21.2; multiple
sclerosis: €14.6; Parkinson's disease: €13.9; epilepsy:
€13.82; neuromuscular disorders: €7.7; brain tumor: €5.2 and eating
disorders: €0.8 (22. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J,
Beghi E, et al. Eur Neuropsychopharmacol. 2011;21(10):718-79.).
Leading scientific journals and primary funding agencies suggest that neuroscience is the
most rapidly growing field within the biomedical sciences in the world (11. Scorza FA, Yacubian EM, Calderazzo L, Scorza CA, Albuquerque Md,
Cavalheiro EA. Training and workforce: an expert panel presents a new approach
to epilepsy in the tropics. Clinics. 2013;68(2):127-8,
http://dx.doi.org/10.6061/clinics/2013(02)OA01.
http://dx.doi.org/10.6061/clinics/2013(0...
). For Latin American countries, especially
Brazil, these assertions are especially relevant. For example, Nitrini conducted a study
in 2006 that assessed the evolution of scientific production by 295 Brazilian clinical
neuroscientists from 1995 to 2004 (33. Nitrini R. The scientific production of Brazilian neurologists:
1995-2004. Arq Neuropsiquiatr. 2006;64(2B):538-42,
http://dx.doi.org/10.1590/S0004-282X2006000300037.
http://dx.doi.org/10.1590/S0004-282X2006...
). The author
showed that more than 40% of the Brazilian papers were published in Arquivos de
Neuro-Psiquiatria, the official journal of the Brazilian Academy of Neurology, and that
epilepsy was one of the sub-areas with the highest scientific production (33. Nitrini R. The scientific production of Brazilian neurologists:
1995-2004. Arq Neuropsiquiatr. 2006;64(2B):538-42,
http://dx.doi.org/10.1590/S0004-282X2006000300037.
http://dx.doi.org/10.1590/S0004-282X2006...
). The growing number of publications on epilepsy
detected in this study may be a consequence of several well-established factors. By
definition, epilepsy is a transient occurrence of signs and/or symptoms due to abnormal,
excessive, or synchronous neuronal activity in the brain (44. Engel Jr J, Pedley TA. Introduction: what is epilepsy? Engel Jr
J., Pedley TA. (Eds.), Epilepsy: a comprehensive textbook, Lippincott
Williams & Wilkins-Wolters Kluwer Business, Philadelphia.
2008;1-11.). Furthermore, epilepsy is considered to be the most common
serious neurological condition. Epilepsy knows no geographic, social, or racial
boundaries, it occurs in both men and women, and it affects people of all ages, though
it more frequently affects young people in the first two decades of life and people over
the age of 60 (55. de Boer HM, Mula M, Sander JW. The global burden and stigma of
epilepsy. Epilepsy Behav. 2008;12(4):540-6,
http://dx.doi.org/10.1016/j.yebeh.2007.12.019.
http://dx.doi.org/10.1016/j.yebeh.2007.1...
,66. Sander JW. The epidemiology of epilepsy revisited. Curr Opin
Neurol. 2003;16(2):165-70,
http://dx.doi.org/10.1097/00019052-200304000-00008.
http://dx.doi.org/10.1097/00019052-20030...
). Epilepsy has a prevalence of approximately 1% in developed countries;
each year, 24 per 100,000 persons suffer from this neurological condition in Europe and
53 per 100,000 in North America (11. Scorza FA, Yacubian EM, Calderazzo L, Scorza CA, Albuquerque Md,
Cavalheiro EA. Training and workforce: an expert panel presents a new approach
to epilepsy in the tropics. Clinics. 2013;68(2):127-8,
http://dx.doi.org/10.6061/clinics/2013(02)OA01.
http://dx.doi.org/10.6061/clinics/2013(0...
,33. Nitrini R. The scientific production of Brazilian neurologists:
1995-2004. Arq Neuropsiquiatr. 2006;64(2B):538-42,
http://dx.doi.org/10.1590/S0004-282X2006000300037.
http://dx.doi.org/10.1590/S0004-282X2006...
,77. Forsgren L, Beghi E, Oun A, Sillanpaa M. The epidemiology of
epilepsy in Europe - a systematic review. Eur J Neurol.
2005;12(4):245-53.
8. Hauser WA, Annegers JL, Kurland LT. Incidence of epilepsy and
unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia.
1993;34(3):453-68,
http://dx.doi.org/10.1111/j.1528-1157.1993.tb02586.x.
http://dx.doi.org/10.1111/j.1528-1157.19...
-99. Forsgren L. Epidemiology and prognosis of epilepsy and its
treatment. S. Shorvon, E. Perucca, D. Fish, E. Dodson (Eds.), The treatment of
epilepsy, Blackwell Science Oxford, Malden. 2004;21-42.). The incidence of epilepsy is higher in
developing countries compared to industrialized countries, with up to 190 affected
individuals per 100,000 people (1010. Kotsopoulos IAW, van Merode T, Kessels FGH, de Krom MCTFM,
Knottnerus JA. Systematic review and meta-analysis of incidence studies of
epilepsy and unprovoked seizures. Epilepsia. 2002;43(11):1402-09,
http://dx.doi.org/10.1046/j.1528-1157.2002.t01-1-26901.x.
http://dx.doi.org/10.1046/j.1528-1157.20...
,1111. Preux PM, Druet-Cabanac M. Epidemiology and aetiology of
epilepsy in sub-Saharan Africa. Lancet Neurol. 2005;4(1):21-31,
http://dx.doi.org/10.1016/S1474-4422(04)00963-9.
http://dx.doi.org/10.1016/S1474-4422(04)...
). Epilepsy is considered a serious chronic
disease, with a number of factors that negatively affect the quality of life of these
individuals. Stigma and exclusion have become common global features of epilepsy (55. de Boer HM, Mula M, Sander JW. The global burden and stigma of
epilepsy. Epilepsy Behav. 2008;12(4):540-6,
http://dx.doi.org/10.1016/j.yebeh.2007.12.019.
http://dx.doi.org/10.1016/j.yebeh.2007.1...
,1212. de Boer HM. Epilepsy stigma: moving from a global problem to
global solutions. Seizure. 2010;19(10):630-6,
http://dx.doi.org/10.1016/j.seizure.2010.10.017.
http://dx.doi.org/10.1016/j.seizure.2010...
,1313. Gzirishvili N, Kasradze S, Lomidze G, Okujava N, Toidze O, de
Boer HM, et al. Knowledge, attitudes, and stigma towards epilepsy in different
walks of life: A study in Georgia. Epilepsy Behav. 2013; 27(2):315-18,
http://dx.doi.org/10.1016/j.yebeh.2013.02.011.
http://dx.doi.org/10.1016/j.yebeh.2013.0...
). In addition, physical, psychological, and
social consequences are very severe, as seizures may cause fear, misunderstanding,
secrecy, stigmatization, and social isolation (55. de Boer HM, Mula M, Sander JW. The global burden and stigma of
epilepsy. Epilepsy Behav. 2008;12(4):540-6,
http://dx.doi.org/10.1016/j.yebeh.2007.12.019.
http://dx.doi.org/10.1016/j.yebeh.2007.1...
,1212. de Boer HM. Epilepsy stigma: moving from a global problem to
global solutions. Seizure. 2010;19(10):630-6,
http://dx.doi.org/10.1016/j.seizure.2010.10.017.
http://dx.doi.org/10.1016/j.seizure.2010...
,1313. Gzirishvili N, Kasradze S, Lomidze G, Okujava N, Toidze O, de
Boer HM, et al. Knowledge, attitudes, and stigma towards epilepsy in different
walks of life: A study in Georgia. Epilepsy Behav. 2013; 27(2):315-18,
http://dx.doi.org/10.1016/j.yebeh.2013.02.011.
http://dx.doi.org/10.1016/j.yebeh.2013.0...
).
Additionally, we must not fail to mention that, unfortunately, epilepsy is associated
with a high rate of premature death compared with the general population (1414. Hesdorffer DC, Tomson T. Sudden unexpected death in epilepsy:
potential role of antiepileptic drugs. CNS Drugs. 2013;27(2):113-9,
http://dx.doi.org/10.1007/s40263-012-0006-1.
http://dx.doi.org/10.1007/s40263-012-000...
,1515. Devinsky O. Sudden, unexpected death in epilepsy.
N Engl J Med. 2011;365(19):1801-11.).
Sudden unexpected death in epilepsy (SUDEP) is the most common epilepsy-related category
of death, accounting for 7.5% to 17% of all deaths in people with epilepsy and 1:500 to
1:1,000 patient-years among adults (1414. Hesdorffer DC, Tomson T. Sudden unexpected death in epilepsy:
potential role of antiepileptic drugs. CNS Drugs. 2013;27(2):113-9,
http://dx.doi.org/10.1007/s40263-012-0006-1.
http://dx.doi.org/10.1007/s40263-012-000...
15. Devinsky O. Sudden, unexpected death in epilepsy.
N Engl J Med. 2011;365(19):1801-11.
16. Ficker DM, So EL, Shen WK, Annegers JF, O'Brien PC, Cascino
GD, Belau PG. Population-based study of the incidence of sudden unexplained
death in epilepsy. Neurology. 1998;51(5):1270-4,
http://dx.doi.org/10.1212/WNL.51.5.1270.
http://dx.doi.org/10.1212/WNL.51.5.1270...
17. Schuele SU, Widdess-Walsh P, Bermeo A, Lüders HO. Sudden
unexplained death in epilepsy: the role of the heart. Cleve
Clin J Med. 2007;74 Suppl 1:S121-7,
http://dx.doi.org/10.3949/ccjm.74.Suppl_1.S121.
http://dx.doi.org/10.3949/ccjm.74.Suppl_...
-1818. Hesdorffer DC, Tomson T, Benn E, Sander JW, Nilsson L, Langan Y,
et al. Combined analysis of risk factors for SUDEP. Epilepsia.
2011;52(6):1150-9,
http://dx.doi.org/10.1111/j.1528-1167.2010.02952.x.
http://dx.doi.org/10.1111/j.1528-1167.20...
). The main risk factors described thus far are
the presence or number of generalized tonic-clonic seizures (GTCS), nocturnal seizures,
young age at epilepsy onset, long duration of epilepsy, dementia, the absence of
cerebrovascular disease, asthma, male gender, the symptomatic etiology of epilepsy, and
alcohol abuse (1414. Hesdorffer DC, Tomson T. Sudden unexpected death in epilepsy:
potential role of antiepileptic drugs. CNS Drugs. 2013;27(2):113-9,
http://dx.doi.org/10.1007/s40263-012-0006-1.
http://dx.doi.org/10.1007/s40263-012-000...
,1515. Devinsky O. Sudden, unexpected death in epilepsy.
N Engl J Med. 2011;365(19):1801-11.,1818. Hesdorffer DC, Tomson T, Benn E, Sander JW, Nilsson L, Langan Y,
et al. Combined analysis of risk factors for SUDEP. Epilepsia.
2011;52(6):1150-9,
http://dx.doi.org/10.1111/j.1528-1167.2010.02952.x.
http://dx.doi.org/10.1111/j.1528-1167.20...
19. Surges R, Thijs RD, Tan HL, Sander JW. Sudden unexpected death
in epilepsy: risk factors and potential pathomechanisms. Nat Rev Neurol.
2009;5(9):492-504, http://dx.doi.org/10.1038/nrneurol.2009.118.
http://dx.doi.org/10.1038/nrneurol.2009....
20. Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in
epilepsy: current knowledge and future directions. Lancet Neurol.
2008;7(11):1021-31,
http://dx.doi.org/10.1016/S1474-4422(08)70202-3.
http://dx.doi.org/10.1016/S1474-4422(08)...
-2121. Hitiris N, Suratman S, Kelly K, Stephen LJ, Sills GJ, Brodie MJ.
Sudden unexpected death in epilepsy: a search for risk factors. Epilepsy Behav.
2007;10(1):138-41,
http://dx.doi.org/10.1016/j.yebeh.2006.11.010.
http://dx.doi.org/10.1016/j.yebeh.2006.1...
). Regarding epilepsy causal factors, experimental and clinical studies
suggest that respiratory and cardiovascular abnormalities during and after seizures and
genetic factors likely contribute to SUPEP risk (1919. Surges R, Thijs RD, Tan HL, Sander JW. Sudden unexpected death
in epilepsy: risk factors and potential pathomechanisms. Nat Rev Neurol.
2009;5(9):492-504, http://dx.doi.org/10.1038/nrneurol.2009.118.
http://dx.doi.org/10.1038/nrneurol.2009....
,2020. Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in
epilepsy: current knowledge and future directions. Lancet Neurol.
2008;7(11):1021-31,
http://dx.doi.org/10.1016/S1474-4422(08)70202-3.
http://dx.doi.org/10.1016/S1474-4422(08)...
,2222. Terra VC, Cysneiros RM, Cavalheiro EA, Scorza FA. Sudden
unexpected death in epilepsy: From the lab to the clinic setting. Epilepsy
Behav. 2013;26(3):415-20,
http://dx.doi.org/10.1016/j.yebeh.2012.12.018.
http://dx.doi.org/10.1016/j.yebeh.2012.1...
23. Nei M, Hays R. Sudden unexpected death in epilepsy. Curr Neurol
Neurosci Rep. 2010;10(4):319-26,
http://dx.doi.org/10.1007/s11910-010-0116-4.
http://dx.doi.org/10.1007/s11910-010-011...
24. Hirsch LJ, Donner EJ, So EL, Jacobs M, Nashef L, Noebels JL, et
al. Abbreviated report of the NIH/NINDS workshop on sudden unexpected death in
epilepsy. Neurology. 2011;76(22):1932-38,
http://dx.doi.org/10.1212/WNL.0b013e31821de7de.
http://dx.doi.org/10.1212/WNL.0b013e3182...
25. Friedman D, Chyou J, Devinsky O. Sudden death in epilepsy: of
mice and men. J Clin Invest. 2013;123(4):1415-6,
http://dx.doi.org/10.1172/JCI67759.
http://dx.doi.org/10.1172/JCI67759...
26. So EL. What is known about the mechanisms underlying SUDEP?
Epilepsia. 2008;49(Suppl. 9):93-8,
http://dx.doi.org/10.1111/j.1528-1167.2008.01932.x.
http://dx.doi.org/10.1111/j.1528-1167.20...
-2727. Scorza FA, Cysneiros RM, Arida RM, Terra-Bustamante VC, de
Albuquerque M, Cavalheiro EA. The other side of the coin: Beneficiary effect of
omega-3 fatty acids in sudden unexpected death in epilepsy. Epilepsy Behav.
2008;13(2):279-83,
http://dx.doi.org/10.1016/j.yebeh.2008.04.011.
http://dx.doi.org/10.1016/j.yebeh.2008.0...
). Obviously, it is extremely
difficult to estimate SUDEP occurrence. However, discovery and careful evaluation of new
risk factors, greater specificity regarding mechanisms, and the development of effective
preventive measures may help prevent the occurrence of fatal events in affected
individuals. Along these lines, proposals for future research that expand on existing
clinical, genetic, and basic science research and that support the education of health
care practitioners and people with epilepsy will be of great value for advancing our
understanding of SUDEP and, ultimately, our capacity to prevent it (2828. Devinsky O, Friedman D. The future of SUDEP research. In:
Chapman D, Panelli R, Hanna J, Jeffs T, eds. 2011. Sudden unexpected death in
epilepsy: continuing the global conversation. Epilepsy Australia, Epilepsy
Bereaved and SUDEP Aware, Camberwell, Australia.,2929. So EL, Bainbridge J, Buchhalter JR, Donalty J, Donner EJ,
Finucane A, et al. Report of the American Epilepsy Society and the Epilepsy
Foundation joint task force on sudden unexplained death in epilepsy. Epilepsia.
2009;50(4):917-22,
http://dx.doi.org/10.1111/j.1528-1167.2008.01906.x.
http://dx.doi.org/10.1111/j.1528-1167.20...
).
Despite the effort, dedication, and enthusiasm of all neuroscientists, we are not yet
fully prepared to implement all of the proposals suggested thus far. For example, one
area that merits further consideration is whether and when to talk about SUDEP with
patients, family members, and caregivers. Although epileptologists have not yet
established a global consensus on this subject (3030. Morton B, Richardson A, Duncan S. Sudden unexpected death in
epilepsy (SUDEP): don't ask, don't tell? J Neurol Neurosurg
Psychiatry. 2006;77(2):199-202,
http://dx.doi.org/10.1136/jnnp.2005.066852.
http://dx.doi.org/10.1136/jnnp.2005.0668...
,3131. Brodie MJ, Holmes GL. Should all patients be told about sudden
unexpected death in epilepsy (SUDEP)? Pros and Cons. Epilepsia. 2008;49(Suppl
9):99-101, http://dx.doi.org/10.1111/j.1528-1167.2008.01933.x.
http://dx.doi.org/10.1111/j.1528-1167.20...
), recent studies suggest that
providing information about SUDEP to individuals, relatives, and caregivers is most
likely more beneficial than harmful in most cases (3232. Surges R, Sander JW. Sudden unexpected death in epilepsy:
mechanisms, prevalence, and prevention. Curr Opin Neurol. 2012;25(2):201-7,
http://dx.doi.org/10.1097/WCO.0b013e3283506714.
http://dx.doi.org/10.1097/WCO.0b013e3283...
). We recently evaluated a survey of the current practice of all 293
epileptologists officially accredited at the Brazilian League of Epilepsy (LBE) (3333. Abdalla IG, Scorza CA, Cavalheiro EA, de Albuquerque M, de
Almeida ACG, Scorza FA. Attitudes of Brazilian epileptologists to discuss about
SUDEP with their patients: truth may hurt but deceit hurts more. Epilepsy Behav.
2013;27(3):470-1,
http://dx.doi.org/10.1016/j.yebeh.2013.03.017.
http://dx.doi.org/10.1016/j.yebeh.2013.0...
). Unfortunately, the participation rate was very
low, as only 44 professionals answered the questions (3333. Abdalla IG, Scorza CA, Cavalheiro EA, de Albuquerque M, de
Almeida ACG, Scorza FA. Attitudes of Brazilian epileptologists to discuss about
SUDEP with their patients: truth may hurt but deceit hurts more. Epilepsy Behav.
2013;27(3):470-1,
http://dx.doi.org/10.1016/j.yebeh.2013.03.017.
http://dx.doi.org/10.1016/j.yebeh.2013.0...
). Of these, 14% of epileptologists discussed SUDEP risk with the majority
of their patients, 76% with a minority of their patients, and 10% with none (3333. Abdalla IG, Scorza CA, Cavalheiro EA, de Albuquerque M, de
Almeida ACG, Scorza FA. Attitudes of Brazilian epileptologists to discuss about
SUDEP with their patients: truth may hurt but deceit hurts more. Epilepsy Behav.
2013;27(3):470-1,
http://dx.doi.org/10.1016/j.yebeh.2013.03.017.
http://dx.doi.org/10.1016/j.yebeh.2013.0...
). Interestingly, of all such professionals who
discuss SUDEP with a minority of their patients, approximately half of them (44%)
discussed the possible occurrence of SUDEP when patients asked about it (3333. Abdalla IG, Scorza CA, Cavalheiro EA, de Albuquerque M, de
Almeida ACG, Scorza FA. Attitudes of Brazilian epileptologists to discuss about
SUDEP with their patients: truth may hurt but deceit hurts more. Epilepsy Behav.
2013;27(3):470-1,
http://dx.doi.org/10.1016/j.yebeh.2013.03.017.
http://dx.doi.org/10.1016/j.yebeh.2013.0...
). It should be noted that although the data
obtained in our study are consistent with the current literature, the low participation
of Brazilian epileptologists in our assessment is an issue that should be reviewed and
discussed. This disinterest becomes more worrisome when we evaluate the report recently
developed by the Brazilian Federal Council of Medicine (3434. Conselho Federal de Medicina (CFM), Conselho Regional de
Medicina do Estado de São Paulo (CREMESP). Demografia Médica no
Brasil: Dados gerais e descrições de desigualdades (Volume 1),
São Paulo, 2011. Available at:
http://www.cremesp.org.br/pdfs/demografia_2_dezembro.pdf.
http://www.cremesp.org.br/pdfs/demografi...
) (Figure 1). In brief, the
report notes that Brazil has a total of 2629 neurologists, the vast majority of whom
(approximately 80%) are concentrated in the south and southeast parts of Brazil. Thus, a
number of questions must be answered: 1 - How can individuals with epilepsy in regions
with extremely low numbers of neurologists be monitored and treated? 2 - How can
campaigns be created in these regions to demystify and reduce the stigma that exists
against people with epilepsy? 3 - Is it possible to create tertiary epilepsy centers in
regions with low numbers of neurologists? 4 - How can we create research institutes in
these regions? 5 - Can discussions regarding SUDEP take place with these professionals?
Despite the existing difficulties, the vast majority of epileptologists located in the
south and southeast actively participate in experimental and clinical epilepsy studies,
including SUDEP. In this regard, this series of questions and proposals could stimulate
the 293 accredited epileptologists in LBE to create an intense task force in poorer
regions. We realize that this venture is not easy, but it is certainly feasible. We have
qualified and credentialed professionals that are ready to initiate and invest in
collaborations. With sustained focus and fundraising for epilepsy and SUDEP research in
both children and adults, the future is very promising (2828. Devinsky O, Friedman D. The future of SUDEP research. In:
Chapman D, Panelli R, Hanna J, Jeffs T, eds. 2011. Sudden unexpected death in
epilepsy: continuing the global conversation. Epilepsy Australia, Epilepsy
Bereaved and SUDEP Aware, Camberwell, Australia.). As the American physicist Robert Hutchings Goddard said: “Just
remember - when you think all is lost, the future remains”.
This study has been supported by the following grants: FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), FAPESP/FAPEMIG, FAPESP/PRONEX, and FAPESP/CNPq/MCT (Instituto Nacional de Neurociência Translacional).
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No potential conflict of interest was reported.
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Publication in this collection
July 2013