The World Health Organization (WHO) website, on its Mental Health Programmes section,
suggests an interesting call of duty: “Epilepsy: Treat it. Defeat it”. It
highlights the fact that over 50 million people have epilepsy worldwide, 80% of whom living in
developing countries, where 3 out of 4 persons with epilepsy do not receive appropriate care
for their seizure disorder11 World Health Organization — WHO. WHO programme on reducing the epilepsy
treatment gap. Geneva: World Health Organizationh; 2015 [cited 2015 jan 13]. Available
from: http://www.who.int/mental_health/neurology/epilepsy/en/
http://www.who.int/mental_health/neurolo...
. The reader is
then directed to the International League Against Epilepsy page, where an opening banner
reads: “Epilepsy is still a puzzle”22 International League Against Epilepsy. ILAE topic-oriented commissions. West
Hartford: International League Against Epilepsy; 2015 [cited 2015 jan 13]. Available from:
http://www.ilae.org/Visitors/Commissions/Topic.cfm
http://www.ilae.org/Visitors/Commissions...
. The combination of these thought provoking statements brings to mind
Sun Tzu´s Art of War33 Sun Tzu. The art of war: classic edition. El Paso: El Paso Norte;
2009. often cited quotation: “know your enemy”. Even with
mesial temporal lobe epilepsy (MTLE) standing as the most systematically studied form of the
disease and hippocampal sclerosis (HS) representing the most common pathology underlying its
drug-resistant cases44 Malmgren K, Thom M. Hippocampal sclerosis: origins and imaging. Epilepsia;
2012;53(suppl 4):19-33.
http://dx.doi.org/10.1111/j.1528-1167.2012.03610.x
https://doi.org/10.1111/j.1528-1167.2012...
, this remains a
somewhat “unknown” and challenging opponent. Thus, every piece of information counts on trying
to understand the intricacies on the clinical presentation of this subset of patients. In that
sense, the paper by Coan and coworkers55 Coan AC, Campos BM, Bergo FPG et al. Patterns of seizure control in patients
with mesial temporal lobe epilepsy with and without hippocampus sclerosis. Arq
Neuropsiquiatr. 2015;73(2):79-82.,
featured in this issue of Arquivos de Neuropsiquiatria, describing similar proportion of
relapse-remitting seizure pattern in MTLE patients with and without HS is a welcome one and it
certainly raises a couple of considerations. Over the past decade or so the epilepsy community
has shown a trend towards more pragmatic definitions. Epilepsy (now a
disease, instead of a condition) is defined by the
occurrence of at least two unprovoked seizures over 24hr apart or even one unprovoked (or
reflex) seizure and a probability of further seizures of at least 60%66 Fischer RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE et al.
ILAE oficial report: a practical clinical definition of epilepsy. Epilepsia.
2014;55(4):475-82. http://dx.doi.org/10.1111/epi.12550
https://doi.org/10.1111/epi.12550...
. Drug-resistant epilepsy is established as failure of adequate
trials of 2 tolerated, appropriately chosen and used antiepileptic drug schedules to achieve
sustained seizure freedom77 Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G et al.
Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the
ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069-77.
http://dx.doi.org/10.1111/j.1528-1167.2009.02397.x
https://doi.org/10.1111/j.1528-1167.2009...
. In epilepsy
management, these definitions represent shortcuts to potential surgical indications. Some 14
years ago, Wiebe´s pivotal paper on the New England Journal of Medicine88 Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of
surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311-8.
http://dx.doi.org/10.1056/NEJM200108023450501
https://doi.org/10.1056/NEJM200108023450...
showed clearly better outcomes on surgical, as opposed to
medically treated, patients on a randomized study involving refractory temporal lobe epilepsy
cases (70% of whom with MRI proven HS). Regardless the unquestionable quality of these data, a
tempting approach emerged with an embedded (and equivocal) idea that MTLE with HS cases
translate, almost by default, into surgical cases. That also includes an excuse to rather
“minimalistic” work-ups (sometimes the mere history of epilepsy and an MRI imaging of HS)
leading to surgical indications. That could eventually be the case, should all HS were created
alike. But they are not, as elegantly demonstrated by ILAE’s Commission on Diagnostic Methods
and its international consensus of HS in TLE99 Blümcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi A et
al. International consensus classification of hippocampal sclerosis in temporal lobe
epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods. Epilepsia.
2013;54(7):1315-29. http://dx.doi.org/10.1111/epi.12220
https://doi.org/10.1111/epi.12220...
. The committee reported both interobserver and intraobserver agreement on
3 types of HS, referring to different patterns of neuronal cell damage. HS ILAE type I is
likely to concur with a better outcome, as compared to types 2 and 3. This data has been
recently validated on a large cohort of MTLE with HS cases1010 Na M, Ge H, Shi C, Shen H, Wang Y, Pu S et al. Long-term seizure outcome for
international consensus classification of hippocampal sclerosis: a survival analysis.
Seizure. 2014 (in press). http://dx.doi.org/10.1016/j.seizure.2014.10.006
https://doi.org/10.1016/j.seizure.2014.1...
. In this survival analysis, HS ILAE type I patients (severe neuronal
cell loss and gliosis in CA1 and CA4 regions) showed better long term seizure outcome, as well
as, differences on clinical history when matched with HS ILAE types 2 and 3. Inevitably, the
hypothesis of subsets within the subset comes to mind when thinking MTLE with (or without) HS.
In their paper, Coan and coworkers55 Coan AC, Campos BM, Bergo FPG et al. Patterns of seizure control in patients
with mesial temporal lobe epilepsy with and without hippocampus sclerosis. Arq
Neuropsiquiatr. 2015;73(2):79-82.
arbitrarily defined relapse-remitting pattern of seizures as a period equal or longer than 2
years without any type of epileptic seizures in 172 consecutive patients with clear cut
diagnosis of MTLE (122 with HS and 50 without). Roughly a third in each group presented with a
relapse-remitting pattern demonstrating that: (a) HS patients may experience fairly long
seizure remission, even being medically intractable and (b) this very feature – i.e, a
relapse-remitting seizure pattern – is of little help as a clinical tool separating lesional
vs nonlesional MTLE. More so, 11% of their MTLE with HS patients were seizure free for fairly
long periods (some up to 9 years, as per Coan´s description). These prolonged remissions
(given the occurrence of relapses) do not prevent surgical indications, but on selected cases,
patients maybe prone to decline the surgical option and choose to risk an occasional relapse.
In other words, not all MTLE with HS patients are necessarily predestinated to the surgical
arena. The authors recognize that data in children are scarce. Although MTLE is frequently
reported in pediatric population, almost all published data focus in comparing kids and adults
in respect to clinical semiology and surgical outcome. One study that evaluated seizure
outcome in surgical and non-surgical children with MTLE comes from Sales et al1111 Sales LV, Velasco TR, Funayama S, Ribeiro LT, Andrade-Valença LP, Neder L et
al. Relative frequency, clinical, neuroimaging, and postsurgical features of pediatric
temporal lobe epilepsy. Braz J Med Biol Res. 2006;39(10):1365-72.
http://dx.doi.org/10.1590/S0100-879X2006001000013
https://doi.org/10.1590/S0100-879X200600...
. Here 31 children (< 12 y/o) were followed
for 3 years, with MTLE (with HS, NL or tumoral etiology). Eight patients had significant
seizure improvement with pharmacotherapy: 3 patients with MTLE-HS had seizure control and one
a seizure reduction (one seizure each 4 months) and 4 patients with MTLE-NL had seizure
control. These findings are close to those observed in Coan´s description. Authors also
observed an inverse relationship between age at seizure onset and seizure frequency,
suggesting that patients with earlier seizure onset had a worst outcome. However, some
questions remain unanswered. Since MTLE, especially when related to HS, is a disease that need
circuitry reorganization are we talking about the same thing? Children with MTLE usually
present with simple clinical semiology and more diffuse interictal and ictal EEG patterns1212 Cersósimo R, Flesler S, Bartuluchi M, Soprano AM, Pomata H, Caraballo R.
Mesial temporal lobe epilepsy with hippocampal sclerosis: study of 42 children. Seizure.
2011;20(2):131-7. http://dx.doi.org/10.1016/j.seizure.2010.11.002.
https://doi.org/10.1016/j.seizure.2010.1...
. Are these secondary to brain maturation or
children with MTLE are “small adults” that will continue to seize during life, with possible
periods of relative control? If on one hand, one cannot avoid a little frustration at the
prospect that what seemed to be our most consolidated epileptic syndrome (MTLE with HS)
remains very much unknown in many aspects, on the other findings such as Coan´s data calls for
double attention and even more educated decision making trees on MTLE cases. Plus, one should
keep in mind distinctive patterns of MTLE and HS may impact not only on seizure prognosis but
perhaps on diverse cognitive and even behavioral curses of the disease. As “little strokes
fell great oaks”1313 Franklin B. Quotation. O que é isso? Não é verbete. In: Bowman JL.
Provocative and contemplative quotations: with author comments and observations.
Bloomington: Authorhouse; 2013. www.authorhouse.com, 2013.
www.authorhouse.com...
, Coan´s welcome paper may
have added a little piece to the epilepsy puzzle.
References
-
1World Health Organization — WHO. WHO programme on reducing the epilepsy treatment gap. Geneva: World Health Organizationh; 2015 [cited 2015 jan 13]. Available from: http://www.who.int/mental_health/neurology/epilepsy/en/
» http://www.who.int/mental_health/neurology/epilepsy/en/ -
2International League Against Epilepsy. ILAE topic-oriented commissions. West Hartford: International League Against Epilepsy; 2015 [cited 2015 jan 13]. Available from: http://www.ilae.org/Visitors/Commissions/Topic.cfm
» http://www.ilae.org/Visitors/Commissions/Topic.cfm -
3Sun Tzu. The art of war: classic edition. El Paso: El Paso Norte; 2009.
-
4Malmgren K, Thom M. Hippocampal sclerosis: origins and imaging. Epilepsia; 2012;53(suppl 4):19-33. http://dx.doi.org/10.1111/j.1528-1167.2012.03610.x
» https://doi.org/10.1111/j.1528-1167.2012.03610.x -
5Coan AC, Campos BM, Bergo FPG et al. Patterns of seizure control in patients with mesial temporal lobe epilepsy with and without hippocampus sclerosis. Arq Neuropsiquiatr. 2015;73(2):79-82.
-
6Fischer RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE et al. ILAE oficial report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-82. http://dx.doi.org/10.1111/epi.12550
» https://doi.org/10.1111/epi.12550 -
7Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Hauser WA, Mathern G et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069-77. http://dx.doi.org/10.1111/j.1528-1167.2009.02397.x
» https://doi.org/10.1111/j.1528-1167.2009.02397.x -
8Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311-8. http://dx.doi.org/10.1056/NEJM200108023450501
» https://doi.org/10.1056/NEJM200108023450501 -
9Blümcke I, Thom M, Aronica E, Armstrong DD, Bartolomei F, Bernasconi A et al. International consensus classification of hippocampal sclerosis in temporal lobe epilepsy: a Task Force report from the ILAE Commission on Diagnostic Methods. Epilepsia. 2013;54(7):1315-29. http://dx.doi.org/10.1111/epi.12220
» https://doi.org/10.1111/epi.12220 -
10Na M, Ge H, Shi C, Shen H, Wang Y, Pu S et al. Long-term seizure outcome for international consensus classification of hippocampal sclerosis: a survival analysis. Seizure. 2014 (in press). http://dx.doi.org/10.1016/j.seizure.2014.10.006
» https://doi.org/10.1016/j.seizure.2014.10.006 -
11Sales LV, Velasco TR, Funayama S, Ribeiro LT, Andrade-Valença LP, Neder L et al. Relative frequency, clinical, neuroimaging, and postsurgical features of pediatric temporal lobe epilepsy. Braz J Med Biol Res. 2006;39(10):1365-72. http://dx.doi.org/10.1590/S0100-879X2006001000013
» https://doi.org/10.1590/S0100-879X2006001000013 -
12Cersósimo R, Flesler S, Bartuluchi M, Soprano AM, Pomata H, Caraballo R. Mesial temporal lobe epilepsy with hippocampal sclerosis: study of 42 children. Seizure. 2011;20(2):131-7. http://dx.doi.org/10.1016/j.seizure.2010.11.002.
» https://doi.org/10.1016/j.seizure.2010.11.002 -
13Franklin B. Quotation. O que é isso? Não é verbete. In: Bowman JL. Provocative and contemplative quotations: with author comments and observations. Bloomington: Authorhouse; 2013. www.authorhouse.com, 2013.
» www.authorhouse.com
Publication Dates
-
Publication in this collection
Feb 2015
History
-
Received
15 Jan 2015 -
Accepted
20 Jan 2015