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Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282XOn-line version ISSN 1678-4227

Arq. Neuro-Psiquiatr. vol.61 no.4 São Paulo Dec. 2003

http://dx.doi.org/10.1590/S0004-282X2003000600010 

Corpora amylacea in temporal lobe epilepsy associated with hippocampal sclerosis

 

Corpos amiláceos associados à esclerose hipocampal na epilepsia do lobo temporal

 

 

Marlise de Castro Ribeiro; Lígia Barbosa-Coutinho; Fabiana Mugnol; Arlete Hilbig; André Palmini; Jaderson Costa da Costa; Eliseu Paglioli Neto; Eduardo Paglioli

Porto Alegre Epilepsy Surgery Program, Hospital São Lucas da Pontificia Universidade Católica (PUC), Porto Alegre RS, Brazil

 

 


ABSTRACT

Hippocampal sclerosis (HS) is the commonest pathology in epileptic patients undergoing temporal lobe epilepsy surgery. Beside, there are an increased density of corpora amylacea (CA) founded in 6 to 63% of those cases.
OBJECTIVE: verify the presence of CA and the clinical correlates of their occurrence in a consective series of patients undergoing temporal surgery with diagnosis of HS.
METHOD: We reviewed 72 hippocampus specimens from January 1997 to July 2000. Student's t test for independent, samples, ANOVA and Tukey test were performed for statistical analysis.
RESULTS: CA were found in 35 patients (49%), whose mean epilepsy duration (28.7 years) was significantly longer than that group of patients without CA (19.5 years, p= 0.001). Besides, when CA were found, duration was also significantly correlated with distribution within hippocampus: 28.7 years with diffuse distribution of CA, 15.4 with exclusively subpial and 17.4 years with distribution subpial plus perivascular (p= 0.001).
CONCLUSION: Our findings corroborate the presence of CA in patients with HS and suggest that a longer duration of epilepsy correlate with a more distribution of CA in hippocampus.

Key words: hippocampal sclerosis, corpora amylacea, temporal lobe epilepsy.


RESUMO

A esclerose hipocampal (EH) é a patologia mais observada em lobectomias temporais de pacientes com epilepsia intratável. Além dos achados histopatológicos clássicos existe a presença de corpos amiláceos (CA) em até 60% dos hipocampos ressecados.
OBJETIVO: Verificar a presença de corpos amiláceos em hipocampos de pacientes submetidos a cirurgia para tratamento de epilepsia e verificar se havia diferenças clínicas entre pacientes que apresentavam CA e aqueles em que eles não foram encontrados.
MÉTODO: Foram revisados 80 hipocampos ressecados entre janeiro de 1997 a dezembro de 2000 e, posteriormente, os prontuários de 72 dos pacientes. Foi realizado o teste t de Student para amostras independentes, ANOVA e posteriormente o teste de Tukey.
RESULTADOS: Dos setenta e dois pacientes estudados, 40 eram homens (55,6%) e trinta e dois mulheres (44,4%). Trinta e cinco (48,6%) apresentavam CA e em trinta e sete (51,4%) não foram encontrados. Houve diferença estatisticamente significativa entre a média de tempo de evolução da epilepsia: o grupo com CA apresentava tempo maior de evolução (28,97 anos) em relação ao grupo que não apresentava CA (19,54 anos), com p= 0,001. Também observou-se diferença significativa quando foi comparada a localização de corpos amiláceos com o tempo de evolução da epilepsia: os pacientes com CA presentes difusamente no hipocampo apresentavam maior tempo de epilepsia (p= 0,001).
CONCLUSÃO: Observamos que o nosso estudo confirma a presença de corpos amiláceos em hipocampos de pacientes com EH e sugerimos que quanto maior o período de epilepsia maior é a distribuição de CA no hipocampo

Palavras-chave: esclerose hipocampal, corpora amylacea, epilepsia de lobo temporal.


 

 

Hippocampal sclerosis (HS) is the commonest histopathological substrate in epileptic patients undergoing temporal lobe epilepsy (TLE) surgery1. Characteristic features include neuronal loss in Ammon's horn fields CA1, CA3 and CA4, with relative sparing of neurons in CA2 and in the subiculum2, associated with axodendritic reorganization. In addition, hippocampal tissue resected in patients with TLE have an increased density of corpora amylacea (CA), reported to be found in 6 to 63% of the cases3-6. These are spherical, basophilic structures which normally accumulate in perivascular and subpial regions of the central nervous system as a result of aging7-9. However, although CA are seen in the context of neurodegenerative disorders2,3,8, their pathogenic mechanisms and other factors related to their occurrence are still largely ignored6,8-10.

We have been systematically examining hippocampal tissue of epileptic patients undergoing surgery for TLE in the last 10 years11. Thus, we decided to study both the presence of CA and the clinical correlates of their occurrence in a consecutive series of patient undergoing temporal lobe surgery with hippocampal resection in more recent years.

 

METHOD

We reviewed the histopathological findings for the presence of CA in 88 consecutive hippocampal specimens in which a diagnosis of HS had been previously established11. Tissue was resected as part of the surgical treatment of patients with refractory TLE, from January 1997 to July 2000. All patients underwent comprehensive preoperative evaluation as previously reported12. We excluded 16 patients with dual pathology (5 patients), from those with more than 60 years of age (3 patients) and also incomplete medical records (8 patients). Histopathological analysis of 72 hippocampal specimens consisted of neuronal loss and gliosis for diagnosis of HS at least in CA1 and CA were characterizaded morphologically: spherical, laminated, hyaline bodies, stained with periodic-acid-Shiff (PAS) and Groccot (Fig 1a and 1b).

 

 

Following the analysis of the histopathological material, the medical records were reviewed to collect data on sex, age at seizure onset, age at operation, preoperative duration of the epileptic disorder, approximate annual preoperative seizure frequency, previous episodes of status epilepticus, and the occurrence of secondary generalization of the complex partial seizures (Table 1). For analysis of the data, the patients were then grouped on the basis of the presence or absence of CA. The group of patients whose hippocampi displayed CA was further subdivided according to their intrahippocampal localization into those in whom CA were observed (i) diffusely in the hippocampus, (ii) only in the subpial region, (iii) and in both the subpial and perivascular regions (Table 2). A SPSS software package (SPSS Inc, Chicago, IL, USA) was used to perform statistical calculations. Student's t test for independent samples were applied to compare possible differences between groups. In addition, the three subgroups of patients harboring CA were compared through analysis of variance (ANOVA) and the Tukey test.

 

 

 

 

RESULTS

Forty of the 72 patients (56%) were male. Age at recurrent seizure onset ranged from 1 to 30 years (mean, 6.7) and preoperative epilepsy duration varied between 3 and 58 years (mean, 24.1). CA were found in 35 patients (49%), whose mean epilepsy duration (28.9 years) was significantly longer than that from the group of patients without CA in the hippocampus (19. 5 years, p = 0.001). Furthermore, when CA were found, epilepsy duration was also significantly correlated with their distribution within the hippocampus. Mean duration of epilepsy was 22.7 years in patients with a diffuse distribution of the CA, while those with exclusively subpial or subpial plus perivascular distribution had seizures for a mean of 15.4 and 17.4 years before operation (p=0.001, Table 2). In contrast, gender, age at seizure onset, age at operation, seizure frequency, history of status epilepticus and occurrence of secondary generalization did not significantly differ between the groups (Table 1).

 

DISCUSSION

CA are roughly round, laminated, structures composed of glucose polymers and a plethora of different proteins, including heat shock proteins (HSP). They usually originate within astrocytic processes, although neuronal and oligodendroglial origins have occasionally been reported13,14. The presence of CA in the resected hippocampus of patients with TLE undergoing surgery has been recently reported by different groups2,4,9,15. Likewise, Loiseau and colleagues5 reported abundant CA in the subcortical white matter of a woman operated for refractory CA in similar series of patients, all showing that about half the patients have these structures in the ressected sclerotic hippocampus4,6 . Furthermore, the lack of correlation between the presence of CA and most epileptic variables like age of seizure or age at operation was also previously reported16. In contrast with the latter study from Belgium however, we actually found that epilepsy duration was significantly related to the presence of CA, which may be a pathogenically relevant finding.

Despite their common occurrence in sclerotic hippocampi, the pathogenesis of CA is largely ignored, despite reports suggesting that HSP9,17 or some proteins of the S100 family may be involved18. Erdamar and colleagues9 reported a significant increase of an HSP subtype in tissue resected form patients with TLE, but the abnormal protein accumulated outside the CA. Studying non-epileptic tissue, Botez et al.8 found abundant CA in the hippocampi and dentate gyri of patients with a history of recurrent episodes of cerebral hypoxemic insults. They suggested that the genesis of CA may be part of a tissue reaction to buffer the accumulation of free radicals and other potentially damaging elements resulting from metabolic derangements secondary to repeated cellular stresses during life. Our finding of a significantly higher occurrence of CA in the hippocampus of exactly those patients who experienced recurrent seizures for longer periods before surgery support this metabolic hypothesis of the genesis of CA. In addition, we showed that a longer duration of epilepsy significantly correlated with a more diffuse distribution of CA in the resected hippocampi, which also suggest that repeated insults may play a role in the generation of these structures. If our findings are independently confirmed, they add another potential metabolic reason to the growing body of evidence suggesting that early rather than late surgery for medically refractory TLE may achieve better overall results.

Acknowledgements - To statistic Alan Birck.

 

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Received 26 February 2003, received in final form 7 July 2003. Accepted 18 July 2003

 

 

Dra. Arlete Hilbig - Rua Quintino Bocaiuva 283 / 401 - 90440-051 Porto Alegre RS - Brasil.

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