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A Study of Monoamine Metabolism in Human Epilepsy

Published online by Cambridge University Press:  18 September 2015

D. Louw
Affiliation:
Departments of Phannacology and Surgery (Neurosurgery), The University of Manitoba, Health Sciences Centre, Winnipeg
G.R. Sutherland*
Affiliation:
Departments of Phannacology and Surgery (Neurosurgery), The University of Manitoba, Health Sciences Centre, Winnipeg
G.B. Glavin
Affiliation:
Departments of Phannacology and Surgery (Neurosurgery), The University of Manitoba, Health Sciences Centre, Winnipeg
J. Girvin
Affiliation:
Department of Neurosciences, University of Western Ontario, University Hospital, London, Ontario
*
Departments of Pharmacology and Surgery (Neurosurgery), 61 Emily Street, Winnipeg, Manitoba, Canada R3E 1Y9
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Abstract:

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Fourteen patients with intractable epilepsy underwent surgical resection of their epileptogenic focus. Hippocampal and temporal cortical samples were obtained, and subjected to high performance liquid chromatography with electrochemical detection. Levels of 5-hydroxyindoleacetic acid (5-HIAA) in actively spiking temporal cortex were 0.454 ± 0.012 ng/mg (mean ± SEM), contrasting with less actively spiking cortex values of 0.248 ± 0.042 ng/mg and normal literature values, obtained from post-mortem material, of 0.140 ± 0.050 ng/mg. Similarly, homovanillic acid (NVA) levels were significantly increased in epileptic tissue compared to normal literature values. Actively spiking cortex values were 0.172 ± 0.001 pg/mg, less active cortex values were 0.058 ±0.012 pg/mg, and literature values were 0.011 ± 0.002 pg/mg. Although a direct statistical comparison between the data reported here and literature values may not be valid, the findings show a continuum from normal through increasingly active electrode sites, likely reflecting a true biologic phenomena. Similarly, statistically significant increases in 5-HIAA and HVA levels were found in hippocampal tissue, which also showed significantly lower dihydroxyphenylacetic acid levels. We conclude that raised levels of serotonin and dopamine metabolites in actively spiking cortex likely reflect an increase in their turnover, and are an epileptic epiphenomenon. Exaggeration of turnover may represent the “metabolic noise” of epilepsy, rather than a concerted strategy of local or distal neurons to contain an epileptogenic focus.

Résumé:

RÉSUMÉ:

Quatorze patients souffrant d'épilepsie résistante au traitement ont subi une résection chirurgicale de leur foyer épileptique. Des échantillons de tissus prélevés au niveau de l'hippocampe et du cortex temporal ont été soumis à une chromatographic en phase liquide à haute performance avec détection électrochimique. Les niveaux d'acide 5-hydroxy-indole acétique (S-HIAA) dans le cortex temporal qui était le site d'une activité électro-encéphalographique importante de type pointe étaient de 0.454 ± 0.012 ng/mg (moyenne de ± SEM), en regard de 0.248 ± 0.042 ng/mg dans le cortex dont l'activité de type pointe était moindre et de 0.140 ± 0.050 ng/mg, correspondant à des valeurs normales selon la littérature, dans du matériel provenant d'autopsies. Les taux d'acide homovanilique (HVA) étaient également élevés de façon significative dans le tissu provenant de patients épileptiques comparés aux taux normaux cités dans la littérature. Les taux du cortex dont l'activité de type pointe était importante étaient de 0.172 ± 0.001 pg/mg, ceux de zones moins actives étaient de 0.058 ±0.012 pg/mg, alors que les taux cités dans la littérature sont de 0.011 ± 0.002 pg/mg. Même si une comparaison statistique directe entre les données rapportées ici et celles de la littérature n'est peut-être pas valide, ces observations montrent qu'il existe un continuum allant de valeurs normales à des valeurs s'élevant progressivement avec l'activité des sites étudiés, reflétant probablement un phénomène biologique réel. De même, des niveaux de S-HIAA et de HVA augmentés de façon significative ont été observés dans le tissu de l'hippocampe ainsi que des taux significativement plus bas d'acide dihydroxy-phényl acétique. Nous concluons que des taux élevés de métabolites de la sérotonine et de la dopamine dans le cortex ayant une activité importante de type pointe reflètent une augmentation de leur turn-over et sont un épiphénomène épileptique. Une exagération du turn-over peut représenter le “bruit métabolique” de l'épilepsie, plutôt qu'une stratégie concertée des neurones locaux ou distaux destinée à contenir un foyer épileptogéne.

Type
Original Articles
Copyright
Copyright © Canadian Neurological Sciences Federation 1989

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