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Deficient memory acquisition in temporal lobe epilepsy is predicted by hippocampal granule cell loss

From the Department of Neurology, Epilepsy Center (ZEE) (E.P., H.S.), Department of Neuropathology (M.H., I.B.), and Department of Neurosurgery, University Medical Center (J.R.), Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.

Address correspondence and reprint requests to Dr. Ingmar Blumcke, Department of Neuropathology, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany; e-mail: bluemcke{at}neuropatho.med.uni-erlangen.de

Background: The hippocampal formation is essentially involved in the formation of conscious memories for facts and events and neurologic diseases affecting the hippocampus associate with severe memory deficits, i.e., temporal lobe epilepsies.

Methods: We studied the degree of declarative memory dysfunction in 24 human subjects with unilateral mesial temporal lobe epilepsy, using the unique possibility to access memory performance of each isolated hippocampus by intracarotid amobarbital anesthesia. Subsequently, hippocampal specimens from the same patients were available for neuropathologic analysis following surgical treatment of intractable seizures.

Results: Neuronal cell loss in the dentate gyrus and all hippocampal subfields correlated with memory performance with the exception of CA2. Moreover, multiple regression and partial correlation analyses identified neuronal cell loss within the internal limb of the dentate gyrus, a developmentally distinct subregion of the hippocampal formation known to generate new neurons throughout life, as highly significant predictor for the patient's ability to learn and recall memories.

Conclusions: In accordance with animal studies, the dentate gyrus may play a critical role in the neuronal network associated with memory formation.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the October 24 issue to find the title link for this article.

Supported by ELAN Fonds of the University Medical Center (to M.H., J.R., and I.B.) and German Research Council (DFG Bl421/1-2).

Disclosure: The authors report no conflicts of interest.

Received October 3, 2005. Accepted in final form June 27, 2006.

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