Imaging and regional distribution of copper, zinc, manganese and iron in sclerotic hippocampi of patients with mesial temporal lobe epilepsy

Abstract

Mesial temporal lobe epilepsy (mTLE) represents the most common subtype of human focal epilepsies and perhaps the best-characterized disorder of this type 1 . Hippocampal sclerosis (HS) is the most common histopathologic abnormality found in adults with drugresistant mTLE 2 . The histopathologic hallmark of HS is segmental pyramidal cell loss, which can affect any field of the cornu Ammonis (CA1-4). Hippocampal neuronal cell loss is always associated with a severe pattern of astrogliosis 3 . Therewithal, disturbed homeostasis of metals is implicated in the pathology of mTLE-HS. Zinc has been considered to play a major role in epileptogenesis in relation to its involvement in the modulation of excitability and synaptic plasticity 4,5. Further, it has been shown that epileptogenic hippocampi are exposed to oxidative stress and that the development of prooxidative conditions in the CNS usually involves the loss of homeostasis of iron 6,7. Low brain levels of copper and manganese have been reported in patients with Menkes disease and in animal models of epilepsy, and linked to seizure development 8,9. Ristić et al. were the first to conduct a case-control study of total concentration of metals in tissue of human HS, and report lower concentrations of copper and manganese 10.