Metabolic parameters of epilepsy: adjuncts to established antiepileptic drug therapy.
Hughlings Jackson at the turn of the century defined epilepsy as a disorder originating in a "morbid nutrition" of the neuron. With the advances in modern neurochemistry, it is becoming increasingly clear that a chronic seizure predisposition or a lowering of the brain's discharge threshold can be demarcated by a number of biochemical markers. They include a tendency for an increased release of glutamate with or without GABAergic impairment, (intra)neural tissue alterations in water redistribution/osmolarity or other distortions of the cytoarchitecture, and an elevation of ionic calcium inside the cell. These changes are dominantly shared parameters of the seizure prone brain. Magnetic resonance spectroscopy (MRS) shows that cerebral levels of glutamate + glutamine (Glx) are increased interictally in epileptogenic regions in human partial epilepsy; other findings using this technique suggest damage to (cellular/mitochondrial) membranes, denoted by N-acetyl-aspartic acid (NAA) changes and a decreased energy capability. The merging of previous in vitro and ex vivo findings in neurophysiology and neurochemistry with magnetic resonance spectroscopy technology provides a powerful new methodology to interpret and to obtain clinical insight into the metabolic alterations that underlie an epileptogenic process. In this review some of these basic neurochemical and electrophysiological mechanisms are discussed. In addition, certain adjuncts to established antiepileptic drug therapy are suggested in the hope that over the long term they may help in correcting the primary metabolic deficits.
van Gelder
Nico M
NM
Queen's University, Department of Chemistry, Kingston, Ontario, Canada. vangeldr@chem.queensu.ca
Sherwin
Allan L
AL
D000927:Anticonvulsants / Q000627:therapeutic use*; D001834:Body Water; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009995:Osmosis
D000927:Anticonvulsants