Normalization of neuronal metabolic dysfunction after surgery for temporal lobe epilepsy

Abstract

Surgery is a safe and effective treatment for patients with temporal lobe epilepsy (TLE) who do not respond adequately to anticonvulsant medication and in whom the seizure generator can be identified and safely removed. Proton MR spectroscopic imaging (MRSI) can image and quantify neuronal damage in patients with TLE based on reduced signals from N-acetylaspartate (NAA), a compound localized exclusively in neurons. We performed proton MRSI in patients with TLE before and after surgical treatment to determine whether NAA or other resonance intensities changed in the temporal lobes of patients with TLE after surgery, and whether these changes correlated with surgical outcome. N-acetylaspartate resonance intensity relative to creatine (NAA/Cr) was abnormally low preoperatively in at least one temporal lobe in all 14 patients examined. It was low ipsilaterally in the patients who became seizure free and bilaterally in those who did not. Postoperatively, it increased to the normal range on the side of surgery in all patients who became seizure free. In the one patient who became seizure free and who had low NAA/Cr in both temporal lobes before surgery, NAA/Cr values in the contralateral, unoperated temporal lobe also increased to the normal range. In contrast, NAA relative intensity ratios did not change in those patients who continued to have seizures after surgery. The creatine resonance intensity (Cr) in the temporal lobes was high, relative to the brainstem, in seven patients preoperatively. After surgery, the Cr remained high in two patients, both of whom continued to have seizures. We conclude that NAA (and Cr) abnormalities in TLE do not result solely from neuronal loss and gliosis but can be reversible after postsurgical control of seizures. This implies that the NAA and Cr abnormalities in patients with TLE, at least in part, are dynamic markers of both local and remote physiologic dysfunction associated with ongoing seizures.

1H and 31P spectroscopy and bioenergetics in the lateralization of seizures in temporal lobe epilepsy

“…However Hugg's report of NAA recovery from the contralateral hippocampus in patients with bilateral abnormalities one year after successful surgery (41) suggested that at least a portion of the observed NAA loss was not solely due to neuronal loss. This finding was later confirmed by Cendes (42). In a follow-up study 50%, on average, of the metabolic recovery occurred over a period of less than six months, demonstrating a slow but responsive nature of neuronal NAA levels (43).…”

The Relationship between Dorsolateral Prefrontal Neuronal N-Acetylaspartate and Evoked Release of Striatal Dopamine in Schizophrenia

“…While the biological role of NAA has yet to be clearly defined, it acts via the glutamatergic NMDA receptor to elevate intracellular calcium (Rubin et al 1995), and its concentrations are reduced by pharmacological inhibition of mitochondrial energy metabolism (Bates et al 1996) as well as by a number of pathological processes affecting the integrity of neurons (Cendes et al 1997;De Stefano et al 1995;Najim et al 1998). Other data also suggest that NAA concentrations vary with the structural and functional state of glutamatergic cells.…”

“…For example, NAA increases during pharmacologically induced status epilepticus and then decreases after neuronal damage has occurred (Najim et al 1998). Surgical removal of the epileptic focus in temporal lobe epilepsy reverses NAA decreases not only in the affected side but also in the contralateral side, presumably by modulating abnormal interhemispheric glutamatergic projections (Cendes et al 1997).…”

Neuronal dysfunction in children with newly diagnosed temporal lobe epilepsy

“…The recovery of NAA in the ipsilateral and contralateral temporal lobes after successful surgical treatment of the epilepsy [28,29] indicates that widespread decreases in NAA in patients with TLE primarily reflect neuronal dysfunction rather than irreversible neuronal loss.…”