Neuroimaging evidence of progressive neuronal loss and dysfunction in temporal lobe epilepsy

Abstract

Whether temporal lobe epilepsy is the result of an isolated, early injury or whether there is ongoing neuronal dysfunction or loss due to seizures is often debated. We attempt to address this issue by using magnetic resonance techniques. Proton magnetic resonance spectroscopic imaging can detect and quantify focal neuronal dysfunction or loss based on reduced signals from the neuronal marker N‐acetylaspartate (NAA), and magnetic resonance imaging (MRI)‐based measurements of hippocampal volumes (MRIvol) can quantify the amount of atrophy in this structure. We performed magnetic resonance spectroscopic imaging and MRIvol in 82 consecutive patients with medically intractable temporal lobe epilepsy to determine whether there was a correlation between seizure frequency, or type or duration of epilepsy, with NAA to creatine (Cr) values or hippocampal volumes. Volumes and spectroscopic resonance intensities were categorized as to whether they were measured from the temporal lobe ipsilateral or contralateral to the predominant electroencephalographic focus. Ipsilateral and contralateral NAA/Cr was negatively correlated with duration of epilepsy. Hippocampal volumes were negatively correlated with duration ipsilaterally but not contralaterally. Frequency of complex partial seizures was not correlated with any of the magnetic resonance measures. However, patients with frequent generalized tonic–clonic seizures had lower NAA/Cr bilaterally and smaller hippocampal volumes ipsilaterally than patients with none or rare generalized tonic–clonic seizures. The results suggest that although an early, fixed injury may cause asymmetric temporal lobe damage, generalized seizures may also cause progressive neuronal dysfunction or loss. Ann Neurol 1999;45:568–576

Relation of Interictal Spike Frequency to 1H‐MRSI‐Measured NAA/Cr

“…In partial epilepsy, one study reported that seizure frequency correlates with the degree of NAA decrease (24). In a recent article investigating 82 patients with TLE, Tasch et al (25) found that NAA/Cr was negatively correlated with the duration of epilepsy and the number of generalized tonic-clonic seizures. The only experimental study, which addressed a question similar to ours by comparing increased electrical brain activity and metabolic changes with phosphorus ("P)-spectroscopy in the penicillin epilepsy model in rats, was reported by Karlik et al (26).…”

Cortical Excitability in Cryptogenic Localization‐Related Epilepsy: Interictal Transcranial Magnetic Stimulation Studies

“…Moreover, proton magnetic resonance spectroscopy revealed that a bilateral reduction in the concentration of N-acetyl-aspartate can exist in many patients with focal epilepsies. This is probably a sign of neuronal loss or dysfunction that extends ipsiand contralateral to the epileptogenic region (45,46). One practical implication of the largely bilateral changes detected is that paired TMS might be of no value in localizing the epileptogenic area.…”

Reduced Cortical Thickness in Children with New-Onset Seizures: Fig 1.

“…[1][2][3][4][5][6][7] Volumetric abnormalities have been reported in neuronal regions involved in the generation and propagation of seizures, including the hippocampus, [8][9][10][11] amygdala, 12 entorhinal cortex, 13 thalamus, 14 and also extratemporal regions 15,16 in patients with chronic temporal lobe epilepsy. Children with idiopathic generalized epilepsies have also shown distributed patterns of abnormality affecting the thalamus and frontal lobe.…”

“…[17][18][19][20][21] It is not known whether the structural alterations developed during a vulnerable phase of cerebral development or are the cumulative effects of recurrent seizures 22 or are a combination of these factors acting synergistically. 11 To determine whether antecedent neurobiologic alterations are present, assessment could be performed in a population of patients with newonset seizures, which would exclude the confounding effects of recurrent seizures and long-term antiepileptic medications on the brain.…”