Neuronal Dysfunction in Children With Newly Diagnosed Temporal Lobe Epilepsy Steven P. Miller, MDCM* ² , Li M. Li, MD*, Fernando Cendes, MD, PhD*, Zografos Caramanos, MA*, Bernard Rosenblatt, MDCM ² , Michael I. Shevell, MDCM ² , Frederick Andermann, MD* ² , and Douglas L. Arnold, MD* We sought to determine whether neuronal dysfunction throughout the temporal lobes of children with tempo- ral lobe epilepsy (TLE) is already as severe at the time of diagnosis as it is in patients with long-standing intractable TLE (INT-TLE). Proton magnetic reso- nance spectroscopic imaging was used to measure N-acetylaspartate/creatine (NAA/Cr) ratios in the tem- poral lobes of five consecutive children with newly diagnosed TLE (ND-TLE), five with INT-TLE, and 30 normal control subjects. The median age of those with ND-TLE and those with INT-TLE did not significantly differ (P  0.92). All five patients with ND-TLE had bilateral reductions in the NAA/Cr ratio. Two of the five patients with INT-TLE had bilateral reductions in the NAA/Cr ratio; three had unilateral reductions in the NAA/Cr ratio. In the three patients with lesions the NAA/Cr ratio decrease extended outside these lesions. No significant differences were detected in any temporal lobe region between the ND-TLE and INT-TLE groups. The severity of the neuronal dysfunction in the children with ND-TLE was at least as severe as in those with INT-TLE and was not restricted to one temporal lobe, implying that the neuronal abnormalities observed in patients with TLE occur before the clinical manifestations. © 2000 by Elsevier Science Inc. All rights reserved. Miller SP, Li LM, Cendes F, Caramanos Z, Rosenblatt B, Shevell MI, Andermann F, Arnold DL. Neuronal dysfunc- tion in children with newly diagnosed temporal lobe epilepsy. Pediatr Neurol 2000;22:281-286. Introduction Whether progressive temporal lobe neuronal damage in humans with temporal lobe epilepsy (TLE) is acquired as a consequence of repeated seizures remains controversial. One form of progressive neuronal damage is secondary epileptogenesis. Secondary epileptogenesis refers to the induction by an actively discharging epileptogenic region of similar paroxysmal behavior in the cellular elements of otherwise normal and often contralateral neuronal net- works [1]. Secondary epileptogenesis is readily demon- strated in animals in the kindling experimental model [2-4]. However, secondary epileptogenesis and other forms of progressive neuronal damage have not conclusively been demonstrated in humans [1-3,5,6]. Knowledge of the extent of neuronal damage present at the clinical onset of TLE would help to clarify the extent to which neuronal damage in TLE relates primarily to recurrent seizures or to the underlying epileptogenic process itself. Proton magnetic resonance spectroscopic imaging ( 1 H- MRSI) allows the measurement of the neuronal marker N-acetylaspartate (NAA) [7,8], the main contributor to the N-acetyl group signal apparent at 2.02 ppm of the brain spectrum [9]. The side of maximal NAA signal reduction has been proved to coincide with the side of seizure origin in patients with TLE [10-16]. The decreased temporal lobe NAA signal indicates neuronal damage that may be secondary to neuronal metabolic dysfunction or acquired microscopic abnormalities not visualized on magnetic resonance imaging (MRI). In patients with intractable TLE (INT-TLE), ipsilateral and contralateral NAA/creatine (Cr) ratios were negatively correlated with the duration of epilepsy [17]. Extrapolation of this data backward in time suggests that NAA values are abnormally low at the onset of epilepsy and that the ipsilateral NAA/Cr ratio is lower than the contralateral values even at an early age [17]. However, to our knowl- edge, no direct observation has been made of the degree of neuronal damage at the time of diagnosis of TLE. The objective of this study was to define the extent of any From the *Department of Neurology and Neurosurgery; Montreal Neurological Institute and Hospital; and ² Montreal Children’s Hospital; McGill University; Montreal, Quebec, Canada. Communications should be addressed to: Dr. Arnold; Montreal Neurological Institute and Hospital; 3801 University Street; Montreal, Quebec H3A 2B4, Canada. Received September 13, 1999; accepted December 7, 1999. 281 © 2000 by Elsevier Science Inc. All rights reserved. Miller et al: Neuronal Dysfunction in Pediatric TLE PII S0887-8994(99)00159-9 ● 0887-8994/00/$20.00