Topography of interictal glucose hypometabolism in unilateral mesiotemporal epilepsy zy S. Arnold, MD; G. Schlaug, MD; H. Niemann, MD; A. Ebner, MD; H. Luders, MD; O.W. Witte, MD; and R.J. Seitz, MD Article abstract-We mapped the regional cerebral glucose metabolism (rCMRGlu) in 20 patients suffering from medically refractory focal epilepsy of either left or right mesiotemporal origin (mTLE) during resting wakefulness. After temporal lobectomy, histology demonstrated hippocampal sclerosis in 18 patients. Pixel-by-pixelcomparisons with healthy control subjects showed significant zyxwvutsr (p zyxwvuts < 0.001) depressions of the mean rCMRGlu ipsilateral to the epileptic focus in the mesiotemporal region, including the hippocampus and the parahippocampal gyrus and middle temporal zyx gyrus. Additional remote rCMRGlu depressions occurred bilaterally in the fronto-orbital cortex and ipsilaterally in the posterior insula and the thalamus. Patients with left-sided mTLE had additional rCMRGlu depressions in the left inferior frontal gyrus (Broca's region) and superior temporal gyrus at the parietotemporal junction, whereas corresponding rCMRGlu depres- sions were not present in patients with right mTLE. Neuropsychological testing showed impaired verbal fluency, verbal intelligence, and verbal memory in the left mTLE patients. Correlations of the specific mean rCMRGlu depressions and the neuropsychological deficits suggest that impaired language functions in patients with left mTLE could result from functional changes beyond the temporal lobe. NEUROLOGY zyxwvutsrqp 1996;46:1422-1430 Patients with intractable complex partial seizures of unilateral temporal lobe origin show interictal de- pressions of the regional cerebral glucose metabolism (rCMRGlu) as measured with PET in areas corre- sponding to the location of the epileptogenic zone. Pioneered by Engel et al.,l this was later confirmed by various groups using different approaches of quantitative image analysis.2-6 Recent evidence sug- gests that in addition to the temporal lobe, hypome- tabolism may also occur in varying extratemporal cortical regions and subcortically in the ipsilateral thalamu~~*~~~ or bilaterally in the caudate nucleu~.~ One could assume that the metabolic depressions outside the epileptic focus represent nonspecific changes, because combined neuroreceptor and meta- bolic studies demonstrated abnormal binding re- stricted to the mesial temporal region compared with the more extended area of metabolic depression.*JO In addition, the metabolic depressions are possibly due to additional cerebral lesions. However, meta- bolic disturbances beyond the area of the electroen- cephalographically defined epileptogenic zone are present both in experimental animals and hu- mans."J2 Therefore, cortical rCMRGlu depressions outside the epileptogenic zone occur in focal epilepsy patients but are of undefined clinical relevance. Patients with complex partial seizures of mesio- temporal lobe origin (mTLE) may exhibit cognitive deficits. Specifically, patients with left mTLE re- vealed deficits in the performance of delayed verbal memory tasks, and those with right mTLE exhibited disturbances of delayed visual-spatial memory tasks.13J4 Patients with left mTLE also have deficits of verbal learning and immediate memory.15 The memory deficits in left TLE patients may be linked to subtle language disturbances such as anomia16 and impairments in phonemic cued recall. l7 The working hypothesis of this study was that the neuropsychological deficits in patients with unilat- eral mTLE might be related to metabolic distur- bances in neocortical areas. Methods. Patients. Of 100 consecutive patients with complex partial seizures scanned with PET, we selected 20 patients who fulfilled all five criteria. First, all patients had seizures of unilateral mesiotemporal origin (mTLE) as demonstrated by continuous interictal and ictal video-EEG monitoring with scalp and sphenoidal electrodes and in three cases also with deep electrodes (table zy 1). Second, patients with a history of cerebral trauma preceding the seizure onset and patients with evidence of another cere- bral or systemic disease with possible cerebral involvement (e.g., diabetes mellitus) were excluded to minimize influ- ences of unrelated disorders on the rCMRGlu patterns. Third, patients who previously underwent neurosurgical procedures were excluded. Fourth, all patients had axial and coronal TI- and T,-weighted MRIs. Their MRIs were From the Department of Neurology (Drs. Arnold, Schlaug, Witte, and Seitz), Heinrich-Heine-University, Diisseldorf, Germany; the Bethel Epilepsy Center (Drs. Arnold, Niemann, Ebner, and Liiders), Bielefeld, Germany; and the Cleveland Clinic Foundation (Dr. Luders), Cleveland, OH. Received February 22, 1995. Accepted in final form September 6, 1995. Address correspondence and reprint requests to Dr. R.J. Seitz, Heinrich-Heine-University Diisseldorf, Department of Neurology, MoorenstraRe 5, P.O. Box 10 10 07, D-40001 Diisseldorf, Germany. 1422 Copyright 0 1996 by the American Academy of Neurology