Hippocampal atrophy, epilepsy duration, and febrile seizures in patients with partial seizures W.H. Theodore, MD; S. Bhatia, MD; J. Hatta, MD; S. Fazilat; C. DeCarli, MD; S.Y. Bookheimer, PhD; and W.D. Gaillard, MD Article abstract—Background: Previous studies have suggested a variety of factors that may be associated with the presence of hippocampal formation (HF) atrophy in patients with complex partial seizures (CPS), including a history of complex or prolonged febrile seizures (FS), age at seizure onset, and epilepsy duration. Objective: To determine whether epilepsy duration is related to HF atrophy. Methods: We performed MRIs on 35 patients with uncontrolled CPS who had temporal lobe ictal onset on video-EEG. None had evidence for an alien tissue lesion or extra-hippocampal seizure onset. All had a history of secondary generalization. Brain structures were drawn on consecutive images and pixel points summed from successive pictures to calculate volumes. Results: Nine patients with a history of complex or prolonged FS had smaller ipsilateral HF volume and ipsilateral/contralateral ratio than did patients without a history of FS. Epilepsy duration had a significant relation to ipsilateral HF volume and ipsilateral/contralateral ratio. In a multivariate analysis, the effect of duration, but not age at onset or scan, was significant. Patients with a history of FS did not have earlier age at epilepsy onset or longer duration. Conclusions: A history of FS predicted the severity of HF atrophy in our patients. Age at onset or study was not a significant factor. Epilepsy duration, however, did have a significant effect, suggesting that, after an initial insult, progressive HF damage may occur in patients with persistent seizures. NEUROLOGY 1999;52:132–136 Pathologic and clinical studies have suggested that repeated complex partial seizures (CPS) of temporal lobe origin might induce progressive neuronal inju- ry. 1,2 There have been limited noninvasive methods to detect such injury. MRI hippocampal volume mea- surements (vMRI) reliably identify hippocampal for- mation (HF) atrophy, which predicts the location of the epileptogenic zone, in patients with temporal lobe epilepsy (TLE). 3-5 Quantitative measurements of HF volume reduction are related to cell loss in patho- logic specimens as well as clinical measures such as the Wechsler Memory Scale. 6-9 It is very difficult to obtain accurate seizure counts over many years, but epilepsy duration might serve as a surrogate marker in patients with persistent TLE. Some previous vMRI studies have suggested that longer epilepsy duration was associated with smaller HF volume ipsilateral to the epileptic focus, 4 whereas others found a relation to a history of com- plicated febrile seizures (FS) but not duration. 10 Evi- dence for a deleterious effect of persistent seizures would argue for more aggressive drug therapy or early surgery. We studied 35 patients referred to the National Institutes of Health (NIH) Clinical Epilepsy Section for uncontrolled CPS who had EEG and MRI evidence of temporal lobe epileptogenic zones. Methods. The patients (mean age 34.8 6 10.2 years; 19 men) had been referred to the Clinical Epilepsy Section, Epilepsy Research Branch, National Institute of Neurolog- ical Disorders and Stroke, for evaluation of uncontrolled partial seizures. Patients were selected for inclusion if ictal video-EEG telemetry with sphenoidal electrodes showed CPS with a temporal lobe epileptogenic zone. Because MRI volumetric studies were the dependent variable, they were not used as an inclusion criterion. Patients with evidence of a mass lesion were excluded. Twenty-two patients had surgery, and seven had invasive electrode studies. Mean age at seizure onset was 11.4 6 5.9 years, and epilepsy duration was 23.1 6 11.4 years. Detailed histories were obtained from patients, their families, and medical records. All patients had a history of secondary generaliza- tion. Nine patients were considered to have had initial “prolonged or complex” FS (FS1)—a seizure associated with fever occurring before the onset of afebrile seizures and lasting longer than 15 minutes, with focal features, or followed by transient or persistent neurologic abnormali- ties. 11 FS2 patients could have a history of simple FS, as defined by Nelson and Ellenberg. 11 FS1 and FS2 patients did not differ in epilepsy duration, age at seizure onset, or age at scan. Contiguous coronal MRIs with a 2-mm slice thickness were obtained on a GE Signa 1.5-T MR scanner (GE Med- ical Systems, Milwaukee, WI). Scanning sequence was re- peat time (TR) 24 msec, echo time (TE) 5 msec with a flip angle of 45°, field of view 24 3 24 cm with a matrix of 256 3 256. The voxel size was 0.9375 3 0.9375 3 2 mm 3 . Images were transferred to a VAX station and analyzed using the Medical Imaging Retrieval, Analysis and Graph- From the Clinical Epilepsy Section (Drs. Theodore, Bhatia, Hatta, DeCarli, and Bookheimer, and S. Fazilat), Epilepsy Research Branch, NINDS, NIH, Bethesda, MD; and Department of Neurology (Dr. Gaillard), Children’s National Medical Center, Washington, DC. Received June 29, 1998. Accepted in final form September 12, 1998. Address correspondence and reprint requests to Dr. William H. Theodore, NIH 10/5N-250, Bethesda, MD 20892. 132 Copyright © 1999 by the American Academy of Neurology