Namsoo Lee

X-linked malformations of neuronal migration

Malformations of neuronal migration such as lissencephaly (agyria-pachygyria spectrum) are wellknown causes of mental retardation and epilepsy that are often genetic. For example, isolated lissencephaly sequence and Miller-Dieker syndrome are caused by deletions involving a lissencephaly gene in chromosome 17p13.3, while many other malformation syndromes have autosomal recessive inheritance. In this paper, we review evidence supporting the existence of two distinct X-linked malformations of neuronal migration. X-linked lissencephaly and subcortical band heterotopia (XLIS) presents with sporadic or familial mental retardation and epilepsy. The brain malformation varies from classical lissencephaly, which is observed in males, to subcortical band heterotopia, which is observed primarily in females. The XLIS gene is located in chromosome Xq22.3 based on the breakpoint of an X-autosomal translocation. Bilateral periventricular nodular heterotopia (BPNH) usually presents with sporadic or familial epilepsy with normal intelligence, primarily in females, although we have evaluated two boys with BPNH and severe mental retardation. The gene for BPNH has been mapped to chromosome Xq28 based on linkage studies in multiplex families and observation of a subtle structural abnormality in one of the boys with BPNH and severe mental retardation. NEUROLOGY 1996;47: 331-339

Seizure outcome after temporal lobectomy for temporal lobe epilepsy A Kaplan-Meier survival analysis

Objective: To determine seizure outcome and its predictors in patients with medically refractory temporal lobe epilepsy (TLE) after temporal lobectomy (TL). Background: TL is the most common surgical procedure performed in adolescents and adults for the treatment of medically refractory TLE. Seizure outcome has been reported extensively during the first few postoperative years, but little is known beyond that time. Methods: The authors analyzed seizure outcome in 79 patients who underwent TL for epilepsy at the Duke University Medical Center from 1962 through 1984. Patients with less than 2 years of follow-up and degenerative disorders were excluded. Predictors of seizure outcome were analyzed using Kaplan-Meier survival analyses. Results: The mean follow-up was 14 years (range, 2.1 to 33.6 years). Using Engel’s classification, 65% of patients were class I, 15% were class II, 11% were class III, and 9% were class IV. At least one postoperative seizure occurred in 55% of subjects. The majority of recurrences (86%) took place within 2 years of surgery. Later recurrences tended not to lead to medical intractability. Higher monthly preoperative seizure frequency was associated with poor seizure outcome. A seizure-free state at 2 years was found to be a better predictor of long-term outcome than the 6-, 12-, and 18-month landmarks. Conclusions: TL provides sustained, long-term benefit in patients with medically refractory TLE. Seizure-free status at 2 years from the time of surgery is predictive of long-term remission.

Magnetic resonance imaging evidence of hippocampal sclerosis in progression: a case report.

Summary: A 32‐month‐old child presented in status epilepticus (SE) involving the left side of the body. Fast spin‐echo magnetic resonance imaging (FSE‐MRI) with hippocampal volumetry performed ≤24 h after the seizure showed increased T2 signal of the right hippocampus, but no atrophy. Complex partial seizures (CPS) appeared at age 33 months, and three more episodes of SE occurred between 33 and 37 months of age. Follow‐up FSE‐MRI at 34 and at 45 months of age demonstrated progressive hippocampal atrophy with resolution of the increased T2 signal. Her CPS became intractable and, at age 51 months, she underwent right temporal lobectomy. In the ensuing 5 months, she has had only one major motor seizure. This case demonstrates that acute increased hippocampal T2 signal intensity can occur soon after SE and hippocampal sclerosis (HS) may become evident within months in the setting of recurrent early childhood SE. This observation may support the hypothesis that early childhood SE can lead to HS. Furthermore, this case suggests that years of temporal lobe CPS may not be necessary for development of HS.

Clinical and electrographic manifestations of lesional neocortical temporal lobe epilepsy

To determine whether lesional neocortical temporal lobe epilepsy (NTLE) can be differentiated from mesial temporal lobe epilepsy (MTLE) during the noninvasive presurgical evaluation, we compared the historical features, seizure symptomatology, and surface EEG of 8 patients seizure free after neocortical temporal resection with preservation of mesial structures and 20 patients after anterior temporal lobectomy for MTLE. Seizure symptomatology of 107 seizures (28 NTLE, 79 MTLE) was analyzed. One hundred one ictal EEGs(19 NTLE, 82 MTLE) were reviewed for activity at seizure onset; presence, distribution, and frequency of lateralized rhythmic activity (LRA); and distribution of postictal slowing. Seizure symptomatology and EEG data were compared between groups, and sensitivity, specificity, and positive and negative predictive values were determined for variables that differed significantly. Multiple logistic regression was used to determine whether patients could be correctly classified as having MTLE or NTLE. MTLE patients were younger at onset of habitual seizures and more likely to have a prior history of febrile seizures, CNS infection, perinatal complications, or head injury. NTLE seizures lacked features commonly exhibited in MTLE, including automatisms, contralateral dystonia, searching head movements, body shifting, hyperventilation, and postictal cough or sigh. NTLE ictal EEG recordings demonstrated lower mean frequency of LRA that frequently had a hemispheric distribution, whereas LRA in MTLE seizures was maximal over the ipsilateral temporal region. We conclude that it may be possible to differentiate lesional NTLE from MTLE on the basis of historical features, seizure symptomatology, and ictal surface EEG recordings. This may assist in the identification of patients with medically refractory nonlesional NTLE who frequently require intracranial monitoring and more extensive or tailored resections.

Fast Spin-Echo, Magnetic Resonance Imaging-Measured Hippocampal Volume: Correlation with Neuronal Density in Anterior Temporal Lobectomy Patients

Summary: To assess the value of magnetic resonance imaging (MRI)‐measured hippocampal volume in the detection of hippocampal sclerosis, we studied 28 patients undergoing anterior temporal lobectomy for medically intractable mesial temporal lobe epilepsy. Hippocampal volumetry and visual analysis of T2 signal change were performed using fast spin‐echo T2‐weighted MRI. Quantitative neuronal density measurements were performed in the resected hippocampal specimens. There was a significant correlation between MRI‐measured absolute hippocampal volume (AHV) and neuronal density in CA1, CA2, and CA3 subfields (p<0. 0001, p < 0.01, and p < 0.05, respectively). Differential hippocampal volume (side‐to‐side volume difference) failed to detect bilateral atrophy in three patients, but the bilateral hippocampal atrophy was recognized by considering AHV in these patients. This study suggests that MRI‐measured AHV can be of value in evaluating patients with mesial temporal lobe epilepsy, especially when there is no side‐to‐side difference in hippocampal volumetry.

Surgical outcome in patients with epilepsy with occult vascular malformations treated with lesionectomy.

Summary: Purpose: This retrospective study reports the long‐term surgical outcome of patients with medically refractory epilepsy and vascular malformations who were treated with lesionectomy. A detailed analysis of surgical failures had been performed in an attempt to define predictors of surgical success and failure.

Outcome of Temporal Lobectomy in Adolescents

We performed temporal lobectomy in 23 young patients with intractable complex partial seizures (CPS) at an average age of 14.5 years. At a mean follow-up interval of 4.8 years, we reevaluated the patients to assess the surgical outcome; 74% were seizure-free. Cognitive testing showed slight improvement in Full-scale I.Q. scores and in some subtest scores. Wechsler Memory Scales had not changed significantly from the preoperative scores. Both pre- and postoperative Minnesota Multiphasic Personality Inventories 168 (MMPIs) were obtained in nine patients; and only postoperative MMPIs were obtained in 18. Pre- and postoperative social function, reported by the patients in a structured interview with a clinical psychologist (H.S.S.), was scored by a rating scale. All patients reported postoperative improvement in social function, although of variable degree. Patients were divided into a well-adjusted and a poorly adjusted group based on their postoperative social function. As compared with the well-adjusted group, the poorly adjusted group reported more preoperative social problems, had lower preoperative and postoperative I.Q. scores, had poorer postoperative seizure control, and had higher postoperative MMPI scores.