Characterization and Prediction of Short-term Outcomes in Memory After Temporal Lobe Resection in Children With Epilepsy.

BACKGROUND AND OBJECTIVES: The aim of this study was to characterize short-term outcomes in episodic memory, as assessed by the Children's Memory Scale (CMS), after temporal lobe resection in children with epilepsy using empirical methods for assessing cognitive change (i.e., reliable change indices [RCI] and standardized regression-based change scores [SRB]) and develop and internally validate clinically applicable models to predict postoperative memory decline. METHODS: This retrospective cohort study included children aged 6-16 years who underwent resective epilepsy surgery that included the temporal lobe (temporal only: "temporal" and multilobar: "temporal plus") and who completed preoperative and postoperative neuropsychological assessments including the CMS. Change scores on the CMS delayed memory subtests (Faces, Stories, and Word Pairs) were classified as decline, no change, or improvement using epilepsy-specific RCI and SRB. Logistic regression models for predicting postoperative memory decline were developed and internally validated with bootstrapping. RESULTS: Of the 126 children included, most of them demonstrated either no significant change (54%-69%) or improvement (8%-14%) in memory performance using RCI on individual measures at a median of 7 months after surgery. A subset of children (23%-33%) showed postoperative declines. Change distributions obtained using RCI and SRB were not statistically significantly different from each other. Preoperative memory test score, surgery side, surgery extent, and preoperative full-scale IQ were predictors of memory decline. Prediction models for memory decline included subsets of these variables with bias-corrected concordance statistics ranging from 0.70 to 0.75. The models were well calibrated although slightly overestimated the probability of verbal memory decline in high-risk patients. DISCUSSION: This study used empiric methodology to characterize memory outcome in children after temporal lobe resection. Provided online calculator and nomograms may be used by clinicians to estimate the risk of postoperative memory decline for individual patients before surgery.

Epilepsy surgery outcome in coexisting symptomatic refractory focal epilepsy and benign focal epilepsy of childhood.

Epilepsy surgery may successfully treat refractory symptomatic focal epilepsy in patients with coexisting benign focal epileptiform discharges. Reported here is the outcome after resective epilepsy surgery in three children with pharmacoresistant lesional focal epilepsy in whom seizures of benign focal epilepsy of childhood had been recorded. Two patients had left temporal epilepsy due to a malformation of cortical development; one of these had dual pathology, with additional ipsilateral hippocampal sclerosis. One child had catastrophic left hemispheric epilepsy due to left hemimegalencephaly. Frequent, habitual seizures of symptomatic epilepsy resolved after surgery (follow-up duration, 32-55 months); however, rare benign focal seizures of childhood have continued. These cases demonstrate that lesional pharmacoresistant focal epilepsy can be successfully treated with resective epilepsy surgery even when coexisting with benign focal epilepsy of childhood. During postoperative follow-up, careful documentation of breakthrough seizures due to benign focal epilepsy of childhood is important, so that these patients are not labeled as surgical failures.

Contralateral MRI abnormalities in candidates for hemispherectomy for refractory epilepsy.

PURPOSE: To assess the impact of contralateral magnetic resonance imaging (MRI) findings on seizure outcome after hemispherectomy for refractory epilepsy. METHODS: We retrospectively reviewed 110 children, 0.4-18 (median 5.9) years of age, who underwent hemispherectomy for severe refractory epilepsy at Cleveland Clinic Children's Hospital. In children with contralateral (as well as ipsilateral) MRI findings appreciated preoperatively, the decision to proceed to surgery was based on other features concordant with the side with the most severe MRI abnormality, including ipsilateral epileptiform discharges, lateralizing seizure semiology, and side of hemiparesis. RESULTS: We retrospectively observed contralateral MRI abnormalities (predominantly small hemisphere, white matter loss or abnormal signal, or sulcation abnormalities) in 81 patients (74%), including 31 of 43 (72%) with malformations of cortical development (MCD), 31 of 42 (73%) with perinatal injury from infarction or hypoxia, and 15 of 25 (60%) with Rasmussen's encephalitis, Sturge-Weber syndrome, or posttraumatic encephalomalacia. Among 84 children (76%) with lesions that were congenital or acquired pre- or perinatally, 67 (83%) had contralateral MRI abnormalities (p = 0.02). Contralateral findings were subjectively judged to be mild or moderate in 70 (86%). At follow-up 12-84 (median 24) months after surgery, 79% of patients with contralateral MRI abnormalities were seizure-free compared to 83% of patients without contralateral MRI findings, with no differences based on etiology group or type or severity of contralateral MRI abnormality. DISCUSSION: MRI abnormalities, usually mild to moderate in severity, were seen in the contralateral hemisphere in the majority of children who underwent hemispherectomy for refractory epilepsy due to various etiologies, especially those that were congenital or early acquired. The contralateral MRI findings, always much less prominent than those in the ipsilateral hemisphere, did not correlate with seizure outcome and may not contraindicate hemispherectomy in otherwise favorable candidates.

Vitamins, not surgery: spinal fluid testing in hemispheric epilepsy.

Metabolic testing in spinal fluid is not routinely obtained in every patient with refractory epilepsy or status epilepticus. A 9-month-old girl who was referred for surgical treatment of refractory status epilepticus suggestive of a right hemispheric focus; cranial magnetic resonance imaging was unremarkable. The patient received a metabolic evaluation according to institutional protocol and was noted to have a spinal fluid peak characteristically seen in folinic acid-responsive epilepsy. Subsequent testing revealed a deleterious mutation in the ALDH7A1 gene. At last follow-up, the patient was seizure free on folinic acid and pyridoxal 5'-phosphate supplementation. Surgery was not performed. Metabolic testing in spinal fluid is strongly urged in all patients with refractory epilepsy or status epilepticus when an underlying etiology is not known.

Epilepsy surgery in children with electrical status epilepticus in sleep.

OBJECTIVE: Pediatric epilepsy surgery candidates with unilateral congenital or early-acquired brain lesions may present with refractory seizures and generalized electroencephalographic features such as electrical status epilepticus in sleep (ESES). The purpose of our study was to review the clinical presentation, neuroimaging findings, and outcome in a series of children with unilateral brain lesions and ESES undergoing resective surgery for refractory epilepsy. METHODS: A total of 415 consecutive patients younger than 18 years of age undergoing video electroencephalographic evaluation and epilepsy surgery at Cleveland Clinic were reviewed for ESES, an underlying pathological lesion, and outcome after surgery. RESULTS: Eight patients were included. All patients presented with medically refractory epilepsy, hemiparesis, and developmental delay. The pathogenesis was perinatal infarction in 7 patients and malformation of cortical development in 1 patient. Preoperative electroencephalography demonstrated generalized interictal spikes, electroencephalographic seizures, and ESES in all cases. Age at the time of surgery ranged from 3 to 14 years. Six patients underwent hemispherectomy, and 2 patients underwent focal resection. Six patients became seizure-free after resection. Two patients with functional hemispherectomy continued to have rare seizures, but were much improved. These patients also had perinatal infarctions in the hemisphere contralateral to the resection, possibly indicating a less beneficial outcome. Postoperative electroencephalography demonstrated resolution of generalized interictal discharges and ESES in all. Formal pre- and postoperative neuropsychological testing showed overall improvement of age-equivalent scores. CONCLUSION: Children with unilateral brain lesions and seizures may become seizure-free after epilepsy surgery, even if the preoperative electroencephalogram shows generalized ESES. The lesion occurring early in life and the location of the lesion may play a role in the development of ESES. Cognitive impairment may be aggravated by the persistence of ESES. Preliminary developmental data in this small sample suggest that termination of seizures and possibly of ESES by epilepsy surgery may have developmental benefits.

Noninvasive correlates of subdural grid electrographic outcome.

PURPOSE: To investigate reasons for patients not proceeding to resective epilepsy surgery after subdural grid evaluation (SDE). To correlate noninvasive investigation results with invasive EEG observations in a set of patients with nonlesional brain MRIs. METHODS: Retrospective study of adult epilepsy patients undergoing SDE during an 8-year period at Cleveland Clinic. Construction of semiquantitative "scores" and Bayesian predictors summarizing the localizing value and concordance between noninvasive parameters in a subset with nonlesional MRIs. RESULTS: One hundred forty patients underwent SDE, 25 of whom were subsequently denied resective surgery. In 10 of 25, this was caused by a nonlocalizing subdural ictal EEG onset. Eight of 10 such patients were nonlesional on MRI. Among all nonlesional patients (n = 34 of 140), n1 = 10 of 34 patients had nonlocalizing and n2 = 24 of 34 had localizing, subdural ictal onsets. As groups, n1 and n2 were statistically disjoint relative to their noninvasive scores. Bayesian measures predictive of focal invasive ictal EEG were highest for complete concordance of noninvasive parameters, decreasing with lesser degrees of concordance. A localizing scalp interictal EEG was a particularly good Bayesian prognosticator. CONCLUSIONS: A small but significant proportion of SDE patients are denied subsequent therapeutic resective surgery. This is due to several reasons, including a nonlocalizing intracranial ictal EEG. The majority of such patients have nonlesional MRIs. The noninvasive data may be summarized by a semiquantitative score, as well as Bayesian likelihood ratios, which correlate with subsequent invasive outcome. This approach may find use in the selection and counseling of potential surgical candidates offered SDE.

Discontinuation of medications after successful epilepsy surgery in children.

To evaluate the need for antiepileptic drugs after successful epilepsy surgery in pediatric patients, we retrospectively reviewed patients who had epilepsy surgery and were seizure free or had rare nondisabling auras during the first 6 postoperative months. Association between drug discontinuation and seizure recurrence was evaluated using Cox proportional hazards multivariable survival analysis. Medications were withdrawn in 68 of 97 patients, seizure free (or with rare nondisabling auras) for >6 months after surgery; 57 of the 68 (84%) remained seizure free; the other 11 (16%) had seizure recurrence after 68 months (median). Seizure recurrence was controlled with medication in 7 of the 11 patients (3 have rare seizures, 1 frequent auras). Discontinuing medications at <6 mo, compared with later or no withdrawal, had significant risk for seizure recurrence (hazard ratio 5.8; 95% confidence interval 1.8, 17.5; P = 0.003). Of 29 patients who continued drugs, 28 (97%) remained seizure free after 37 months (median). Freedom from seizures 6 months after surgery predicted good outcome (95% seizure free, with or without medication). If discontinuation is offered after 6 months, the majority of patients (84%) can be expected to remain seizure free with no further need for medication. Although seizure breakthrough is possible in a smaller percentage, restarting drugs is likely to restore seizure control.

Pediatric epilepsy surgery in focal lesions and generalized electroencephalogram abnormalities.

Generalized abnormalities on scalp electroencephalograms (EEG) are not uncommon in children with partial epilepsy in whom a dominant focus of interictal and ictal abnormalities concordant to the brain lesion usually clarifies surgical candidacy. Children with exclusively generalized or multiregional EEG abnormalities and mental retardation are usually not considered surgical candidates, even when brain lesions are seen on imaging. Of 176 pediatric epilepsy surgeries at our center, we describe 10 children with exclusively generalized and multiregional interictal and ictal EEG abnormalities who had resection of a focal lesion seen on brain MRI. Surgical decisions were strengthened by clinical data. Surgery was offered as a last resort because of catastrophic epilepsy and treatment failures. At 26 months' mean postoperative follow-up, eight had no seizures, and two had infrequent seizures. Six months after surgery, generalized electroencephalographic abnormalities had resolved in all. We conclude that generalized and multiregional EEG abnormalities in the absence of dominant focus may not preclude epilepsy surgery in children with a congenital or acquired lesion seen on MRI. Generalized EEG abnormalities are likely secondary phenomena that resolve after surgery. Maladaptive neural plasticity and secondary epileptogenesis are potential mechanisms that mask an epileptogenic lesion with generalized EEG abnormalities.

Intracranial lipomas and epilepsy.

INTRODUCTION: Intracranial lipomas are rare, mostly congenital lesions. Sporadic case reports suggest an association with focal epilepsy. METHODS: All admissions to our epilepsy monitoring unit who had had brain MRI were reviewed for intracranial lipomas during 6 consecutive years. RESULTS: Five patients with intracranial lipomas were identified (0.14%). Lipomas were located in the midline (3 cases), in the tectal region, and over the parietal cortex. Another intracranial pathology was identified in two patients causing the epilepsy in these cases (head trauma and hemimegaencephaly). In two other cases the Video EEG monitoring findings were not congruent with the location of the lipoma, but no other explanation for their epilepsy was found. In one patient a large midline lipoma extending into the right lateral ventricle was thought to be the cause of the patient's right hemispheric seizures. No other clinical symptoms or complications of the lipomas were noted. DISCUSSION: Intracranial lipomas are rare, incidental, often asymptomatic findings and usually located near the midline. In only one of our five patients was the lipoma interpreted as the definite cause of the epilepsy.

Pediatric epilepsy surgery: lessons and challenges.

Pediatric epilepsy surgery has come of age, from being considered as a last resort in medically refractory focal epilepsy, after failure of numerous antiepileptic drug trials spanning many years, to a preferred treatment option in carefully selected candidates. There have been certain key developments that have catalyzed this change. First, we are able to predict medical intractability earlier during the course of epilepsy. Second, improved understanding of how the maturing brain recovers from neurologic insults has led to earlier consideration of surgical intervention during a window of developmental plasticity. Finally, improved diagnostic and surgical capabilities now enable us to identify more candidates suitable for surgery. At the same time, as the surgical frontier has been rapidly pushed to new horizons, we have also unearthed new challenges. In this review, several pediatric epilepsy syndromes are discussed to highlight these important developments.