Robert Sassen

Analysis of different types of resection for pediatric patients with temporal lobe epilepsy.

OBJECTIVEResection strategies for the treatment of temporal lobe epilepsy (TLE) are a matter of discussion. Few data on the significance of resection type are available for pediatric patients with TLE. METHODSData for a series of 89 children who were surgically treated for TLE were analyzed. A first cohort of patients were mainly surgically treated with anterior temporal lobectomies. For a second cohort, resections were preoperatively “tailored” to the lesion and presumed epileptogenic area. RESULTSThe follow-up period was 46 months (range, 14–118 mo). Seventy-seven patients (87%) attained satisfactory seizure control (82% Engel Class I and 5% Class II). For 12 patients (13%), seizure control was unsatisfactory (8% Class III and 5% Class IV). Anterior temporal lobectomies resulted in 94% satisfactory seizure control (33 patients), whereas the success rates were only 74% (20 patients) for amygdalohippocampectomy (AH) (P = 0.023) and 77% (13 patients) for lesionectomy plus hippocampectomy (not significant). All patients who underwent purely lateral temporal lesionectomies became seizure-free (14 patients). Logistic regression revealed the factors of AH (P = 0.021) and left-side surgery (P = 0.017) as significant predictors of unsatisfactory seizure control. Satisfactory seizure control was not dependent on the histopathological diagnoses. There was a low rate of verbal memory deterioration after left-side operations. Neuropsychological deterioration was rare after right temporal resections. Attentional and contralateral functions improved after surgery. CONCLUSIONSurgery for the treatment of juvenile TLE is successful and safe, but the resection type may influence outcomes. Results after AHs were disappointing, probably because of difficulties in precise localization of the epileptogenic focus among children. Neuropsychological results demonstrated minimal rates of deterioration and significant improvements in contralateral functions. Surgical treatment of juvenile TLE should be encouraged, but the use of especially left AH should possibly be restricted.

Pre- and postoperative verbal memory in pediatric patients with temporal lobe epilepsy

Outcome studies concerning memory after pediatric temporal lobe surgery in the treatment of epilepsy are rare and have not yielded consistent results. In the present study, 55 children and adolescents with temporal lobe epilepsy (TLE; 26 left, 29 right, 6-17 years) performed a verbal memory test before and 3 as well as 12 months after different types of temporal lobe resections (anterior lobectomy, amygdalo-hippocampectomy (AH), lesionectomy (LX)). Groups did not significantly differ before surgery. Three months after surgery, the left resected group showed a decline in learning and delayed recall, and performed significantly lower than the right resected group. Recoveries were evident 1 year after surgery. The postoperative memory declines were associated with a left-sided resection and a higher preoperative performance. Comparisons on the different resection types suggest a special risk in patients undergoing a left-sided AH. In summary, our results indicate a functional association of verbal memory functions with the left temporal lobe similar to findings in adult patients. Declines after left-sided temporal resections seem to be reversible at least for part of the children, perhaps due to the greater plasticity of the immature brain.

Neuropsychological Outcome in Children after Frontal Lobe Epilepsy Surgery

We investigated the neuropsychological performance of children with frontal lobe epilepsy (FLE, n = 12) before and 1 year after surgery. Children with temporal lobe epilepsy (TLE, n = 12) were included as control group. Preoperatively, children with FLE had a significantly higher IQ than children with TLE, but were significantly more often impaired in manual motor coordination. Postoperatively, both groups improved in attention, short-term and long-term memory, and manual coordination, although the latter was not significant. Neuropsychological outcome in FLE patients was not better in seizure-free patients than in patients with continuing seizures. To avoid deterioration in language functions of patients in whom surgery involved left area 44, correspondence of results in cortical stimulation and intracarotid amytal test may be essential. All in all, our data indicate a favorable cognitive outcome in children 1 year after frontal lobe surgery.

An open study of tacrolimus therapy in Rasmussen encephalitis

Seven patients with Rasmussen encephalitis (RE) were treated with the immunosuppressant tacrolimus and followed for a median of 22.4 months. They were compared with 12 historical untreated RE patients (median follow-up 13.9 months). The tacrolimus-treated patients had a superior outcome regarding neurologic function and progression rate of cerebral hemiatrophy but no better seizure outcome. No treated patient, but 7 of 12 control patients, became eligible for hemispherectomy. Tacrolimus did not have any major side effects.

Rasmussen encephalitis: Incidence and course under randomized therapy with tacrolimus or intravenous immunoglobulins

Purpose:  Rasmussen encephalitis (RE) leads to progressive tissue and function loss of one brain hemisphere and often intractable epilepsy. This is the first randomized prospective treatment trial in RE.

Postsurgical Outcome in Pediatric Patients with Epilepsy: A Comparison of Patients with Intellectual Disabilities, Subaverage Intelligence, and Average-Range Intelligence

Summary:  Purpose: Intellectual disabilities are often associated with bilateral or diffuse morphologic brain damage. The chances of becoming seizure free after focal surgery are therefore considered to be worse in patients with intellectual disabilities. The risk of postoperative cognitive deficits could increase because diffuse brain damage lowers the patients ability to compensate for surgically induced deficits. Several studies in adult patients have indicated that IQ alone is not a good predictor of postoperative cognitive and seizure outcome. Our study evaluated this subject in children and adolescents.

Intelligence quotient improves after antiepileptic drug withdrawal following pediatric epilepsy surgery.

Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop (TTS) study, we showed that timing of AED withdrawal does not majorly influence long‐term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative intelligence quotient (IQ), and change in IQ (delta IQ) following pediatric epilepsy surgery.

Clonally Expanded Mitochondrial DNA Mutations in Epileptic Individuals With Mutated DNA Polymerase γ

The instability of the mitochondrial genome in individuals harboring pathogenic mutations in the catalytic subunit of mitochondrial DNA (mtDNA) polymerase &ggr; (POLG) is well recognized, but the underlying molecular mechanisms remain to be elucidated. In 5 pediatric patients with severe myoclonic epilepsy and valproic acid-induced liver failure, we identified 1 novel and 4 previously described pathogenic mutations in the linker region of this enzyme. Although muscle biopsies in these patients showed unremarkable histologic features, postmortem liver tissue available from 1 individual exhibited large cytochrome c oxidase-negative areas. These cytochrome c oxidase-negative areas contained 4-fold less mtDNA than cytochrome c oxidase-positive areas. Decreased copy numbers of mtDNA were observed not only in the liver, skeletal muscle, and brain but also in blood samples from all patients. There were also patient-specific patterns of multiple mtDNA deletions in different tissues, and in 2 patients, there were clonally expanded mtDNA point mutations. The low amount of deleted mtDNA molecules makes it unlikely that the deletions contribute significantly to the general biochemical defect. The clonal expansion of a few individual-specific deletions and point mutations indicates an accelerated segregation of early mtDNA mutations that likely are a consequence of low mtDNA copy numbers. Moreover, these results suggest a potential diagnostic approach for identifying mtDNA depletion in patients.

The validity of the Child Behavior Checklist for children with epilepsy.

The validity of the Child Behavior Checklist (CBCL) for patients with epilepsy has been questioned, because several items may reflect seizure semiology rather than habitual behavior. This study compared a standard version of the CBCL with an adjusted version that excluded those ambiguous items. Participants were 58 pediatric patients with epilepsy who were assessed preoperatively and 1 year after successful surgical treatment. Before surgery, the adjusted version indicated significantly lower values for the scales Attention Problems, Thought Problems, and Total Problems than the standard version. After surgery, the difference between the standard and adjusted versions and the scores for the ambiguous items were unchanged, although all patients were completely seizure free at that time. Elevated scores on the ambiguous items thus probably reflect real behavioral problems and are not due to confusion with seizure semiology. The results support the CBCL as a valid assessment tool in children with epilepsy.

Long-term outcome of hemispheric surgery at different ages in 61 epilepsy patients

Objective Hemispheric neurosurgery is an established treatment for severe epilepsy caused by extended unilateral brain pathology. However, it is still an unresolved question at which age surgery should best be performed. In light of decreasing plasticity and the cumulative impact of seizures and anticonvulsants on neurodevelopment, early surgery appears preferable. Methods We retrospectively investigated the medical, cognitive-behavioural and psychosocial long-term outcome (follow-up: 9.4 years (1.1–19.4)) of hemispherectomy as a function of age at surgery (early: <7 years/intermediate: 7–16 years/late: >16 years) based on a structured postal survey in a large patient sample (N=61/81, return rate: 75%). Results At follow-up, 45 (74%) patients were seizure free. Presurgical levels of intelligence were below average in most patients (79%) and postsurgical cognition largely resembled the presurgical capacities. Best seizure outcome was obtained for early surgery patients (90% seizure free). Patients with late surgery, however, exhibited higher presurgical and postsurgical intelligence and better psychosocial achievements. Binary logistic regression identified better presurgical intelligence and higher age at surgery as positive predictors of postsurgical intelligence. Lower presurgical intelligence and postsurgical seizure freedom predicted intellectual pre-post improvements. Conclusions Our data confirm the efficacy and cognitive safety of hemispheric surgeries performed at different ages. Eligible older and high functioning patients can be perfect candidates. Presurgical intelligence serves as indicator of the functional integrity of the contralateral hemisphere, which mainly determines postsurgical cognition and psychosocial outcome. Seizure freedom promotes cognitive improvement. As many unknown factors determined age at surgery, our retrospective data neither question early surgeries nor suggest postponing surgery.