Cognitive change after DBS in refractory epilepsy: A randomized-controlled trial.

OBJECTIVES: Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) reduces seizure frequency in patients with refractory epilepsy. There are, however, few studies on treatment-related changes in cognitive functions. The main objective of this study was to investigate cognitive changes in patients receiving ANT-DBS. We also explored whether possible effects were related to stimulation duration and whether change in seizure frequency was associated with cognitive changes. MATERIALS AND METHODS: Bilateral ANT electrodes were implanted in 18 patients with refractory epilepsy, aged 18-52 years. Immediately after implantation, patients were randomized to stimulation ON (n = 8) or OFF (n = 10) for the first 6 months (blinded phase). During the following 6-month open phase, both groups received stimulation. Neuropsychological assessments were conducted before implantation (T1), at the end of the blinded period (T2), and 1 year after implantation (T3). RESULTS: Groupwise comparisons across the three time points revealed changes in performance in two of 22 cognitive test scores: motor speed and sustained attention. We found no significant group differences in cognitive change from T1 to T2. Patients reported fewer symptoms of executive dysfunction after 12 months of stimulation. Patients showing significant improvement in seizure frequency had better performance in a measure of verbal learning. CONCLUSION: Our results indicate that ANT-DBS has very limited effects on cognitive functioning, as measured by formal tests after 6- or 12-month stimulation. ANT-DBS may have a positive influence on executive function. Our findings provide limited support for an association between change in seizure frequency and cognitive functioning.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Seizure outcomes in relation to the extent of resection of the perifocal fluorodeoxyglucose and flumazenil PET abnormalities in anteromedial temporal lobectomy.

BACKGROUND: The area of predominant perifocal [(18)F]fluorodeoxyglucose ((18)F-FDG) hypometabolism and reduced [(11)C]flumazenil ((11)C-FMZ) -binding on PET scans is currently considered to contain the epileptogenic zone and corresponds anatomically to the area localizing epileptogenicity in patients with temporal lobe epilepsy (TLE). The question is whether the volume of the perifocal pre-operative PET abnormalities, the extent of their resection, and the volume of the non-resected abnormalities affects the post-operative seizure outcome. METHODS: The sample group consisted of 32 patients with mesial temporal sclerosis who underwent anteromedial temporal lobe resection for refractory TLE. All patients had pathologic perifocal findings on both of the PET modalities as well as on the whole-brain MRI. The volumetric data of the PET and MRI abnormalities within the resected temporal lobe were estimated by automated quantitative voxel-based analysis. The obtained volumetric data were investigated in relation to the outcome subgroups of patients (Engel classification) determined at the 2-year post-operative follow-up. RESULTS: The mean volume of the pre-operative perifocal (18)F-FDG- and (11)C-FMZ PET abnormalities in the volumes of interest (VOI) of the epileptogenic temporal lobe, the mean resected volume of these PET abnormalities, the mean volume of the non-resected PET abnormalities, and the mean MRI-derived resected volume were not significantly related to the outcome subgroups and had a low prediction for individual freedom from seizures. CONCLUSIONS: The extent of pre-surgical perifocal PET abnormalities, the extent of their resection, and the extent of non-resected abnormalities were not useful predictors of individual freedom from seizures in patients with TLE.

Subclinical epileptiform activity in children with electrical status epilepticus during sleep: effects on cognition and behavior before and after treatment with levetiracetam.

We performed a double-blind placebo-controlled crossover study of the effects of spike activity during sleep and when awake on learning, long-term memory, vigilance and behavior before and after treatment with levetiracetam in children with electrical status epilepticus during sleep. At baseline, verbal learning declined with increasing spike activity, but there were no relations between spike activity and memory, vigilance or behavior. Levetiracetam was effective in reducing sleep-related spike activity, but on a group level, this had no clear effects on behavior, vigilance or learning and memory. Our results do not allow firm conclusions whether to treat nocturnal epileptiform activity or not; larger samples and longer follow-up may be needed.

[Epilepsy surgery--assessment and patient selection]. / Epilepsikirurgi--utredning og pasientseleksjon.

BACKGROUND: Considerable progress in diagnostic imaging and video EEG monitoring has improved the possibilities of localising the epileptogenic zone of the brain in patients with epilepsy. Despite the fact that epilepsy surgery can therefore be offered to more patients today than previously, relatively few patients are referred for an assessment for surgery. The aim of this review is to provide a brief account of the patient selection procedures and the investigations prior to epilepsy surgery. METHOD: The review is based on a literature search in PubMed and the personal experiences of the authors in this field. RESULTS: If the epilepsy does not respond to any kind of pharmacological treatment, and idiopathic generalised epilepsy and pseudoresistance have been ruled out, the patient should be evaluated for surgery. The evaluation is multidisciplinary, and the aim is to localise the epileptogenic zone, which can be identified by both structural and functional abnormalities. It must be determined before the operation whether the zone can be removed without leaving severe neurological or cognitive impairment. The best results after epilepsy surgery are seen in patients with a morphological substrate, particularly temporal lobe epilepsy associated with hippocampal sclerosis. INTERPRETATION: Epilepsy surgery plays an ever more important role in the treatment of patients with drug resistant seizures. Doctors who treat epileptic patients should refer candidates for surgery at an early stage of the disease.

The effect of levetiracetam on focal nocturnal epileptiform activity during sleep--a placebo-controlled double-blind cross-over study.

Electric Status Epilepticus during Sleep (ESES) occurs in children with and without epilepsy. It may be related to disturbances as autism spectrum disorder, attention-deficit hyperactivity disorder and acquired aphasia (Landau-Kleffner syndrome). Antiepileptic drug (AED) treatment has been reported in small studies without placebo control. This study was designed to assess AED effect in a placebo-controlled double-blind cross-over study. Levetiracetam (LEV) was chosen based on clinical evidence. Eighteen patients fulfilled the inclusion criteria. The mean spike index at baseline was 56, falling to a mean of 37 at the end of the LEV treatment period. Assessed with a 2-way ANOVA, there is a significant treatment effect (p<0.0002). To the best of our knowledge, this is the first placebo-controlled double-blind cross-over study for any AED in patients with ESES. The effect of LEV is comparable with its effect in treatment of epileptic seizures.

Selective posterior cerebral artery amobarbital test: its role in presurgical memory assessment in temporal lobe epilepsy.

PURPOSE: To evaluate the efficacy and risk of complications of selective posterior cerebral artery (PCA) amobarbital anesthesia in memory assessment of patients with epilepsy under consideration for temporal lobe resection. METHODS: Thirty-two candidates for temporal lobectomy in whom conclusive memory assessment could not be obtained by the standard intracarotid amobarbital procedure were submitted to a selective PCA amobarbital test. A mean dose of 75 mg amobarbital was injected via microcatheter into the P2 segment of the PCA. Ten common objects were presented for naming and remembering while the anesthesia was judged efficient. After return to neurologic baseline, recall and recognition memory were assessed. RESULTS: In all of the 32 patients, angiography and PCA anesthesia were successfully accomplished without serious adverse events. All but one of the patients remained alert and cooperative for memory testing under the anesthesia, and 28 of these patients showed adequate memory capacity of the hemisphere contralateral to the side targeted for surgery. So far, 19 patients have proceeded to surgery, and no case of global amnesia or serious, material-specific memory impairment has resulted. Three patients failed the PCA test (fewer than 67% items correctly recognized) and were excluded from surgery, partly on the basis of the PCA test results, but also supported by an overall evaluation of all the diagnostic procedures used. CONCLUSIONS: The selective PCA amobarbital test appears justifiable when performed by interventional neuroradiologists and may significantly reduce the risk of erroneously excluding patients with epilepsy from temporal resection. Further corroboration of the safety of the procedure seems warranted.

Resective surgery for intractable focal epilepsy in patients with low IQ: predictors for seizure control and outcome with respect to seizures and neuropsychological and psychosocial functioning.

PURPOSE: To investigate possible predictive factors for seizure control in a group of children and adults with low IQs (IQ, < or =70) who underwent resective surgery for intractable focal epilepsy and to study outcome with respect to seizures and neuropsychological functioning. We also studied psychosocial outcome in the adult patients. METHODS: Thirty-one patients (eight children younger than 18 years) with a Wechsler Full Scale IQ of 70 or less underwent comprehensive neuropsychological assessments before and 2 years after surgery. Adults also completed the Washington Psychosocial Seizure Inventory (WPSI). Univariate analyses were used to identify variables differentiating between patients who became seizure free and those who did not. Pre- and postoperative test results were compared by t test for dependent samples. RESULTS: Forty-eight percent of the patients became seizure free, 52% of those with temporal lobe resection and 38% of those with extratemporal resection. Only one variable was predictive for seizure outcome: duration of epilepsy. In one third of the patients, who had the shortest duration of epilepsy (<12 years), 80% became seizure free. Significant improvement was seen regarding vocational adjustment in adults (WPSI). Seizure-free adults improved their Full Scale IQ scores. No cognitive changes were found in seizure-free children or in patients who did not become seizure free. CONCLUSIONS: A good seizure outcome was obtained after resective surgery in patients with intractable focal epilepsy and low IQ, provided that treatment was done relatively shortly after onset of epilepsy. No adverse effects were seen on cognitive and psychosocial functioning.