Kristina Källén

Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation

Summary:  Purpose: To study pharmacokinetics of levetiracetam (LEV) during pregnancy, delivery, lactation, and in the neonatal period.

Long-term outcomes of epilepsy surgery in Sweden A national prospective and longitudinal study

Objective: To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden. Methods: Ten- and 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls. Results: In the long term (mean 7.6 years), 62% of operated adults and 50% of operated children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p < 0.0005). Multivariate analysis identified ≥30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p < 0.0005). Conclusions: This population-based, prospective study shows good long-term seizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedom since surgery. Many patients who gain seizure freedom can successfully discontinue AEDs, more often children than adults. Classification of evidence: This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients.

Does SISCOM contribute to favorable seizure outcome after epilepsy surgery

Summary:  Purpose: To assess the additional value of subtraction ictal single‐photon emission computed tomography (SPECT) coregistered to MRI (SISCOM) for localization of the epileptogenic zone in patients with drug‐resistant epilepsy scheduled for invasive video‐EEG (VEEG) before epilepsy surgery by a descriptive study from clinical practice.

Pre-surgical epilepsy evaluation using 3T MRI. Do surface coils provide additional information?

PURPOSE To assess if 3T MRI can be further improved by adding surface coil imaging, in the context of detection and characterization of cerebral lesions in patients with drug-resistant epilepsy. METHODS Twenty five patients with drug-resistant epilepsy undergoing evaluation for epilepsy surgery were examined with high resolution 3T MRI. The patients were MRI-negative (n = 15), or had unclear findings (n = 10), on previous MRI at 1.0-1.5T. Surface coils were applied over the suspected epileptogenic zone after imaging in the head coil. In MRI-negative patients, placement of the coils was defined by semiological analysis, extracranial video-EEG, and, in selected cases, subtraction ictal SPECT co-registered with MRI and PET. Coil placement was re-analyzed and graded, based on the degree of convergence between different investigational modalities. RESULTS Surface coil MRI allowed visualization of the cortical lesions with somewhat better demarcation and detail, but did not contribute to detection of previously undiagnosed lesions and did not provide additional information regarding type of lesion. Possible epileptogenic lesions were detected on 3T MRI in 12 patients. No abnormalities were found in the remaining 13 patients. 3T MRI provided new or additional information about the cortex, compared with reports from previous 1.0-1.5T MRI in 5 patients (20%). CONCLUSION 3T MRI with high resolution is valuable for lesion detection, especially MCD, in patients with drug-resistant epilepsy. We question the additional contribution from supplementary surface coil imaging at 3T MRI.

Maternal smoking during pregnancy and daughters' risk of gestational diabetes and obesity.

Aims/hypothesisThe primary aim of the study was to investigate the risk of developing gestational diabetes in women who were exposed to tobacco smoke in utero. Secondary aims were to assess the risk of obesity and non-gestational diabetes.MethodsData were retrieved from the Medical Birth Register of Sweden for women who were born in 1982 (when smoking data were first registered) or later and who had given birth to at least one child; 80,189 pregnancies were included. The associations between in utero smoking exposure (three categories: non-smokers, 1–9 cigarettes/day [moderately exposed] and >9 cigarettes/day [heavily exposed]) and subsequent gestational diabetes (n = 291), non-gestational diabetes (n = 280) and obesity (n = 7,300) were assessed.ResultsThe adjusted ORs (aORs) of gestational diabetes were increased among women who were moderately (1.62, 95% CI 1.24, 2.13) and heavily (1.52, 95% CI 1.12, 2.06) exposed. The corresponding aORs of obesity were 1.36 (95% CI 1.28, 1.44) and 1.58 (95% CI 1.48, 1.68), respectively. A reduced OR for non-gestational diabetes was seen in the offspring of heavy smokers (aOR 0.66, 95% CI 0.45, 0.96).Conclusions/interpretationWomen exposed to smoking during fetal life were at higher risk of developing gestational diabetes and obesity.

Hypomotor Seizures in Infants and Children

Summary:  Purpose: Hypomotor seizures (characterized by diminished behavioral activity with indeterminate level of consciousness) have been identified as an important seizure type in infants. Our goal was to investigate further the clinical and EEG features of hypomotor seizures.

Evaluation of malignancy in ring enhancing brain lesions on CT by thallium-201 SPECT

Objective—To investigate patients with cystic enhancing lesions on CT and to determine whether thallium-201 (201Tl) SPECT adds to further preoperative information in differential diagnosis between gliomas and abscesses. Methods—Twenty one patients with cystic ring enhancing CT findings were studied and uptake indices were compared with CT enhancement volumes, histopathology, and survival times. Results—Fourteen high grade gliomas, three low grade gliomas, and four abscesses were found. Uptake was higher in the highly malignant glioma group (median thallium index (TI)=2.1), than in the low grade glioma group (median TI=1.4) or among the abscesses (median TI=1.6). Overlapping indices were found between high and low malignant cystic gliomas as well as between either one of the glioma groups and the infectious lesions, and there were no significant differences between groups. There was a level at the value 2, where TI⩾2 correlated with tumour diagnosis. One low grade tumour had an extremely high index and a very high enhancement volume. Indices correlated significantly with CT enhancement volumes (P=0.005). There was no significant correlation between Tl indices and patient survival times among the high grade gliomas. One patient with a highly malignant tumour but low Tl uptake <2, had a survival> five years. CONCLUSIONS It is concluded that high201Tl uptake in enhancing cystic lesions is an indicator of highly malignant glioma. However, the differentiation between the high malignant gliomas and abscesses or low malignant gliomas by201TL SPECT is only partial with an overlap between these groups.

fMRI memory assessment in healthy subjects: a new approach to view lateralization data at an individual level

We present a comprehensive and clinically applicable fMRI test—including both a verbal and a visuospatial task—for assessment of hemispheric specific memory in the medial temporal lobe (MTL). fMRI data was collected from 15 healthy right-handed volunteers. Whole-brain activation was analyzed as well as activation in two regions of interest: the MTL and the anterior speech area. Laterality indices (LI) and LI-curves were calculated using the LI toolbox of Wilke and Lidzba, 2007. The fMRI paradigms successfully visualized memory-related activity in the MTL, the verbal memory measure also provided information of language lateralization. Eleven subjects showed left lateralized verbal encoding in the MTL, visuospatial memory activation was divided equally between left and right, and 14/15 subjects had left lateralized language. Lateralization data at the group level were consistent with previous studies, but a variety of activation effects were found at the individual level indicating differences in strategy during verbal and visuospatial processing. Further studies using the presented method are needed to determine its clinical usefulness.

Quantitative 201Tl SPET imaging in the follow-up of treatment for brain tumour: a sensitive tool for the early identification of response to chemotherapy?

The aim of this study was to establish if repeated quantitative 201Tl SPET scanning during follow-up of astrocytoma therapy can provide information that is relevant for clinical management. Sixteen consecutive patients, with histopathologically verified highly malignant astrocytoma, were followed during PCV chemotherapy. Imaging with 201Tl SPET and CT was performed repeatedly over 8-16 weeks until treatment discontinuation, with a maximum follow-up of 74 weeks. Tumour uptake volume (TUV), a measure of metabolically active tumour tissue, was calculated from the SPET images. The reliability of early identification of treatment failure, defined as >25% tumour volume increase, following one course (week 8) and three courses (week 24) of chemotherapy, was calculated for the two imaging methods. 201Tl SPET positive patients (>25% tumour volume increase) were compared with 201Tl SPET negative patients in terms of time to treatment discontinuation (TTD) and survival time (ST). The patients were followed with a total of 59 SPET examinations, and treatment was continued for a median 27 weeks (range 16-78 weeks). The comparative reliability of SPET and CT showed the highest sensitivity and accuracy for SPET in the early identification of astrocytoma treatment failure at the week 24 assessment. Patients with positive 201Tl SPET after three courses of chemotherapy had a significantly reduced TTD (P = 0.040) but not significantly reduced ST. Of the ten patients who received concomitant radiation and chemotherapy, five had a small (0-10 ml) TUV at the week 24 assessment. Patients with a TUV >10 ml at this assessment had a shorter TTD (P = 0.016) and a reduced ST (P = 0.024) compared to patients with a TUV <10 ml. In conclusion, the assessment of progressive disease by quantitative 201Tl SPET appears to provide information on treatment response, earlier and with a higher reliability than CT. Repeated 201Tl SPET scanning during follow-up of astrocytoma treatment is an alternative tool for the early identification of treatment failure.

Epilepsy in Sweden: health care costs and loss of productivity—a register-based approach

PurposeThe objective was to estimate health care costs and productivity losses due to epilepsy in Sweden and to compare these estimates to previously published estimates.MethodsRegister data on health care utilisation, pharmaceutical sales, permanent disability and mortality were used to calculate health care costs and costs that accrue due to productivity losses. By linkage of register information, we were able to distinguish pharmaceuticals prescribed against epilepsy from prescriptions that were prompted by other indications.ResultsThe estimated total cost of epilepsy in Sweden in 2009 was €441 million, which corresponds to an annual per-patient cost of €8,275. Health care accounted for about 16% of the estimated total cost, and drug costs accounted for about 7% of the total cost. The estimated health care cost corresponded to about 0.2% of the total health care cost in Sweden in 2009. Indirect costs were estimated at €370 million, 84% of which was due to sickness absenteeism. Costs resulting from epilepsy-attributable premature deaths or permanent disability to work accounted for about 1% of the total indirect cost in Sweden in 2009.DiscussionThe per-patient cost of epilepsy is substantial. Thus, even though the prevalence of the illness is relatively small, the aggregated cost that epilepsy incurs on society is significant.