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1.
  • Forsberg, Lisa, et al. (författare)
  • School performance at age 16 in children exposed to antiepileptic drugs in utero-A population-based study.
  • 2011
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; Dec, s. 364-369
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: In order to evaluate long-term effects on neurodevelopment in children born to women with epilepsy during pregnancy we studied the children's school grades at age 16. Methods: We used the Patient Register, the Medical Birth Register, and a local study at South Hospital, Stockholm, to identify women with epilepsy in Sweden who had given birth between 1973 and 1986. The Swedish School Mark Registry was used to obtain information about school grades from the last year of compulsory school, at age 16. Exposed children were compared to all other children born in Sweden between 1973 and 1986. Key Findings: Medical records were analyzed for 1,235 children. Six hundred forty-one children had been exposed in utero to antiepileptic drugs (AEDs) in monotherapy, 429 in polytherapy, and 165 to no known AED. Children exposed to polytherapy had an increased risk of not receiving a final grade-odds ratio (OR) 2.99 [95% confidence interval (CI) 2.14-4.17]. Children exposed to monotherapy, mainly carbamazepine or phenytoin, did not have a significantly increased risk of not receiving a final grade-OR 1.19 (95% CI 0.79-1.80). Children born to women with epilepsy had a decreased chance of getting a "pass with excellence." Significance: Exposure to several AEDs in utero may have negative effects on neurodevelopment, and polytherapy should, if possible, be avoided in pregnant women.
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  • Beghi, Ettore, et al. (författare)
  • Recommendation for a definition of acute symptomatic seizure
  • 2010
  • Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 51:4, s. 671-675
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To consider the definition of acute symptomatic seizures for epidemiological studies, and to refine the criteria used to distinguish these seizures from unprovoked seizures for specific etiologies. Methods: Systematic review of the literature and of epidemiologic studies. Results: An acute symptomatic seizure is defined as a clinical seizure occurring at the time of a systemic insult or in close temporal association with a documented brain insult. Suggestions are made to define acute symptomatic seizures as those events occurring within 1 week of stroke, traumatic brain injury, anoxic encephalopathy, or intracranial surgery; at first identification of subdural hematoma; at the presence of an active central nervous system (CNS) infection; or during an active phase of multiple sclerosis or other autoimmune diseases. In addition, a diagnosis of acute symptomatic seizure should be made in the presence of severe metabolic derangements (documented within 24 h by specific biochemical or hematologic abnormalities), drug or alcohol intoxication and withdrawal, or exposure to well-defined epileptogenic drugs. Discussion: Acute symptomatic seizures must be distinguished from unprovoked seizures and separately categorized for epidemiologic purposes. These recommendations are based upon the best available data at the time of this report. Systematic studies should be undertaken to better define the associations in question, with special reference to metabolic and toxic insults, for which the time window for the occurrence of an acute symptomatic seizure and the absolute values for toxic and metabolic dysfunction still require a clear identification.
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  • Berger, Itai, et al. (författare)
  • Intractable epilepsy of infancy due to homozygous mutation in the EFHC1 gene
  • 2012
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 53:8, s. 1436-1440
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The molecular etiology of primary intractable epilepsy in infancy is largely unknown. We studied a nonconsanguineous Moroccan-Jewish family, where three of their seven children presented with intractable seizures and died at 18-36 months.Methods:  Homozygous regions were searched using 250 K DNA single nucleotide polymorphism (SNP) array. The sequence of 50 Mb exome of a single patient was determined using SOLiD 5500XL deep sequencing analyzer.Key Findings: A single homozygous 11.3 Mb genomic region on chromosome 6 was linked to the disease in this family. This region contained 110 genes encoding a total of 1,000 exons. Whole exome sequencing revealed a single pathogenic homozygous variant within the critical region. The mutation, Phe229Leu in the EFHC1 gene was previously shown, in a carrier state, to be associated with juvenile myoclonic epilepsy.Significance:  Although heterozygosity for the Phe229Leu mutation is known to be associated with a relatively benign form of epilepsy in adolescence; homozygosity for the same mutation is associated with lethal epilepsy of infancy. Given the considerable carrier rate of this mutation worldwide, the sequence of the EFHC1 gene should be determined in all patients with primary intractable epilepsy in infancy.
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  • Froriep, Ulrich P, et al. (författare)
  • Altered theta coupling between medial entorhinal cortex and dentate gyrus in temporal lobe epilepsy
  • 2012
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 53:11, s. 1937-1947
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Temporal lobe epilepsy is often accompanied by neuron loss and rewiring in the hippocampus. We hypothesized that the interaction of subnetworks of the entorhinalhippocampal loop between epileptic events should show significant signatures of these pathologic changes.Methods: We combined simultaneous recording of local field potentials in entorhinal cortex (EC) and dentate gyrus (DG) in freely behaving kainate-injected mice with histologic analyses and computational modeling.Key Findings: In healthy mice, theta band activity was synchronized between EC and DG. In contrast, in epileptic mice, theta activity in the EC was delayed with respect to the DG. A computational neural mass model suggests that hippocampal cell loss imbalances the coupling of subnetworks, introducing the shift.Significance: We show that pathologic dynamics in epilepsy encompass ongoing activity in the entorhinal-hippocampal loop beyond acute epileptiform activity. This predominantly affects theta band activity, which links this shift in entorhinal-hippocampal interaction to behavioral aspects in epilepsy.
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6.
  • Halawa, Imad, et al. (författare)
  • Hyponatremia and risk of seizures : A retrospective cross-sectional study
  • 2011
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 52:2, s. 410-413
  • Tidskriftsartikel (refereegranskat)abstract
    • This retrospective cross-sectional study was carried out to study the association between different levels of hyponatremia and the occurrence of epileptic seizures in patients without a prior epilepsy diagnosis. We identified from the hospital database, 363 inpatients of a Swedish County hospital who between March 2003 and August 2006 were found to have serum sodium levels < 125 mm. Medical records were reviewed and we identified 11 patients with seizures in conjunction with their hyponatremia. Seizures were the only neurologic manifestation of hyponatremia in patients with serum sodium levels > 115 mm. Of 150 patients reviewed with serum sodium levels of 120-124 mm, one had a seizure. Using 120-124 mm as reference, odds ratios (95% confidence interval) for having seizures at serum sodium levels of 115-119 mm was 3.85 (0.40-37.53), 8.43 (0.859-82.85) at 110-114 mm, and 18.06 (1.96-166.86) at < 110 mm.
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  • Igelström, Kajsa, 1980- (författare)
  • Preclinical antiepileptic actions of selective serotonin reuptake inhibitors – implications for clinical trial design
  • 2012
  • Ingår i: Epilepsia. - : Elsevier. - 0013-9580 .- 1528-1167. ; 53, s. 596-605
  • Tidskriftsartikel (refereegranskat)abstract
    • Selective serotonin reuptake inhibitors (SSRIs) can reduce seizure frequency in humans, but no large‐scale clinical trials have been done to test the utility of SSRIs as potential antiepileptic drugs. This may be caused in part by a small number of reports on seizures triggered by SSRI treatment. The preclinical literature on SSRIs is somewhat conflicting, which is likely to contribute to the hesitance in accepting SSRIs as possible anticonvulsant drug therapy. A careful review of preclinical studies reveals that SSRIs appear to have region‐specific and seizure subtype–specific effects, with models of chronic partial epilepsy being more likely to respond than models of acute generalized seizures. Moreover, this preclinical profile is similar to that of clinical antiepileptic drugs. These observations suggest that SSRIs are promising antiepileptic agents, and that clinical trials may benefit from defining patient groups according to the underlying pathology.
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  • Krauss, Gregory, et al. (författare)
  • Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures.
  • 2010
  • Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 51:6, s. 951-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary Purpose: Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200-800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures. Methods: This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2-5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations. Results: A total of 160 patients received lacosamide 200-800 mg/day, i.v., for 2-5 days, of which 69% received 400-800 mg/day doses. The most common AEs (reported by /=400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts. Discussion: This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2-5 days) replacement for patients temporarily unable to take oral lacosamide.
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  • Krauss, G. L., et al. (författare)
  • Perampanel, a selective, noncompetitive α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid receptor antagonist, as adjunctive therapy for refractory partial-onset seizures: Interim results from phase III, extension study 307
  • 2013
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 54:1, s. 126-134
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To evaluate safety, tolerability, and seizure outcome data during long-term treatment with once-daily adjunctive perampanel (up to 12 mg/day) in patients with refractory partial-onset seizures. Methods: Study 307 was an extension study for patients completing the double-blind phase of three pivotal phase III trials (studies 304, 305, and 306). The study consisted of two phases: an open-label treatment phase (including a 16-week blinded conversion period and a planned 256-week maintenance period) and a 4-week follow-up phase. Patients were blindly titrated during the conversion period to their individual maximum tolerated dose (maximum 12 mg/day). Adverse events (AEs) were monitored throughout the study and seizure frequency recorded. The interim data cutoff date for analyses was December 1, 2010. Key Findings: In total, 1,218 patients were enrolled in the study. At the interim cutoff date, 1,186 patients were in the safety analysis set; 1,089 (91.8%) patients had >16 weeks of exposure to perampanel, 580 (48.9%) patients had >1 year of exposure, and 19 (1.6%) patients had >2 years of exposure. At the interim analysis, 840 (70.8%) patients remained on perampanel treatment. The large majority of patients (n = 1,084 [91%]) were titrated to 10 mg or 12 mg/day. Median (range) duration of exposure was 51.4 (1.1-128.1) weeks. Treatment-emergent AEs were reported in 87.4% of patients. The most frequent were dizziness (43.9%), somnolence (20.2%), headache (16.7%), and fatigue (12.1%). Serious AEs were reported in 13.2% of patients. In the intent-to-treat analysis set (n = 1,207), the frequency of all seizures decreased over the first 26 weeks of perampanel treatment in patients with at least 26 weeks of exposure to perampanel (n = 1,006 [83.3%]); this reduction was maintained in patients with at least 1 year of exposure (n = 588 [48.7%]). The overall median percent changes in seizure frequency in patients included in each 13-week interval of perampanel treatment were -39.2% for weeks 14-26 (n = 1,114), -46.5% for weeks 40-52 (n = 731), and -58.1% for weeks 92-104 (n = 59). Overall responder rates in patients included in each 13-week interval of perampanel treatment were 41.4% for weeks 14-26 (n = 1,114), 46.9% for weeks 40-52 (n = 731), and 62.7% for weeks 92-104 (n = 59). During the blinded conversion period, the reduction in seizure frequency in patients previously randomized to placebo (-42.4%, n = 369) was similar to that in patients previously randomized to perampanel (-41.5%, n = 817). Significance: Consistent with pivotal phase III trials, these interim results demonstrated that perampanel had a favorable tolerability profile in patients with refractory partial-onset seizures over the longer term. The decrease in seizure frequency was consistent and maintained in those patients over at least 1 year of perampanel exposure. © 2012 International League Against Epilepsy.
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  • Malmgren, Kristina, 1952, et al. (författare)
  • Successful epilepsy surgery in a patient with neurosarcoidosis
  • 2010
  • Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 51:6, s. 1101-1103
  • Tidskriftsartikel (refereegranskat)abstract
    • This case concerns a patient with generalized neurosarcoidosis and pharmacoresistant focal epilepsy. Although immunosuppressive therapy resulted in remission of the neurosarcoidosis, seizures continued and were shown to originate from the right temporal lobe (TL). The patient underwent a right anterior temporal lobe resection (TLR) and obtained >90% reduction of seizure frequency.
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  • Igelström, Kajsa, 1980-, et al. (författare)
  • Inhibition of hippocampal excitability by citalopram
  • 2012
  • Ingår i: Epilepsia. - : Wiley-Blackwell Publishing Inc.. - 0013-9580 .- 1528-1167. ; 53, s. 2034-2042
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Preclinical data have suggested that selective serotonin reuptake inhibitors (SSRIs) may have anticonvulsant properties, and some SSRIs are known to modulate ion channels in vitro. We screened citalopram, fluoxetine, and sertraline for anticonvulsant actions in mouse hippocampal slices, and studied the effects of citalopram on active membrane properties and repetitive action potential firing.Methods: To enable testing of antiepileptic effects and target modulation in a single experimental system, we used the simplistic low‐Ca2+ model, which is strongly dependent on the intrinsic excitability of CA1 pyramidal neurons. Field potentials and whole‐cell currents were recorded from brain slices, and SSRIs were bath‐applied.Key Findings: We found that citalopram, fluoxetine, and sertraline inhibited epileptiform activity recorded from area CA1. The effect of citalopram was more potent and less variable than that of fluoxetine and sertraline. The anticonvulsant action of citalopram was accompanied by marked slowing of action potential rise and decay, and robust inhibition of repetitive firing. This depression of membrane excitability appeared to be mediated in part by inhibition of a sustained potassium current.Significance: These findings confirm that SSRIs can have anticonvulsant effects in the hippocampus, and further suggest that citalopram may exert these effects at least in part by inhibition of voltage‐gated ion currents.
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20.
  • Immonen, Arto, et al. (författare)
  • Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe epilepsy
  • 2010
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 51:11, s. 2260-2269
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high-resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long-term outcomes of consecutive true MRI-negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes. METHODS: In this study we present all adult MRI-negative TLE surgery candidates evaluated between January 1990 and December 2006 at Kuopio Epilepsy Center in Kuopio University Hospital, which provides a national center for epilepsy surgery in Finland. During this period altogether 146 TLE surgery candidates were evaluated with intracranial electrodes, of whom 64 patients with normal high-resolution MRI were included in this study. RESULTS: Among the 38 patients who finally underwent surgery, at the latest follow-up (mean 5.8 years), 15 (40%) were free of disabling seizures (Engel class I) and 6 (16%) were seizure-free (Engel class IA). Twenty-one (55%) of 38 patients had poor outcomes (Engel class III-IV). Outcomes did not change compared to 12-month follow-up. Histopathologic examination failed to reveal any focal pathology in 68% of our MR-negative cases. Only patients with noncongruent positron emission tomography (PET) results had worse outcomes (p = 0.044). DISCUSSION: Our results suggest that epilepsy surgery outcomes in MRI-negative TLE patients are comparable with extratemporal epilepsy surgery in general. Seizure outcomes in the long-term also remain stable. Modern imaging techniques could further improve the postsurgical seizure-free rate. However, these patients usually require chronic intracranial EEG evaluation to define epileptogenic areas.
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  • Klatt, Juliane, et al. (författare)
  • The EPILEPSIAE database : An extensive electroencephalography database of epilepsy patients
  • 2012
  • Ingår i: Epilepsia. - : Wiley-Blackwell. - 0013-9580 .- 1528-1167. ; 53:9, s. 1669-1676
  • Tidskriftsartikel (refereegranskat)abstract
    • From the very beginning the seizure prediction community faced problems concerning evaluation, standardization, and reproducibility of its studies. One of the main reasons for these shortcomings was the lack of access to high-quality long-term electroencephalography (EEG) data. In this article we present the EPILEPSIAE database, which was made publicly available in 2012. We illustrate its content and scope. The EPILEPSIAE database provides long-term EEG recordings of 275 patients as well as extensive metadata and standardized annotation of the data sets. It will adhere to the current standards in the field of prediction and facilitate reproducibility and comparison of those studies. Beyond seizure prediction, it may also be of considerable benefit for studies focusing on seizure detection, basic neurophysiology, and other fields.
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  • Mattsson, Peter, et al. (författare)
  • Association between sociodemographic status and antiepileptic drug prescriptions in children with epilepsy
  • 2012
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 53:12, s. 2149-2155
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We investigated whether in Sweden sociodemographic differences are associated with access to expert health care and antiepileptic drug (AED) prescriptions in children with epilepsy.Methods: Data on epilepsy, prescription of AEDs, and sociodemographic variables were obtained from several national administrative registers. We linked individual data to examine whether access by pediatric epilepsy patients to neuropediatricians and the prescription of individual AEDs differed according to gender, age, parental education, place of residence, parental region of birth, and household income. We also assessed whether AEDs are prescribed differently to patients with epilepsy by neuropediatricians as compared to other physicians.Key Findings: Of 1,788,382 children aged 1–17 years in 2006, living in the country by the end of 2006, 9,935 had a diagnosis of epilepsy (0.56%). Patients with epilepsy on AED treatment (n = 3,631) comprised 0.24% of the total Swedish population aged 1–17 years. Out of 3631 patients with epilepsy on AED treatment, 2301 (63.4%) received prescriptions from a neuropediatrician. Children with epilepsy aged 1–5 years old—as opposed to older children and adolescents—and children with epilepsy residing in large cities—as opposed to children living in smaller cities and rural areas—were more likely to be treated by a neuropediatrician. Children living in large cities received oxcarbazepine to a greater extent than children living in rural areas. Levetiracetam was prescribed more extensively to children whose parents had higher incomes. Of the five most frequently used AEDs, three (lamotrigine, oxcarbazepine, and levetiracetam) were prescribed to a larger extent by a neuropediatrician rather than by other specialists, and one AED (carbamazepine) was prescribed to a lesser extent.Significance: The results of this nationwide cross-sectional study of children with epilepsy are important because they show that universal coverage for medical care does not eliminate inequalities of access to health care services among children and adolescents. No data are available that can guide us as to whether the density of child neurologists is of importance to access to expert health care, but this seems likely. Prescription patterns of AEDs differ between child neurologists and other specialists.
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  • Peltola, Maria E., et al. (författare)
  • The effect of surgery in encephalopathy with electrical status epilepticus during sleep
  • 2011
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 52:3, s. 602-609
  • Tidskriftsartikel (refereegranskat)abstract
    • P>Purpose: We analyzed clinical and electroencephalography (EEG) outcomes of 13 patients with pharmacoresistant encephalopathy with electrical status epilepticus during sleep (ESES) following epilepsy surgery. Methods: All patients had symptomatic etiology of ESES and preoperative neuropsychological deterioration. Ten patients had daily atypical absences. Clinical outcome was assessed at 6 months and at 2 years after surgery. Clinical and EEG data were reviewed retrospectively. The spike propagation pattern and area and source strength in source montage were analyzed from preoperative and postoperative EEG studies. Key Findings: Preoperative sleep EEG showed electrical status epilepticus during sleep (SES) with one-way interhemispheric propagation in nine patients and with two-way interhemispheric propagation in four. The age of the patients at the time of surgery ranged from 3.6-9.9 years. Focal resection (two patients) or hemispherotomy (one patient with postoperative EEG) either terminated SES or restricted the discharge to one region. Either reduced SES propagation area or source strength was found in four of eight callosotomy patients with postoperative EEG. Of patients who had seizures preoperatively, Engel class I-II seizure outcome was observed in two of three children after focal resection or hemispherotomy and in two of eight children after callosotomy. None of these patients with Engel class I-II outcome had SES with two-way interhemispheric propagation on preoperative EEG. Cognitive deterioration was halted postoperatively in all except one patient. Cognitive catch-up of more than 10 IQ points was seen in three patients, all of whom had shown a first measured IQ of > 75. Significance: Patients with pharmacoresistant ESES based on symptomatic etiology may benefit from resective surgery or corpus callosotomy regarding both seizure outcome and cognitive prognosis.
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  • Beniczky, Sandor, et al. (författare)
  • Standardized Computer-based Organized Reporting of EEG: SCORE
  • 2013
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 54:6, s. 1112-1124
  • Tidskriftsartikel (refereegranskat)abstract
    • The electroencephalography (EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free-text format. The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video-EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan-European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, episodes (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make possible the build-up of a multinational database, and it will help in training young neurophysiologists.
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  • Eeg-Olofsson, Orvar, et al. (författare)
  • The way out of Babel
  • 2013
  • Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 54:4, s. 767-768
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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33.
  • Fisher, Robert S., et al. (författare)
  • ILAE official report : a practical clinical definition of epilepsy
  • 2014
  • Ingår i: Epilepsia. - : Wiley-Blackwell. - 0013-9580 .- 1528-1167. ; 55:4, s. 475-482
  • Tidskriftsartikel (refereegranskat)abstract
    • Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10years and off antiseizure medicines for at least the last 5years. "Resolved" is not necessarily identical to the conventional view of "remission or "cure." Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section.
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  • Glauser, Tracy, et al. (författare)
  • Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes.
  • 2013
  • Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 54:3, s. 551-63
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy/effectiveness between study treatment and comparator using an intent-to-treat analysis. Since July, 2005, three class I randomized controlled trials (RCT) and 11 class III RCTs have been published. The combined analysis (1940-2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta-analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup. Levetiracetam and zonisamide join carbamazepine and phenytoin with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures. Although ethosuximide and valproic acid now have level A efficacy/effectiveness evidence as initial monotherapy for children with absence seizures, there continues to be an alarming lack of well designed, properly conducted epilepsy RCTs for patients with generalized seizures/epilepsies and in children in general. These findings reinforce the need for multicenter, multinational efforts to design, conduct, and analyze future clinically relevant adequately designed RCTs. When selecting a patient's AED, all relevant variables and not just efficacy and effectiveness should be considered.
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  • Ibinda, Fredrick, et al. (författare)
  • Burden of epilepsy in rural Kenya measured in disability-adjusted life years
  • 2014
  • Ingår i: Epilepsia. - : John Wiley & Sons. - 0013-9580 .- 1528-1167. ; 55:10, s. 1626-1633
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesThe burden of epilepsy, in terms of both morbidity and mortality, is likely to vary depending on the etiology (primary [genetic/unknown] vs. secondary [structural/metabolic]) and with the use of antiepileptic drugs (AEDs). We estimated the disability-adjusted life years (DALYs) and modeled the remission rates of active convulsive epilepsy (ACE) using epidemiologic data collected over the last decade in rural Kilifi, Kenya.MethodsWe used measures of prevalence, incidence, and mortality to model the remission of epilepsy using disease-modeling software (DisMod II). DALYs were calculated as the sum of Years Lost to Disability (YLD) and Years of Life Lost (YLL) due to premature death using the prevalence approach, with disability weights (DWs) from the 2010 Global Burden of Disease (GBD) study. DALYs were calculated with R statistical software with the associated uncertainty intervals (UIs) computed by bootstrapping.ResultsA total of 1,005 (95% UI 797-1,213) DALYs were lost to ACE, which is 433 (95% UI 393-469) DALYs lost per 100,000 people. Twenty-six percent (113/100,000/year, 95% UI 106-117) of the DALYs were due to YLD and 74% (320/100,000/year, 95% UI 248-416) to YLL. Primary epilepsy accounted for fewer DALYs than secondary epilepsy (98 vs. 334 DALYs per 100,000 people). Those taking AEDs contributed fewer DALYs than those not taking AEDs (167 vs. 266 DALYs per 100,000 people). The proportion of people with ACE in remission per year was estimated at 11.0% in males and 12.0% in females, with highest rates in the 0-5year age group.SignificanceThe DALYs for ACE are high in rural Kenya, but less than the estimates of 2010 GBD study. Three-fourths of DALYs resulted from secondary epilepsy. Use of AEDs was associated with 40% reduction of DALYs. Improving adherence to AEDs may reduce the burden of epilepsy in this area.
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  • Krauss, G. L., et al. (författare)
  • Long-term safety of perampanel and seizure outcomes in refractory partial-onset seizures and secondarily generalized seizures: Results from phase III extension study 307
  • 2014
  • Ingår i: Epilepsia. - : Blackwell Publishing Inc.. - 0013-9580 .- 1528-1167. ; 55:7, s. 1058-1068
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate safety, tolerability, seizure frequency, and regional variations in treatment responses with the AMPA antagonist, perampanel, in a large extension study during up to 3 years of treatment. Methods Patients ≥12 years old with partial-onset seizures despite treatment with 1-3 antiepileptic drugs at baseline completed a perampanel phase III trial and entered extension study 307 (NCT00735397). Patients were titrated to 12 mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open-label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [ECG], laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions. Results Among 1,216 patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in ≥10% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only serious AEs reported in >1% of patients were epilepsy-related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or laboratory parameters were seen. After titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9 months (in 980 patients with ≥9 months' exposure) and 58% and 60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). Median percentage reduction in frequency of secondarily generalized (SG) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance data ≥1 year, 5.3% were seizure-free for the entire year. Significance No new safety signals emerged during up to 3 years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in SG seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
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  • Reilly, Colin, 1977, et al. (författare)
  • Academic achievement in school-aged children with active epilepsy: A population-based study.
  • 2014
  • Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 55:12, s. 1910-1917
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To provide population-based data on the performance of school-aged children with epilepsy on measures of academic achievement and factors associated with this performance after controlling for IQ. METHODS: Eighty-five (74%) of 115 children with "active" epilepsy (experienced a seizure in the past year and/or on antiepileptic drugs [AEDs]) underwent psychological assessment including measures of IQ, aspects of working memory and processing speed. Sixty-five of the 85 were able to complete subtests on the Wide Range Achievement Test-Fourth Edition (WRAT-4). Paired sample t-tests were conducted to compare subtest scores. Factors associated with academic performance after controlling for IQ were examined using linear regression. RESULTS: Seventy-two percent of the children, who could complete subtests on the WRAT-4, displayed "low achievement" (1 standard deviation [SD] below test mean) and 42% displayed "underachievement" (1 SD below assessed IQ) on at least one of the four WRAT-4 subtests. The mean scores on the Math Computation subtest and Sentence Comprehension subtest were significantly lower than scores on the Word Reading (p < 0.05) and Spelling (p < 0.001) subtests. Younger age at seizure onset was associated (p < 0.05) with decreased scores on three of the four WRAT-4 subtests after controlling for IQ. Difficulties with auditory working memory were associated with difficulties on reading comprehension (p < 0.05), and parent-reported difficulties with school attendance were associated with decreased scores on the Spelling and Word Reading subtests after controlling for IQ (p < 0.05). SIGNIFICANCE: Difficulties with academic achievement are common in school-aged children with "active" epilepsy. Much of the difficulties can be attributed to lowered global cognition. However, specific cognitive deficits, younger onset of first seizure, and school attendance difficulties may contribute to difficulties independent of global cognition. There is a need to screen all children with "active" epilepsy for difficulties in school achievement, to identify contributory factors and to identify efficacious interventions for ameliorating such difficulties.
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  • Rydenhag, B., et al. (författare)
  • Long term follow-up after callosotomy
  • 2013
  • Ingår i: Epilepsia. - 0013-9580 .- 1528-1167. ; 54:S3, s. 180-180
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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