Seizure: European Journal of Epilepsy

Editorial Board

2012-03-01

The enigma of long-term forgetting

Nils Muhlert, Adam Zeman — 2012-01-24

Memory symptoms are common among people with epilepsy (pwe). Their complaints are often corroborated by impairments on traditional tests of memory which assess learning and retention over delays of up to 30min. Yet a substantial minority of patients report memory problems which are not identified on standard testing. This discrepancy has sometimes been ascribed to mood disorders. There is, however, an alternative, or complementary, explanation: that established methods of memory testing fail to detect some genuine memory problems. Standard tests, for example, seldom assess autobiographical memory or retention of new information over delays greater than 30min. A growing literature reports patients with epilepsy, usually arising from the temporal lobes (TLE), who show normal or near normal retention of information over 30min delays, but increased forgetting over longer delays of days or weeks. This phenomenon has been described as ‘accelerated long-term forgetting’ – or ALF. Whilst there is growing evidence that ALF is measurable and clinically relevant, several key questions remain: (i) Is ALF a widespread phenomenon among pwe? (ii) Does ALF help to explain discrepancies between subjective memory complaints and results of memory testing? (iii) What are the underlying mechanisms of ALF? We consider these questions in turn.

Genes and molecular mechanisms involved in the epileptogenesis of idiopathic absence epilepsies

Özlem Yalçın — 2011-12-30

Abstract: Idiopathic absence epilepsies (IAE), that have high prevalence particularly among children and adolescents, are complex disorders mainly caused by genetic factors. Childhood absence epilepsy and juvenile absence epilepsy are among the most common subtypes of IAEs. While the role of ion channels has been the primary focus of epilepsy research, the analysis of mutation and association in both patients with absence epilepsies and animal models revealed the involvement of GABA receptors and calcium channels, but also of novel non-ion channel proteins in inducing spike wave discharges (SWD). Functional studies on a mutated variant of these proteins also support their role in the epileptogenesis of absence seizures. Studies in animal models point to both the thalamus and cortex as the origin of SWDs: the abnormalities in the components of these circuits leading to seizure activity. This review examines the current research on mutations and susceptibility alleles determined in the genes that code for the subunits of GABA receptors (GABRG2, GABRA1, GABRB3, GABRA5, GABA(B1) and GABA(B2)), calcium channels (CACNA1A, CACNA1G, CACNA1H, CACNA1I, CACNAB4, CACNAG2 and CACNG3), and novel non-ion channel proteins, taking into account the results of functional studies on these variants.

Impact of benign childhood epilepsy with centrotemporal spikes (BECTS) on school performance

2012-01-06

Abstract: BECTS represents the vast majority of childhood focal epilepsy. Owing to the age peculiarity of children who suffer from this disease, i.e., school-going age of between 6 and 9 years, the condition is often referred to as a school disorder by parents and teachers.Objective: The aim of this study was to evaluate the academic performance of children with BECTS, according to the clinical and electroencephalographic ILAE criteria, and compare the results of neuropsychological tests of language and attention to the frequency of epileptic discharges.Methods: The performances of 40 school children with BECTS were evaluated by applying a school performance test (SBT), neuropsychological tests (WISC and Trail-Making), and language tests (Illinois Test Psycholinguistic Abilities – ITPA – and Staggered Spondaic Word – SSW). The same tests were applied in the control group.Results: Children with BECTS, when compared to those in the control group, showed lower scores in academic performance (SPT), digits and similarities subtests of WISC, auditory processing subtest of SSW, and ITPA – representational and automatic level. The study showed that epileptic discharges did not influence the results.Conclusion: Children with BECTS scored significantly lower scores in tests on academic performance, when compared with those in the control group probably due to executive dysfunction.

The evolving electroclinical syndrome of “epilepsy with ring chromosome 20”

2011-10-17

Abstract: Purpose: Ring chromosome 20 {r(20)} – manifests as a refractory epilepsy syndrome with complex partial seizures (CPS), nocturnal frontal lobe seizures and non-convulsive status epilepticus (NCSE) in the majority of cases. r(20) lacks a specific phenotypic expression or dysmorphic features. Psychomotor development may be normal, making the diagnosis difficult unless there is a high index of suspicion. This description of further cases is intended to improve recognition of this syndrome.Methods: Karyotyping for r(20) was done in patients presenting with cryptogenic refractory epilepsy suggestive of r(20) from August 2008 to September 2010. We identified three patients with r(20) associated with refractory epilepsy. All were investigated with long-term video EEG. Their unique electro clinical features; epilepsy syndrome and outcome are discussed and compared to the available literature.Results: Karyotyping revealed ring 20 in 6–40% of lymphocytes. All manifested with seizures beginning at 2–10years of age. All had CPS; two had NCSE and one a seizure disorder resembling Lennox–Gastaut syndrome. The interictal EEG showed epileptiform abnormalities predominantly over the frontotemporal regions. Two patients had NCSE with generalized, frontally dominant theta and spike and wave discharges. None had facial dysmorphism or imaging abnormalities. They remained resistant to antiepileptic drugs.Conclusions: The use of routine karyotyping can easily pick up r(20); this information is especially useful in resource-poor countries. We have evolved an algorithm stating the indications to attempt r(20) karyotyping in a given patient in the light of the results of the present study and the existing literature.

An observational electro-clinical study of status epilepticus: From management to outcome

2011-10-20

Abstract: Status epilepticus (SE) is a neurological emergency associated with a high morbidity and mortality. A prospective 3-year study was conducted in our hospital on 56 consecutive inpatients with SE. Demographic and clinical data were collected. EEG and clinical SE features were considered for the SE classification, both separately and together. The etiology of SE was determined. Patients were treated according to international standardized protocols of guidelines for the management of epilepsy. Response to treatment was evaluated clinically and electrophysiologically. Outcome at 30 days was considered as good, poor or death. Convulsive SE (CSE) was observed in 35 patients and non-convulsive SE (NCSE) in 21. Patients with CSE, in particular focal-CSE, were older than those with NCSE. As regards etiology, patients with SE secondary to cerebral lesions were the oldest, followed by patients with anoxic SE and those with toxic dysmetabolic SE. A first-line treatment was usually sufficient to control seizure activity in lesional and epileptic SE, while more aggressive treatment was necessary in all anoxic SE patients. Outcome was good in 35 patients, poor in 12, while 9 died. A prompt neurophysiological EEG evaluation, combined with the clinical evaluation, helps to make a rapid prognosis and take therapeutic management decisions. First-line treatments may be sufficient to control electro-clinical status in lesional and epileptic SE, while intensive care unit management, a more aggressive therapeutic approach and continuous EEG monitoring are recommended for refractory SE.

Illness perceptions of neurologists and psychiatrists in relation to epilepsy and nonepileptic attack disorder

Kimberley Whitehead, Markus Reuber — 2011-10-24

Abstract: Previous studies have demonstrated that the illness perceptions of doctors can affect treatment outcomes. This is likely to be particularly relevant in chronic disorders such as epilepsy or nonepileptic attack disorder (NEAD) in which treatment success depends on adherence to tablet treatments with significant side effects or a potentially difficult process of engagement in psychological treatment. This study describes the illness perceptions of neurologists and psychiatrists to epilepsy and NEAD. 85 doctors (45 neurologists and 40 psychiatrists) completed the adapted Illness Perception Questionnaire-Revised (IPQ-R) and the Symptom Attribution Question for epilepsy and NEAD. Both groups of doctors thought that patients with NEAD had greater personal control over their condition than patients with epilepsy (p<.02) and that NEAD was a more cyclical condition than epilepsy (p<.001). Both groups of doctors professed a greater understanding of epilepsy than NEAD (p<.001). Psychiatrists alone believed epilepsy to be more chronic than NEAD (p=.002). Psychiatrists felt that epilepsy had less of an emotional impact on patients (p=.004) and were more likely to endorse psychological causes for epilepsy (p=.008) when compared to neurologists. Psychiatrists felt that NEAD had less negative consequences (p=.014) and were more likely to endorse nonpsychological causes for NEAD (p=.020) when compared to neurologists. The IPQ-R and Symptom Attribution Question demonstrated important differences in attitudes of neurologists and psychiatrists towards epilepsy and NEAD. Different attitudes towards the two seizure disorders may cause problems with communication and treatment if patients are referred from one speciality to the other.

Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy

2011-11-07

Abstract: Valproic acid (VPA) is a well-established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Although there are many reports of adverse effects of VPA, studies focusing on the concentration–response relationships of VPA and its metabolites in patients with epilepsy are extremely limited. In this study, a rapid and specific high performance liquid chromatography-ultraviolet (HPLC-UV) method to simultaneously detect the concentrations of VPA and its major hepatotoxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in human plasma has been established, using 2,4′-dibromoacetophenone and octanoic acid as the derivatization reagent and internal standard, respectively. This method was used to analyze plasma samples (n=64) of Chinese patients with epilepsy. The results revealed that 4-ene VPA concentrations in Chinese patients were much higher than those in patients in other countries such as United States and Iran. Significant correlations between aspartate aminotransferase (AST), alanine aminotransferase (ALT) and 4-ene VPA concentration suggest that the simultaneous determination of VPA and 4-ene VPA is an effective tool for the prediction of clinical hepatotoxicity in epileptic patients. Furthermore, the present study describes a less costly and complex technique for the clinical monitoring of VPA plasma levels and the risk of hepatotoxicity which may be of particular interest in developing countries like China.

Mutations in familial nocturnal frontal lobe epilepsy might be associated with distinct neurological phenotypes

Ortrud K. Steinlein, Jean-Charles Hoda, Sonia Bertrand, Daniel Bertrand — 2011-10-31

Abstract: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare familial seizure disorder caused by mutations in at least two different subunit genes of the neuronal nicotinic acetylcholine receptor (nAChR), CHRNA4 and CHRNB2. ADNFLE was initially described as a “pure” seizure disorder with a mostly benign course. We have analysed the clinical features of 19 ADNFLE families from 12 countries with a total of 150 patients and grouped them with respect to their nAChR mutations. These data suggest that certain nAChR mutations might be associated with an increased risk for major neurological symptoms such as mental retardation, schizophrenia-like symptoms or marked cognitive deficits, but the risk for these disorders seems to be low for most other ADNFLE mutations. The functional data confirm that the mutations differ from each other with respect to the size of their gain-of function effects and other biopharmacological characteristics although these functional changes are not predictive for the severity of the clinical phenotype.

Improving safety outcomes in the epilepsy monitoring unit

Marie Atkinson, Karthika Hari, Kimberly Schaefer, Aashit Shah — 2011-11-17

Abstract: Long term video electroencephalography (EEG) in epilepsy monitoring units (EMU) is used to diagnose and treat patients with epilepsy. Injury occurs in the EMU, including reports of death. No standardized patient safety protocols exist. Our objective is to determine the frequency and contributing factors to injury in the EMU.We reviewed medical records and video EEG of patients with epilepsy admitted to our EMU from December 1, 2008 to June 1, 2009. Data was collected on seizure type, onset, length, and frequency. Seizure related falls, injury, and adverse events were recorded. Data regarding the physical environment and treatment during seizures were analyzed too.20 patients with 170 seizures were collected. Of the 170 total seizures captured, only 1 injury (0.6%) and 6 falls occurred (3.5%). 5 of the 6 falls were related to patients being ambulatory. No seizures resulted in prolonged stay. Of the 170 seizures captured, other adverse events included 1 status epilepticus (0.6%), 2 postictal aggression (1.2%), 4 objects in mouth (2.4%), 14 ambulatory at seizure onset (8.2%) and 5 postictal ambulation from bed (2.9%). Staff responded to 69 out of 170 seizures (40.6%). Of the 101 seizures without staff response, 57 seizures were electrographic without seizure detection software or push button activation.Falls and adverse events that can lead to injury occur in the EMU, yet the degree of actual injury is minimal. To improve safety outcomes, standardized protocols with appropriate outlined nursing care and procedures for continuous monitoring of patients by staff need to be employed.

MEG-based identification of the epileptogenic zone in occult peri-insular epilepsy

2011-11-28

Abstract: Introduction: Presurgical work-ups of patients with pharmacoresistant epileptic seizures can require multiple diagnostic methods if magnetic resonance imaging (MRI) combined with video-EEG monitoring fails to show an epileptogenic lesion. Yet, the added value of available methods is not clear. In particular, only a minority of epilepsy centres apply magnetoencephalography (MEG). This study explores the potential of MEG for patients whose previous sophisticated work-ups missed deep-seated, peri-insular epileptogenic lesions.Patients and methods: Three patients with well documented, frequent, stereotypical hypermotor seizures without clear focus hypotheses after repeated presurgical work-ups including video-EEG-monitoring, 3Tesla (3T) magnetic resonance imaging (MRI), morphometric MRI analysis, PET and SPECT were referred to MEG source localisation.Results: In two out of three patients, MEG source localisation identified very subtle morphological abnormalities formerly missed in MRI or classified as questionable pathology. In the third patient, MEG was not reliable due to insufficient detection of epileptic patterns. Here, a 1mm×1mm×1mm 3T fluid-attenuated inversion recovery (FLAIR) MRI revealed a potential epileptogenic lesion. A minimal invasive work-up via lesion-focused depth electrodes confirmed the intralesional seizure onset in all patients, and histology revealed dysplastic lesions. Seizure outcomes were Engel 1a in two patients, and Engel 1d in the third.Discussion: MEG can contribute to the identification of epileptogenic lesions even when multiple previous methods failed, and when the lesions are located in deep anatomical structures such as peri-insular cortex. For epilepsy centres without MEG capability, referral of patients with cryptogenic focal epilepsies to centres with MEG systems may be indicated.

Extended retention intervals can help to bridge the gap between subjective and objective memory impairment

Juri-Alexander Witt, Carina Glöckner, Christoph Helmstaedter — 2011-11-28

Abstract: Purpose: Despite their excellent clinical validity, objective measures of memory often do not reflect self-perceived memory impairment. This discordance has mostly been attributed to depressed mood. Alternatively, a lack of ecological validity due to the rather short standard retention intervals of 20–60min may be responsible for this discordance. Therefore, we explored the value of extended retention intervals in regard to subjective memory deficits.Methods: Our prospective study was based on 73 patients with epilepsy. In addition to the standard 30-min retention interval of a verbal learning and memory test (VLMT) patients were randomized to either a free delayed recall after 1 week or after 4 weeks. Mood was assessed by the Beck Depression Inventory (BDI).Results: Forty-four patients (60%) reported self-perceived memory deficits, whereas objective verbal memory impairment was present in 26 patients (36%). Concordance between subjective and objective memory performance was observed in 53% of the patients. Multivariate analyses identified memory performance after 4 weeks and self-rated mood as determinants of subjective memory impairment. Self-perceived memory impairment correlated with the number of remembered words after 4 weeks (r=−0.361, p=0.030) and the BDI total score (r=0.332, p=0.004) but neither with recall performance after 30min nor after 1 week.Conclusion: Subjective memory appears to follow a different time scale than routine memory testing. Thus, the introduction of longer retention intervals may enhance the ecological validity of standard memory tests. Furthermore, the findings again underscore that controlling for mood is mandatory when dealing with subjective memory complaints.

Fever as a seizure precipitant factor in Panayiotopoulos syndrome: A clinical and genetic study

2011-10-19

Abstract: Purpose: To examine fever as a precipitating factor for focal seizures in patients with Panayiotopoulos syndrome (PS) and evaluate the role of SCN1A in PS patients with seizures triggered by fever.Methods: From January 2000 to June 2008, we identified patients referred for seizures who fulfilled the criteria of PS. Patients were divided into two groups, according to the presence (group A) or the absence (group B) of seizures triggered by fever. Electroclinical features of the two groups were compared. In addition, an analysis of SCN1A in patients of group A was performed.Results: Thirty patients fulfilled the inclusion criteria. Eleven patients (36%) had at least one focal autonomic seizure triggered by fever (group A). In group A, 7/11 patients (63.5%) had the first focal autonomic seizure during a febrile illness. Two of these 7 patients were misdiagnosed at the onset of PS. The median age at the onset of PS was slightly lower in group A than in group B (p=.050). Moreover, patients in group A more frequently had a positive familial history of febrile seizures (FS) (p=.047). No mutations of SCN1A were found in any of the 10 patients screened.Conclusion: Fever is a common trigger for focal autonomic seizures in PS. Knowing that an autonomic manifestation during fever can be an epileptic seizure could facilitate diagnosis and prevent unnecessary investigations and erroneous treatments. Moreover, our data show that SCN1A gene does not contribute significantly to susceptibility to autonomic seizures during fever in patients with PS.

S100B proteins in febrile seizures

2011-12-02

Abstract: S100B protein concentrations correlate with the severity and outcome of brain damage after brain injuries, and have been shown to be markers of blood–brain barrier damage. In children elevated S100B values are seen as a marker of damage to astrocytes even after mild head injuries. S100B proteins may also give an indication of an ongoing pathological process in the brain with respect to febrile seizures (FS) and the likelihood of their recurrence. To evaluate this, we measured S100B protein concentrations in serum and cerebrospinal fluid from 103 children after their first FS. 33 children with acute infection without FS served as controls for the serum concentrations. In the FS patients the mean S100B concentration in the cerebrospinal fluid samples was 0.21μg/L and that in the serum samples 0.12μg/L. The mean serum concentration in the controls was 0.11μg/L (difference 0.01μg/L, 95% confidence interval −0.02 to 0.04μg/L, P=0.46). There was a correlation between age and serum S100B concentration (r=−0.28, P=0.008) in children under four years, but S100B concentrations did not predict the clinical severity of the FS nor their recurrence. There was no correlation between time of arrival at the hospital after FS and S100B concentration in serum (r=−0.130, P=0.28) or in cerebrospinal fluid samples (r=−0.091, P=0.52). Our findings indicate that FS does not cause significant blood–brain barrier openings, and increase the evidence that these seizures are relatively harmless for the developing brain.

Extremely sustained startle-induced clonus: Non epileptic motor attacks mimicking clonic seizures in children with encephalopathy

Francesco Mari, Simone Gana, Francesca Piras, Renzo Guerrini — 2011-11-14

Abstract: Clonus is a pathological motor pattern characterised by involuntary, rhythmic and brisk muscular contractions in response to peripheral stimuli producing muscle stretching. It indicates pathological involvement of the corticospinal tract and can be considered as a functional spastic movement disorder of variable clinical presentation and duration. We documented severe and prolonged episodes of startle-induced clonic attacks associated with severe apnoea, occurring in three infants with severe encephalopathy. The clinical characteristics of such episodes are very similar to those of clonic epileptic seizures. Video-EEG recordings confirmed the non epileptic origin of the episodes. Previous anti-epileptic drug treatment was unsuccessful but myorelaxing drugs produced a dramatic improvement.

Helicobacter pylori's potential association with epilepsy

2011-10-26

We have read with interest the study by Asadi-Pooya et al. who concluded that the rate of Helicobacter pylori infection (Hp-I) was not higher in patients with epilepsy compared to healthy individuals. However, due to problems mainly encountered during recruitment of the patients and controls of this study, the conclusion of this trial might be not reasonable.