Seizure: European Journal of Epilepsy - Articles in Press

The pathogenesis of tumor-related epilepsy and its implications for clinical treatment - Corrected Proof

Gan You, Zhiyi Sha, Tao Jiang — 2012-02-02

Abstract: Approximately 30–50% of patients with brain tumors present with seizures as the initial symptom. Seizures play a very important role in the quality of life, particularly in patients with slow-growing primary brain tumors. Tumor-related seizures are often refractory to antiepileptic treatment. Despite the importance of this subject to the fields of neurology, neurosurgery and neurooncology, the pathogenesis of tumor-related epilepsy remains poorly understood. This review summarizes possible mechanisms underlying the pathogenesis of tumor-related epilepsy, including both tumoral and peri-tumoral aspects. Tumor cells themselves may create intrinsic epileptogenicity, and inadequate homeostasis in the peri-tumoral tissues may lead to seizure susceptibility. Other local changes in electrolytes, perfusion, metabolism, and enzymes could also contribute. It is generally accepted that changes in amino acid neurotransmission are the most important mechanism underlying tumor-related seizures, and changes in extracellular ions also play an important role. Hypoxia, acidosis, and metabolic, immunological, and inflammatory changes may also be involved in the occurrence of seizures. Knowledge of these mechanisms may provide guidance in the search for new strategies for the surgical and medical treatment of tumor-related epilepsy.

8p deletion and 9p duplication in two children with electrical status epilepticus in sleep syndrome - Corrected Proof

2012-02-02

Abstract: We describe two individuals with the same chromosomal aberrations derived from an unbalanced translocation between chromosomes 8p and 9p, who presented with intellectual disabilities, dysmorphic features, and localization-related epilepsy. Several years after the onset of epilepsy, aggravation of widespread epileptic discharges during sleep resulted in the emergence of absence and/or atonic seizures in both patients; one patient additionally presented with psychomotor deterioration. These symptoms completely disappeared after treatment with ethosuximide and benzodiazepines, and marked improvement was observed in electroencephalographic findings. We review the clinical features of der(8)t(8;9) with particular focus on epileptic complications. We conclude that particular types of chromosomal aberrations may have a propensity to develop the condition categorized as electrical status epilepticus in sleep.

Factors influencing the costs of epilepsy in adults with an intellectual disability - Corrected Proof

2012-01-30

Abstract: Purpose: Despite the common occurrence of intellectual disability (ID) in people with epilepsy, most studies of the cost of epilepsy have focussed primarily or exclusively on people without ID. This paper estimates the costs of supporting people with epilepsy and ID.Methods: Prospective resource use and outcome data were collected on 91 participants from the east of England for seven months. Multivariate analysis was used to investigate the relationship between costs and patient and healthcare provider characteristics.Results: Mean health care costs relating to epilepsy or ID were £2800 (3500 Euros, 5200 USD) p.a. Modelling suggests costs are lower for patients with more severe ID (p=0.014); and higher for patients managed by a consultant neurologist (p=0.037).Discussion: Our findings support limited evidence from the literature of increased epilepsy costs in people with ID. Patterns of expenditure suggest clinical variation in the treatment of epilepsy according to the severity of ID, particularly in the absence of management by a consultant neurologist.

Lacosamide treatment of juvenile myoclonic epilepsy - Corrected Proof

Pegah Afra, Bola Adamolekun — 2012-01-27

Abstract: Juvenile myoclonic epilepsy is the most common form of idiopathic generalized epilepsy with onset at puberty or late teenage years. About 80–90% of patients with juvenile myoclonic epilepsy respond to appropriate antiepileptic treatment and achieve seizure freedom, and about 15% of patients become intractable. Valproic acid, levetiracetam, lamotrigine, topiramate and zonisamide are used as first line or adjunctive therapy of this disorder. Lacosamide is approved for adjunctive treatment of partial onset epilepsies. The role of lacosamide in treatment of idiopathic generalized epilepsy including juvenile myoclonic epilepsy is unknown. We present three patients with classic clinical and electrographic features of juvenile myoclonic epilepsy that were maintained on lacosamide (one on monotherapy and two as adjuvant therapy). There were no special pharmacodynamic actions causing exacerbation or worsening of myoclonic jerks or generalized seizures in these three patients. In conclusion, although, the data from our three patients’ suggest that lacosamide may be effective in the treatment of juvenile myoclonic epilepsy, larger studies are needed to explore efficacy and role of lacosamide in the treatment of this disorder.

Minocycline as potent anticonvulsant in a patient with astrocytoma and drug resistant epilepsy - Corrected Proof

2012-01-20

Abstract: Minocycline, a tetracycline family antibiotic, is known to inhibit microglial activation and proinflammatory cytokine release in animal models. Experimental data show that these immune processes may play a role in epilepto- and ictogenesis. We present the case of a patient with marked reduction in seizure frequency during minocycline therapy with severe symptomatic epilepsy due to an astrocytoma.

Neurocognitive evaluation in children with occipital lobe epilepsy - Corrected Proof

Muzaffer Polat, Sarenur Gokben, Ayse Tosun, Gul Serdaroglu, Hasan Tekgul — 2012-01-20

Abstract: Purpose: This study aimed to explore cognitive functions in patients with childhood epilepsy with occipital paroxysms (CEOP) and to compare the performance of these patients with that of patients with symptomatic occipital epilepsy (SOE) and healthy control subjects.Method: Twenty-eight patients with epilepsy (17 CEOP, 11 SOE) were enrolled. The control group had similar demographical characteristics. Cognitive functions evaluated with Wechsler Intelligence Scale for Children-revised edition (WISC-R), The Visual Aural Digit Span (VADS) and Bender Visual Motor Gestalt Test (BVMG).Results: The WISC-R showed lower performance IQ with WISC-R in patients with occipital epilepsy than in healthy controls. The VADS test only showed lower scores in children with symptomatic occipital epilepsy. Mean BVMG test scores were significantly abnormal in both subgroups of childhood epilepsy with occipital paroxysms (early-onset CEOP/late-onset CEOP) and the group with SOE.Conclusion: Patients with CEOP, especially the late-onset form, have significant problems in the domains of visuomotor coordination, memory and attention. The academic performance of these patients should be monitored carefully in follow-up and appropriate educational support should be given as necessary.

Carbamazepine-induced hypogammaglobulinemia - Corrected Proof

2012-01-17

Abstract: Carbamazepine is used to control seizures. Its common side effects are sleep disorders, anorexia, nausea, vomiting, polydipsia, irritability, ataxia, and diplopia. Involvement of the immune system is rare, and few cases of decreased immunoglobulin levels have been reported. We describe a patient with low immunoglobulin levels due to carbamazepine use who presented with recurrent urinary tract infection. Intravenous immunoglobulin was administered, and immunoglobulin levels increased to safer levels after discontinuation of carbamazepine. Previous reports describe severe infection after carbamazepine-induced hypogammaglobulinemia. Therefore, in patients using antiepileptics, particularly carbamazepine, serum immunoglobulin levels should be checked in those with recurrent infections.

Differences in iron deficiency anemia and mean platelet volume between children with simple and complex febrile seizures - Corrected Proof

2012-01-17

Abstract: Objective: The relationship between iron deficiency anemia and febrile seizures (FSs) were examined in several studies before. The aim of our study is to find out the differences regarding iron deficiency anemia, demographic characteristics and mean platelet volume (MPV) which is an inflammatory marker between simple and complex febrile seizure groups.Methods: In this study, the authors investigated the recordings of 493 children with a diagnosis of simple and complex febrile seizure, aged between 6 months and 6 years, followed between 2002 and 2010 retrospectively.Results: Mean age and male/female ratio were similar in two groups. There was no significant difference regarding with age, gender and family history of FS between two groups. We found significant difference statistically with respect to gestational age, consanguinity, family history of epilepsy and birth weight between two groups. The mean levels of Hb, Htc, MCV were lower and Plt and RDW levels were higher in children with CFS than SFS group, the differences were statistically significant (p: 0.001).A higher proportion of children with CFS (16.2%) had iron deficiency anemia compared to SFS group (12.1%). Mean platelet volume (MPV) of CFS (7.99±0.96fL) were significantly lower than that of SFS group (8.77±0.75) (p<0.001).Conclusions: The results of this study suggests that iron deficiency anemia is more frequently seen among the patients with CFS than the patients with SFS. The lower levels of MPV as an inflammatory marker, supports the idea that CFS is a brain inflammatory disease and the consequence of this inflammatory mechanism is the development of the epilepsy. Further studies are necessary to highlight the relationship between iron metabolism, inflammation and seizures.

Self-injury in people with intellectual disability and epilepsy: A matched controlled study - Corrected Proof

2012-01-16

Abstract: We aimed to identify the presence of self-injurious behavior in a sample of 158 people with intellectual disability and epilepsy as compared with a control sample consisting of 195 people with intellectual disability without epilepsy. The Italian Scale for the Assessment of self-injurious behaviors was used to describe self-injurious behavior in both groups. The groups were matched for ID degree: mild/moderate (20 and 20 respectively), severe/profound (45 in both samples) and unknown (4 in both samples). Seventy-four percent of the first sample were diagnosed with symptomatic partial epilepsy.The prevalence of self-injurious behaviors was 44% in the group with intellectual disability and epilepsy and 46.5% in the group with intellectual disability without epilepsy (difference not significant).The areas most affected by self-injurious behaviors in both samples were the hands, the mouth and the head. The most frequent types of self-injurious behaviors were self-biting, self-hitting with hands and with objects.Self-injurious behavior is frequently observed in individuals with epilepsy and intellectual disability.Our study does not suggest that the presence of epilepsy is a risk factor for self-injurious behavior in this patient group.

Intravenous Lacosamide in refractory nonconvulsive status epilepticus - Corrected Proof

L. Mnatsakanyan, J.M. Chung, E.I. Tsimerinov, D.S. Eliashiv — 2012-01-13

Abstract: Background: Many patients present with refractory Status epilepticus (SE) despite multiple anti-epileptic drugs (AEDs). Lacosamide (LCM) was recently approved as an adjunct AED for partial-onset seizures. It has unique mechanism of modulating voltage-gated sodium channels by enhancing their slow inactivation. LCM has demonstrated efficacy in animal models of pharmacoresistant seizures. To date, there are isolated anecdotal reports of LCM use in SE.Objective: To report a single center experience with IV Lacosamide in patients with NCSE.Methods: Pharmacy records were reviewed to identify patients with SE who received IV LCM in our institution. Data on demographics, response to therapy and adverse effects/outcomes were analyzed. All patients had continuous EEG monitoring.Results: 10 patients (4 men, 6 women), age 16–90 years with refractory SE were given LCM. Eight patients were in focal non-convulsive SE (NCSE), 2 were in generalized non-convulsive SE. The etiologies included anoxic brain injury, idiopathic, encephalitis, tumor, posterior reversible encephalopathy syndrome (PRES), stroke, and AVM. IV LCM was added after traditional AEDs, including drug-induced coma in some, failed to control the SE. NCSE resolved in 7/10 patients whereas 1/10 patient showed partial response with cessation of NCSE but still frequent electrographic seizures and 2/10 patients were resistant to therapy.Conclusions: LCM is a useful adjunct in refractory NCSE. The IV formulation allows prompt administration in the intensive care unit setting. Response was seen especially in focal SE. Similar to other AEDs, response was poor in patients with postanoxic injury. Our data is limited by the small number of patients. Larger controlled studies are necessary to assess accurately the efficacy of IV LCM as an early treatment of SE.

Short-term efficacy and safety of zonisamide as adjunctive treatment for refractory partial seizures: A multicenter open-label single-arm trial in Korean patients - Corrected Proof

2012-01-06

Abstract: Objective: To evaluate the efficacy and safety of adjunctive zonisamide (ZNS) therapy in Korean adults with uncontrolled partial epilepsy.Methods: Study patients had an average of at least one seizure per 4-week (averaged over a 12-week historical baseline) despite the use of one to three antiepileptic drugs. The starting dose of ZNS was 100mg/day, and was increased to 200mg/day after 2weeks. During the 12-week maintenance period, the dose of ZNS was adjusted to 200–400mg/day based on the physicians’ discretion. The global evaluation scale (GES) and quality of life (QOLIE-31) were also evaluated.Results: A total of 121 patients were enrolled, of which 88 patients completed the study. The median percent reduction in weekly seizure frequency over the treatment period was 59.0%. The ≥50% and ≥75% responder rates were 57.3% and 38.5%, respectively. Seizure freedom over the treatment period was observed in 25 patients, but seizure freedom throughout the 16-week treatment period was attained in only 16 patients. On investigator's GES, 84 patients were considered improved, with 33 patients showing marked improvement. In QOLIE-31 scale, seizure worry improved significantly but emotional well-being deteriorated. Treatment-emergent adverse events (AEs) were reported in 80 patients. The most common AEs were dizziness (28.1%), somnolence (24.0%), anorexia (18.2%), headache (14.0%), nausea (13.2%), and weight loss (10.7%). Twenty-two patients discontinued the trial due to drug-related AEs.Conclusions: Our results suggest that adjunctive ZNS therapy for the treatment of refractory partial epilepsy, though efficacious, is associated with significant tolerability problems.

Serum S100B levels in children with simple febrile seizures - Corrected Proof

2012-01-05

Abstract: Purpose: Recent studies have found that S100B is a useful marker for astroglial activation seen in various neurologic disorders. The purpose of this study was to evaluate whether simple febrile seizures (SFS) was associated with an elevation in serum S100B levels.Methods: In this study the samples consisted of 39 patients with SFS ranging from 6 to 36 months of age, and age-matched and sex-matched controls including 30 patients with fever and 30 healthy subjects. Two serum samples were obtained for S100B from the study group at 0–1h and 6–24h following seizure. Serum samples were drawn once in the control group. The serum samples were then analyzed using ELISA.Results: In the study group, the mean values of the serum S100B concentrations at 0–1h and 6–24h were 32.6±7.8pg/ml and 32.1±5.8pg/ml, respectively, while the concentrations were 32.1±8.8pg/ml and 29.5±7.8pg/ml in the control groups. No significant differences were detected in serum S100B levels at 0–1h or 6–24h in the study when compared to the control groups.Conclusions: These results suggest that SFS do not raise serum S100B concentration above the normal range.

Increased asymmetric dimethylarginine level after antiepileptic drug treatment may be independent of the changes in plasma homocysteine level - Corrected Proof

Oğuzhan Öz, Mehmet Yücel, Hakan Akgün, Zeki Gökçil, Zeki Odabaşı — 2012-01-05

We have read the recent article by Sniezawska and colleagues with great interest. The authors investigated the frequency of polymorphism in the MTHFR (C677T), MTR (A2756G), and MTHFD1 (G1958A) genes and analysed the levels of homocysteine (Hcy), methionine, asymmetric dimethylarginine (ADMA), and arginine in epileptic patients treated with various antiepileptic drugs (AEDs). They found that AED pharmacotherapy in epileptic patients increases Hcy and ADMA levels. These authors suggested that their study showed an increase in Hcy level accompanied by an increase in ADMA level in epileptic patients receiving AEDs and concluded that hyperhomocysteinemia (HHcy) disrupts the feedback control of Hcy over ADMA.

IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom - Corrected Proof

2012-01-04

Abstract: Introduction: Seizures are the most common initial symptom in patients with low-grade glioma and their occurrence strongly depends on the tumor location. The majority of low-grade gliomas reveal mutations in the genes encoding isocitrate-dehydrogenase 1 (IDH1) or 2 (IDH2). These mutations are associated with metabolic changes that are potentially epileptogenic. We investigated the correlation between IDH1/2 mutations and tumor localization and seizure as the initial symptom.Materials and methods: This retrospective study included patients with a diagnosis of WHO grade II astrocytoma and cortical infiltration and in whom initial symptoms were documented and biopsy tissue was available for IDH1/2 analysis. IDH1/2 mutation analysis was performed by direct sequencing or by immunohistochemistry with an antibody which detects mutated protein IDH1 R132H. Sequencing was carried out if immunohistochemistry was negative. IDH1/2 status was defined as mutated if either of these investigations were positive.Results: Seventy-nine patients were included. IDH1 or IDH2 mutation was present in 63 (80%) patients who on average were younger than patients without IDH1/2 mutation (40 vs. 47 years, p=0.0331, t-test). IDH1/2 mutations were associated with frontal tumor location (p=0.0202). All 12 tumors in the insula revealed IDH1/2 mutations. Seizure as the initial symptom was recorded in 57 (72%) patients and was associated with IDH1 or IDH2 mutation by multivariate analysis (OR 22.563, p=0.0019).Conclusion: In WHO grade II astrocytomas, IDH1/2 mutations mostly occur in tumors infiltrating the frontal lobe. Seizure as the initial symptom is associated with IDH1 or IDH2 mutation.

Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients - Corrected Proof

2012-01-03

Abstract: Introduction: The cognitive and behavioral effect of deep brain stimulation (DBS) administered to the deep cerebral nuclei for epilepsy treatment is unknown. We investigated the cognitive outcomes at least 12 months after DBS to the bilateral anterior thalamic nucleus (ATN) for controlling intractable epilepsy.Methods: Nine patients with intractable epilepsy who were not candidates for resective surgery, but who were treated by bilateral ATN DBS underwent cognitive and behavioral assessments before implantation and more than 1 year after DBS surgery. Postoperative cognitive assessments were carried out under a continuous stimulation mode.Results: The mean seizure-reduction rate of these patients after ATN DBS was 57.9% (35.6–90.4%). Cognitive testing showed favorable results for verbal fluency tasks (letter and category, p<0.05), and a significant improvement in delayed verbal memory was observed (p=0.017). However, we did not observe any significant changes in general abilities (IQ, MMSE), information processing (digit forward and backward, Trail A, and Digit Symbol), or executive function (Trail B and WCST). Interestingly, we did not observe any significant cognitive decline approximately 1 year (mean, 15.9 months) after ATN DBS surgery.Conclusions: We showed that ATN DBS not only resulted in promising clinical effects but was also associated with improvements in both verbal recall and oral information processing, which may be related to the bilateral activation of the fronto-limbic circuit following DBS surgery. Further controlled, long-term studies with larger populations are warranted for elucidating the clinical effects of ATN DBS.

Memory rehabilitation and brain training for surgical temporal lobe epilepsy patients: A preliminary report - Corrected Proof

Loes Koorenhof, Sallie Baxendale, Natalie Smith, Pam Thompson — 2011-12-26

Abstract: The short term impact of a memory rehabilitation programme on verbal memory test performance and subjective ratings of memory in everyday life was assessed in healthy controls and left temporal lobe epilepsy (LTLE) surgical patients. The intervention involved training in the use of external and internal memory support strategies. Half of the sample in addition undertook computerised brain training exercises as homework. LTLE patients were seen either before surgery or 3–6 months after their operation. Improvements in verbal memory were observed in both groups. An effect of brain training was recorded but this did not occur in a consistent direction. Subjective ratings of memory indicated improvements that were significant for the LTLE group but not the controls. Positive changes in the memory outcome measures were associated with improvements in mood. Pre-operative memory rehabilitation was not associated with better outcomes than post-operative intervention. Further research is needed to explore the persistence of the changes observed and to explore if pre-operative rehabilitation offsets post-operative memory decline.

A case report of surgically treated drug resistant epilepsy associated with subependymal nodular heterotopia - Corrected Proof

Göksemin Acar, Feridun Acar, İbrahim Öztura, Barış Baklan — 2011-12-09

Abstract: Subependymal nodular heterotopia (SNH) is a cortical development malformation that is commonly associated with medically resistant epilepsy. Cases of SNH are challenging to treat surgically because there are typically multiple nodules, which may be involved in epileptogenesis. Moreover, dual pathology may exist in these patients. Here, we present a case with unilateral subependymal heterotopic nodules associated with ipsilateral hippocampal atrophy. Invasive and non-invasive work-ups revealed that the hippocampus was the actual ictal onset zone and that the SNH was not involved. An anterior temporal lobectomy was carried out, and postoperative seizure outcome was class Ia at the end of 2 years. The case demonstrates that SNH may not play a major role in patients with dual pathology. However, direct electroencephalography (EEG) recording from areas of SNH and other possible epileptogenic regions is indispensable in defining the ictal onset zone and avoiding poor surgical outcomes.

Physical injuries in patients with epilepsy and their associated risk factors - Corrected Proof

Ali A. Asadi-Pooya, Alireza Nikseresht, Ehsan Yaghoubi, Maromi Nei — 2011-11-30

Highlights: ► Physical injuries are common in patients with epilepsy; however most of these injuries are mild. ► Severe injuries rarely occur with seizures other than generalized tonic–clonic seizures. ► There is not a definite model to predict having injury in patients with epilepsy.Abstract: Objectives: To determine the frequency, nature, and risk factors associated with physical injuries in patients with epilepsy.Methods: In this retrospective cohort study, patients 18years of age and older with active epilepsy for at least 1year were included. A questionnaire (including age, gender, education, type of epilepsy, seizure frequency, having aura, drug compliance, polypharmacy, comorbidity, type and place of injury) was completed from patients and healthy individuals. Statistical analyses were performed using multiple logistic regression and Chi-square tests.Results: 264 patients with epilepsy and 289 healthy participants were studied. Among patients, 8.7% reported severe injuries and 44.3% had mild injuries. Most patients reported soft tissue injuries, followed by dental injury, burn, and head injury. Severe injuries were 2.9 times more frequent among patients having generalized tonic–clonic seizures (GTCS) compared to healthy control; this was not statistically significant (P=0.07). No patient reported having severe injuries due to SPS, myoclonic or absence seizures. Mild injuries were 10.3 times more frequent among those with GTCS compared to healthy control (P=0.001). The relative risk for having injury in patients compared to control group was 3.42 (95% confidence interval: 2.50–4.69). Injury was significantly related to having GTCSs, illiteracy, having fall with seizures, comorbidity and having uncontrolled seizures.Conclusion: Physical injuries are common in patients with epilepsy; however most of these injuries are mild. Severe injuries rarely occur in patients with seizures other than GTCS.

Co-morbidity of epilepsy in Tanzanian children: A community-based case–control study - Corrected Proof

2011-11-30

Abstract: Purpose: To define the prevalence and associations of co-morbidity and school attendance in older children with epilepsy (CWE) from a rural district of Tanzania by conducting a community-based case–control study.Methods: Children aged 6–14 years old with active epilepsy (at least two unprovoked seizures in the last five years) were identified in a cross-sectional survey in Tanzania. Co-morbidities were assessed and cases were compared with age-matched controls.Results: Co-morbidity was very common amongst cases (95/112, 85%), with 62/112 (55%) having multiple co-morbidities. Co-morbidities consisted of cognitive impairment (72/112, 64%), behaviour disorder 68/112 (61%), motor difficulties 29/112 (26%), burns and other previous injuries (29/112, 26%). These complications were significantly more common in cases than in controls (odds ratio 14.8, 95%CI 7.6–28.6, p<0.001). Co-morbidity in CWE was associated with structural cause, abnormal electroencephalogram and early onset seizures. Cognitive impairment was very common in CWE (64%) and was not associated with Phenobarbital use but was associated with motor difficulties, early onset and recurrent seizures. Poor school attendance was found in 56/112 (50%) of CWE, but not in the controls: it was associated with the presence of multiple co-morbidities, especially with motor difficulties in CWE.Conclusion: Children with epilepsy in a rural area of sub-Saharan Africa had a high level of co-morbidity. Cognitive impairment and poor school attendance were very common. These associated difficulties in CWE in the region need to be addressed to reduce the negative impact of epilepsy on these children.

De-novo simple partial status epilepticus presenting as Wernicke's aphasia - Corrected Proof

Bhimanagouda Patil, Agyepong Oware — 2011-11-24

Abstract: Language disturbances manifesting as brief periods of speech arrest occur with seizures originating in the frontal or temporal lobes. These language disturbances are usually present with other features of seizures or may occur in an episodic fashion suggesting their likely epileptic origin. Sustained but reversible aphasia as the sole manifestation of partial status epilepticus is rare, particularly without a history of prior seizures. A few cases have been described in the literature where Broca's or mixed aphasia seems to be more common than Wernicke's aphasia. Here we describe a patient who presented with Wernicke's aphasia secondary to simple partial status epilepticus but without any other features of seizures. The diagnosis was confirmed on EEG and the aphasia reversed after antiepileptic treatment.

WITHDRAWN: Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures - Corrected Proof

2011-01-07

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.