Persistent Seizures Research Articles

Early add-on treatment vs alternative monotherapy in patients with partial epilepsy.

The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment. We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability. A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (p=0.53). The quality of life and the tolerability did not significantly differ between the two groups. Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.

Surgery for Intractable Epilepsy Due to Unilateral Brain Disease: A Retrospective Study Comparing Hemispherectomy Techniques

BackgroundHemispherectomy is a surgical procedure used to treat medically intractable epilepsy in children with severe unilateral cortical disease secondary to acquired brain or congenital lesions. The major surgical approaches for hemispherectomy are anatomic hemispherectomy, traditional functional hemispherectomy, and peri-insular hemispherotomy. We describe the epilepsy outcome, including the need for reoperation, after hemispherectomy in patients with brain malformations or acquired brain lesions who underwent hemispherectomy for refractory epilepsy. MethodsWe conducted a retrospective observational study at Children's Hospital Boston. Cases were ascertained from a research database of patients who underwent epilepsy surgery from 1997 to 2011. Data were obtained from electronic medical records and office charts. Outcome after surgery was defined as improvement in seizures (quantity and severity) represented by the Engel classification score measured at last follow-up, with a minimum of 12 months of follow-up. The need for reoperation for completion of hemispheric disconnection. We also examined whether placement of ventriculoperitoneal shunt was required after hemispherectomy was a secondary outcome. ResultsWe identified 36 patients who underwent hemispherectomy for severe, medically intractable epilepsy. Group 1 (n = 14) had static acquired lesions, and group 2 (n = 22) had malformations of cortical development. Mean age at surgery for group 1 was 9 years (S.D. 5.5) and 2.77 years for group 2 (S.D. 4.01; P < 0.001). The seizure outcome was good in both groups (Engel score I for 25, II for three, III for six, and IV for two patients) and did not differ between the two groups. In group 1, five patients underwent anatomic hemispherectomy (one had prior focal resection), four underwent functional hemispherectomy, and five underwent peri-insular hemispherotomy; none required a second procedure. In group 2, a total of 14 patients had anatomic hemispherectomy (of these, three had had limited prior focal resection), five had functional hemispherectomy, and three had peri-insular hemispherotomy. Among the patients in group 2 who had had functional hemispherectomy, one required reoperation to complete the disconnection and one required peri-insular hemispherotomy because of persistent seizures. In group 1, three patients underwent a ventriculoperitoneal shunt, and from these patients two underwent anatomic hemispherectomy and one had functional hemispherectomy. In group 2, 12 patients had ventriculoperitoneal shunt, and all of them had anatomic hemispherectomy as a first or second procedure. ConclusionSeizure outcome after hemispherectomy is good in patients with acquired lesions and with developmental malformations. Although the seizure outcome was similar in the three procedures, the complication rate was higher with anatomic hemispherectomy than with the more recent functional hemispherectomy and peri-insular hemispherotomy. The group with cortical malformations generally had surgery at a younger age; two patients with malformations of cortical development who underwent functional hemispherectomy required second surgeries. The need for reoperation in these cases may reflect the anatomic complexity of developmental hemispheric malformations, which may lead to incomplete disconnection.

The preoperative evaluation and surgical treatment of epilepsy.

One-third of all patients with epilepsy have persistent seizures despite medical treatment. If the origin of the seizures can be localized to a particular site in the brain, epilepsy surgery is a treatment option that addresses the cause of the problem. The presurgical assessment and surgical treatment of epilepsy are discussed on the basis of a selective literature review and the authors' clinical experience. Recent studies give further evidence that surgical treatment is superior to continued medical treatment for patients with seizures of focal origin that persist despite treatment with two antiepileptic drugs. Modern imaging and electrophysiological techniques enable the demonstration of subtle structural and functional changes of the cerebral cortex as a basis for individually tailored surgical resection. 60-80% of surgically treated patients become seizure-free. According to recent reviews, epilepsy surgery is associated with a permanent morbidity of 6% and with a mortality well under 1%; these figures are in the typical range for neurosurgical procedures. In the authors' series, 2% of patients had permanent complications, and the death rate was less than 0.1%. Advances in presurgical assessment and the broad range of available surgical techniques have widened the applicability of surgical treatment for children and adults with medically refractory epilepsy. Patients should be referred early in the course of their disease to an epilepsy center for evaluation of the surgical options.

PET in Infancy Predicts Long-Term Outcome during Adolescence in Cryptogenic West Syndrome

Developmental and seizure outcomes in patients with cryptogenic West syndrome are variable. Our aim was to clarify the relationship between FDG-PET findings in infancy and long-term seizure and developmental outcome in cryptogenic West syndrome. From 1991 to 1999, we prospectively performed FDG-PET from the onset of cryptogenic West syndrome in 27 patients. PET was performed at onset and at 10 months of age. In 2012, we evaluated the educational status, psychomotor development, and seizure outcome in 23 of the 27 patients (13-22 years of age). The correlation between PET findings and outcome was evaluated. At onset, PET showed hypometabolism in 13 patients (57%). The second PET after the initial treatment revealed cortical hypometabolism in 7 patients (30%). While hypometabolism at onset disappeared on the second PET in 9 patients, it was newly revealed in 3 patients on the second PET. In 2012, seven patients had persistent or recurrent seizures. Eight patients had intellectual impairment. The first PET did not correlate with seizure or developmental outcome. Five of 7 patients (71%) with hypometabolism seen on the second PET had persistent or recurrent seizures, while 14 of 16 (88%) patients with normal findings on the second PET were free of seizures. Five of 7 patients (71%) showing hypometabolism on the second PET had intellectual impairment. Thirteen of 16 (81%) patients with normal findings on the second PET showed normal intelligence. A significant correlation was found between the second PET and long-term seizure (P = .01) or developmental outcome (P = .03). Cortical hypometabolism is not permanent; it changes with clinical symptoms. Hypometabolism after initial treatment predicts long-term seizures and poor developmental outcome.

Low potency and limited efficacy of antiepileptic drugs in the mouse 6 Hz corneal kindling model

Corneal kindling is a useful alternative to electrically induced amygdala or hippocampal kindling, which requires advanced surgical and EEG techniques that may not be easily available in many laboratories. Therefore the first aim of this study was to evaluate whether repeated 6 Hz corneal stimulation in mice would lead to an increased and persistent seizure response as described for higher frequency (50/60 Hz) corneal kindling. Male NMRI mice stimulated twice daily (except weekends) for 3 s with 6 Hz electrical current at 44 mA displayed robust kindling development, i.e., a progressive increase in seizure severity. The majority of the animals (about 90%) developed a fully kindled state, defined as at least 10 consecutive stage 3-5 seizures within 5 weeks of corneal stimulation. Afterwards, the fully kindled state was maintained for at least 8 weeks with only two days of stimulations per week. Next, the protective efficacy of four mechanistically different antiepileptic drugs (AEDs; clonazepam, valproate, carbamazepine and levetiracetam) was assessed and compared between 6 Hz and 50 Hz fully kindled mice. All tested AEDs showed a relatively lower potency in the 6 Hz kindling model and a limited efficacy against partial seizures was observed with carbamazepine and levetiracetam. We can conclude that 6 Hz kindling may be more advantageous than the previously described 50/60 Hz corneal kindling models due to its robustness and persistence of the fully kindled state. Furthermore, the observed low potency and limited efficacy of AEDs in 6 Hz fully kindled mice suggest that this model could be a useful tool in the discovery of novel AEDs targeting treatment resistant epilepsy.

Changes in psychiatric comorbidity during early postsurgical period in patients operated for medically refractory epilepsy—A MINI-based follow-up study

PurposeThe purpose of this study was to assess axis-I DSM-IV psychiatric disorders in patients at baseline and 3months after surgery for medically refractory temporal lobe epilepsy. MethodThe Mini International Neuropsychiatric Interview (MINI) and Quality of Life in Epilepsy Inventory-10 (QOLIE-10) were evaluated before and 3months after surgery in 50 consecutive patients (21 females, 29 males) with medically refractory temporal lobe epilepsy (persistent seizures>2/month, despite treatment with ≥2 appropriate drugs in adequate doses for ≥2years) who underwent surgery [anterior temporal lobectomy with amygdalo-hippocampectomy (for mesial temporal sclerosis in 40), electrocorticography-guided lesionectomy (for other lesions in 10)]. ResultsTwenty-six patients (52%) had an axis-I psychiatric disorder [26% depressive disorder, 28% anxiety disorder] at baseline, while 30 (60%) patients had an axis-I psychiatric disorder [28% depressive disorder, 28% anxiety disorder] at 3months after surgery. Twenty percent developed a new psychiatric disorder, while 12% showed improvement postsurgery. Mean QOLIE-10 scores improved from 23.78 to 17.80 [24 (48%) patients showed ≥5-point improvement]. Thirty-four (68%) patients had no seizure, 6 (12%) had non-disabling seizures, while 2 (4%) had disabling seizures after surgery. High frequency of seizures prior to surgery (p<0.038) and seizure occurrence after surgery (p<0.055) predicted the presence of psychiatric disorders after surgery. No clinical characteristic could predict development of new psychiatric disorder after surgery. ConclusionPsychiatric dysfunction in the early postsurgery period is seen in nearly half of patients undergoing surgery for temporal lobe epilepsy, is mild in nature, and does not adversely affect quality of life but may cause significant clinical problems when it arises de novo postsurgery.

Clinical heterogeneity of juvenile myoclonic epilepsy: Follow-up after an interval of more than 20 years

PurposeThe view that juvenile myoclonic epilepsy (JME) is a uniform and life-long disorder is currently being challenged. The aim of this study was to assess the seizure and psychosocial outcome of JME at least 20 years after onset. MethodsIn 1992, 42 patients with JME were identified. In 2012, 37 agreed to a semi-structured interview. In the remaining five, only medical records were available. ResultsOf 40 patients with known seizure outcome, 21 were in remission for >5 years. Seven were off antiepileptic drugs (AEDs), four being seizure free for >10 years. Myoclonic seizures (MC) evolving to generalized tonic–clonic seizures (GTC) were associated with seizure persistence (p=0.013), whereas >1 year between MC and GTC onset was associated with a trend to GTC remission (p=0.069). Of 19 patients with uncontrolled seizures, eight experienced remission with second generation AEDs.Favorable psychosocial outcome by interview was found in a third, whereas another third had psychiatric comorbidity, seven with substance or alcohol abuse. Psychosocial and seizure outcome did not correlate. ConclusionThis study corroborates the heterogeneity of JME in terms of seizure and psychosocial outcome, but without a clear association between the two. It confirms that seizure control may persist after AED withdrawal in some and supports MC evolving to GTC as a predictor of seizure persistence. Moreover, it suggests that newer broad spectrum AEDs may improve the prognosis of JME; their impact should be focus of prospective studies.

Automated immunohistochemical method to quantify neuronal density in brain sections: Application to neuronal loss after status epilepticus

To study neurotoxic processes, it is necessary to quantify the number of neurons in a given brain structure and estimate neuronal loss. Neuronal densities can be estimated by immunohistochemical quantitation of a neuronal marker such as the protein NeuN. However, NeuN expression may vary, depending on certain pathophysiological conditions and bias such quantifications. We have developed a simple automatic quantification of neuronal densities in brain sections stained with DAPI and antibody to NeuN. This method determines the number of DAPI-positive nuclei also positive for NeuN in at least two adjacent sections within a Z-stack of optical sections. We tested this method in animals with induced status epilepticus (SE) a state of intractable persistent seizure that produces extensive neuronal injury. We found that SE significantly reduced neuronal density in the piriform cortex, the amygdala, the dorsal thalamus, the CA3 area of the hippocampus, the dentate gyrus and the hilus, but not in the somatosensory cortex or the CA1 area. SE resulted in increases in the total density of cellular nuclei within these brain structures, suggesting gliosis. This automated method was more accurate than simply estimating the overall NeuN fluorescence intensity in the brain section, and as accurate, but less time-consuming, than manual cell counts. This method simplifies and accelerates the unbiased quantification of neuronal density. It can be easily applied to other models of brain injury and neurodegeneration, or used to screen the efficacy of neuroprotective treatments.

Language and social functioning in children and adolescents with epilepsy

Individuals with epilepsy have difficulties with social function that are not adequately accounted for by seizure severity or frequency. This study examined the relationship between language ability and social functioning in 193 children with epilepsy over a period of 36months following their first recognized seizure. The findings show that children with persistent seizures have poorer language function, even at the onset of their seizures, than do their healthy siblings, children with no recurrent seizures, and children with recurrent but not persistent seizures. They continue to demonstrate poorer language function 36months later. This poor language function is associated with declining social competence. Intervention aimed at improving social competence should include consideration of potential language deficits that accompany epilepsy and social difficulty.

The Suicidal Cowdung Powders of Kongunadu

Suicide in India is a common cause of death. Common means employed are consumption of pesticides and chemical compounds. Newer compounds are frequently consumed and often the composition is unknown. Here we describe a prevalent ‘Cow Dung power’ poisoning. It is available in green and yellow variety and can cause gastrointestinal symptoms and sometimes persistent seizures. The compound was analyzed and found to be Malachite green and Auromine O respectively. These compounds and the clinical profile require to be studied in more detail and steps taken to curb its use and availability.

Terminal remission is possible in some patients with juvenile myoclonic epilepsy without therapy.

Juvenile myoclonic epilepsy is considered to be a chronic disease requiring lifelong antiepileptic treatment. The aim of this study was both to identify factors predicting the kind of seizure control and to investigate the outcome in patients after therapy withdrawal. The study included 87 patients (49 female, 38 male), aged from 17.5 to 43.5 years, referred to our Department between 1987 and 2008, with the seizure onset at the age of 14.3±2.9, and followed up for 13.3±5.8 years on average (from 5 to 23 years). Sixty seven (77.0%) patients were fully controlled; whereas 13.8% had persistent seizures and 9.2% showed pseudoresistance. The combination of three seizure types and focal electroencephalogram features were independent factors of poor seizure control. Therapy was discontinued in 34 patients either by the treating physician (in 21 patients) or by the patients themselves (in 13 cases). In 18 subjects, all seizure types relapsed after 1.1 year on average (from 7 days to 4 years) and therapy was resumed in them. All patients but three (10/13), who stopped the treatment themselves, experienced recurrences. Seizure freedom off drugs was recorded in 10.3% patients. Nonintrusive myoclonic seizures recurred in 0.5-3 years as their only seizure type in four patients, but without reintroducing medication in three patients. Combination of seizure types and focal electroencephalogram features are significant factors of pharmacoresistancy. Continuous pharmacotherapy is required in majority of patients, although about 10% of them appear to have permanent remission without therapy in adolescence.

Postictal psychosis and aripiprazole treatment in an adolescent with epilepsy and mild mental retardation: Case report

In patients with epilepsy, psychotic symptoms are divided into three groups as ictal, interictal and postictal according to their occurence time. In this case, a 16 years-old boy who had an intracranial hemorrhage when he is 1,5 months-old followed up in the Pediatric Neurology Department with epilepsy; in the last three weeks , after the epileptic seizures visual-auditory halucinations, persecution, delusions and disorganized behavior detected. Patient\'s epilepsy treatment is reorganized by Pediatric Neurology Department but because of persistent psychotic symptoms and seizures he is consulted to Child and Adolescent Psychiatry. According to patient\'s psychiatric and psychometric examination, aripirazole 2,5 mg/day treatment started, after three days the dose increased to 5mg/day and at the end of one week the dose increased to 7,5mg/day. After 10 days at the first polyclinic control, despite the existing seizures, the psychotic symptoms and disorganized behavior disappeared. In the literature case reports about some antipsychotic drugs used for treating PIP symptoms are reported but there is no information about aripiprazole treatment. This point makes this case important.

Common Complications after Hypoxic-ischemic Encephalopathy

Seong Hoon Lim, M.D., Ph.D.Department of Rehabilitation Medicine, School of Medicine, The Catholic University of KoreaHypoxic-ischemic encephalopathy (HIE) is one of the major disease for neuro-rehabilitation, as well as one of the important impairment. HIE typically shows global deterioration of brain function with relative preservation of brain stem reflexes, and topographic pattern of damage; the CA1 hippocampal cells, cerebellar Purkinje cells, neocortical neurons in layers 3, 5, 6 and basal ganglia. The characteristics of patho-mechanism including persistent vegetative state, seizure, autonomic dysfunction and secondary Parkinsonism are causative factors of several complications. Ma nagement of these complications sometimes curative, but more often re-adaptive and palliative. Understanding and proper rehabilitation of complications will be one of the most important therapeutic strategies for pa tients with HIE. (Brain & NeuroRehabilitation 2014; 7: 10-15)Key Words: autonomic dysfunction, hypoxic-ischemic encephalopathy, persistent vegetative state, seizure, secondary parkinsonism

Long-term outcomes of hemispheric disconnection in pediatric patients with intractable epilepsy.

Background and PurposeHemispherectomy reportedly produces remarkable results in terms of seizure outcome and quality of life for medically intractable hemispheric epilepsy in children. We reviewed the neuroradiologic findings, pathologic findings, epilepsy characteristics, and clinical long-term outcomes in pediatric patients following a hemispheric disconnection.MethodsWe retrospectively studied 12 children (8 males) who underwent a hemispherectomy at Asan Medical Center between 1997 and 2005. Clinical, EEG, neuroradiological, and surgical data were collected. Long-term outcomes for seizure, motor functions, and cognitive functions were evaluated at a mean follow-up of 12.7 years (range, 7.6-16.2 years) after surgery.ResultsThe mean age at epilepsy onset was 3.0 years (range, 0-7.6 years). The following epilepsy syndromes were identified in our cohort: focal symptomatic epilepsy (n=8), West syndrome (n=3), and Rasmussen's syndrome (n=1). Postoperative histopathology of our study patients revealed malformation of cortical development (n=7), encephalomalacia as a sequela of infarction or trauma (n=3), Sturge-Weber syndrome (n=1), and Rasmussen's encephalitis (n=1). The mean age at surgery was 6.5 years (range, 0.8-12.3 years). Anatomical or functional hemispherectomy was performed in 8 patients, and hemispherotomy was performed in 4 patients. Eight of our 12 children (66.7%) were seizure-free, but 3 patients with perioperative complications showed persistent seizure. Although all patients had preoperative hemiparesis and developmental delay, none had additional motor or cognitive deficits after surgery, and most achieved independent walking and improvement in daily activities.ConclusionsThe long-term clinical outcomes of hemispherectomy in children with intractable hemispheric epilepsy are good when careful patient selection and skilled surgical approaches are applied.

Hypothalamic hamartoma: Is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis

Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two-step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans.

Outcome prediction of initial lamotrigine monotherapy in adult patients with newly diagnosed localization related epilepsies

To develop and test model to predict outcome of treatment with initial lamotrigine monotherapy in adult patients with newly diagnosed localization - related epilepsy, using data available at the time of diagnosis. Prospective longitudinal study included consecutive series of adult patients with newly diagnosed localization - related epilepsy started of lamotrigine monotherapy. Logistic regression analysis using backward procedure was performed with treatment failure as the outcome variable. We evaluated both calibration and discrimination of the model. Internal validation of the model was performed with bootstrapping techniques. A total of 159 patients on lamotrigine monotherapy have been included in final analysis. Among them 78 (49.06%) patients had persistent seizures. Finally fitted multivariate model included: 1) age at therapy start, 2) presence of complex partial seizures, 3) aetiology of epilepsy and 4) interaction of age and epilepsy aetiology. Estimated odds ratio for seizure relapse in old patients with symptomatic epilepsy is lower than for the old patients with cryptogenic epilepsy, despite strong positive covariate effect of epilepsy aetiology. The model correctly classified 69.23% patients with seizure relapses and 81.48% of patients with seizure freedom, with estimated c - statistic of 0.80. Testing practical application we observed threefold increase or reduction of odds for the seizure relapse after model's positive or negative prediction respectively. Standard clinical data were modesty adequate to predict response to the initial trial of lamotrigine in adult patients with localization related epilepsy. Better markers of antiepileptic failure are required to guide optimal patient counselling and clinical decisions. Formal interaction analysis of variables improves outcome prediction and may be a key to correct interpretation of data.

Risk Factors for Apnea in Pediatric Patients Transported by Paramedics for Out-of-Hospital Seizure

Apnea is a known complication of pediatric seizures, but patient factors that predispose children are unclear. We seek to quantify the risk of apnea attributable to midazolam and identify additional risk factors for apnea in children transported by paramedics for out-of-hospital seizure. This is a 2-year retrospective study of pediatric patients transported by paramedics to 2 tertiary care centers. Patients were younger than 15 years and transported by paramedics to the pediatric emergency department (ED) for seizure. Patients with trauma and those with another pediatric ED diagnosis were excluded. Investigators abstracted charts for patient characteristics and predefined risk factors: developmental delay, treatment with antiepileptic medications, and seizure on pediatric ED arrival. Primary outcome was apnea defined as bag-mask ventilation or intubation for apnea by paramedics or by pediatric ED staff within 30 minutes of arrival. There were 1,584 patients who met inclusion criteria, with a median age of 2.3 years (Interquartile range 1.4 to 5.2 years). Paramedics treated 214 patients (13%) with midazolam. Seventy-one patients had apnea (4.5%): 44 patients were treated with midazolam and 27 patients were not treated with midazolam. After simultaneous evaluation of midazolam administration, age, fever, developmental delay, antiepileptic medication use, and seizure on pediatric ED arrival, 2 independent risk factors for apnea were identified: persistent seizure on arrival (odds ratio [OR]=15; 95% confidence interval [CI] 8 to 27) and administration of field midazolam (OR=4; 95% CI 2 to 7). We identified 2 risk factors for apnea in children transported for seizure: seizure on arrival to the pediatric ED and out-of-hospital administration of midazolam.

Long-term seizure outcomes following resection of supratentorial cavernous malformations

ObjectiveSymptomatic supratentorial cavernous malformations may present with seizure, headache, neurological deficit, or a combination thereof. Factors that contribute to treatment algorithms commonly include patient age, lesion size and location, lesion multiplicity, hemorrhage history, and the ability to control seizure activity with medication. A better appreciation of the impact of patient and lesion characteristics on post-operative seizure control may provide insight into management strategies. To determine long-term seizure outcomes following surgical resection of supratentorial cavernous malformations, the predictive value of characteristics including seizure duration and number, presence of generalized seizures, and lesion multiplicity and size on seizure control rate was evaluated. MethodsWe performed a single institution retrospective review of consecutive patients with supratentorial cavernous malformations presenting with at least one seizure between 1995 and 2008. Univariate and multivariate analyses were used to determine the influence of patient and lesion characteristics on postoperative seizure control. ResultsFifty-six patients met inclusion criteria. Mean follow-up duration was 87.9 months. At last follow-up there were 46 patients (82.1%) that were free from impairing seizures (Engel Class 1). Ten patients (17.9%) were classified as Engel Class 2–4. Univariate analysis demonstrated that only the presence of multiple cavernomas was associated with worse post-operative seizure outcome (p=0.006). Multivariate analysis demonstrated that multiple cavernomas remained a significant predictor for development of worse seizure outcome controlling for number and duration of seizures prior to operation, presence of generalized tonic-clonic seizures, and size (odds ratio, 0.17; 95% confidence interval, 0.03, 0.99). ConclusionResection of supratentorial cavernomas is associated with a high rate of postoperative seizure freedom. The presence of multiple cavernomas is predictive of seizure persistence following surgery.

Drug screening in Scn1a zebrafish mutant identifies clemizole as a potential Dravet syndrome treatment

Dravet syndrome (DS) is a catastrophic pediatric epilepsy with severe intellectual disability, impaired social development and persistent drug-resistant seizures. One of its primary monogenic causes are mutations in Nav1.1 (SCN1A), a voltage-gated sodium channel. Here we characterise zebrafish Nav1.1 (scn1Lab) mutants originally identified in a chemical mutagenesis screen. Mutants exhibit spontaneous abnormal electrographic activity, hyperactivity and convulsive behaviors. Although scn1Lab expression is reduced, microarray analysis is remarkable for the small fraction of differentially expressed genes (~3%) and lack of compensatory expression changes in other scn subunits. Ketogenic diet, diazepam, valproate, potassium bromide and stiripentol attenuate mutant seizure activity; seven other antiepileptic drugs have no effect. A phenotype-based screen of 320 compounds identifies a US Food and Drug Administration-approved compound (clemizole) that inhibits convulsive behaviors and electrographic seizures. This approach represents a new direction in modeling pediatric epilepsy and could be used to identify novel therapeutics for any monogenic epilepsy disorder.

Disparities in access to specialized epilepsy care

To examine the impact of individual and community characteristics on access to specialized epilepsy care. This retrospective cross-sectional study analyzed data from the California State Inpatient Sample, the State Ambulatory Surgery Database, and the State Emergency Department Database, that were linked with the 2009 Area Resource File and the location of the National Association of Epilepsy Center's epilepsy centers. The receipt of video-EEG monitoring was measured and used to indicate access to specialized epilepsy care in subjects with persistent seizures, identified as those who had frequent seizure-related hospital admissions and/or ER visits. A hierarchical logistic regression model was employed to assess barriers to high quality care at both individual and contextual levels. Among 115,632 persons with persistent seizures, individuals who routinely received care in an area where epilepsy centers were located were more likely to have access to specialized epilepsy care (OR: 1.81, 95% CI: 1.20, 2.72). Interestingly, the availability of epilepsy centers did not influence access to specialized epilepsy care in people who had private insurance. In contrast, uninsured individuals and those with public insurance programs including Medicaid and Medicare had significant gaps in access to specialized epilepsy care. Other individual characteristics such as age, race/ethnicity, and the presence of comorbid conditions were also associated with disparities in access to specialized care in PWE. Both individual and community characteristics play substantial roles in access to high quality epilepsy care. Policy interventions that incorporate strategies to address disparities at both levels are necessary to improve access to specialized care for PWE.