Effect of late-onset epilepsy on cognitive functioning in patients with small vessel disease.

RATIONALE: Late-onset epilepsy (LOE) often has underlying cerebrovascular cause and has been associated with neurocognitive deficits and dementia. Nevertheless, the interplay between these factors has not been studied thus far. Hence, we conducted a retrospective cross-sectional study aimed to explore how unprovoked epileptic seizures along with vascular-related factors contribute to neurocognitive impairments in patients with cerebral small vessel disease. METHODS: Twenty-seven patients with LOE aged > 60 years with concomitant cerebral small vessel disease (cSVD) and a matched group of cSVD without epilepsy were cognitively assessed. Demographic, clinical, and vascular information were obtained and vascular burden score was calculated for each patient. Multiple linear regression models were used to explore the relationship between epilepsy and cognitive measures adjusting for demographic and vascular risk factors. RESULTS: Compared with cSVD, cSVD-LOE group showed a poorer performance on verbal memory measures, visuomotor tracking and speed processing and phonetic fluency. In the multiple regression analysis, the presence of epilepsy was found to be the major predictor for verbal memory dysfunction, specifically in verbal short recall (p = 0.008) and verbal learning (p < 0.001). No interactions between vascular burden and epilepsy were found. CONCLUSION: Patients who had cSVD with concurrent LOE showed poorer performance on memory function compared with patients with cSVD without epilepsy, and they showed a different cognitive profile from that typically manifested by patients with cSVD. The presence of epilepsy, but not seizure localization nor vascular burden, was the major contributor to the decrease in verbal memory.

Efficacy, retention, and safety of brivaracetam in adult patients with genetic generalized epilepsy.

OBJECTIVE: The aim of this study was to evaluate the efficacy, tolerability, and retention of brivaracetam (BRV) in genetic generalized epilepsy (GGE) in real-life practice. METHODS: This is a retrospective cohort study of adult patients with GGE in whom BRV was started between 2016 and 2018, completing a follow-up period of ≥6 months. Clinical and electroencephalogram (EEG) characteristics were analyzed at baseline and at follow-up as outcome measures. RESULTS: Brivaracetam was started in 37 patients (mean age: 29.9 ±â€¯12.3 years; 73% women). Juvenile myoclonic epilepsy was the most common syndrome (43.2%). The primary indications for starting BRV were lack of efficacy (51.4%) and adverse events (AEs) (27%) of other antiepileptic drugs (AEDs). In total, 32.4% of patients received BRV monotherapy. Retention rate at 6 months was 81.1%; 83.8% of patients were considered responders, and 62.2% achieved seizure freedom. The primary reasons for withdrawal were treatment-emergent adverse events (TEAEs, 57.1%) and lack of efficacy (42.9%). The higher number of prior AED use was a risk factor for a lack of response [median = 4 (interquartile range (IQR): 3-4) vs 2 (IQR: 1-3); p < 0.05]. Patients with a previous response to valproic acid tended to have a higher response rate to BRV (86.7% vs 50%, p = 0.169). Eighty-three point eight percent (83.8%) of previous levetiracetam (LEV) responders also showed a good response to BRV. In terms of patients who presented LEV-related AEs, AE resolution was observed in 79.8%, particularly with regard to psychiatric AEs. Follow-up EEGs were compared with baseline EEGs in 25 patients (67.6%) during follow-up. Most patients showed a reduction (52%) or no change (36%) in interictal epileptiform discharge (IED) frequency. SIGNIFICANCE: Brivaracetam shows good responder and retention rates in GGE and is generally well tolerated. It is an appropriate alternative treatment for GGE, especially in refractory epilepsy and when other AEDs are not tolerated.

Vascular risk factors as independent predictors of neurocognitive impairments in patients with late-onset epilepsy who have small-vessel disease.

RATIONALE: Late-onset epilepsy is often accompanied by underlying cerebrovascular disease and has been associated with neurocognitive deficits even dementia, but the interrelation between them remains unknown. In this study, we aimed to explore the contribution of vascular-related and epilepsy-related factors on neurocognitive outcomes in a sample of late-onset epilepsy with history of cerebral small vessel disease. METHODS: In this retrospective cross-sectional study, a comprehensive neurocognitive assessment was performed in 25 patients aged >60 years with one or more unprovoked seizures and history of small-vessel disease. Raw scores of cognitive tests were transformed in T-scores and were grouped in 6 cognitive domains. Regression models were performed to explore the contribution of vascular risk factors (diabetes mellitus, arterial hypertension, dyslipidemia, and smoking habit) and epilepsy-related factors (drug-resistance, number of antiepileptic drugs, age at epilepsy onset, and epileptic focus localization). RESULTS: Diabetes (p = 0.03) and smoking habit (p = 0.05) were the best independent factors to predict attention performance; diabetes also predicted visual memory function (p = 0.02); gender was related to verbal memory performance (p = 0.04) and speed processing (p = 0.02). Age at onset predicted that executive function (p = 0.05); age (p = 0.01) and gender (p = 0.03) were the major contributors to language performance. Epilepsy-related variables did not predict any cognitive outcomes. CONCLUSIONS: Vascular risk factors and sociodemographic characteristics were the best predictors of cognitive outcomes in a sample of late-onset epilepsy with cerebral small-vessel disease. Epilepsy did not show influence on cognitive function. Longitudinal studies are necessary to clarify the relationship between vascular risk factors and epilepsy on progression of cognitive deterioration in patients with late-onset epilepsy. This article is part of the Special Issue "Seizures & Stroke".

Usefulness of brain perfusion CT in focal-onset status epilepticus.

OBJECTIVE: To evaluate the perfusion computed tomography (PCT) patterns in patients with status epilepticus (SE). METHODS: We included consecutive SE patients, diagnosed by ictal encephalography (EEG) findings and clinical semiology, who prospectively underwent a dedicated PCT study of SE in the ictal phase. The perfusion maps were visually analyzed. For the quantitative assessment, regions of interest in areas where the maps suggested abnormalities were compared with the corresponding area in the unaffected contralateral cortex. Asymmetry indices between affected and unaffected hemispheres were calculated for the regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), time to peak (TTP), and mean transit time (MTT). Nine patients underwent a follow-up PCT after SE resolution, and the corresponding maps were compared to the ictal maps. In addition, we included a control group of 10 sex- and age-matched patients with SE mimics or postictal phenomena, who also underwent acute PCT during the study period. RESULTS: The study included 19 patients: mean age 69.47 ± (standard deviation) 15.9 years, 68.4% men. On visual analysis of parametric perfusion maps during the ictal phase, regional cortical hyperperfusion was depicted in 78.9% of patients. Quantitative analysis showed significantly increased rCBF (P = 0.002) and rCBV (P = 0.004) values and decreased TTP (P < 0.001) and MTT (P = 0.001) in cortical areas of the affected vs the unaffected side. The mean asymmetry index was 12.8 for rCBF, 13.7 for rCBV, -3.0 for TTP, and -3.7 for MMT. In the nine patients with a follow-up PCT, eight showed decreased intensity, rCBV (P = 0.035), and rCBF (P = 0.024) in the hyperperfusion areas. The sensitivity of hyperperfusion detection for the diagnosis of SE was 78.95%, specificity 90%, positive predictive value 93.75%, and negative predictive value 69.23%. Comparative quantitative analysis of asymmetry indices for rCBF, rCBV, and MTT between ictal PCT and control patients showed significant differences for all parameters (rCBF P = 0.001; rCBV P = 0.002; TTP P = 0.001; and MTT P = 0.001). SIGNIFICANCE: Visual and quantitative analysis of perfusion maps detects regional hyperperfusion in SE patients with good diagnostic capability. Perfusion was increased in PCT maps of the affected cerebral hemisphere as compared to the contralateral region during the ictal phase. PCT may provide valuable diagnostic information in patients with SE and complement the diagnostic value of EEG.

Accidental injuries in patients with generalized tonic-clonic seizures. A multicenter, observational, cross-sectional study (QUIN-GTC study).

PURPOSE: Patients with epilepsy have a higher risk of accidental injuries. The aim of this study was to determine the incidence of accidental injuries and quality of life in patients with epilepsy and generalized tonic-clonic seizures and their association with patient-related factors. METHODS: This is an observational, cross-sectional, multicenter study of patients with epilepsy and primary generalized tonic-clonic seizures and/or focal to bilateral tonic-clonic seizures in the routine clinical practice of epilepsy clinics. In a single visit, demographic and clinical data and information on the type and severity of injuries were collected, and patients' quality of life was evaluated with the QOLIE-10 questionnaire. RESULTS: In total, 406 patients with a median age of 41.1 years (range: 13-87) were included; 47.5% were women. Age at onset of tonic-clonic seizures was 25.4 (range: 0-83) years. Epileptic seizures were primary tonic-clonic (67.2%), focal to bilateral tonic-clonic (32.8%), focal with impairment of awareness (23.6%), focal without impairment of awareness (13.5%), absences (14.8%), and myoclonic (9.6%). Etiology was symptomatic or with unknown etiology focal (42.9%), genetic generalized (36.9%), symptomatic or with unknown etiology generalized (18.0%), and others (2.2%). The number of generalized tonic-clonic seizures in the last 12 months was as follows: 1 (41.9%), 2-5 (42.4%), and >5 (15.8%). Antiepileptic treatment at the time of the visit was monotherapy in 44.1% of the patients. The most commonly used drugs were levetiracetam (45.1%), valproate (20.7%), lamotrigine (20.0%), and perampanel (18.7%). In total, 59.6% of the patients had experienced at least one accidental injury associated with tonic-clonic seizures in the last 12 months, the most common being head injuries (35.5%), dental injuries (4.9%), burns (4.9%), and fractures (3.9%). A total of 25.1% had suffered at least one serious injury. The multiple logistic regression model showed that the factors associated with suffering an injury were the following: etiology (symptomatic or with unknown etiology focal and genetic generalized vs. symptomatic or with unknown etiology generalized, p = 0.0008 and p = 0.0077, respectively), number of seizures in the last year (2-5 vs. 1, p = 0.0115; >5 vs. 1, p = 0.0004), and psychiatric comorbidities (p = 0.0151). Patients with injuries had a worse quality of life than patients without injuries, according to the overall QOLIE-10 score (p = 0.0003). CONCLUSIONS: More than half of the patients had accidental injuries related with seizures. Symptomatic or with unknown etiology focal epilepsy and genetic generalized epilepsy, >1 seizure in the last year, and concomitant psychiatric disease are the risk factors associated with accidental injuries in patients with tonic-clonic seizures, with the consequent worsening of quality of life.

Etiology, seizure type, and prognosis of epileptic seizures in the emergency department.

Epileptic seizures are a common reason for emergency department (ED) admittance. We aimed to describe the etiological distribution of epileptic seizures and the relationships between etiology and semiology in patients admitted to the emergency room, and to identify early prognostic factors for recurrence and mortality. METHODS: A retrospective observational study was conducted in adult patients consecutively attended in the emergency room with epileptic seizures over a 2-year period. We recorded data on the etiological and syndromic classification of the seizure, and on recurrence and mortality at 1 year of follow-up. RESULTS: In total, 289 patients were included. Mean age was 55.9 (±21.9 years). There were 38.6% with a previous diagnosis of epilepsy and 49.8% with new-onset seizures. Among structural epilepsies, a vascular etiology was the most common overall (28.3%) but particularly in elderly (>65 years) patients (50.9%), followed by brain tumors (15.5%). In both etiologies, most patients presented with nonconvulsive seizures. Seizure recurrence during follow-up was reported in 37.1% and was most common in patients with symptomatic remote seizures (50 patients, 41%). Brain tumors (odds ratio (OR): 5.1, confidence interval (CI): 1.7-11.8; p < 0.01), younger age (OR: 0.9, CI: 0.97-0.99; p < 0.05), and a previous diagnosis of epilepsy (OR: 3.5, CI: 1.9-6.3; p < 0.01) were independent predictors of recurrence. Overall mortality was 8.6%. Symptomatic epilepsy was an independent predictor of mortality (hazard ratio (HR): 6.3, CI 1.4-23.4; p < 0.05). CONCLUSIONS: The most common etiologies of seizures in patients admitted to the ED are seizures of unknown cause and vascular disorder-related seizures. Seizures are more likely to recur in younger patients with a tumor whereas symptomatic epilepsy is associated with a higher risk of death at a 1-year follow-up.

Cost of status epilepticus (SE): Effects of delayed treatment and SE duration.

BACKGROUND: The health expenditure related to status epilepticus (SE) is high because of lengthy hospitalization requirements and possible sequelae. We aimed to study the factors associated with this cost including the different timings of the treatment and SE duration. METHODS: We evaluated retrospectively all SE recorded in 2 hospitals. The factors studied included the mean cost of hospitalization, demographics, clinical data, duration of hospitalization, in-hospital/out-of-hospital debut, time from onset to treatment, duration of SE, and destination at discharge. RESULTS: Three hundred five patients were evaluated (December/2012-July/2017), 195 with out-of hospital and 110 with in-hospital debut. The cost of SE with out-of-hospital onset was significantly lower (6559€ vs 15,174€; p = 0.0001). In out-of-hospital cases, the factors independently related to expenditure were the level of consciousness (p < 0.001), presence of complications (p = 0.005), a potentially fatal etiology (p = 0.008), and duration of the episode (p = 0.003). Duration was significantly higher in patients discharged to a convalescence center (p = 0.006); this variable was significantly related to the time SE onset-arrival to hospital, and SE onset-administration of the treatment. In the in-hospital cases, cost was related to male sex (p = 0.002), the development of complications (p = 0.003), and the etiology (p = 0.016) but was not directly related to the SE duration or to the time onset-treatment. CONCLUSIONS: The duration of SE and the speed with which proper management is applied have a direct impact on the healthcare expenditure resulting from out-of-hospital SE. In contrast, the etiology and development of complications are the main factors responsible for expenditure related to in-hospital SE.

Psychosocial factors and antiepileptic drug use related to delayed diagnosis of refractory psychogenic nonepileptic seizures.

OBJECTIVE: We analyzed clinical and psychosocial factors in patients with refractory psychogenic nonepileptic seizures, seeking characteristics that could hasten diagnosis. BACKGROUND: Psychogenic nonepileptic seizures remain a diagnostic challenge. Prognosis is best if patients are treated within 2 years of symptom onset. Psychosocial factors have been shown to provide important information for differential diagnosis. METHODS: Over a year and 1132 consecutive patients, our hospital's Epilepsy Unit suspected 93 patients of having psychogenic nonepileptic seizures and confirmed refractory psychogenic nonepileptic seizures in 67. We referred these patients to our psychiatric consultation unit for detailed diagnostic interviews, and 53 of the patients followed through. Two months after the psychiatric evaluation we gave them a psychiatric intervention, explaining the diagnosis and treating their comorbidities. We also tracked the patients' use of antiepileptic drugs for 3 months, from just before the psychiatric evaluation until a month after they started the intervention. RESULTS: Women, patients with an inadequate primary support group, and patients who had tried many antiepileptic drugs were most likely to have their diagnosis of psychogenic nonepileptic seizures delayed by >2 years after onset. A stepwise logistic regression showed that the 2 best predictors of late diagnosis were lack of availability of a primary support group and patients trying many antiepileptic drugs. CONCLUSIONS: Clinicians evaluating patients with questionable seizures should raise their suspicion of psychogenic nonepileptic seizures especially in female patients with an insufficient primary support group and a history of taking multiple antiepileptic drugs.

Localisation value of ictal arterial spin-labelled sequences in partial seizures.

Perfusion-based magnetic resonance imaging (MRI) using pulsed arterial spin-labelled (ASL) sequences is becoming a more commonly used tool for the diagnosis of patients with focal epilepsy. We report a patient with post-traumatic epilepsy and cortical haemorrhage who had a complex partial seizure characterised mainly by ictal speech (verbalisation) during MRI acquisition. Ictal ASL showed focal hyperperfusion over the right temporal region which had resolved on follow-up MRI, two weeks later. Seizure semiology and interictal EEG suggested seizure origin in the non-dominant temporal lobe, which matched the increased ictal blood flow observed by ASL. The patient had language dominance in the left hemisphere, as observed by functional MRI. Our findings suggest that focal hyperperfusion, as observed by ASL, may have localising value in temporal epilepsies when performed in the ictal period.

Long-term retention rates of antiepileptic drugs used in acute seizures.

PURPOSE: A number of antiepileptic drugs (AEDs) are currently available for treating acute seizures. It is recommended to select the initial treatment option according to the type of epileptic syndrome and the patient's clinical characteristics, but little is known about the long-term retention rates of AEDs started in the emergency department. METHODS: We recruited patients admitted with seizures over a two-year period. All patients underwent early neurological assessment, EEG testing, and neuroimaging. The treatments received at baseline and at one year of follow-up were compared. RESULTS: In total, 225 patients were included. Overall, monotherapy with levetiracetam was the regimen most often used in patients with new-onset seizures, whereas other AEDs were mainly used in patients previously treated with other drugs. Lacosamide use was most likely associated with the presence of lesion related seizures in elderly patients, and carboxamides with focal onset seizures of unknown cause. The mean retention rate of the total of AED treatments was nearly 70%. The main cause leading to discontinuation was the development of intolerable adverse events. Levetiracetam use decreased as lacosamide use increased in the overall group of patients. CONCLUSION: Our study shows that there is a trend to use newer AEDs, particularly levetiracetam, as the first option in new-onset seizures in the emergency room. However, levetiracetam use significantly decreased over follow-up, mainly because of the development of adverse events. The use of other, better-tolerated AEDs, such lacosamide predominated in elderly patients and patients with lesion related seizures, or carboxamides in epilepsies of unknown etiology.

Anger Assessment in Patients Treated With Brivaracetam.

OBJECTIVES: To assess state and trait anger, adjusted by epilepsy type, seizure control, anxiety-depression status and quality of life, in patients treated with brivaracetam (BRV) from an open study. METHODS: We evaluated prospectively consecutive patients with partial onset seizures in an open-label study. Patients had 5 years or longer of epilepsy and were taking between 1 and 3 antiepileptic drugs. They were treated with BRV and compared with a control group selected from outpatients attending our epilepsy unit who met the following criteria: age ≥16 years and diagnosis of epilepsy with focal-onset seizures at least 1 year before inclusion in the study. The following tests were assessed: State-Trait Anger with the Expression Inventory-2, Hospital Anxiety and Depression Scale, and Quality of Life in Epilepsy Inventory. RESULTS: We recruited 39 patients, 17 treated with BRV and 22 with other drugs, including 13 with levetiracetam (LEV). Mean age was 47.3 years, 43.6% were men. Symptomatic cases, 66% and 52% temporal lobe epilepsy. Antiepileptic drug polytherapy was present in 82.1% of the cases (100% BRV vs 68.2% control group). Demographic and clinical characteristics, as well as Quality of Life in Epilepsy Inventory and Hospital Anxiety and Depression Scale scores were similar in both groups. When compared with the subgroup of LEV groups did not differ significantly on their Hospital Anxiety and Depression Scale scores. CONCLUSIONS: This small, open study suggests that BRV increases anger measures less than LEV in epilepsy patients. However, larger, blinded control studies are required to establish whether this apparent difference can be confirmed.

A novel EPM2A mutation yields a slow progression form of Lafora disease.

Lafora disease (LD, OMIM 254780) is a rare disorder characterized by epilepsy and neurodegeneration leading patients to a vegetative state and death, usually within the first decade from the onset of the first symptoms. In the vast majority of cases LD is related to mutations in either the EPM2A gene (encoding the glucan phosphatase laforin) or the EPM2B gene (encoding the E3-ubiquitin ligase malin). In this work, we characterize the mutations present in the EPM2A gene in a patient displaying a slow progression form of the disease. The patient is compound heterozygous with Y112X and N163D mutations in the corresponding alleles. In primary fibroblasts obtained from the patient, we analyzed the expression of the mutated alleles by quantitative real time PCR and found slightly lower levels of expression of the EPM2A gene respect to control cells. However, by Western blotting we were unable to detect endogenous levels of the protein in crude extracts from patient fibroblasts. The Y112X mutation would render a truncated protein lacking the phosphatase domain and likely degraded. Since minute amounts of laforin-N163D might still play a role in cell physiology, we analyzed the biochemical characteristics of the N163D mutation. We found that recombinant laforin N163D protein was as stable as wild type and exhibited near wild type phosphatase activity towards biologically relevant substrates. On the contrary, it showed a severe impairment in the interaction profile with previously identified laforin binding partners. These results lead us to conclude that the slow progression of the disease present in this patient could be either due to the specific biochemical properties of laforin N163D or to the presence of alternative genetic modifying factors separate from pathogenicity.

Effect of adjunctive perampanel on the quality of sleep and daytime somnolence in patients with epilepsy.

This prospective uncontrolled study evaluated the effect of low-dose adjunctive perampanel therapy (4 mg/day for 3 months) on the sleep-wake cycle and daytime somnolence in adult patients (n = 10) with focal seizures. A > 50% reduction in the number of seizures was reported in 80% of the study patients; treatment had no significant effect on any sleep parameters as evident by the Maintenance of Wakefulness Test, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale scores. Two patients reported dizziness with treatment. In conclusion, low-dose perampanel may improve seizure control without affecting the sleep characteristics or daytime somnolence in patients with epilepsy.

Levetiracetam and Valproate Retention Rate in Juvenile Myoclonic Epilepsy.

BACKGROUND: Valproic acid (VPA) is an effective treatment in juvenile myoclonic epilepsy (JME), but concerns on its use during pregnancy are remarkable. Levetiracetam (LEV) is approved as second-line therapy, and used as monotherapy in clinical practice. Our objective was to analyze the outcome of LEV and VPA in JME. MATERIALS AND METHODS: We analyzed patients with JME attending our epilepsy unit between 2010 and 2014, including all patients treated with LEV and/or VPA at some point of the disease course. The primary end point was drug retention rate in monotherapy after the final analysis. RESULTS: We identified 58 patients (62% women). All had myoclonic seizures, 86% had generalized tonic-clonic seizures (GTCS) before the diagnosis, and 9% also had absences. All had generalized spike and wave on the interictal electroencephalogram, and 86% of them also had generalized polyspike and wave discharges. In total, LEV monotherapy was maintained in 15 (65%) of 23 patients, and VPA was maintained in 37 (74%) of 50 patients (P = 0.062). In women younger than 35 years, LEV had a similar retention rate with VPA (P = 0.939). More VPA patients achieved seizure freedom during follow-up (P < 0.01), whereas LEV patients showed a trend toward higher myoclonic freedom (0.085). CONCLUSIONS: Levetiracetam showed lower retention rate than VPA, primarily due to poorer seizure control during long-term follow-up. More LEV patients achieved myoclonic seizure freedom than VPA patients. In women younger than 35 years, LEV and VPA had comparable retention rate; therefore, LEV could be a good option for women with JME with prominent myoclonic seizures.

Epilepsia partialis continua: aetiology, semiology and prognosis in a Spanish adult cohort.

To describe the semiological features in patients suffering with Epilepsia Partialis Continua (EPC), also referred as Kozhevnikov syndrome and their relationship with aetiology, duration, and prognosis, as well as recurrence during follow-up. We analysed consecutive EPC patients diagnosed and followed in our centre over a seven-and-a half year period. We collected demographic and clinical data, along with neuroimaging and EEG recordings. All patients were followed for more than six months. Patients were categorised with single body area or multiple body area involvement according to the body parts affected. Recurrence was defined as a second EPC episode after one week. We collected data from 27 adult patients; 70.4% were men, the mean age was 65.2 years old (range: 17-89 years), and 40.7% had previous epilepsy. EPC causes were structural in 85.1% (stroke being the most frequent; 44.4%), metabolic in 11.1%, and of unknown origin in 7.4%. A cortical lesion on neuroimaging was shown in 70.4%. Involvement of multiple body areas was reported in 55.6% of patients. The optimal cut-off period to predict death was nine days (with a sensitivity of 62.5% and specificity of 75%; p=0.039), and this group of patients exhibited more multiple body area involvement (88.9% vs 38.9%; p=0.04). During follow-up, patients with cortical lesions had more EPC relapses (p=0.037). The most frequent aetiology of EPC in our patients was stroke. Multiple body area involvement and duration were associated with mortality. Patients with cortical lesions had more EPC relapses during follow-up.

Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report.

UNLABELLED: Proper treatment of hypoxic myoclonic status is not clearly determined. Induced hypothermia is improving prognosis and a more aggressive treatment might be beneficial in some patients. Among the new options of antiepileptic drugs, perampanel (PER) is a drug with a novel mechanism, and it might be a promising drug for myoclonic status or as an antimyoclonic drug. We describe the use of PER in one patient with hypoxic super-refractory myoclonic status. DESCRIPTION: A 51-year-old patient presented after an out-of-hospital cardiac arrest due to an acute myocardial infarction. The patient was diagnosed with clinical and electrical (EEG) myoclonic status at the rewarming phase. Several treatments were used, starting with clonazepam, valproate, sedation (midazolam, propofol), and subsequently barbiturate-induced coma with persistent myoclonic status. Finally, we decided to try PER (dose: 6-8 mg) through a nasogastric tube, resulting in a marked improvement of EEG activity and myoclonus decrease. The patient had a progressive clinical improvement, with a CPC (Cerebral Performance Category) scale score of 1. CONCLUSION: This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

Causes of CNS inflammation and potential targets for anticonvulsants.

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1ß, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1ß, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

3 TESLA MR imaging in adults with focal onset epilepsy.

OBJECTIVE: The finding of cerebral epileptogenic lesions in magnetic resonance (MR) has demonstrated to be a relevant prognostic factor for potential surgical candidates. In a series of consecutive adults with focal onset epilepsy, we investigated the yield of 3T MR imaging for detecting epileptogenic cerebral lesions. MATERIALS AND METHODS: We prospectively recruited 161 adult patients with a diagnosis of focal epilepsy, all of whom underwent standardized MR imaging study performed with a 3T magnet. RESULTS: Lesion-related epilepsy was observed in 48% of patients, and 12% of cryptogenic patients showed subtle or non-specific lesions related to the epileptogenic source. The most common findings were focal cortical dysplasia and vascular lesions, followed by mesial temporal sclerosis, tumors, and scars from previous cerebral injuries. Patients older than 72 years were more likely to have vascular epilepsy. CONCLUSIONS: Diagnostic assessment using a standardized 3T MR imaging protocol for focal-onset epilepsy detects lesions in nearly half the patients. Our results indicate that elders with focal epilepsy should be searched for vascular lesions.

Usefulness of intravenous lacosamide in status epilepticus.

Lacosamide (LCM) is a treatment option for status epilepticus (SE) described in several series. We therefore proposed to describe its use in status epilepticus patients in our hospital. All patients admitted to our hospital for SE from September 2010 to April 2012 were evaluated. We collected related variables including the type of SE, etiology, antiepileptic drugs (AEDs) used, loading dose of AEDs, cessation of SE after AEDs, ICU admission and mortality. In those patients receiving LCM, we reviewed the infusion rate and time to response. We compared patients receiving LCM with patients in whom it was not used. This was a retrospective and uncontrolled study. A total of 92 patients were included; 67.7 % of SE patients who received LCM responded to treatment. The vast majority of the patients presented non-convulsive and motor focal SE. When we selected patients to receive four or more AEDs, the LCM efficacy was 55.6 %, a very similar result compared to when it was not used. Subsequently, we analyzed the sample regarding the AED administered as the second or third line of treatment, and the responder rate was significantly higher when LCM was used (84.6 vs. 47.8 %, p 0.041). After an adjusted regression analysis, the use of LCM was independently associated with cessation of SE. The total percentage of undesirable effects was very low (12 %), and they were all mild. No relationship was found between a specific etiology and better response. LCM is a useful drug that represents an alternative in the treatment of non-convulsive or focal motor SE. Its efficacy might be more important when it is administered as a second or third option after benzodiazepines. A randomized trial is required to confirm these results.