Atypical duration of epileptic and psychogenic nonepileptic events.

OBJECTIVES: We aimed to estimate the frequency of epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) with atypical duration in our epilepsy monitoring unit (EMU), in order to raise awareness of atypical durations of both types of events. MATERIALS & METHODS: We retrospectively reviewed all consecutive video-electroencephalogram (vEEG) recordings in our medical center's EMU from January 2013 to December 2017 and identified patients with seizures with atypical duration. Short PNES were defined as those lasting fewer than 2 min and long ES as those lasting for more than 5 min. RESULTS: The files of 830 adult (age >16 years) patients were reviewed, of whom 26 patients (3.1%, mean age: 33.3 ±â€¯9.8 years, 12 females) were diagnosed as having an unusual seizure duration. Among 432 patients with ES during monitoring, fourteen patients [3.2% (95% confidence interval (CI): 1.5%-5.0%), mean age: 33.0 ±â€¯12.2, 5 females [had long ES durations (exceeding 5 min). In 64% of patients with long ES, the events were provoked by antiepileptic drug (AED) withdrawal during vEEG, 62% had focal lesion on brain imaging, and 64% had a frontotemporal or a temporal seizure focus. Among 223 patients diagnosed with PNES, 12 patients [5.4% (95% CI: 2.2%-8.6%), mean age: 33.6 ±â€¯6.6, 7 females] had short PNES durations (less than 2 min) and demonstrated motor (9/12, 75%), altered responsiveness (6/12, 50%), and vocalization (5/12, 42%) as the most prominent clinical features. CONCLUSIONS: The data from our case files highlight two main considerations in the diagnosis of paroxysmal events: prolonged event can be due to ES, while short events can be psychogenic.

Use of antiepileptic drugs during pregnancy and lactation: Type of information provided by searching Google.

Surveys among women with epilepsy (WWE) show that they receive their essential pregnancy-related information from many sources, including the internet. Our aim was to assess the types of websites provided by searching Google for the use of four antiepileptic drugs (AEDs) during pregnancy and lactation. The search was performed on 40 computers used by health-care professionals, on 40 computers used by nonhealth-care professionals, and on 5 computers used by WWE in Israel and on 8 computers used by nonhealth-care professionals in the U.S. On each computer, a Google search was conducted for term combinations that included one AED name ("carbamazepine","valproic acid", "lamotrigine", "levetiracetam", or "Keppra") and "Pregnancy", "Lactation", or "Breastfeeding". The top three and top ten websites retrieved in every search were mapped (a total of 45 and 150 websites, respectively, from each computer). Across all searches in English, on both U.S. and Israeli computers, the majority of websites listed among the first three and first ten results were those of independent health portals. The representation of the Epilepsy Foundation website was 10% or less, and only a few results were obtained from the NIH's general public-oriented MedlinePlus. In Hebrew, results included almost exclusively Israeli or Hebrew-translated websites. As in English, results from public-oriented, professionally-written websites in Hebrew accounted for less than 50% of entries. Overall, the availability of readable and high-quality information on AEDs used by pregnant and breastfeeding women is limited. Guiding patients towards accurate web resources can help them navigate among the huge amount of available online information.

Vocational factors which predict seizure prognosis in young adults during military service.

BACKGROUND: The vocational parameters regarding epilepsy are not well established. Our aim was to assess the risk of seizures as a function of occupational stress and disease severity in military recruits of the IDF (Israel Defense Force) and to examine the effect of new classification criteria (used between the late nineties and early two thousands) in comparison with that of previous criteria (used during the mid-eighties to mid-nineties). METHODS: The medical records of over 150,000 18-year-old men recruited to the IDF between the mid-nineties and the mid-two thousands were used to assemble a cohort, which was followed for a period of 36months. The severity of the disease was determined according to 3 categories, according to the medical history. The recruits were subdivided according to their occupational categories to Combat Units (CUs), Maintenance Units (MUs), and Administrative Units (AUs). We compared the incidence rates of the different groups with the findings from a previous follow-up. RESULTS: The annual incidence rates during 36months of follow-up were 0.026%, 4.7%, and 8.8%, in categories 1 to 3, respectively. The relative risk of seizure incidence in CU and MU was lower than in AU (0.42 and 0.81, p<0.0001). Similar findings were found in other disease categories. CONCLUSIONS: Job assignment to CU (less convenient conditions like sleep deprivation and strenuous physical activity) did not increase the incidence of seizures. It was found that EEG examination is an important criterion in the vocational evaluation of subjects that have had one or more seizures. This study supports the establishment of vocational criteria and recommends the integration of people diagnosed with epilepsy in most occupations.

Asystole in the epilepsy unit.

BACKGROUND: Early identification of cardiac asystole as a reason for syncope is of uttermost significance, as insertion of a cardiac pacemaker can save the patient's life and prevent severe injury. The aim of this work was to emphasize the subtle and unusual presentations of asystole in patients evaluated in epilepsy units. METHODS: We reviewed the clinical presentation, ECG and EEG data of a series of seven patients who were evaluated in four epilepsy units and were diagnosed with asystole. RESULTS: Three patients had unusual clinical manifestations of cardiac asystole, resembling epileptic seizures. Three patients had asystole induced by epileptic seizures and in one patient the diagnosis was not clear. All patients except one were implanted with a pacemaker and improved clinically. CONCLUSIONS: Seizure-induced asystole is a rare complication of epilepsy and asystole may clinically mimic epileptic seizures. A high level of suspicion and thorough prolonged cardiac and EEG monitoring are mandatory for reaching the right diagnosis. As the diagnosis is rare and difficult to reach, a flow chart to assist diagnosis is suggested.

Spatial and object-based attention modulates broadband high-frequency responses across the human visual cortical hierarchy.

One of the puzzling aspects in the visual attention literature is the discrepancy between electrophysiological and fMRI findings: whereas fMRI studies reveal strong attentional modulation in the earliest visual areas, single-unit and local field potential studies yielded mixed results. In addition, it is not clear to what extent spatial attention effects extend from early to high-order visual areas. Here we addressed these issues using electrocorticography recordings in epileptic patients. The patients performed a task that allowed simultaneous manipulation of both spatial and object-based attention. They were presented with composite stimuli, consisting of a small object (face or house) superimposed on a large one, and in separate blocks, were instructed to attend one of the objects. We found a consistent increase in broadband high-frequency (30-90 Hz) power, but not in visual evoked potentials, associated with spatial attention starting with V1/V2 and continuing throughout the visual hierarchy. The magnitude of the attentional modulation was correlated with the spatial selectivity of each electrode and its distance from the occipital pole. Interestingly, the latency of the attentional modulation showed a significant decrease along the visual hierarchy. In addition, electrodes placed over high-order visual areas (e.g., fusiform gyrus) showed both effects of spatial and object-based attention. Overall, our results help to reconcile previous observations of discrepancy between fMRI and electrophysiology. They also imply that spatial attention effects can be found both in early and high-order visual cortical areas, in parallel with their stimulus tuning properties.

Emergence of sensory patterns during sleep highlights differential dynamics of REM and non-REM sleep stages.

Despite the profound reduction in conscious awareness associated with sleep, sensory cortex remains highly active during the different sleep stages, exhibiting complex interactions between different cortical sites. The potential functional significance of such spatial patterns and how they change between different sleep stages is presently unknown. In this electrocorticography study of human patients, we examined this question by studying spatial patterns of activity (broadband gamma power) that emerge during sleep (sleep patterns) and comparing them to the functional organization of sensory cortex that is activated by naturalistic stimuli during the awake state. Our results show a high correlation (p < 10(-4), permutation test) between the sleep spatial patterns and the functional organization found during wakefulness. Examining how the sleep patterns changed through the night highlighted a stage-specific difference, whereby the repertoire of such patterns was significantly larger during rapid eye movement (REM) sleep compared with non-REM stages. These results reveal that intricate spatial patterns of sensory functional organization emerge in a stage-specific manner during sleep.

A widely distributed spectral signature of task-negative electrocorticography responses revealed during a visuomotor task in the human cortex.

While research of human cortical function has typically focused on task-related increases in neuronal activity, there is a growing interest in the complementary phenomenon-namely, task-induced reductions. Recent human BOLD fMRI studies have associated such reductions with a specific network termed the default mode network (DMN). However, detailed understanding of the spatiotemporal patterns of task-negative responses and particularly how they compare across different cortical networks is lacking. Here we examined this issue in a large-scale electrocorticography study in patients performing a demanding backward masking task. Our results uncovered rapid (<1 s) task-induced reductions in gamma power, often concomitant with power increase in alpha/beta bands. Importantly, these responses were found both in the DMN and sensory-motor networks. Comparing the task-negative responses across these different networks revealed similar spectral signatures and dynamics. We hypothesize that the task-negative responses may reflect a cortical switching mechanism whose role is to steer activity away from cortical networks, which are inappropriate for the task at hand.

Selectivity of audiovisual ECoG responses revealed under naturalistic stimuli in the human cortex.

A fundamental debate in the study of cortical sensory systems concerns the scale of functional selectivity in cortical networks. Brain imaging studies have repeatedly demonstrated functional selectivity in entire cortical areas and networks using predetermined stimuli. However, it is not clear to what extent these networks are heterogeneous, i.e., whether the selectivity profiles in subregions within each sensory network show significant dissimilarity. Here, we studied local functional selectivity in the human cortex using naturalistic movie clips shown to 12 patients implanted with intracranial electrocorticography electrodes (590 in total), providing extensive cortical coverage. We examined the similarity of response profiles (40- to 80-Hz gamma-power modulations) across electrodes using a novel data driven approach without assuming any predefined category. Our results show that the functional selectivity of each highly responsive electrode was different from that of all other electrodes across the sensory cortex. Thus most responsive electrodes showed an activation profile that was unique in each patient and was similar to that of only 0.3% (1-2) of all other electrodes across all patients. Functional similarity between electrodes was linked to anatomical proximity. While in most electrodes the source of selectivity was complex, a small subset showed the well-documented selectivity to faces and actions. Our results indicate that the human sensory cortex is organized as a mosaic of functionally unique subregions in which each site manifests its own special response profile.

Acquired oculomotor nerve paresis with cyclic spasms in a young woman, a rare subtype of neuromyotonia.

BACKGROUND: To report an unusual case of cyclic oculomotor nerve paresis and spasms, which developed 5 years following brain radiotherapy for cerebellar medulloblastoma. METHODS: Observational case report. RESULTS: The cyclic oculomotor nerve paresis and spasms resolved in our patient when treated with carbamazepine. However, because of severe photophobia and tearing, carbamazepine had to be discontinued leading to reappearance of the eye movement disorder. CONCLUSION: Cyclic oculomotor nerve paresis and spasms appear to be a delayed effect of radiotherapy and respond to carbamazepine therapy. It may be a rare form of ocular neuromyotonia.

Vagal nerve stimulation for refractory epilepsy: the surgical procedure and complications in 100 implantations by a single medical center.

In 1997, the US Food and Drug Administration approved the use of intermittent stimulation of the left vagal nerve as adjunctive therapy for seizure control. Vagal nerve stimulation (VNS) has since been considered a safe and effective treatment for medically intractable seizures. The objective of this study is to present our experience with the surgical procedure and outcomes after VNS insertion in the first 100 consecutive patients treated at the Tel-Aviv "Sourasky" Medical Center (TASMC). All patients who underwent VNS device implantation by the authors at TASMC between 2005 and 2011 were studied. The collected data included age at onset of epilepsy, seizure type, duration of epilepsy, age at VNS device implantation, seizure reduction, surgical complications, and adverse effects of VNS over time. Fifty-three males and 47 females, age 21.2 ± 11.1 years, underwent VNS implantation. Indications for surgery were medically refractory epilepsy. The most common seizure type was focal (55 patients, 55 %). Seizure duration until implantation was 14.4 ± 9 years. Mean follow-up time after device insertion was 24.5 ± 22 months. Complications were encountered in 12 patients. The most common complication was local infection (6 patients, 6 %). Six devices were removed-four due to infection and two due to loss of clinical effect. Currently, 63 patients remain in active long-term follow-up; of these, 35 patients have >50 % reduction in frequency of attacks.VNS is a well-tolerated and effective therapeutic alternative in the management of medically refractory epilepsy. The surgical procedure is safe and has a low complication rate.

Sensitivity and specificity of seizure-onset zone estimation by ictal magnetoencephalography.

PURPOSE: Ictal video-electroencephalography (EEG) is commonly used to establish ictal onset-zone location. Recently software development has enabled systematic studies of ictal magnetoencephalography (MEG). In this article, we evaluate the ability of ictal MEG signals to localize the seizure-onset zone. METHODS: Twenty-six patients underwent ictal MEG and epilepsy surgery. Prediction of seizure-onset zone by ictal and interictal MEG was retrospectively compared with ictal-onset area found by intracranial EEG in 12 patients. The specificity and sensitivity of the prediction were calculated at hemisphere-lobe (HL) and at hemisphere-lobe-surface (HLS) levels. KEY FINDINGS: The sensitivity of ictal MEG source localization was 0.958 on HL and 0.706 on HLS levels, and its specificity was 0.900 on HL and 0.731 on HLS levels. The interictal MEG dipole cluster, defined as >10 dipoles on one lobar surface, had sensitivity of 0.400 and specificity of 0.769. Ictal MEG was equally sensitive and specific on dorsolateral and nondorsolateral neocortical surfaces up to a depth of 4 cm from the scalp. SIGNIFICANCE: Sources of ictal-onset MEG signals and interictal dipole clusters are essentially equally specific in estimation of the ictal-onset zone on lobar surface resolution, but ictal MEG is more sensitive. On the lobe resolution, ictal MEG estimates ictal-onset zone with high sensitivity and specificity.

Antagonistic relationship between gamma power and visual evoked potentials revealed in human visual cortex.

Scalp electroencephalography and magnetoencephalography studies have revealed a rapid evoked potential "adaptation" where one visual stimulus suppresses the event-related potential (ERP) of the second stimulus. Here, we investigated a similar effect revealed in subdural intracranial recordings in humans. Our results show that the suppression of the subdural ERP is not associated with a reduction in the gamma frequency power, considered to reflect the underlying neural activity. Furthermore, the evoked potential suppression (EPS) phenomenon was not reflected in recognition behavior of the patients. Rather, the EPS was tightly linked to the level of gamma activity preceding the event, and this effect was independent of the interstimulus time interval. Analyzing other frequency bands failed to reveal a similar link. Our results thus show a consistent antagonism between subdural ERP and gamma power although both are considered markers for neural activity. We hypothesize that the ERP suppression is due to a desynchronization of neuronal firing resulting from recurrent neural activity in the vicinity of the freshly stimulated neurons and not an attenuation of the overall neural activity.

Spatio-temporal indications of sub-cortical involvement in leftward bias of spatial attention.

A leftward bias is well known in humans and animals, and commonly related to the right hemisphere dominance for spatial attention. Our previous fMRI study suggested that this bias is mediated by faster conduction from the right to left parietal cortices, than the reverse (Siman-Tov et al., 2007). However, the limited temporal resolution of fMRI and evidence on the critical involvement of sub-cortical regions in orienting of spatial attention suggested further investigation of the leftward bias using multi-scale measurement. In this simultaneous EEG-fMRI study, healthy participants were presented with face pictures in either the right or left visual fields while performing a central fixation task. Temporo-occipital event related potentials, time-locked to the stimulus onset, showed an association between faster conduction from the right to the left hemisphere and higher fMRI activation in the left pulvinar nucleus following left visual field stimulation. This combined-modal finding provides original evidence of the involvement of sub-cortical central attention-related regions in the leftward bias. This assertion was further strengthened by a DCM analysis designated at cortical (i.e., inferior parietal sulcus; IPS) and sub-cortical (pulvinar nucleus) attention-related nodes that revealed: 1. Stronger inter-hemispheric connections from the right to left than vice versa, already at the pulvinar level. 2. Stronger connections within the right than the left hemisphere, from the pulvinar to the IPS. This multi-level neural superiority can guide future efforts in alleviating attention deficits by focusing on improving network connectivity.

Epilepsy surgery in children compared to adults.

AIM: The purpose of this study was to compare the frequency of various surgical techniques and surgical outcome between pediatric and adult populations that underwent epilepsy surgery by the same team. METHODS: All patients who underwent epilepsy surgery at the Tel Aviv Medical Center between 1997 and 2006 and had been followed up for >2 years were eligible for this study. The majority (90%) of all epilepsy surgeries carried out in Israel were performed in this institution and by a single neurosurgeon. Only patients that underwent video-EEG monitoring as part of the presurgical evaluation were included in the study. RESULTS: A total of 186 patients (131 adults and 55 children) underwent epilepsy surgery in our institute during the study period, and follow-up was available for 177 patients (95%). While the adults underwent significantly more temporal lobe resections (51 vs. 20%, p < 0.0001), the children had significantly more extra-temporal non-lesional resections (18 vs. 1%, p < 0.0001) and hemispherectomies (5 vs. 1%, p = 0.002). Over one half (54%) of all the patients had a postoperative reduction in seizures of >90%, and 72% had a reduction of >50%, with no group difference in surgical success. Among the lesionectomies, the outcome was better for tumors, especially those in the temporal lobe. Only 1% of the patients had a long-term neurological deficit. CONCLUSIONS: Children comprised 30% of the epilepsy surgical cases during the study period. Children underwent more non-lesional resections and hemispherectomies, while adults underwent more temporal lobe resections. There was no age-related difference in surgical outcome.

Bilateral hippocampal lesion and a selective impairment of the ability for mental time travel.

Mental time travel allows individuals to mentally project themselves backwards and forwards in subjective time. This case report describes a young woman suddenly rendered amnesic as a result of bilateral hippocampal damage following an epileptic seizure and brain anoxia. Her neuropsychological profile was characterized by a high-average general level of cognitive functioning, selective deficit in episodic memory of past events and a significant difficulty to envisage her personal future. This case provides clinical support for the concept of mental time travel with its retrospective and prospective components and for the hippocampus being its critical neural substrate.

Spatial distribution and hemispheric asymmetry of electrically evoked experiential phenomena in the human brain.

OBJECTIVE: Experiential phenomena (EP), such as illusions and complex hallucinations, are vivid experiences created in one's mind. They can occur spontaneously as epileptic auras or can be elicited by electrical brain stimulation (EBS) in patients undergoing presurgical evaluation for drug-resistant epilepsy. Previous work suggests that EP arise from activation of different nodes within interconnected neural networks mainly in the temporal lobes. Yet, the anatomical extent of these neural networks has not been described and the question of lateralization of EP has not been fully addressed. To this end, an extended number of brain regions in which electrical stimulation elicited EP were studied to test whether there is a lateralization propensity to EP phenomena. METHODS: A total of 19 drug-resistant focal epilepsy patients who underwent EBS as part of invasive presurgical evaluation and who experienced EP during the stimulation were included. Spatial dispersion of visual and auditory illusions and complex hallucinations in each hemisphere was determined by calculation of Euclidean distances between electrodes and their centroid in common space, based on (x, y, z) Cartesian coordinates of electrode locations. RESULTS: In total, 5857 stimulation epochs were analyzed; 917 stimulations elicited responses, out of which 130 elicited EP. Complex visual hallucinations were found to be widely dispersed in the right hemisphere, while they were tightly clustered in the occipital lobe of the left hemisphere. Visual illusions were elicited mostly in the occipital lobes bilaterally. Auditory illusions and hallucinations were evoked symmetrically in the temporal lobes. CONCLUSIONS: These findings suggest that complex visual hallucinations arise from wider spread in the right compared to the left hemisphere, possibly mirroring the asymmetry in the white matter organization of the two hemispheres. These results offer some insights into lateralized differences in functional organization and connectivity that may be important for functional mapping and planning of surgical resections in patients with epilepsy.

Quality of life in seizure-free patients with epilepsy on monotherapy.

Epilepsy is a multifaceted chronic disorder which has diverse and complex effects on the well-being of the patient. Although it is evident that seizure type and frequency play a critical role in the quality of life (QOL) of patients with epilepsy, it is less clear what the major determinants are that influence QOL in seizure-free patients receiving monotherapy. The aim of this study was to evaluate demographic, clinical, and socioeconomic factors influencing the QOL of seizure-free patients receiving monotherapy. All participants were patients from four medical centers who had epilepsy, were on monotherapy, and had been seizure-free for at least 1 year. Responders completed three questionnaires on demographic and clinical information, QOL, and antiepileptic drug (AED) side effects during routine follow-up visits in the epilepsy clinics. We present the data of 103 patients: 59 females (57.3%), mean age 37.75+/-13.66 years. Treatment side effects and unemployment (p<0.0001, p=0.037, respectively) were significant predictors for poor overall QOL, whereas age, gender, education, family status, comorbidity, seizure type, age of seizure onset, and epilepsy duration did not significantly affect overall QOL. There was no significant difference in side effects and QOL between patients receiving older versus newer AEDs. Ninety-four (92.2%) patients reported experiencing at least one side effect of AEDs when queried about specific symptoms, while only 11 (10.7%) patients replied affirmatively when asked whether they experienced "any" side effects. The most common side effects involved the central nervous system. In conclusion, this study reveals that the most significant factor influencing the QOL in seizure-free patients on monotherapy is AED side effects. QOL is a crucial component in the clinical care of patients with epilepsy, and physicians should take the time to ask specific questions on side effects of AEDs.

Ketogenic diet treatment in adults with refractory epilepsy: a prospective pilot study.

PURPOSE: To assess the efficacy of ketogenic diet (KD) in adults with refractory epilepsy. METHODS: Eligible subjects were 18-45 years old with at least two monthly focal seizures (with or without secondary generalization) documented by 8 weeks' follow-up. Classic form of KD treatment (90% fat) was planned for 12 weeks: daily seizure diaries were kept and measurements of the urinary ketones were recorded. Blood studies were done monthly and resting energy expenditure (REE), substrate utilization; body composition and quality of life (QOL) were measured before and after intervention. RESULTS: Nine patients were enrolled (average age 28+/-6 years; seven women). Only two subjects concluded the study per protocol due to an early drop-out. The average length of KD treatment was 8+/-4 weeks (two patients completed 12 weeks of KD; feelings of hunger and lack of efficacy resulted in withdrawal of the rest). The two patients who concluded the study had a more than 50% reduction in the frequency of the seizures. The others experienced no improvement. Adherence to the KD protocol (100%) was documented by constant ketonuria and increased fat utilization as indicated by the change in respiratory quotient (p<0.031). The KD increased the cholesterol levels (mainly LDL; p=0.0001). CONCLUSIONS: In our experience with relatively small adult population, adherence to KD is difficult. In patients who had compliance over 3 weeks (6/8), KD does not seem to have a significant effect. Yet, the significant reduction in the two patients who concluded the study per protocol may indicate that some patients may benefit from this diet. Significant increase in LDL levels and the unlikable dietary changes are additional impediments to its implementation among adults with refractory epilepsy.

[Epilepsy in the elderly].

Elderly persons with epilepsy are expected to be an increasing larger group among patients with epilepsy in view of population aging and the higher onset of epilepsy in the elderly as compared to any other age group. Cerebrovascular disease is the most common cause of seizures in the elderly, and complex partial seizures (CPS) are the most common seizure type in this age group. CPS semiology is often different in the elderly compared to young adults, since strokes usually involve extratemporal regions. The absence of familiar clinical characteristics of seizures, such as aura and automatisms, can delay the correct diagnosis of epilepsy or Lead to misdiagnosis. As a result of age-related pharmacokinetic changes, the clearance of most old and new antiepileptic drugs (AEDs] is reduced by 20-40% in elderly persons compared to younger adults, and there may be a longer elimination half-life of certain AEDs. In addition to measurements of serum AED concentration, it is important to monitor clinical response, since age-related pharmacodynamic changes can alter the relationship between serum AED concentration and pharmacological effects. Newer AEDs have a lower potential for drug interactions and are better tolerated by the elderly compared to old generation AEDs. Monotherapy is the preferred therapeutic strategy for initial treatment of seizures due to fewer adverse events, decreased risk of drug interactions, improved adherence and lower treatment costs. Elderly patients with epilepsy are more likely to remain seizure-free on AED treatment than younger age groups. Elderly patients with refractory epilepsy and precise localization of the seizure focus can be appropriate surgical candidates, and a favorable prognosis is expected with curative surgical procedures.

Systemic thrombin inhibition ameliorates seizures in a mouse model of pilocarpine-induced status epilepticus.

Status epilepticus (SE) is a life-threatening condition characterized by ongoing seizure activity which can lead to severe brain damage and death if not treated properly. Recent work suggests that alterations in blood-brain barrier (BBB) function and subsequent cortical exposure to coagulation factors may initiate, promote, and/or sustain SE. This suggestion is based on the observation that the serine protease thrombin, which plays a fundamental role in the blood coagulation cascade, increases neural excitability through the activation of protease-activated receptor 1 (PAR1). However, it remains unclear whether systemic inhibition of thrombin asserts "anti-epileptic" effects in vivo. We here used the pilocarpine model of SE in adult 3-month-old male mice to address the question whether intraperitoneal injection of the thrombin inhibitor α-NAPAP (0.75 mg/kg) counters SE. Indeed, pharmacological inhibition of thrombin ameliorates the behavioral outcome of pilocarpine-induced SE. Similar results are obtained when the thrombin receptor PAR1 is pharmacologically blocked using intraperitoneal injection of SCH79797 (25 µg/kg) prior to SE induction. Consistent with these results, an increase in thrombin immunofluorescence is detected in the hippocampus of pilocarpine-treated animals. Moreover, increased hippocampal serine protease activity is detected 90 min after SE induction, which is not observed in animals treated with α-NAPAP prior to SE induction. Together, these results corroborate and extend recent studies suggesting that novel oral anticoagulants which target thrombin (and PAR1) may assert anti-epileptic effects in vivo. KEY MESSAGES: Systemic thrombin/PAR1-inhibition ameliorates anticoagulants behavioral seizures. Status epilepticus increases thrombin levels in the hippocampus. Increased serine protease activity in the hippocampus after status epileptic. Anti-epileptic potential of clinically used anticoagulants must be evaluated.