Neuroinflammatory mediators in acquired epilepsy: an update.

Epilepsy is a group of chronic neurological disorders that have diverse etiologies but are commonly characterized by spontaneous seizures and behavioral comorbidities. Although the mechanisms underlying the epileptic seizures mostly remain poorly understood and the causes often can be idiopathic, a considerable portion of cases are known as acquired epilepsy. This form of epilepsy is typically associated with prior neurological insults, which lead to the initiation and progression of epileptogenesis, eventually resulting in unprovoked seizures. A convergence of evidence in the past two decades suggests that inflammation within the brain may be a major contributing factor to acquired epileptogenesis. As evidenced in mounting preclinical and human studies, neuroinflammatory processes, such as activation and proliferation of microglia and astrocytes, elevated production of pro-inflammatory cytokines and chemokines, blood-brain barrier breakdown, and upregulation of inflammatory signaling pathways, are commonly observed after seizure-precipitating events. An increased knowledge of these neuroinflammatory processes in the epileptic brain has led to a growing list of inflammatory mediators that can be leveraged as potential targets for new therapies of epilepsy and/or biomarkers that may provide valued information for the diagnosis and prognosis of the otherwise unpredictable seizures. In this review, we mainly focus on the most recent progress in understanding the roles of these inflammatory molecules in acquired epilepsy and highlight the emerging evidence supporting their candidacy as novel molecular targets for new pharmacotherapies of acquired epilepsy and the associated behavioral deficits.

Effect of morphine administration after status epilepticus on epileptogenesis in rats.

INTRODUCTION: Morphine is widely used in patients and has been reported to alter seizure threshold, but its role in the development of epilepsy is unknown. In this study, role of morphine administration in the development of epilepsy using the status epilepticus (SE) model was determined in rats. METHODS: Rats experiencing SE with lithium-pilocarpine (LiP) were randomized into four groups- saline, morphine low dose (5 mg/kg, s.c.), morphine high dose (5-20 mg/kg, s.c.), and naloxone (1 mg/kg, s.c.). Treatments were started 90 min after termination of SE and repeated twice daily for next three days. Rats were video monitored daily for 21 days to determine onset and frequency of spontaneous convulsive seizures (SS). RESULTS: Morphine in low doses increased frequency of SS (1.51 ± 0.15 vs LiP 0.60 ± 0.12 seizures/rat/day, p-value = 0.0026) and seizures occurred during handling (SDH) (0.08 ± 0.02 vs LiP control 0.01 ± 0.01) (p-value = 0.0018). In high doses, no significant change in SS and SDH was found as compared to LiP. No effect of morphine on the onset of SS and percentage of rats experienced SS was found. No effect of naloxone per se was found on SS. CONCLUSION: Morphine administration after SE does not affect epileptogenesis as no change in the onset of SS and percentage of rats experiencing SS was found. However, it might alter the susceptibility and frequency of SS. As no other study is available with a similar finding, it needs further evaluation.

Psychogenic non-epileptic seizure-status in patients admitted to the intensive care unit.

BACKGROUND: Psychogenic non-epileptic seizure-status (PNES-status), defined by psychogenic non-epileptic seizures (PNES) over 30 min, are often misdiagnosed as status epilepticus. We aimed to describe the features of patients who experienced PNES-status, admitted to an intensive care unit (ICU). METHODS: We screened the patients hospitalized in our epilepsy unit during a 4-year period, with a diagnosis of PNES-status and ICU admission. RESULTS: Among 171 patients with PNES, we identified 25 patients (15%) who presented 39 episodes of PNES-status leading to ICU admission. Some 76% of the patients were women. The median age at the time of the PNES-status episode was 35 years. Half (48%) alleged a history of epilepsy, but epilepsy was confirmed in only 12%. A history of psychiatric disease was found in 68%. PNES were present in 85% of patients before PNES-status, and semiology of PNES and PNES-status was similar for 79% of the patients, including hyperkinetic movements in 95% of the episodes and suspected loss of consciousness in 87%. Benzodiazepines were administrated in 77% of the episodes, antiepileptic drugs in 87%, and antibiotherapy for a ICU-related infection in 15% of the episodes. Oral intubation was performed in 41% of the episodes. Blood tests showed normal levels of creatine phosphokinase and leucocytes in 90% and 95% of the episodes, respectively. No epileptic activity was found during per-event electroencephalography but interictal epileptic activity was found in 10% of the episodes. CONCLUSION: Hyperkinetic PNES-status should always be considered as a differential diagnosis of status epilepticus, with a high risk of iatrogenic consequences.

Comparative efficacy of valnoctamide and sec-butylpropylacetamide (SPD) in terminating nerve agent-induced seizures in pediatric rats.

OBJECTIVES: Children and adults are likely to be among the casualties in a civilian nerve agent exposure. This study evaluated the efficacy of valnoctamide (racemic-VCD), sec-butylpropylacetamide (racemic-SPD), and phenobarbital for stopping nerve agent seizures in both immature and adult rats. METHODS: Female and male postnatal day (PND) 21, 28, and 70 (adult) rats, previously implanted with electroencephalography (EEG) electrodes were exposed to seizure-inducing doses of the nerve agents sarin or VX and EEG was recorded continuously. Five minutes after seizure onset, animals were treated with SPD, VCD, or phenobarbital. The up-down method was used over successive animals to determine the anticonvulsant median effective dose (ED50 ) of the drugs. RESULTS: SPD-ED50 values in the VX model were the following: PND21, 53 mg/kg (male) and 48 mg/kg (female); PND28, 108 mg/kg (male) and 43 mg/kg (female); and PND70, 101 mg/kg (male) and 40 mg/kg (female). SPD-ED50 values in the sarin model were the following: PND21, 44 mg/kg (male) and 28 mg/kg (female); PND28, 79 mg/kg (male) and 34 mg/kg (female); and PND70, 53 mg/kg (male) and 53 mg/kg (female). VCD-ED50 values in the VX model were the following: PND21, 34 mg/kg (male) and 43 mg/kg (female); PND28, 165 mg/kg (male) and 59 mg/kg (female); and PND70, 87 mg/kg (male) and 91 mg/kg (female). VCD-ED50 values in the sarin model were the following: PND21, 45 mg/kg (male), 48 mg/kg (female); PND28, 152 mg/kg (male) 79 mg/kg (female); and PND70, 97 mg/kg (male) 79 mg/kg (female). Phenobarbital-ED50 values in the VX model were the following: PND21, 43 mg/kg (male) and 18 mg/kg (female); PND28, 48 mg/kg (male) and 97 mg/kg (female). Phenobarbital-ED50 values in the sarin model were the following: PND21, 32 mg/kg (male) and 32 mg/kg (female); PND28, 58 mg/kg (male) and 97 mg/kg (female); and PND70, 65 mg/kg (female). SIGNIFICANCE: SPD and VCD demonstrated anticonvulsant activity in both immature and adult rats in the sarin- and VX-induced status epilepticus models. Phenobarbital was effective in immature rats, whereas in adult rats, higher doses were required that were accompanied by toxicity. Overall, significantly less drug was required to stop seizures in PND21 animals than in the older animals, and overall, males required higher amounts of drug than females.

Brivaracetam-Associated Rhabdomyolysis Requiring Renal Replacement Therapy: A Case Report and Review of the Literature.

Rhabdomyolysis is a rare adverse reaction that has a previously established association with levetiracetam use, which selectively binds the synaptic vesicle glycoprotein 2A (SV2A). Its structural analogue, brivaracetam, is a new third-generation antiseizure medication that has a higher affinity for SV2A, and current data suggests it provides a more favorable adverse event profile. Here, however, we report a case of rhabdomyolysis requiring dialysis in which serum creatine kinase level increased rapidly for several days until brivaracetam was discontinued. The delayed creatine kinase peak, rapid decline upon discontinuation of brivaracetam, and prior association of rhabdomyolysis with levetiracetam strongly suggest a causal relationship. To date, there are three reported cases of brivaracetam-associated rhabdomyolysis in the food and drugs administration adverse event reporting system (FAERS). Despite its favorable side effects profile, the use of brivaracetam may be associated with life-threatening rhabdomyolysis.

Delayed Serotonin Syndrome and Non-cardiogenic Pulmonary Edema Following Bupropion Overdose in a Seven-Year-Old Female: A Case Report and Review of Literature.

Bupropion is an atypical antidepressant prescribed for depression and attention-deficit/hyperactivity disorder and to aid in smoking cessation. Bupropion overdose management is largely aimed toward common sequelae, including seizures, tachycardia, and QTc prolongation. In this case report, we identify a rare event of pediatric bupropion overdose with aforementioned common sequela and atypical features, including a delayed presentation of serotonin syndrome and non-cardiogenic pulmonary edema. This case follows a seven-year-old Caucasian female with autism spectrum disorder (ASD) who presented in status epilepticus following an accidental bupropion overdose and required multiple anti-seizure medications, endotracheal intubation, and admission to the pediatric intensive care unit (PICU). The patient's condition improved, and she was extubated 25 hours after admission and transitioned to high-flow nasal cannula therapy. On day 3 of admission, she became febrile and developed dyspnea with decreased breath sounds and intercostal retractions, tachycardia, a rigid abdomen and extremities with sporadic tremors, pulmonary edema, and a prolonged QTc interval. Targeted therapies were initiated, and following treatment, our patient showed remarkable improvement in the subsequent 24 hours and was discharged home five days after the initial presentation. This case identifies a delayed presentation of uncommon and serious complications of bupropion overdose, including pulmonary edema and serotonin syndrome, in a pediatric patient. Prompt investigation and identification of bupropion toxicity can help practitioners mitigate further complications during admission and reduce morbidity and mortality.

Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review.

Neuropsychiatric systemic lupus erythematosus (NPSLE) refers to the neurological and psychiatric manifestations of systemic lupus erythematosus (SLE), which remain poorly understood yet often have a profound effect on the lives of afflicted patients. The aim of this study is to synthesize the available information on the pathogenesis, diagnostics, management, and prognosis of this disease. Our hope is to increase awareness and call for further investigations that may optimize NPSLE patient outcomes and quality of life. We performed a literature review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, resulting in 11 studies of inclusion. Within each study, we extracted data on epidemiologic factors, diagnostics, therapeutic modalities, and prognosis for each neuropsychiatric condition. The most widely discussed neuropsychiatric manifestations of SLE based on the American College of Rheumatology (ACR) classifications included status epilepticus (SE) and seizures, transverse myelitis (TM), and cognitive dysfunction. SE and TM had a prevalence of 1-2%, while cognitive dysfunction was nearly 38%. Diagnostics varied depending on symptom presentation but often included brain magnetic resonance imaging (MRI) and antibody testing. Treatment for NPSLE is still widely understudied, but concurrent treatment with immunosuppressants and anti-inflammatories for symptom control and more targeted immunotherapies based on the specific condition is often effective. Prognosis is highly symptom dependent, ranging from a 12.5% one-year mortality in SE and seizure patients to near resolution of symptoms in certain presentations including idiopathic intracranial hypertension and cerebellar ataxia. Further studies are needed to better understand the pathophysiology, diagnostics, and effective therapeutic measures for NPSLE. The severity of these manifestations and generally poor prognosis highlight the need for more research to accurately diagnose and treat this disease. While there is still little data available, this literature review serves to provide updated context on this condition.

Neurofilament light (NfL) as biomarker in serum and CSF in status epilepticus.

OBJECTIVE: We explored the potential of neurofilament light chain (NfL) in serum and cerebrospinal fluid as a biomarker for neurodestruction in status epilepticus. METHODS: In a retrospective analysis, we measured NfL in serum and cerebrospinal fluid samples of patients with status epilepticus using a highly sensitive single-molecule array technique (Simoa). Status epilepticus was diagnosed according to ILAE criteria. Additionally, we employed an alternative classification with more emphasis on the course of status epilepticus. We used data from three large control groups to compare NfL in status epilepticus versus neurologically healthy controls. RESULTS: We included 28 patients (mean age: 69.4 years, SD: 15 years) with a median status duration of 44 h (IQR: 80 h). Twenty-one patients (75%) suffered from convulsive status epilepticus and seven (25%) from non-convulsive status epilepticus. Six patients died (21%). Cerebrospinal fluid and serum NfL concentrations showed a high correlation (r = 0.73, p < 0.001, Pearson). The main determinant of NfL concentration was the status duration. NfL concentrations did not differ between convulsive status epilepticus and convulsive status epilepticus classified according to the ILAE or to the alternative classification without and with adjusting for status duration and time between status onset and sampling. We found no association of NfL concentration with death, treatment refractoriness, or prognostic scores. CONCLUSION: The results suggest that neurodestruction in status epilepticus measured by NfL is mainly determined by status duration, not status type nor therapy refractoriness. Therefore, our results suggest that regarding neurodestruction convulsive and non-convulsive status epilepticus are both neurological emergencies of comparable urgency.

Out-of-hospital rescue medication in dogs with emergency seizure disorders: an owner perspective.

Background: Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date. Hypothesis or objectives: To evaluate the use of rescue medication in dogs with seizure emergencies by the owner at home. Method: Observational study based on online surveys of owners of dogs with emergency seizure disorders. Results: The questionnaire was answered by 1,563 dog owners, of which 761 provided complete and accurate answers suitable for analysis. Of these, 71% administered diazepam, 19% midazolam, 6% levetiracetam, 3% lorazepam, and 4% more than one rescue or other medication. Overall, the success rates based on owners' perspective for intranasal midazolam and rectal diazepam were 97 and 63%, respectively. Owners reported a compliance level of 95 and 66% for intranasal midazolam and rectal diazepam administration, respectively. Conclusions and clinical importance: Even though rectal diazepam was the most used rescue medication in this survey population, intranasal midazolam was perceived by the owners as a better option regarding effectiveness, time to seizure cessation and owner compliance.

Dendritic reorganization in the hippocampus, anterior temporal lobe, and frontal neocortex of lithium-pilocarpine induced Status Epilepticus (SE).

Status Epilepticus (SE) is a distributed network disorder, which involves the hippocampus and extra-hippocampal structures. Epileptogenesis in SE is tightly associated with neurogenesis, plastic changes and neural network reorganization facilitating hyper-excitability. On the other hand, dendritic spines are known to be the excitatory synapse in the brain. Therefore, dendritic spine dynamics could play an intricate role in these network alterations. However, the exact reason behind these structural changes in SE are elusive. In the present study, we have investigated the aforementioned hypothesis in the lithium-pilocarpine treated rat model of SE. We have examined cytoarchitectural and morphological changes using hematoxylin-eosin and Golgi-Cox staining in three different brain regions viz. CA1 pyramidal layer of the dorsal hippocampus, layer V pyramidal neurons of anterior temporal lobe (ATL), and frontal neocortex of the same animals. We observed macrostructural and layer-wise alteration of the pyramidal layer mainly in the hippocampus and ATL of SE rats, which is associated with sclerosis in the hippocampus. Sholl analysis exhibited partial dendritic plasticity in apical and basal dendrites of pyramidal cells as compared to the saline-treated weight-/age-matched control group. These findings indicate that region-specific alterations in dendritogenesis may contribute to the development of independent epileptogenic networks in the hippocampus, ATL, and frontal neocortex of SE rats.

A Comparison of Epileptogenic Effect of Status Epilepticus Treated With Diazepam, Midazolam, and Pentobarbital in the Mouse Pilocarpine Model of Epilepsy.

Status epilepticus (SE) is a medical emergency associated with acute severe systemic damage and high mortality. Moreover, symptomatic SE is one of the highest risk factors for epileptogenesis. While the antiepileptic drugs (AEDs) are chosen in favor of acute control of SE, the potential short-term and long-term effects of such AEDs have been ignored in clinics. In this study, we hypothesized that AEDs that are used to control acute SE might affect the feasibility for the chronic development of epileptogenesis after SE. Therefore, we sought to compare the epileptogenic effects of SE that are terminated by three AEDs, i.e., diazepam, midazolam, and pentobarbital, which are widely used as first-line anti-SE AEDs. For this purpose, we used a mouse model of SE induced by intraperitoneal (i.p.) injection of lithium chloride (LiCl)-pilocarpine. The pilocarpine-induced SE was terminated with diazepam, midazolam, or pentobarbital. Then we compared short-term and long-term effects of SE with different AED treatments by examining SE-associated mortality and behavioral spontaneous recurrent seizures (SRSs) and by using magnetic resonance imaging (MRI) and immunohistochemistry to evaluate pathological and cellular alterations of mice in the different treatment groups. We found that i.p. injections of diazepam (5 mg/kg), midazolam (10 mg/kg), and pentobarbital (37.5 mg/kg) were able to terminate acute pilocarpine-SE effectively, while pentobarbital treatment showed less neuroprotective action against lethality in the short phase following SE. Long-term evaluation following SE revealed that SE treated with midazolam had resulted in relatively less behavioral SRS, less hippocampal atrophy, and milder neuronal loss and gliosis. Our data revealed an obvious advantage of midazolam vs. diazepam or pentobarbital in protecting the brain from epileptogenesis. Therefore, if midazolam provides as strong action to quench SE as other AEDs in clinics, midazolam should be the first choice of anti-SE AEDs as it provides additional benefits against epileptogenesis.

New-Onset Seizures as an Acute Presentation With Atypical EEG Findings in a Previously Healthy Child With Asymptomatic COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) infection is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This infection usually presents with upper respiratory symptoms; however, it can also present with a wide variety of other multisystem and neurological symptoms, including seizures. There are several proposed mechanisms by which COVID-19 can cause systemic signs of infections, including neurological complications and seizures. This case report describes a pediatric patient without a previously documented history of epilepsy who was admitted for new-onset focal seizures with impaired consciousness. No other cause and triggers of seizures were found, and the child was tested positive for COVID-19 infection. The patient had six electroclinical seizures during EEG. Video EEG findings showed atypical features of onset of intermittent rhythmic delta activity (IRDA) slowing over the left hemisphere with evolution/generalization of rhythmic delta/theta activity and without clear typical generalized epileptiform discharges. These EEG findings correlated with a clinical change of behavior arrest, staring, and yawning. Similar spells were reported multiple times a day prior to the admission, and past EEG was normal. A review of current literature on COVID-19 and neurological manifestations in children, including new seizures and prior diagnosis of epilepsy, is also provided in this case report. The clinical experience in children with newly diagnosed or chronic epilepsy suggests that exacerbation of seizures, especially from systemic effects such as those caused by severe COVID-19 infection, will be a major concern.

A Novel Hydrogen Sulfide Donor Reduces Pilocarpine-Induced Status Epilepticus and Regulates Microglial Inflammatory Profile.

Although epilepsy is one of the most common neurologic disorders, there is still a lack of effective therapeutic drugs for it. Recently, we synthesized a novel hydrogen sulfide (H2S) donor, which is found to reduce seizures in animal models effectively. But it remains to be determined for its mechanism. In the present study, we found that the novel H2S donor could reduce pilocarpine-induced seizures in mice. It alleviated the epileptic behavior, the hippocampal electroencephalography (EEG) activity of seizures, and the damage of hippocampal neurons in status epilepticus mice. In addition, the novel H2S donor could reduce microglial inflammatory response. It not only reduced the upregulation of pro-inflammatory markers [inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)] in status epilepticus mice, but also increased the levels of microglial anti-inflammatory marker arginase-1 (Arg-1). In lipopolysaccharide-treated microglia BV2 cells, administration of the H2S donor also significantly reduced the lipopolysaccharide-induced upregulation of the expression of the pro-inflammatory markers and increased the expression of the anti-inflammatory markers. Thus, the novel H2S donor regulates microglial inflammatory profile in status epilepticus mice and in vitro. These results suggested that the novel H2S donor can reduce seizures and regulate microglial inflammatory profile, which may be a novel mechanism and potential therapeutic strategy of the H2S donor anti-seizures.

Super-Refractory Status Epilepticus: Prognosis and Recent Advances in Management.

Super-refractory status epilepticus (SRSE) is a life-threatening neurological emergency with high morbidity and mortality. It is defined as "status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthesia, including those cases in which SE recurs on the reduction or withdrawal of anesthesia." This condition is resistant to normal protocols used in the treatment of status epilepticus and exposes patients to increased risks of neuronal death, neuronal injury, and disruption of neuronal networks if not treated in a timely manner. It is mainly seen in patients with severe acute onset brain injury or presentation of new-onset refractory status epilepticus (NORSE). The mortality, neurological deficits, and functional impairments are significant depending on the duration of status epilepticus and the resultant brain damage. Research is underway to find the cure for this devastating neurological condition. In this review, we will discuss the wide range of therapies used in the management of SRSE, provide suggestions regarding its treatment, and comment on future directions. The therapies evaluated include traditional and alternative anesthetic agents with antiepileptic agents. The other emerging therapies include hypothermia, steroids, immunosuppressive agents, electrical and magnetic stimulation therapies, emergent respective epilepsy surgery, the ketogenic diet, pyridoxine infusion, cerebrospinal fluid drainage, and magnesium infusion. To date, there is a lack of robust published data regarding the safety and effectiveness of various therapies, and there continues to be a need for large randomized multicenter trials comparing newer therapies to treat this refractory condition.

Ketogenic diet (KD) therapy in the acute phase of febrile infection-related epilepsy syndrome (FIRES): a case report.

Management of frequent epileptic seizures in febrile infection-related epilepsy (FIRES) is often challenging. FIRES is an uncommon disease condition. Children with FIRES develop refractory epilepsy with severe cognitive deficits that affect the function of the temporal and frontal lobes. However, better seizure control during the acute stage of FIRES could protect against injury to the nervous system. Ketogenic diet (KD) can effectively resolve super-refractory status epilepticus (SRSE) in the acute phase and improve the prognosis of FIRES. We present the case of a previously healthy 3-year-old male with new-onset status epilepticus (SE) admitted to the paediatric intensive care unit for 55 days. Despite treatment with multiple anti-epileptic agents in addition to IV anaesthetics, the patient remained in SRSE and continued to have generalised epileptic activity on electroencephalography (EEG). KD therapy was initiated on the 14th day of the onset, and the patient achieved complete neurological recovery following the KD. Throughout the remainder of admission, the patient was successfully weaned off the ventilator, tolerated oral meals, and worked with occupational and physical therapists to return to his baseline functional status. The convulsions were well controlled after discharge. We discuss the treatment strategies for FIRES and highlight the role of KD therapy in the acute phase to control disease progression and improve the prognosis, and early diagnosis of FIRES and early initiation of KD therapy combined with anti-epileptic drugs (AEDs) could improve the prognosis.

Comparing the efficacy of sodium valproate and levetiracetam following initial lorazepam in elderly patients with generalized convulsive status epilepticus (GCSE): A prospective randomized controlled pilot study.

PURPOSE: This randomized control study was conducted to compare the efficacy of sodium valproate (SVP) and levetiracetam (LEV) following initial intravenous lorazepam in elderly patients (age: >60years) with generalized convulsive status epilepticus (GCSE) and to identify predictors of poor seizure control. METHODS: A total of 118 patients (mean age: 67.5 ± 7.5 years, M:F = 1.6:1), who had presented with GCSE were randomized into the SVP or LEV treatment arms. All patients received initial intravenous lorazepam (0.1 mg/kg) followed by one of the two antiepileptic drugs (AEDs), parenteral SVP (20-25 mg/kg) or LEV (20-25 mg/kg). Those who failed to achieve control with the initial AED, were crossed over to receive the other AED. One-hundred patients (SVP = 50; LEV = 50) completed the study. RESULTS: SE could be controlled with lorazepam and one of the AEDs (SVP or LEV) in 71.18% (84/118). Intention-to-treat analysis showed that the two groups did not differ significantly in terms of seizure control [SVP: 41/60 (68.3%); LEV: 43/58 (74.1%), p = 0.486]. Of 100 patients who completed the study, seizure control was achieved in 38/50(76%) in the SVP and 43/50(86%) in the LEV group (p = 0.202). After crossing over to the second AED, SE could be controlled in an additional in 50% (6/12) in SVP (+LEV) group and in 14.3% (1/7) in LEV (+SVP) group. Overall, after the second AED, seizure control was achieved in 77.1% (91/118). Higher STESS was associated with poor therapeutic response (p = 0.049). CONCLUSIONS: The efficacy of SVP and LEV following initial lorazepam in controlling GCSE in elderly population was comparable, hence the choice of AED could be individualized.

The SAMUKeppra study in prehospital status epilepticus: lessons for future study.

In the Lancet Neurology article "Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial" the authors conducted a prehospital, randomized controlled study to determine which treatment is more effective for status epilepticus (SE): benzodiazepine alone, or in combination with levetiracetam (LEV). Although the study had negative results, several aspects of the trial design likely masked any added effect that LEV may have had in controlling SE, including: higher doses of benzodiazepines, lower thresholds for determining cessation of SE, and a smaller sample size. Regardless, the study reaffirms the effectiveness and importance of early and adequate benzodiazepine dosing and helps guide us in designing future studies for treatment of SE.

Repetitive transcranial magnetic stimulation for the treatment of refractory epilepsy.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive neurostimulation technique that is able to induce neuromodulatory effects outlasting the duration of the stimulation train. The cortical excitability disturbance in epilepsy provides a rationale for investigating the efficacy of low-frequency rTMS as a treatment for epilepsy patients. Sofar clinical trials in epilepsy patients have shown conflicting results ranging from ineffective to very effective. AREAS COVERED: This manuscript provides an overview of the performed studies, retrieved from a PubMed search, and a critical appraisal of their results. A number of conclusions are drawn and potential optimization strategies are discussed. Expert commentary: Although the therapeutic efficacy of rTMS in refractory epilepsy has not yet been established, the non-invasiveness of the technique warrants further investigation of rTMS as a treatment for epilepsy.

Adult Status Epilepticus: A Review of the Prehospital and Emergency Department Management.

Seizures are a common presentation in the prehospital and emergency department setting and status epilepticus represents an emergency neurologic condition. The classification and various types of seizures are numerous. The objectives of this narrative literature review focuses on adult patients with a presentation of status epilepticus in the prehospital and emergency department setting. In summary, benzodiazepines remain the primary first line therapeutic agent in the management of status epilepticus, however, there are new agents that may be appropriate for the management of status epilepticus as second- and third-line pharmacological agents.