Practical Drug Treatment Recommendations on the Drug Refractory Epilepsy Patients: 2021 Clinical Guideline Subcommittee for Epilepsy in the Korean Neurological Association

One third of the overall epilepsy population are estimated to be a drug refractory epilepsy (DRE), defined as the patients who failed to control seizure reduction, even tried two or more appropriate antiepileptic drugs (AEDs) trials. Those people need additional AEDs trials or other treatment options (resective surgery, neuromoulation, etc.). Here, we, clinical guideline committee of the Korean Neurological Association (KNA) introduce the recommendations of AEDs treatments including not only old and new AEDs currently available in Korea but also AEDs planned to be launched in the new future for DRE patients with literature review to help efficient decision of the clinician. The authors reviewed literatures and assessed efficacy and tolerability on 12 currently available and four newly introduced/or planned AEDs applied to DRE patients, published from November 2015 to July 2021. Brivaracetam, eslicarbazepine, canabidiol and cenobamate are the four AEDs that are newly introduced or planned to be launched soon. The reviewed articles are publications after November 2015, 2018 American Association of Neurology guideline, new AEDs which were introduced or planned to be launched as of 2021. All AEDs are classified based on the therapeutic rating scheme, generating recommendations. Overall 173 papers have been reviewed and analyzed for recommendation rationales. KNA introduce additional add-on treatment or conversional monotherapy guidelines on the drug refractory focal and generalized epilepsy. We hope these guidelines or recommendations to help clinical decision for the treatment of drug refractory epilepsy patients

Anti-Convulsive Effect of Thiamine and Melatonin Combination in Mice; Involvement of Oxidative Stress

Background: Epilepsy, the second most frequent neurological disease, is a chronic disorder with a high lifetime prevalence. Therefore, various studies are needed to find new effective therapeutic agents to treat seizures or prevent its complications. In this study, we investigated the effects of thiamine, melatonin, and their combination on pentylenetetrazol (PTZ)-induced tonic-clonic seizures in mice. Methods: Male mice were randomly divided into six groups, including control, seizure control, diazepam, melatonin, thiamine, and melatonin and thiamine combination groups. Drugs were given orally in drinking water for 14 days. On the 15th day, the seizure was induced (except the control group) by intraperitoneal injection of PTZ. In all groups, the time between the injection the start of the seizure (latency) and the length of the seizure attack (duration) were measured in a 30-minute period. After measuring the latency and duration in all groups, mice were killed by CO2 Box, and their brains were dissected to be analyzed for malondialdehyde (MDA) level as a marker of oxidative stress. Results: The seizure duration was significantly lower in the groups of melatonin, thiamine, and thiamine and melatonin combination compared to the seizure control group. The latency times in these groups were significantly greater than the seizure control group. Moreover, MDA concentrations were lower in these groups compared to the seizure control group. Conclusion: Thiamine, melatonin and their combination can decrease the duration time of seizure and increase the latency period, which may result from inhibition of oxidative stress in the brain.

A Build Up of Seizure Prediction and Detection Software: A Review Article

Introduction: Neurological diseases are much often due to our stressed daily life, and epilepsy is considered as a second cause of hospitalization in neurological illness. It is about 30% of epileptic cases where medicine would not stop or control seizure; hence, a surgical intervention is required to delineate abnormal hyperexcitable cortical tissue. Defining these epileptogenic zones is a challenge that require physiological and anatomical acquisition. Discussion: Clinicians, researcher and engineer researcher are multiplying advanced techniques in order to exploit these acquisitions for a better diagnosis. Several software are used to enhance epilepsy diagnosis. Here we proposed a software that rely on space-time evolution of inter- ictal gamma oscillations. Conclusion: Our proposed software would predict a build up of seizure during monitoring of stereo-electroencephalographic SEEG recording. It allows also detection of seizure during analysis and diagnosis of SEEG. This software would assist neurologist in recognition of seizure and in defining epileptogenic zone EZ.

A build up of seizure prediction and detection Software: A review

Introduction: Neurological diseases are much often due to our stressed daily life, and epilepsy is considered as a second cause of hospitalization in neurological illness. It is about 30% of epileptic cases where medicine would not stop or control seizure; hence, a surgical intervention is required to delineate abnormal hyperexcitable cortical tissue. Defining these epileptogenic zones is a challenge that require physiological and anatomical acquisition. Discussion: Clinicians, researcher and engineer researcher are multiplying advanced techniques in order to exploit these acquisitions for a better diagnosis. Several software are used to enhance epilepsy diagnosis. Here we proposed a software that rely on spacetime evolution of inter- ictal gamma oscillations. Conclusion: Our proposed software would predict a build up of seizure during monitoring of stereo-electroencephalographic SEEG recording. It allows also detection of seizure during analysis and diagnosis of SEEG. This software would assist neurologist in recognition of seizure and in defining epileptogenic zone EZ. Keywords: Pharmaco-ressistant epilepsy; SEEG; Seizure build up; Prediction; Detection.

Predication and Analysis of Epileptic Seizure Neurological Disorder using Intracranial Electroencephalography (iEEG)

Epileptic seizure is one of the neurological brain disorder approximately 50 million of world’s population is affected. Diagnosis of seizure is done using medical test Electroencephalography. Electroencephalography is a technique to record brain signal by placing electrodes on scalp. Electroencephalography suffers from disadvantage such as low spatial resolution and presence of artifact. Intracranial Electroencephalography is used to record brain electrical activity by mounting strip, grid and depth electrodes on surface of brain by surgery. Online standard Intracranial Electroencephalography data is analyzed by our system for predication and analysis of Epileptic seizure. The pre-processing of Intracranial Electroencephalography signal is done and is further analyzed in wavelet domain by implementation of Daubechies Discrete Wavelet Transform. Features were extracted to classify as preictal and ictal state. Analysis of preictal state was carried out for predication of seizure. Intracranial Electroencephalography signals provide better result and accuracy in seizure detection and predication. Earlier warning can also be issued to control seizure with anti- epileptic drugs

Drug Use Review of Intravenous Levetiracetam in Patients with Epilepsy, Tertiary Care Hospital

Background: Epilepsy is a current important health problem. Status epilepticus is a medical emergency condition which may be lifethreatening, increased mortality rate and hospitalization. However, some patients with epilepsy could not control their symptoms and anticonvulsant medications have some adverse effects. Intravenous levetiracetam (ivLEV) is a new antiepileptic drug which its use tends to be increased. Objective: To study the prescription pattern of ivLEV and its adverse drug reactions (ADRs) in hospitalized patients and to define the efficacy of iv LEV as first line treatment for status epilepticus. Materials and Methods: This was a descriptive retrospective study to review medical records of all inpatients receiving ivLEV at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University during January 1st 2010 to December 31st 2014. Results: During the study period, there were 406 hospital visits that met the study criteria. The average age of the patients was 54.32+20.36 years with nearly equal sex distribution. The indications of ivLEV were status epilepticus (22.4%), previous treatment with oral levetiracetam (9.6%), perioperative craniectomy/craniotomy (8.6%), and acute seizure with non-status epilepticus (59%). Most of the patients (63.3%) received ivLEV as first line treatment antiepileptic drug and the most loading dose range of ivLEV that the patients received was 500 to 1,000 mg/day (78.3%). All of the patients had been followed vital signs and plasma electrolytes. 98.5% and 45.8% of hospital visits had been monitored liver/kidney function and electroencephalogram (EEG), respectively. Adverse effects during the treatment of ivLEV occurred 0.98%, which were hypotension, drowsiness, and maculopapular rash. No major ADRs were detected in any patients after the ivLEV treatment. Regarding process indicators, overall seizure control rate was 76.4%, of which 35.2% and 85.9% were for the patients with status epilepticus and acute seizure with non-status epilepticus, respectively. ivLEV could be used as first line treatment effectively in patients with status epilepticus (80.2%). In the patients with renal impairment receiving adjusted dosage regimen ivLEV could be control seizure 73.1%. Conclusion: The treatment of ivLEV was effective and safe for control seizure, including status epilepticus and acute seizure with non-status epilepticus. Thus, ivLEV could be the first line antiepileptic drug for the treatment of status epilepticus and brain surgery prevention. However, due to the high cost of the drug and the treatment course, there would be further study of cost-effectiveness. Keywords: Levetiracetam, Epilepsy, Acute seizure, Status epilepticus, Drug use review, Inpatient

Epilepsy in older people

SummaryEpilepsy is the third most common neurological disorder of older adults, with huge functional and psychological implications. It is often difficult to diagnose in the presence of cognitive impairment and lack of a witness account. The most common identifiable causes of epilepsy in old age are cerebrovascular disease and dementia. New guidelines recommend starting treatment after first unprovoked seizure. If there is any doubt about the diagnosis, electroencephalography (EEG) should be considered, or ‘wait and watch’. The aim of treatment should be to fully control seizure activity with the most effective monotherapy and fewest possible side-effects. Drug compliance is often difficult to achieve in older adults.

Seizure outcomes following radiosurgery for cerebral arteriovenous malformations

Object Seizures are a common presentation of cerebral arteriovenous malformations (AVMs). The authors evaluated the efficacy of stereotactic radiosurgery (SRS) for the management of seizures associated with AVMs and identified factors influencing seizure outcomes following SRS for AVMs. Methods A systematic literature review was performed using PubMed. Studies selected for review were published in English, included at least 5 patients with both cerebral AVMs and presenting seizures treated with SRS, and provided post-SRS outcome data regarding obliteration of AVMs and/or seizures. Demographic, radiosurgical, radiological, and seizure outcome data were extracted and analyzed. All seizure outcomes were categorized as follows: 1) seizure free, 2) seizure improvement, 3) seizure unchanged, and 4) seizure worsened. Systematic statistical analysis was conducted to assess the effect of post-SRS AVM obliteration on seizure outcome. Results Nineteen case series with a total of 3971 AVM patients were included for analysis. Of these, 28% of patients presented with seizures, and data for 997 patients with available seizure outcome data who met the inclusion criteria were evaluated. Of these, 437 (43.8%) patients achieved seizure-free status after SRS, and 530 (68.7%) of 771 patients with available data achieved seizure control (seizure freedom or seizure improvement) following SRS. Factors associated with improved seizure outcomes following SRS for AVMs were analyzed in 9 studies. Seizure-free status was achieved in 82% and 41.0% of patients with complete and incomplete AVM obliteration, respectively. Complete AVM obliteration offered superior seizure-free rates compared with incomplete AVM obliteration (OR 6.13; 95% CI 2.16–17.44; p = 0.0007). Conclusions Stereotactic radiosurgery offers favorable seizure outcomes for AVM patients presenting with seizures. Improved seizure control is significantly more likely with complete AVM obliteration.

Dyke Davidoff Masson Syndrome – A Case Report

A 10 year old male child reported to paediatric neurology OPD of BIRDEM General Hospital with the complaints of weakness of left side of body, seizure and facial asymmetry for 2 years. He was on regular anti convulsive therapy and failed to control seizure. General examination revealed no significant abnormality neither delayed mile stones of development happened. Neurological examination revealed left sided spastic hemiparesis, brisk tendon reflexes and extensor planter on left side. With detailed history and examination he was diagnosed as a case of infantile seizure and undergone CT scan of brain followed by MRI scan. Both the reports revealed severe atrophy of right cerebral hemisphere, thinning of cortical gyri, widening of sulci and dilatation of right lateral ventricle with ipsilateral midline shift and was concluded as hemiatrophy of right cerebral hemisphere with suspicion of Dyke Davidoff Masson Syndrome (DDMS), Hemimegalencephaly and Sturge-Weber syndrome. Dyke-Davidoff-Masson syndrome (DDMS) is a rare condition characterized by asymmetric cerebral hemispheric growth with unilateral atrophy, ipsilateral compensatory osseous hypertrophy, hyperpneumatization of the paranasal sinuses and mastoid cells, and contralateral paresis. Varying degrees of hemiparesis, hemiplegia, seizures, mental retardation, and facial asymmetry can be associated with DDMS. Considering clinical history and imaging findings, final Diagnosis was Dyke Davidoff Masson Syndrome. Birdem Med J 2013; 3(2): 196-109 DOI: http://dx.doi.org/10.3329/birdem.v3i2.17215

RESPONSIVE NEUROMODULATORS BASED ON ARTIFICIAL NEURAL NETWORKS USED TO CONTROL SEIZURE-LIKE EVENTS IN A COMPUTATIONAL MODEL OF EPILEPSY

Deep brain stimulation (DBS) has been noted for its potential to suppress epileptic seizures. To date, DBS has achieved mixed results as a therapeutic approach to seizure control. Using a computational model, we demonstrate that high-complexity, biologically-inspired responsive neuromodulation is superior to periodic forms of neuromodulation (responsive and non-responsive) such as those implemented in DBS, as well as neuromodulation using random and random repetitive-interval stimulation. We configured radial basis function (RBF) networks to generate outputs modeling interictal time series recorded from rodent hippocampal slices that were perfused with low Mg2+/high K+solution. We then compared the performance of RBF-based interictal modulation, periodic biphasic-pulse modulation, random modulation and random repetitive modulation on a cognitive rhythm generator (CRG) model of spontaneous seizure-like events (SLEs), testing efficacy of SLE control. A statistically significant improvement in SLE mitigation for the RBF interictal modulation case versus the periodic and random cases was observed, suggesting that the use of biologically-inspired neuromodulators may achieve better results for the purpose of electrical control of seizures in a clinical setting.