Drug Resistant Epilepsy Among Patients Attended The Neurosciences Hospital

Background: Drug resistant epilepsy is defined as failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules to achieve sustained seizure freedom. Up to 30% of patients referred to clinics with a diagnosis of pharmaco-resistant epilepsy may have been misdiagnosed, and many can be helped by optimizing their treatment.Pseudoresistance, in which seizures persist because the underlying disorder has not been adequately or appropriately treated, must be ruled out or corrected before drug treatment can be considered to have failed. Objectives: The objectives of this study were to determine the causes of drug failure in patients with epilepsy and to differentiate between drug resistant epilepsy and pseudoresistant epilepsy. Type of the study: This is a retrospective study. Method: It is conducted in Baghdad governorate at the epilepsy clinic in the neurosciences hospital during the period from the 1st of February through July 2013. Two hundred patients with refractory epilepsy were involved. These patients attended the epilepsy clinic during 2011 and 2012. The data was collected from the files of the patients including age, gender, weight, history of presenting illness, type of seizure, drugs used, duration of disease, EEG and imaging findings, compliance and follow up. Results: Drug resistance epilepsy constituted a prevalence of 24% (128) as the total number of patients with epilepsy attending the hospital during the same period was 527.The mean age of patients with refractory epilepsy was 25 years. Male were 56.5% (113/200) and urban residents were 70.5% (141/200). The study revealed that 64% (128/200) of refractory epilepsy was attributed to drug resistance; while the remaining proportion was pseudoresistance 36% (72/200). The main cause of pseudoresistance was poor compliance 36.1% (26/72).The most common type of seizure in the sampled patients was generalized tonic clonic seizures in 51.5% (103/200).Compliance was found to be statistically associated with abnormal EEG finding, past medical history (hypertension, cardiac diseases, encephalitis, diabetes mellitus and any significant history) and quality of follow up. The follow-up was found to be statistically associated with the family history, past medical history( encephalitis and hypertension) and compliance of patient. Conclusion:A considerable number of patientsdiagnosed as cases of drug resistant epilepsy had another explanation causing drug failure.The study recommends the application of consensus definition for drug resistant epilepsy and periodic evaluation of patients with drug resistant epilepsy to exclude pseudoresistance.

Download Full-text

Efficacy of Vagal Nerve Stimulation for Drug-Resistant Epilepsy: Is it the Stimulation or Medication?

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2017.46 ◽

2017 ◽

Vol 44 (5) ◽

pp. 532-537 ◽

Cited By ~ 8

Author(s):

Jaylynn Arcand ◽

Karen Waterhouse ◽

Lizbeth Hernandez-Ronquillo ◽

Aleksander Vitali ◽

Jose F. Tellez-Zenteno

Keyword(s):

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Drug Resistant ◽

Idiopathic Generalized Epilepsy ◽

Drug Resistant Epilepsy ◽

Generalized Epilepsy ◽

Patients With Epilepsy ◽

Seizure Classification

AbstractBackground: Vagus nerve stimulation (VNS) therapy has been widely recognized as an alternative for the treatment of drug-resistant epilepsy, although modification of antiepileptic drugs (AEDs) during VNS treatment could explain the improvement in patients. Methods: We retrospectively assessed the efficacy of VNS in 30 adult patients with epilepsy treated with >6 months of follow-up. The criteria for implantation were the following: (1) not a candidate for resective epilepsy surgery, (2) drug-resistant epilepsy, (3) impairment of quality of life, (4) no other option of treatment, and (5) patients with idiopathic generalized epilepsy who fail to be controlled with appropriate AEDs. We assessed sociodemographics, seizure etiology, seizure classification, and AEDs used during treatment with VNS. We assessed adverse effects and efficacy. Responder rate was defined as >50% seizure improvement from baseline. Results: Thirty patients (females, 18; males, 12; age, 35.1±13.3 years) were included. After 6, 12, 24, and 36 months of follow-up, the response rates were: 13/30 (43%), 13/27 (48%), 9/22 (41%), and 8/16 (50%), respectively; none was seizure free. Fifty-seven percent, 33%, 59%, and 81% of patients had changes of medication type or dose at 6, 12, 24, and 36 months respectively. In the majority of patients, the change of medication consisted of an increase in the dose of AEDs. Conclusions: Our study shows that VNS is an effective therapy, although significant changes in medications were done along with the therapy; therefore, the real effect of VNS could be controversial.

Download Full-text

Analysis and Construction of a Molecular Diagnosis Model of Drug-Resistant Epilepsy Based on Bioinformatics

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.683032 ◽

2021 ◽

Vol 8 ◽

Author(s):

Tenghui Han ◽

Zhenyu Wu ◽

Jun Zhu ◽

Yao Kou ◽

Jipeng Li ◽

...

Keyword(s):

Drug Resistance ◽

Network Analysis ◽

Protein Interaction ◽

Resistance Genes ◽

Recursive Feature Elimination ◽

Support Vector ◽

Drug Resistant ◽

Svm Model ◽

Drug Resistant Epilepsy ◽

Patients With Epilepsy

Background: Epilepsy is a complex chronic disease of the nervous system which influences the health of approximately 70 million patients worldwide. In the past few decades, despite the development of novel antiepileptic drugs, around one-third of patients with epilepsy have developed drug-resistant epilepsy. We performed a bioinformatic analysis to explore the underlying diagnostic markers and mechanisms of drug-resistant epilepsy.Methods: Weighted correlation network analysis (WGCNA) was applied to genes in epilepsy samples downloaded from the Gene Expression Omnibus database to determine key modules. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to screen the genes resistant to carbamazepine, phenytoin, and valproate, and sensitivity of the three-class classification SVM model was verified through the receiver operator characteristic (ROC) curve. A protein–protein interaction (PPI) network was utilized to analyze the protein interaction relationship. Finally, ingenuity pathway analysis (IPA) was adopted to conduct disease and function pathway and network analysis.Results: Through WGCNA, 72 genes stood out from the key modules related to drug resistance and were identified as candidate resistance genes. Intersection analysis of the results of the LASSO and SVM-RFE algorithms selected 11, 4, and 5 drug-resistant genes for carbamazepine, phenytoin, and valproate, respectively. Subsequent union analysis obtained 17 hub resistance genes to construct a three-class classification SVM model. ROC showed that the model could accurately predict patient resistance. Expression of 17 hub resistance genes in healthy subjects and patients was significantly different. The PPI showed that there are six resistance genes (CD247, CTSW, IL2RB, MATK, NKG7, and PRF1) that may play a central role in the resistance of epilepsy patients. Finally, IPA revealed that resistance genes (PRKCH and S1PR5) were involved in “CREB signaling in Neurons.”Conclusion: We obtained a three-class SVM model that can accurately predict the drug resistance of patients with epilepsy, which provides a new theoretical basis for research and treatment in the field of drug-resistant epilepsy. Moreover, resistance genes PRKCH and S1PR5 may cooperate with other resistance genes to exhibit resistance effects by regulation of the cAMP-response element-binding protein (CREB) signaling pathway.

Download Full-text

Tailored multilobar disconnective epilepsy surgery in the posterior quadrant

Journal of Neurosurgery ◽

10.3171/2019.1.jns183103 ◽

2020 ◽

Vol 132 (5) ◽

pp. 1345-1357 ◽

Cited By ~ 3

Author(s):

Michele Rizzi ◽

Martina Revay ◽

Piergiorgio d’Orio ◽

Pina Scarpa ◽

Valeria Mariani ◽

...

Keyword(s):

Safety Profile ◽

Class I ◽

Seizure Outcome ◽

Seizure Freedom ◽

Type I ◽

Drug Resistant ◽

Presurgical Evaluation ◽

Posterior Quadrant ◽

Drug Resistant Epilepsy

OBJECTIVESurgical treatment of drug-resistant epilepsy originating from the posterior quadrant (PQ) of the brain often requires large multilobar resections, and disconnective techniques have been advocated to limit the risks associated with extensive tissue removal. Few previous studies have described a tailored temporoparietooccipital (TPO) disconnective approach; only small series with short postoperative follow-ups have been reported. The aim of the present study was to present a tailored approach to multilobar PQ disconnections (MPQDs) for epilepsy and to provide details about selection of patients, presurgical investigations, surgical technique, treatment safety profile, and seizure and cognitive outcome in a large, single-center series of patients with a long-term follow-up.METHODSIn this retrospective longitudinal study, the authors searched their prospectively collected database for patients who underwent MPQD for drug-resistant epilepsy in the period of 2005–2017. Tailored MPQDs were a posteriori grouped as follows: type I (classic full TPO disconnection), type II (partial TPO disconnection), type III (full temporooccipital [TO] disconnection), and type IV (partial TO disconnection), according to the disconnection plane in the occipitoparietal area. A bivariate statistical analysis was carried out to identify possible predictors of seizure outcome (Engel class I vs classes II–IV) among several presurgical, surgical, and postsurgical variables. Preoperative and postoperative cognitive profiles were also collected and evaluated.RESULTSForty-two consecutive patients (29 males, 24 children) met the inclusion criteria. According to the presurgical evaluation (including stereo-electroencephalography in 13 cases), 12 (28.6%), 24 (57.1%), 2 (4.8%), and 4 (9.5%) patients received a type I, II, III, or IV MPQD, respectively. After a mean follow-up of 80.6 months, 76.2% patients were in Engel class I at last contact; at 6 months and 2 and 5 years postoperatively, Engel class I was recorded in 80.9%, 74.5%, and 73.5% of cases, respectively. Factors significantly associated with seizure freedom were the occipital pattern of seizure semiology and the absence of bilateral interictal epileptiform abnormalities at the EEG (p = 0.02). Severe complications occurred in 4.8% of the patients. The available neuropsychological data revealed postsurgical improvement in verbal domains, whereas nonunivocal outcomes were recorded in the other functions.CONCLUSIONSThe presented data indicate that the use of careful anatomo-electro-clinical criteria in the presurgical evaluation allows for customizing the extent of surgical disconnections in PQ epilepsies, with excellent results on seizures and an acceptable safety profile.

Download Full-text

Safety of responsive neurostimulation in pediatric patients with medically refractory epilepsy

Journal of Neurosurgery Pediatrics ◽

10.3171/2020.5.peds20118 ◽

2020 ◽

Vol 26 (5) ◽

pp. 525-532 ◽

Cited By ~ 1

Author(s):

Fedor Panov ◽

Sara Ganaha ◽

Jennifer Haskell ◽

Madeline Fields ◽

Maite La Vega-Talbott ◽

...

Keyword(s):

Pediatric Patients ◽

Pediatric Population ◽

Complete Removal ◽

Seizure Freedom ◽

Drug Resistant ◽

Invasive Treatment ◽

Single Center Study ◽

Drug Resistant Epilepsy ◽

Main Complication

OBJECTIVEApproximately 75% of pediatric patients who suffer from epilepsy are successfully treated with antiepileptic drugs, while the disease is drug resistant in the remaining patients, who continue to have seizures. Patients with drug-resistant epilepsy (DRE) may have options to undergo invasive treatment such as resection, laser ablation of the epileptogenic focus, or vagus nerve stimulation. To date, treatment with responsive neurostimulation (RNS) has not been sufficiently studied in the pediatric population because the FDA has not approved the RNS device for patients younger than 18 years of age. Here, the authors sought to investigate the safety of RNS in pediatric patients.METHODSThe authors performed a retrospective single-center study of consecutive patients with DRE who had undergone RNS system implantation from September 2015 to December 2019. Patients were followed up postoperatively to evaluate seizure freedom and complications.RESULTSOf the 27 patients studied, 3 developed infections and were treated with antibiotics. Of these 3 patients, one required partial removal and salvaging of a functioning system, and one required complete removal of the RNS device. No other complications, such as intracranial hemorrhage, stroke, or device malfunction, were seen. The average follow-up period was 22 months. All patients showed improvement in seizure frequency.CONCLUSIONSThe authors demonstrated the safety and efficacy of RNS in pediatric patients, with infections being the main complication.

Download Full-text

Magnesium as an Effective Adjunct Therapy for Drug Resistant Seizures

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100013457 ◽

2012 ◽

Vol 39 (3) ◽

pp. 323-327 ◽

Cited By ~ 15

Author(s):

Peter A. Abdelmalik ◽

Nina Politzer ◽

Peter L. Carlen

Keyword(s):

Intractable Epilepsy ◽

Retrospective Chart Review ◽

Epileptic Seizures ◽

Controlled Study ◽

Seizure Freedom ◽

Drug Resistant ◽

Cns Depressant ◽

Drug Resistant Epilepsy ◽

Double Blinded

Objective:To explore the use of magnesium (Mg), an endogenous ion and enzymatic co-factor used in a variety of medical applications, for the treatment of epileptic seizures resistant to traditional medical therapy.Background:For almost a century, Mg has been used as prophylaxis and treatment of seizures associated with eclampsia. Mg is a CNS depressant, with numerous functions intracellularly and extracellularly. However, because of the availability of well studied anticonvulsant drugs, Mg has not been tested widely in the treatment of epileptic seizures.Methods:A retrospective chart review of 22 cases of drug resistant epilepsy, where a trial of empiric oral Mg supplementation (mainly in the form of Mg-oxide) was conducted.Results:Oral Mg supplementation was associated with a significant decrease in the number of seizure days per month, from 15.3 ± 13.2 (mean ± SD) to 10.2 ± 12.6 at first follow up (3-6 months, p=0.021), and to 7.8 ± 10.0 seizure days/month at second follow up (6-12 months, p=0.004). Thirty-six percent had a response rate of 75% or greater at second follow-up. Two patients reported seizure freedom. Most patients were well maintained on MgO 420mg twice a day, or in 2 cases, Mg Lactate, without significant adverse effects, the most frequent being diarrhea (4/22).Discussion:These results suggest that oral Mg supplementation may prove to be a worthwhile adjunctive medication in treating drug intractable epilepsy.Conclusions:A prospective, double-blinded, placebo controlled study is warranted to evaluate the potential of Mg for the treatment of drug-resistant seizures.

Download Full-text

Successful treatment with adjunctive lacosamide in a patient with long term “drug resistant” focal epilepsy

Journal of Epileptology ◽

10.1515/joepi-2015-0014 ◽

2014 ◽

Vol 22 (1) ◽

pp. 51-55

Author(s):

Walter Fröscher ◽

Alois Rauber

Keyword(s):

Case Report ◽

Focal Epilepsy ◽

Adjunctive Treatment ◽

High Dose ◽

Seizure Freedom ◽

Drug Resistant ◽

Off Label ◽

Number Of Patients ◽

Drug Resistant Epilepsy

SUMMARY Introduction. A significant number of patients suffering from epilepsy prove to be resistant to antiepileptic drugs (AEDs). Recent studies, however, suggest that 10–20% of seemingly drug resistant patients may still become seizure-free under the influence of subsequent dosage modifications. Case report. We report on a young man with cryptogenic focal epilepsy. He had his first seizure at the age of fifteen. His seizure frequency was decreased during the following 11 years. However, seizure-freedom was never achieved even though he was treated with twelve to fourteen different AEDs during this time. Intensive presurgical evaluations did not allow identification of a surgically remediable focus. Adjunctive treatment with lacosamide 400 mg/day was not successful. However, the patient became seizure-free immediately after an increase of the lacosamide dose up to 500 mg/day. The patient is now seizure-free for more than two years based on a combination of 500 mg lacosamide and 350 mg lamotrigine, followed by 550 mg and 250 mg, respectively. Discussion and conclusion. This case report highlights that there is always a chance that modifying the medication can result in a drug-resistant epilepsy patient experiencing a significant reduction of seizures and becoming seizure-free. The decisive step in this example was the off-label prescription of a high dose of lacosamide which the patient tolerated well.

Download Full-text

A Novel Approach to Refractory Epilepsy by Targeting Pgp peripherally and centrally: Therapeutic targets and Future perspectives

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319999200819093109 ◽

2020 ◽

Vol 19 ◽

Cited By ~ 1

Author(s):

Urvashi Langeh ◽

Pooja Chawla ◽

Ghanshyam Das Gupta ◽

Shamsher Singh

Keyword(s):

Drug Resistance ◽

Refractory Epilepsy ◽

Present Review ◽

Management Approach ◽

Channel Blockers ◽

Drug Efflux ◽

Drug Resistant ◽

P Glycoprotein ◽

Novel Approach ◽

Drug Resistant Epilepsy

Abstract:: Refractory epilepsy is a type of epilepsy involving seizures uncontrolled by first or second-line anticonvulsant drugs at a regular therapeutic dose. Despite considerable growth in epileptic pharmacotherapy, one-third of the patients are resistant to current therapies. In this, the mechanisms responsible for resistant epilepsy are either increased expulsion of an-tiepileptic drugs (AEDs) by multidrug resistance (MDR) transporters from the epileptogenic tissue or reduced sensitivity of drug in epileptogenic brain tissue. The difficulty to treat refractory epilepsy is because of drug resistance due to cellular drug efflux, use of drug monotherapy, and subtherapeutic dose administration. Increased expression of Pgp is also responsible for resistance epilepsy or refractory epilepsy. Increase glutamate expression via inhibition of cyclooxygenase-II (COX-II) en-zyme also upregulate P-glycoprotein (Pgp) expression and augment instance of recurrent seizures. Peripheral and central in-hibition of Pgp is a powerful tool to control this drug resistance epilepsy. Drug resistance primarily involves multidrug re-sistance (MDR1) gene which is responsible for encoding P-glycoprotein (PgP1 or MDR1). Currently, there is no drug under clinical practice which inhibits MDR1. The present review cites some drugs like calcium channel blockers, COX-II inhibi-tors, and glutamate receptors antagonists that inhibit P-gp. The exploitation of these targets may emerge as a beneficial ap-proach for patients with drug-resistant epilepsy. The present review further highlights the mechanistic role of Pgp in drug-resistant epilepsy, glutamate role in drug efflux, and management approach.

Download Full-text

Defining the optimal target for anterior thalamic deep brain stimulation in patients with drug-refractory epilepsy

Journal of Neurosurgery ◽

10.3171/2020.2.jns193226 ◽

2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Wendy Guo ◽

Bang-Bon Koo ◽

Jae-Hun Kim ◽

Rafeeque A. Bhadelia ◽

Dae-Won Seo ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Refractory Epilepsy ◽

Drug Resistant ◽

Seizure Reduction ◽

Optimal Target ◽

Drug Resistant Epilepsy ◽

Drug Refractory Epilepsy ◽

Deep Brain

OBJECTIVEThe anterior thalamic nucleus (ATN) is a common target for deep brain stimulation (DBS) for the treatment of drug-refractory epilepsy. However, no atlas-based optimal DBS (active contacts) target within the ATN has been definitively identified. The object of this retrospective study was to analyze the relationship between the active contact location and seizure reduction to establish an atlas-based optimal target for ATN DBS.METHODSFrom among 25 patients who had undergone ATN DBS surgery for drug-resistant epilepsy between 2016 and 2018, those who had follow-up evaluations for more than 1 year were eligible for study inclusion. After an initial stimulation period of 6 months, patients were classified as responsive (≥ 50% median decrease in seizure frequency) or nonresponsive (< 50% median decrease in seizure frequency) to treatment. Stimulation parameters and/or active contact positions were adjusted in nonresponsive patients, and their responsiveness was monitored for at least 1 year. Postoperative CT scans were coregistered nonlinearly with preoperative MR images to determine the center coordinate and atlas-based anatomical localizations of all active contacts in the Montreal Neurological Institute (MNI) 152 space.RESULTSNineteen patients with drug-resistant epilepsy were followed up for at least a year following bilateral DBS electrode implantation targeting the ATN. Active contacts located more adjacent to the center of gravity of the anterior half of the ATN volume, defined as the anterior center (AC), were associated with greater seizure reduction than those not in this location. Intriguingly, the initially nonresponsive patients could end up with much improved seizure reduction by adjusting the active contacts closer to the AC at the final postoperative follow-up.CONCLUSIONSPatients with stimulation targeting the AC may have a favorable seizure reduction. Moreover, the authors were able to obtain additional good outcomes after electrode repositioning in the initially nonresponsive patients. Purposeful and strategic trajectory planning to target this optimal region may predict favorable outcomes of ATN DBS.

Download Full-text

Ketogenic Diet and Epilepsy

Nutrients ◽

10.3390/nu11102510 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2510 ◽

Cited By ~ 8

Author(s):

Marzena Ułamek-Kozioł ◽

Stanisław J. Czuczwar ◽

Sławomir Januszewski ◽

Ryszard Pluta

Keyword(s):

Ketogenic Diet ◽

Pharmacological Treatment ◽

Randomized Clinical Trials ◽

Drug Resistant ◽

Treatment Of Epilepsy ◽

Diet Treatment ◽

Limited Effectiveness ◽

Number Of Patients ◽

Drug Resistant Epilepsy ◽

Patients With Epilepsy

Currently available pharmacological treatment of epilepsy has limited effectiveness. In epileptic patients, pharmacological treatment with available anticonvulsants leads to seizure control in <70% of cases. Surgical intervention can lead to control in a selected subset of patients, but still leaves a significant number of patients with uncontrolled seizures. Therefore, in drug-resistant epilepsy, the ketogenic diet proves to be useful. The purpose of this review was to provide a comprehensive overview of what was published about the benefits of ketogenic diet treatment in patients with epilepsy. Clinical data on the benefits of ketogenic diet treatment in terms of clinical symptoms and adverse reactions in patients with epilepsy have been reviewed. Variables that could have influenced the interpretation of the data were also discussed (e.g., gut microbiota). The data in this review contributes to a better understanding of the potential benefits of a ketogenic diet in the treatment of epilepsy and informs scientists, clinicians, and patients—as well as their families and caregivers—about the possibilities of such treatment. Since 1990, the number of publications on attempts to treat drug-resistant epilepsy with a ketogenic diet has grown so rapidly that it has become a challenge to see the overall trajectory and major milestones achieved in this field. In this review, we hope to provide the latest data from randomized clinical trials, practice guidelines, and new research areas over the past 2 years.

Download Full-text

Mechanisms of Drug Resistance in the Pathogenesis of Epilepsy: Role of Neuroinflammation. A Literature Review

Brain Sciences ◽

10.3390/brainsci11050663 ◽

2021 ◽

Vol 11 (5) ◽

pp. 663

Author(s):

Elena D. Bazhanova ◽

Alexander A. Kozlov ◽

Anastasia V. Litovchenko

Keyword(s):

Drug Resistance ◽

Premature Death ◽

Resistance Mechanisms ◽

Biomedical Literature ◽

Drug Resistant ◽

Psychological Consequences ◽

Text Documents ◽

Neural Connections ◽

Inflammatory Processes ◽

Drug Resistant Epilepsy

Epilepsy is a chronic neurological disorder characterized by recurring spontaneous seizures. Drug resistance appears in 30% of patients and it can lead to premature death, brain damage or a reduced quality of life. The purpose of the study was to analyze the drug resistance mechanisms, especially neuroinflammation, in the epileptogenesis. The information bases of biomedical literature Scopus, PubMed, Google Scholar and SciVerse were used. To obtain full-text documents, electronic resources of PubMed Central and Research Gate were used. The article examines the recent research of the mechanisms of drug resistance in epilepsy and discusses the hypotheses of drug resistance development (genetic, epigenetic, target hypothesis, etc.). Drug-resistant epilepsy is associated with neuroinflammatory, autoimmune and neurodegenerative processes. Neuroinflammation causes immune, pathophysiological, biochemical and psychological consequences. Focal or systemic unregulated inflammatory processes lead to the formation of aberrant neural connections and hyperexcitable neural networks. Inflammatory mediators affect the endothelium of cerebral vessels, destroy contacts between endothelial cells and induce abnormal angiogenesis (the formation of “leaky” vessels), thereby affecting the blood–brain barrier permeability. Thus, the analysis of pro-inflammatory and other components of epileptogenesis can contribute to the further development of the therapeutic treatment of drug-resistant epilepsy.

Download Full-text