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Drug resistant epilepsy

Chinekwu Anyanwu, Gholam K Motamedi
Despite appropriate trials of at least two antiepileptic drugs, about a third of patients with epilepsy remain drug resistant (intractable; refractory). Epilepsy surgery offers a potential cure or significant improvement to those with focal onset drug-resistant seizures. Unfortunately, epilepsy surgery is still underutilized which might be in part because of the complexity of presurgical evaluation. This process includes classifying the seizure type, lateralizing and localizing the seizure onset focus (epileptogenic zone), confirming the safety of the prospective brain surgery in terms of potential neurocognitive deficits (language and memory functions), before devising a surgical plan...
March 21, 2018: Brain Sciences
Chen Jia, Shanshan Han, Liming Wei, Xiangji Dang, Qianqian Niu, Mengyu Chen, Boqun Cao, Yuting Liu, Haisheng Jiao
CONTEXT: Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment. OBJECTIVE: This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined...
December 2018: Pharmaceutical Biology
Hua Tao, Xu Zhou, Bin Zhao, Keshen Li
According to an update from the World Health Organization, approximately 50 million people worldwide suffer from epilepsy, and nearly one-third of these individuals are resistant to the currently available antiepileptic drugs, which has resulted in an insistent pursuit of novel strategies for seizure treatment. Recently, methylglyoxal (MG) was demonstrated to serve as a partial agonist of the gamma-aminobutyric acid type A (GABAA ) receptor and to play an inhibitory role in epileptic activities. However, MG is also a substrate in the generation of advanced glycation end products (AGEs) that function by activating the receptor of AGEs (RAGE)...
2018: Frontiers in Molecular Neuroscience
Erin D'Agostino, Vyacheslav Makler, David F Bauer
BACKGROUND: Vagal nerve stimulation (VNS) is a safe and well-tolerated treatment for drug resistant epilepsy. Complications and failure of the device can result from lead fracture, device malfunction, disconnection, or battery displacement and can result in a variety of symptoms. We present an interesting case of stimulator malfunction with increased impedance change seen only with a change in head position. CASE DESCRIPTION: Patient is a 25-year-old male with a vagal nerve stimulator (VNs) placed for medically refractory epilepsy who presented with neck pain and an electrical pulling sensation in his neck whenever he turned his head to the right...
March 16, 2018: World Neurosurgery
Ludovica Pasca, Roberto H Caraballo, Valentina De Giorgis, J Gabriela Reyes, Joyce A Macasaet, Silvia Masnada, Marisa Armeno, Massimo Musicco, Anna Tagliabue, Pierangelo Veggiotti
PURPOSE: To evaluate the efficacy and tolerability of the ketogenic diet (KD) as a treatment for drug-resistant epilepsy secondary to malformations of cortical development. METHODS: A two-centre retrospective analysis of 45 paediatric patients with refractory epilepsy due to malformation of cortical development was carried out. Patients were divided into three groups based on malformation type: abnormal neural proliferation (Group 1); abnormal neural migration (Group 2) and abnormal post-migrational development (Group 3)...
March 8, 2018: Seizure: the Journal of the British Epilepsy Association
Gopal Krishna Dash, Chaturbhuj Rathore, Malcolm K Jeyaraj, Pandurang Wattamwar, Sankara P Sarma, Kurupath Radhakrishnan
OBJECTIVE: Interictal regional paroxysmal fast activity (RPFA) on scalp EEG is common in patients with focal cortical dysplasia (FCD). Little data exists regarding the presence of RPFA in other etiologies. METHODS: We studied the association between RPFA and etiology on MRI in patients with drug resistant focal epilepsy undergoing presurgical evaluation in 2011. RPFA was defined as ≥3 consecutive spikes with a frequency of ≥10 Hz lasting ≥300 ms but <4 s...
February 27, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Brian Nils Lundstrom, Christian Meisel, Jamie Van Gompel, Matt Stead, Greg Worrell
OBJECTIVES: To develop quantitative measures for estimating seizure probability, we examine intracranial EEG data from patient groups with three qualitative seizure probabilities: patients with drug resistant focal epilepsy (high), these patients during cortical stimulation (intermediate), and patients who have no history of seizures (low). METHODS: Patients with focal epilepsy were implanted with subdural electrodes during presurgical evaluation. Patients without seizures were implanted during treatment with motor cortex stimulation for atypical facial pain...
February 27, 2018: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
Piero Perucca, Ingrid E Scheffer, Michelle Kiley
The International League Against Epilepsy has recently published a new classification of epileptic seizures and epilepsies to reflect the major scientific advances in our understanding of the epilepsies since the last formal classification 28 years ago. The classification emphasises the importance of aetiology, which allows the optimisation of management. Antiepileptic drugs (AEDs) are the main approach to epilepsy treatment and achieve seizure freedom in about two-thirds of patients. More than 15 second generation AEDs have been introduced since the 1990s, expanding opportunities to tailor treatment for each patient...
March 19, 2018: Medical Journal of Australia
Tawfeeq Shekh-Ahmad, Ramona Eckel, Sharadha Dayalan Naidu, Maureen Higgins, Masayuki Yamamoto, Albena T Dinkova-Kostova, Stjepana Kovac, Andrey Y Abramov, Matthew C Walker
Hippocampal sclerosis is a common acquired disease that is a major cause of drug-resistant epilepsy. A mechanism that has been proposed to lead from brain insult to hippocampal sclerosis is the excessive generation of reactive oxygen species, and consequent mitochondrial failure. Here we use a novel strategy to increase endogenous antioxidant defences using RTA 408, which we show activates nuclear factor erythroid 2-related factor 2 (Nrf2, encoded by NFE2L2) through inhibition of kelch like ECH associated protein 1 (KEAP1) through its primary sensor C151...
March 12, 2018: Brain: a Journal of Neurology
Vejay N Vakharia, Rachel Sparks, Kuo Li, Aidan G O'Keeffe, Anna Miserocchi, Andrew W McEvoy, Michael R Sperling, Ashwini Sharan, Sebastien Ourselin, John S Duncan, Chengyuan Wu
OBJECTIVE: Surgical resection of the mesial temporal structures brings seizure remission in 65% of individuals with drug-resistant mesial temporal lobe epilepsy (MTLE). Laser interstitial thermal therapy (LiTT) is a novel therapy that may provide a minimally invasive means of ablating the mesial temporal structures with similar outcomes, while minimizing damage to the neocortex. Systematic trajectory planning helps ensure safety and optimal seizure freedom through adequate ablation of the amygdalohippocampal complex (AHC)...
March 12, 2018: Epilepsia
Lisa Vaugier, Stanislas Lagarde, Aileen McGonigal, Agnès Trébuchon, Mathieu Milh, Anne Lépine, Didier Scavarda, Romain Carron, Fabrice Bartolomei
Management of patients after initial epilepsy surgical failure is challenging. In this study, we report our experience in using the stereoelectroencephalography (SEEG) method in the reevaluation of patients after initial epilepsy surgical failure. We selected 28 patients examined through SEEG in our department for drug-resistant focal epilepsy following initial epilepsy surgical failure. For each patient, the residual seizure onset zone (rSOZ) as defined by SEEG was classified as either contiguous if the seizure onset zone (SOZ) was focal and close to the surgical cavity (same lobe) or noncontiguous in cases where the SOZ included site(s) distant from the surgical cavity...
March 8, 2018: Epilepsy & Behavior: E&B
Marine Loizon, Sylvain Rheims
Epilepsy is considered as drug-resistant when seizures persist despite the administration of 2 antiepileptic drugs adapted to the patient's needs, with an effective dosage, well-tolerated, whether as a single agent or in combination. Any patient suffering from drug-resistant focal epilepsy should be evaluated at least once in a tertiary epilepsy centre to discuss the appropriateness of a pre-surgical work-up. In drug-resistant epilepsy, the determinants of quality of life are multifactorial and not exclusively linked to the seizure frequency...
March 7, 2018: La Presse Médicale
O Fernández-Concepción, M López Jiménez, C Valencia-Calderón, A Calderón-Valdivieso, A Recasén-Linares, L Reyes-Haro, C Vásquez-Ham
INTRODUCTION: There is sufficient evidence on the usefulness of surgery as a therapeutic alternative for patients with drug-resistant epilepsy; however this treatment is underutilized, especially in developing countries. METHODS: We describe the outcomes of epilepsy surgery in 27 paediatric patients at Hospital Baca Ortiz in Quito, Ecuador. Our analysis considered the following variables: reduction in seizure frequency, surgery outcome according to the Engel classification, improvement in quality of life, and serious complications due to surgery...
March 7, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Mehmet Tecellioglu, Ozden Kamisli, Suat Kamisli, Fatma Ebru Yucel, Cemal Ozcan
BACKGROUND: Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. AIMS: To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. METHODS: Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified...
March 9, 2018: Irish Journal of Medical Science
Tommi Nora, Hanna Heinonen, Mirja Tenhunen, Sirpa Rainesalo, Soila Järvenpää, Kai Lehtimäki, Jukka Peltola
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up...
2018: Frontiers in Neurology
J Wickham, N G Brödjegård, R Vighagen, L H Pinborg, J Bengzon, D P D Woldbye, M Kokaia, M Andersson
Resected hippocampal tissue from patients with drug-resistant epilepsy presents a unique possibility to test novel treatment strategies directly in target tissue. The post-resection time for testing and analysis however is normally limited. Acute tissue slices allow for electrophysiological recordings typically up to 12 hours. To enable longer time to test novel treatment strategies such as, e.g., gene-therapy, we developed a method for keeping acute human brain slices viable over a longer period. Our protocol keeps neurons viable well up to 48 hours...
March 7, 2018: Scientific Reports
Emily Stockings, Dino Zagic, Gabrielle Campbell, Megan Weier, Wayne D Hall, Suzanne Nielsen, Geoffrey K Herkes, Michael Farrell, Louisa Degenhardt
Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies...
March 6, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
Giovanni Tringali, Beatrice Bono, Ivano Dones, Roberto Cordella, Giuseppe Didato, Flavio Villani, Francesco Prada
BACKGROUND: Type II focal cortical dysplasia is the most common malformation of cortical development associated with drug resistant epilepsy and susceptible to surgical resection. Although advanced imaging modalities are nowadays capable to detect the majority of such cortical disorders, it is still a challenge for the surgeon to visualize them intraoperatively. The lack of direct boundaries' identification between normal brain and subtle dysplastic tissue may explain poor results in terms of seizure-free patients compared to other forms of epilepsy...
March 3, 2018: World Neurosurgery
Adriana Fernanda K Vizuete, Fernanda Hansen, Elisa Negri, Marina Concli Leite, Diogo Losch de Oliveira, Carlos-Alberto Gonçalves
BACKGROUND: Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and is accompanied, in one third of cases, by resistance to antiepileptic drugs (AED). Most AED target neuronal activity modulated by ionic channels, and the steroid sensitivity of these channels has supported the use of corticosteroids as adjunctives to AED. Assuming the importance of astrocytes in neuronal activity, we investigated inflammatory and astroglial markers in the hippocampus, a key structure affected in TLE and in the Li-pilocarpine model of epilepsy...
March 5, 2018: Journal of Neuroinflammation
Sara Gasparini, Edoardo Ferlazzo, Giuseppe Pustorino, Michele Ascoli, Vittoria Cianci, Chiara Sueri, Silvio Calabrò, Mauro Campello, Emilio Africa, Antonio Gangemi, Paolo Versace, Umberto Aguglia
OBJECTIVE: The purpose of this case-control study is to evaluate the prevalence of occult temporal encephalomeningocele (OTE) in patients with temporal lobe epilepsy (TLE) of unknown etiology presenting to an epilepsy center, independently from drug sensitivity. METHODS: We studied 95 patients with TLE (51 female, mean age 49.4 ± 17.1 years) and 151 controls (88 female, mean age 54.1 ± 21.0 years) using a 1.5T brain MRI, including balanced steady-state gradient echo sequences, targeted to the temporal lobes...
March 2, 2018: Neurology
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