Nicola Specchio, Valentina Di Micco, Marina Trivisano, Alessandro Ferretti, Paolo Curatolo
doi : 10.1111/epi.17115
Pages: 6-21 First Published: 06 November 2021
Autism spectrum disorder (ASD) is frequently associated with infants with epileptic encephalopathy, and early interventions targeting social and cognitive deficits can have positive effects on developmental outcome. However, early diagnosis of ASD among infants with epilepsy is complicated by variability in clinical phenotypes. Commonality in both biological and molecular mechanisms have been suggested between ASD and epilepsy, such as occurs with tuberous sclerosis complex. This review summarizes the current understanding of causal mechanisms between epilepsy and ASD, with a particularly genetic focus. Hypothetical explanations to support the conjugation of the two conditions include abnormalities in synaptic growth, imbalance in neuronal excitation/inhibition, and abnormal synaptic plasticity. Investigation of the probable genetic basis has implemented many genes, although the main risk supports existing hypotheses in that these cluster to abnormalities in ion channels, synaptic function and structure, and transcription regulators, with the mammalian target of rapamycin (mTOR) pathway and “mTORpathies� having been a notable research focus. Experimental models not only have a crucial role in determining gene functions but are also useful instruments for tracing disease trajectory. Precision medicine from gene therapy remains a theoretical possibility, but more contemporary developments continue in molecular tests to aid earlier diagnoses and better therapeutic targeting.
Udaya Seneviratne, Mark Cook, Wendyl D’Souza
doi : 10.1111/epi.17119
Pages: 22-41 First Published: 10 November 2021
Electroencephalography (EEG) has long been used as a versatile and noninvasive diagnostic tool in epilepsy. With the advent of digital EEG, more advanced applications of EEG have emerged. Compared with technologically advanced practice in focal epilepsies, the utilization of EEG in idiopathic generalized epilepsy (IGE) has been lagging, often restricted to a simple diagnostic tool. In this narrative review, we provide an overview of broader applications of EEG beyond this narrow scope, discussing how the current clinical and research applications of EEG may potentially be extended to IGE. The current literature, although limited, suggests that EEG can be used in syndromic classification, guiding antiseizure medication therapy, predicting prognosis, unraveling biorhythms, and investigating functional brain connectivity of IGE. We emphasize the need for longer recordings, particularly 24-h ambulatory EEG, to capture discharges reflecting circadian and sleep–wake cycle-associated variations for wider EEG applications in IGE. Finally, we highlight the challenges and limitations of the current body of literature and suggest future directions to encourage and enhance more extensive applications of this potent tool.
Hans Holthausen, Roland Coras, Yingying Tang, Lily Bai, Irene Wang, Tom Pieper, Manfred Kudernatsch, Till Hartlieb, Martin Staudt, Peter Winkler, Wiebke Hofer, Samir Jabari, Katja Kobow, Ingmar Blumcke
doi : 10.1111/epi.17114
Pages: 42-60 First Published: 06 November 2021
Focal cortical dysplasia (FCD) Type 1 and its three subtypes have yet not been fully characterized at the clinical, anatomopathological, and molecular level (International League Against Epilepsy [ILAE] FCD classification from 2011). We aimed to describe the clinical phenotype of patients with histopathologically confirmed FCD1A obtained from a single epilepsy center between 2002 and 2016.
Konrad Wagstyl, Kirstie Whitaker, Armin Raznahan, Jakob Seidlitz, Petra E. Vértes, Stephen Foldes, Zachary Humphreys, Wenhan Hu, Jiajie Mo, Marcus Likeman, Shirin Davies, Matteo Lenge, Nathan T. Cohen, Yingying Tang, Shan Wang, Mathilde Ripart, Aswin Chari, Martin Tisdall, Nuria Bargallo, EstefanÃa Conde-Blanco, Jose Carlos Pariente, Saül Pascual-Diaz, Ignacio Delgado-MartÃnez, Carmen Pérez-EnrÃquez, Ilaria Lagorio, Eugenio Abela, Nandini Mullatti, Jonathan O'Muircheartaigh, Katy Vecchiato, Yawu Liu, Maria Caligiuri, Ben Sinclair, Lucy Vivash, Anna Willard, Jothy Kandasamy, Ailsa McLellan, Drahoslav Sokol, Mira Semmelroch, Ane Kloster, Giske Opheim, Clarissa Yasuda, Kai Zhang, Khalid Hamandi, Carmen Barba, Renzo Guerrini, William Davis Gaillard, Xiaozhen You, Irene Wang, SofÃa González-Ortiz, Mariasavina Severino, Pasquale Striano, Domenico Tortora, Reetta Kalviainen, Antonio Gambardella, Angelo Labate, Patricia Desmond, Elaine Lui, Terry O'Brien, Jay Shetty, Graeme Jackson, John S. Duncan, Gavin P. Winston, Lars Pinborg, Fernando Cendes, Judith Helen Cross, Torsten Baldeweg, Sophie Adler
doi : 10.1111/epi.17130
Pages: 61-74 First Published: 29 November 2021
Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome.
Theo Demerath, Christoph P. Kaller, Marcel Heers, Anke Staack, Ralf Schwarzwald, Tobias Kober, Marco Reisert, Andreas Schulze-Bonhage, Hans-Jürgen Huppertz, Horst Urbach
doi : 10.1111/epi.17127
Pages: 75-85 First Published: 20 November 2021
The detection of focal cortical dysplasia (FCD) in magnetic resonance imaging is challenging. Voxel-based morphometric analysis and automated FCD detection using an artificial neural network (ANN) integrated into the Morphometric Analysis Program (MAP18) have been shown to facilitate FCD detection. This study aimed to evaluate whether the detection of FCD can be further improved by feeding this approach with magnetization prepared two rapid acquisition gradient echoes (MP2RAGE) instead of magnetization-prepared rapid acquisition gradient echo (MPRAGE) datasets.
Sarah Grace Buttle, Katherine Muir, Sajjad Dehnoei, Richard Webster, Albert Tu
doi : 10.1111/epi.17122
Pages: 86-95 First Published: 08 November 2021
Patients with epilepsy who do not respond to two trials of appropriate antiepileptic drugs are considered to have drug-resistant epilepsy (DRE). The International League Against Epilepsy recommends patients with DRE be referred for surgical evaluation; however, prior literature suggests this is an underutilized intervention, especially in the pediatric setting. This study captures practices of North American pediatric neurologists regarding the management of DRE and factors that may promote or limit referrals for epilepsy surgical evaluation.
Michael Scott Perry, Sabrina Shandley, Max Perelman, Rani K. Singh, Lily Wong-Kisiel, Joseph Sullivan, Ernesto Gonzalez-Giraldo, Erin Fedak Romanowski, Nancy A. McNamara, Ahmad Marashly, Adam P. Ostendorf, Allyson Alexander, Krista Eschbach, Jeffrey Bolton, Steven Wolf, Patricia McGoldrick, Dewi F. Depositario-Cabacar, Michael A. Ciliberto, Satyanarayana Gedela, Kumar Sannagowdara, Samir Karia, Daniel W. Shrey, Priya Tatachar, Srishti Nangia, Zachary Grinspan, Shilpa B. Reddy, Patel Shital, Jason Coryell
doi : 10.1111/epi.17124
Pages: 96-107 First Published: 15 November 2021
Drug-resistant epilepsy (DRE) occurs at higher rates in children <3Â years old. Epilepsy surgery is effective, but rarely utilized in young children despite developmental benefits of early seizure freedom. The present study aims to identify unique patient characteristics and evaluation strategies in children <3Â years old who undergo epilepsy surgery evaluation as a means to assess contributors and potential solutions to health care disparities in this group.
Susanne Fauser, Christian E. Elger, Friedrich Woermann, Christian G. Bien
doi : 10.1111/epi.17131
Pages: 108-119 First Published: 24 November 2021
Rasmussen encephalitis (RE) is a progressive and destructive inflammatory disease of one hemisphere. Its cause is unknown. We investigated comorbidity and laterality factors that might predispose to RE.
Yong Xu, Lin Wan, Wen He, Yang-Yang Wang, Qiu-Hong Wang, Xiao-Mei Luo, Kun Liu, Xiao-Yan Yang, Jing Wang, Xiu-Yu Shi, Guang Yang, Fang Han, Jing Gao, Li-Ping Zou
doi : 10.1111/epi.17121
Pages: 120-129 First Published: 17 November 2021
Vigabatrin (VGB) is the first-line treatment for infantile spasms (IS). Previous studies have shown that VGB exposure may cause vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM). Based on previous studies, this study aimed to go further to explore the possible risk factors and the incidence of VABAM. In addition, diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) were compared to explore whether DWI should be used as a routine examination sequence when MRI is performed in children receiving VGB.
Joseph Sullivan, Nicola Specchio, Orrin Devinsky, Stéphane Auvin, M. Scott Perry, Adam Strzelczyk, Antonio Gil-Nagel, David Dai, Bradley S. Galer, Arnold R. Gammaitoni
doi : 10.1111/epi.17106
Pages: 130-138 First Published: 22 October 2021
The number, unpredictability, and severity of seizures experienced by patients with Dravet syndrome (DS) negatively impact quality of life (QOL) for patients, caregivers, and families. Metrics are needed to assess whether patients with residual seizures have moved meaningfully toward seizure freedom after treatment with new antiseizure medications.
Josemir W. Sander, William E. Rosenfeld, Jonathan J. Halford, Bernhard J. Steinhoff, Victor Biton, Manuel Toledo
doi : 10.1111/epi.17134
Pages: 139-149 First Published: 23 November 2021
We determined retention on open-label cenobamate therapy in the clinical development program to assess the long-term efficacy and tolerability of adjunctive cenobamate in individuals with uncontrolled focal seizures.
Brad K. Kamitaki, Mubeen Janmohamed, Padmaja Kandula, Christopher Elder, Ram Mani, Stephen Wong, Piero Perucca, Terence J. O’Brien, Haiqun Lin, Gary A. Heiman, Hyunmi Choi
doi : 10.1111/epi.17104
Pages: 150-161 First Published: 27 October 2021
We sought to determine which combination of clinical and electroencephalography (EEG) characteristics differentiate between an antiseizure medication (ASM)–resistant vs ASM-responsive outcome for patients with idiopathic generalized epilepsy (IGE).
Cheng-Chia Lee, Chien-Chen Chou, Fu-Jung Hsiao, Yi-Hsiu Chen, Chun-Fu Lin, Ching-Jen Chen, Syu-Jyun Peng, Hao-Li Liu, Hsiang-Yu Yu
doi : 10.1111/epi.17105
Pages: 162-175 First Published: 02 November 2021
The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal epilepsy models; however, the safety and efficacy of FUS in humans with epilepsy have not been well established. Patients with drug-resistant epilepsy (DRE) undergoing stereo-electroencephalography (SEEG) provide an opportunity to investigate the neuromodulatory effects of FUS in humans.
Andrew L. Ko, Ai Phuong S. Tong, Mahmud Mossa-Basha, Kurt E. Weaver, Jeffrey G. Ojemann, John W. Miller, Shahin Hakimian
doi : 10.1111/epi.17059
Pages: 176-189 First Published: 24 November 2021
Laser interstitial thermal therapy (LITT) is a minimally invasive surgery for mesial temporal lobe epilepsy (mTLE), but the effects of individual patient anatomy and location of ablation volumes affect seizure outcomes. The purpose of this study is to see if features of individual patient structural connectomes predict surgical outcomes after LITT for mTLE.
Daniel Zelig, Ilan Goldberg, Oded Shor, Shira Ben Dor, Amit Yaniv-Rosenfeld, Dan Z. Milikovsky, Jonathan Ofer, Hamza Imtiaz, Alon Friedman, Felix Benninger
doi : 10.1111/epi.17110
Pages: 190-198 First Published: 09 November 2021
Management of a patient presenting with a first seizure depends on the risk of additional seizures. In clinical practice, the recurrence risk is estimated by the treating physician using the neurological examination, brain imaging, a thorough history for risk factors, and routine scalp electroencephalogram (EEG) to detect abnormal epileptiform activity. The decision to use antiseizure medication can be challenging when objective findings are missing. There is a need for new biomarkers to better diagnose epilepsy following a first seizure. Recently, an EEG-based novel analytical method was reported to detect paroxysmal slowing in the cortical network of patients with epilepsy. The aim of our study is to test this method's sensitivity and specificity to predict epilepsy following a first seizure.
Sharon Chiang, Joline M. Fan, Vikram R. Rao
doi : 10.1111/epi.17113
Pages: 199-208 First Published: 01 November 2021
This study was undertaken to measure the duration of chronic electrocorticography (ECoG) needed to attain stable estimates of the seizure laterality ratio in patients with drug-resistant bilateral temporal lobe epilepsy (BTLE).
Sebastian Brandner, Sarah Schroeter, Gürsel Çalışkan, Seda Salar, Katja Kobow, Roland Coras, Ingmar Blümcke, Hajo Hamer, Michael Schwarz, Michael Buchfelder, Anna Maslarova
doi : 10.1111/epi.17107
Pages: 209-221 First Published: 23 October 2021
Memory impairment is common in patients with temporal lobe epilepsy and seriously affects life quality. Chronic stress is a recognized cofactor in epilepsy and can also impair memory function. Furthermore, increased cortisol levels have been reported in epilepsy patients. Animal models have suggested that aggravating effects of stress on memory and synaptic plasticity were mediated via glucocorticoids. The aim of this study was, therefore, to investigate the effect of glucocorticoid receptor (GR) modulation on synaptic plasticity in the human cortex of epilepsy patients.
Ayushe A. Sharma, Adam M. Goodman, Jane B. Allendorfer, Noah S. Philip, Stephen Correia, W. Curt LaFrance Jr., Jerzy P. Szaflarski
doi : 10.1111/epi.17109
Pages: 222-236 First Published: 03 November 2021
Psychogenic nonepileptic seizures (PNES) are characterized by multifocal and global abnormalities in brain function and connectivity. Only a few studies have examined neuroanatomic correlates of PNES. Traumatic brain injury (TBI) is reported in 83% of patients with PNES and may be a key component of PNES pathophysiology. In this study, we included patients with TBI preceding the onset of PNES (TBI-PNES) and TBI without PNES (TBI-only) to identify neuromorphometric abnormalities associated with PNES.
Maria Stefanidou, Jayandra J. Himali, Orrin Devinsky, Jose R. Romero, Mohammad Arfan Ikram, Alexa S. Beiser, Sudha Seshadri, Daniel Friedman
doi : 10.1111/epi.17108
Pages: 237-243 First Published: 16 November 2021
Stroke is the most common cause of epilepsy in older age. Subclinical cerebrovascular disease is believed to underlie some of the 30%–50% of late-onset epilepsy without a known cause (Li et al. Epilepsia. 1997;38:1216; Cleary et al. Lancet. 2004;363:1184). We studied the role of modifiable vascular risk factors in predicting subsequent epilepsy among participants ages 45 or older in the Framingham Heart Study (FHS), a longitudinal, community-based study.
Lu Lu, Qi Zhang, Jing Xiao, Yingying Zhang, Wei Peng, Xiong Han, Shengli Chen, Dan Yang, Josemir W. Sander, Dong Zhou, Weixi Xiong
doi : 10.1111/epi.17138
Pages: 244-251 First Published: 21 November 2021
This study was undertaken to investigate the COVID-19 vaccine uptake rate and possible postvaccination effects in adults with epilepsy.
Simona Lattanzi, Valentina Chiesa, Edoardo Ferlazzo, Angela La Neve, Pietro Pignatta, Carlo Di Bonaventura, BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST) Group
doi : 10.1111/epi.17123
Pages: 252-253 First Published: 14 November 2021
Ali A. Asadi-Pooya, Sándor Beniczky, Guido Rubboli, Michael R. Sperling, Stefan Rampp, Emilio Perucca
doi : 10.1111/epi.17129
Pages: 254-255 First Published: 19 November 2021
doi : 10.1111/epi.17148
Pages: 256-257 First Published: 08 January 2022
Lauren Elizabeth Walker, Graeme John Sills, Andrea Jorgensen, Tiina Alapirtti, Jukka Peltola, Martin J. Brodie, Anthony Guy Marson, Annamaria Vezzani, Munir Pirmohamed
doi : 10.1111/epi.17116
Pages: e1-e6 First Published: 08 November 2021
Currently no sensitive and specific biomarkers exist to predict drug-resistant epilepsy. We determined whether blood levels of high-mobility group box 1 (HMGB1), a mediator of neuroinflammation implicated in drug-resistant epilepsies, identifies patients with drug-resistant seizures. Patients with drug-resistant epilepsy express significantly higher levels of blood HMGB1 than those with drug-responsive, well-controlled seizures and healthy controls. No correlation existed between blood HMGB1Â levels and total pretreatment seizure count or days since last seizure at new epilepsy diagnosis, indicating that blood HMGB1 does not solely reflect ongoing seizures. HMGB1 distinguishes with high specificity and selectivity drug-resistant versus drug-responsive patients. This protein therefore has potential clinical utility to act as a biomarker for predicting response to therapy, which should be addressed in prospective clinical studies.
Francesco Miceli, Renzo Guerrini, Mario Nappi, Maria Virginia Soldovieri, Elena Cellini, Christina A. Gurnett, Lucio Parmeggiani, Davide Mei, Maurizio Taglialatela
doi : 10.1111/epi.17118
Pages: e7-e14 First Published: 14 November 2021
A wide phenotypic spectrum of neurological diseases is associated with KCNA1 (Kv1.1) variants. To investigate the molecular basis of such a heterogeneous clinical presentation and identify the possible correlation with in vitro phenotypes, we compared the functional consequences of three heterozygous de novo variants (p.P403S, p.P405L, and p.P405S) in Kv1.1 pore region found in four patients with severe developmental and epileptic encephalopathy (DEE), with those of a de novo variant in the voltage sensor (p.A261T) identified in two patients with mild, carbamazepine-responsive, focal epilepsy. Patch-clamp electrophysiology was used to investigate the functional properties of mutant Kv1.1Â subunits, both expressed as homomers and heteromers with wild-type Kv1.1Â subunits. KCNA1 pore mutations markedly decreased (p. P405S) or fully suppressed (p. P403S, p. P405L) Kv1.1-mediated currents, exerting loss-of-function (LoF) effects. By contrast, channels carrying the p.A261T variant exhibited a hyperpolarizing shift of the activation process, consistent with a gain-of-function (GoF) effect. The present results unveil a novel correlation between in vitro phenotype (GoF vs LoF) and clinical course (mild vs severe) in KCNA1-related phenotypes. The excellent clinical response to carbamazepine observed in the patients carrying the A261T variant suggests an exquisite sensitivity of KCNA1Â GoF to sodium channel inhibition that should be further explored.
Dennis L. Cheung, Matthew J. Cooke, Chelsea S. Goulton, Chanchanok Chaichim, Louis F. Cheung, Ashor Khoshaba, Junichi Nabekura, Andrew J. Moorhouse
doi : 10.1111/epi.17097
Pages: e15-e22 First Published: 17 November 2021
Reduced anticonvulsant efficacy of benzodiazepines is a problem in the treatment of status epilepticus, with up to 50% of patients failing to respond to their first dose. KCC2 is a neuronal K+-Cl− co-transporter that helps set and maintain intracellular Cl− concentrations. KCC2 functional downregulation is a potential contributor to benzodiazepine resistance. We tested this idea using male and female doxycycline-inducible, conditional transgenic mice to increase the functional expression of KCC2 in pyramidal neurons. We administered mice with two doses of the chemoconvulsant kainic acid (5 mg/kg, i.p.) 60 min apart and quantified the resultant seizures with electroencephalography (EEG) recordings. Overexpression of KCC2 prior to the chemoconvulsant challenge did not affect seizure latency or other measures of seizure severity, but it did increase diazepam's efficacy in stopping EEG seizures. Spike rate, time in seizure, and EEG spectral power following diazepam (5 mg/kg, i.p) were all significantly lower in KCC2 overexpression mice as compared to control mice. Our results indicate that, in the context of benzodiazepine resistance during sustained seizures, addressing impaired Cl− homeostasis alone appreciably improves the efficacy of γ-aminobutyric acid (GABA)ergic inhibition. We therefore suggest the simultaneous targeting of KCC2 and GABAA receptors as a pathway for improving current anticonvulsant therapeutic strategies.
Giada Giovannini, Roberta Bedin, Diana Ferraro, Anna Elisabetta Vaudano, Jessica Mandrioli, Stefano Meletti
doi : 10.1111/epi.17132
Pages: e23-e29 First Published: 21 November 2021
Biomarkers of neuronal damage in status epilepticus (SE) would be of great relevance for clinical and research purposes. In a retrospective cross-sectional study, serum neurofilament light chain (NfL) levels were measured in patients with SE (30 subjects), patients with drug-resistant epilepsy (30 subjects), and healthy controls (30 subjects). Serum NfL levels were higher in patients with SE (median = 26.15 pg/ml) compared to both epilepsy patients (median = 7.35 pg/ml) and healthy controls (median = 6.81 pg/ml; p < .001). In patients with SE, serum NfL levels showed a high correlation with cerebrospinal fluid (CSF) NfL (τ = .68, p < .001) as well as with CSF total tau (t-tau) levels (τ = .627, p < .001); they were higher in SE lasting >24 h (p = .013), in refractory/superrefractory SE (p = .004), and in patients who died within 30 days or who presented a worsening of clinical conditions (p = .001). Values of >28.8 pg/ml predicted 30-day clinical worsening or death (odds ratio [OR] = 10.83, 95% confidence interval [CI] = 1.96–59.83, p = .006) and SE refractoriness (OR = 9.33, 95% CI = 1.51–57.65, p = .016). In conclusion, serum NfL levels are increased in SE and correlate with SE treatment response, duration, and outcomes, therefore representing a promising biomarker of seizure-related neuronal damage.
Avisha Kumar, Reese Martin, William Chen, Andrew Bauerschmidt, Mark W. Youngblood, Courtney Cunningham, Yang Si, Cel Ezeani, Zachary Kratochvil, Jared Bronen, James Thomson, Katherine Riordan, Ji Yeoun Yoo, Romina Shirka, Louis Manganas, Heinz Krestel, Lawrence J. Hirsch, Hal Blumenfeld
doi : 10.1111/epi.17136
Pages: e30-e34 First Published: 24 November 2021
People with epilepsy face serious driving restrictions, determined using retrospective studies. To relate seizure characteristics to driving impairment, we aimed to study driving behavior during seizures with a simulator. Patients in the Yale New Haven Hospital undergoing video-electroencephalographic monitoring used a laptop-based driving simulator during ictal events. Driving function was evaluated by video review and analyzed in relation to seizure type, impairment of consciousness/responsiveness, or motor impairment during seizures. Fifty-one seizures in 30 patients were studied. In terms of seizure type, we found that focal to bilateral tonic–clonic or myoclonic seizures (5/5) and focal seizures with impaired consciousness/responsiveness (11/11) always led to driving impairment; focal seizures with spared consciousness/responsiveness (0/10) and generalized nonmotor (generalized spike–wave bursts; 1/19) usually did not lead to driving impairment. Regardless of seizure type, we found that seizures with impaired consciousness (15/15) or with motor involvement (13/13) always led to impaired driving, but those with spared consciousness (0/20) or spared motor function (5/38) usually did not. These results suggest that seizure types with impaired consciousness/responsiveness and abnormal motor function contribute to impaired driving. Expanding this work in a larger cohort could further determine how results with a driving simulator may translate into real world driving safety.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟