title: Diagnostic methods and treatment options for focal cortical dysplasia.
abstract: Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high-frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high-field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Proof for a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Although review of current strategies underscores the serious shortcomings of treatment-resistant cases, initial evidence from novel approaches suggests that future success is possible.
authors.affiliation: Pediatric Neurology and Neurogenetics Unit and Laboratories, Children's Hospital Meyer-University of Florence, Florence, Italy.|IRCCS Stella Maris Foundation, Pisa, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Neuroscience Program and the Comprehensive Epilepsy Center, Miami Children's Hospital, Miami, Florida, U.S.A.
authors.forename: Michael
authors.initials: M
authors.lastname: Duchowny
authors.affiliation: Department of Neurology, Miami Children's Hospital, Miami, Florida, U.S.A.
authors.forename: Prasanna
authors.initials: P
authors.lastname: Jayakar
authors.affiliation: Department of Pediatric Neurology, 2nd Faculty of Medicine, Motol University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Krsek
authors.affiliation: INSERM U836, University of Grenoble Alpes, GIN, Grenoble, France.|Epilepsy Unit, Michallon Hospital, Grenoble, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Kahane
authors.affiliation: Epilepsy Surgery Center, Niguarda Hospital, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tassi
authors.affiliation: Pediatric Neurology and Neurogenetics Unit and Laboratories, Children's Hospital Meyer-University of Florence, Florence, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Melani
authors.affiliation: Department of Child Neurology, Bethel Epilepsy Center, Bielefeld, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Polster
authors.affiliation: UCB Pharma, Neurosciences Therapeutic Area, Braine-l'Alleud, Belgium.
authors.forename: Véronique M
authors.initials: VM
authors.lastname: Andre
authors.affiliation: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, U.S.A.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cepeda
authors.affiliation: Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, U.S.A.
authors.forename: Darcy A
authors.initials: DA
authors.lastname: Krueger
authors.affiliation: UCL-Institute of Child Health, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.|Young Epilepsy, Lingfield, United Kingdom.
authors.forename: J Helen
authors.initials: JH
authors.lastname: Cross
authors.affiliation: Clinical Epileptology and Experimental Neurophysiology Unit, Neurological InstituteC. Besta", Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Spreafico
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Mirco
authors.initials: M
authors.lastname: Cosottini
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Gotman
authors.affiliation: Epilepsy Unit, Sainte-Anne Hospital, Paris, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Chassoux
authors.affiliation: Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.|Translational and Integrative Group in Epilepsy Research (TIGER) and Institute for Epilepsies (IDEE), Lyon's Neuroscience Center, INSERM U1028, CNRS 5292, UCBL, Le Vinatier Hospital, Bron, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ryvlin
authors.affiliation: Faculty of Medicine, INSERM, U1106, Institute of Neurosciences of Systems, Marseille, France.|Faculty of Medicine, Aix Marseille University, Marseille, France.|Clinical Neurophysiology Unit, Department of Clinical Neurosciences, CHU Timone, Marseille, France.|Henri-Gastaut Hospital, Saint-Paul Center, Marseille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bartolomei
authors.affiliation: Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Center, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bernasconi
authors.affiliation: Epilepsy Center Erlangen (ZEE), University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Stefan
authors.affiliation: Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children's Hospital, Miami, Florida, U.S.A.
authors.forename: Ian
authors.initials: I
authors.lastname: Miller
authors.affiliation: Neurosurgery Department, Sainte-Anne Hospital, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Devaux
authors.affiliation: Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, U.S.A.
authors.forename: Imad
authors.initials: I
authors.lastname: Najm
authors.affiliation: Pediatric Neurosurgery Unit, Children's Hospital Meyer-University of Florence, Florence, Italy.
authors.forename: Flavio
authors.identifier: http://orcid.org/0000-0002-9006-9225
authors.initials: F
authors.lastname: Giordano
authors.affiliation: Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent, Belgium.
authors.forename: Kristl
authors.initials: K
authors.lastname: Vonck
authors.affiliation: Pediatric Neurology and Neurogenetics Unit and Laboratories, Children's Hospital Meyer-University of Florence, Florence, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Barba
authors.affiliation: Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Blumcke
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D000069279:Drug Resistant Epilepsy / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D004569:Electroencephalography / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D054220:Malformations of Cortical Development / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants
keywords: Drug resistance; EEG; Epilepsy surgery; Epileptogenesis; Focal cortical dysplasia; MRI; PET