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Epilepsia. 2015 Nov;56(11):1669-86. doi: 10.1111/epi.13200. Epub 2015 Oct 5.

Diagnostic methods and treatment options for focal cortical dysplasia.

Author information

1
Pediatric Neurology and Neurogenetics Unit and Laboratories, Children's Hospital Meyer-University of Florence, Florence, Italy.
2
IRCCS Stella Maris Foundation, Pisa, Italy.
3
Neuroscience Program and the Comprehensive Epilepsy Center, Miami Children's Hospital, Miami, Florida, U.S.A.
4
Department of Neurology, Miami Children's Hospital, Miami, Florida, U.S.A.
5
Department of Pediatric Neurology, 2nd Faculty of Medicine, Motol University Hospital, Charles University, Prague, Czech Republic.
6
INSERM U836, University of Grenoble Alpes, GIN, Grenoble, France.
7
Epilepsy Unit, Michallon Hospital, Grenoble, France.
8
Epilepsy Surgery Center, Niguarda Hospital, Milan, Italy.
9
Department of Child Neurology, Bethel Epilepsy Center, Bielefeld, Germany.
10
UCB Pharma, Neurosciences Therapeutic Area, Braine-l'Alleud, Belgium.
11
Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, U.S.A.
12
Division of Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, U.S.A.
13
UCL-Institute of Child Health, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
14
Young Epilepsy, Lingfield, United Kingdom.
15
Clinical Epileptology and Experimental Neurophysiology Unit, Neurological InstituteC. Besta", Milan, Italy.
16
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
17
Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
18
Epilepsy Unit, Sainte-Anne Hospital, Paris, France.
19
Department of Clinical Neurosciences, CHUV, Lausanne, Switzerland.
20
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.
21
Faculty of Medicine, INSERM, U1106, Institute of Neurosciences of Systems, Marseille, France.
22
Faculty of Medicine, Aix Marseille University, Marseille, France.
23
Clinical Neurophysiology Unit, Department of Clinical Neurosciences, CHU Timone, Marseille, France.
24
Henri-Gastaut Hospital, Saint-Paul Center, Marseille, France.
25
Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Center, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
26
Epilepsy Center Erlangen (ZEE), University Erlangen-Nürnberg, Erlangen, Germany.
27
Department of Neurology and Comprehensive Epilepsy Program, Brain Institute, Miami Children's Hospital, Miami, Florida, U.S.A.
28
Neurosurgery Department, Sainte-Anne Hospital, Paris, France.
29
Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, U.S.A.
30
Pediatric Neurosurgery Unit, Children's Hospital Meyer-University of Florence, Florence, Italy.
31
Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Department of Neurology, Ghent University, Ghent, Belgium.
32
Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.

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.

KEYWORDS:

Drug resistance; EEG; Epilepsy surgery; Epileptogenesis; Focal cortical dysplasia; MRI; PET

PMID:
26434565
DOI:
10.1111/epi.13200
[Indexed for MEDLINE]
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