RSS-Feed abonnieren
DOI: 10.1055/s-0044-1786781
Focal Cortical Dysplasia: Diagnosis, Classification, and Treatment Options
![](https://www.thieme-connect.de/media/10.1055-s-00029030/202402/lookinside/thumbnails/10-1055-s-0044-1786781_2400015-1.jpg)
Abstract
Focal cortical dysplasias (FCDs) include a spectrum of anomalies of cortical development that consist in one or more areas with altered lamination and in some cases, neurons of abnormal morphology. Clinically, these structural anomalies led to arise of epilepsy, which is more often a focal, drug-resistant type with onset in pediatric or adolescent age. Occasionally, other symptoms have been reported in patients with FCDs, such as headache, movement disorders, and cognitive impairment. According to International League against Epilepsy scheme of 2011, three main subtypes of FCD can be distinguished, based of anatomopathological feature, radiological signs, and clinical expression. Magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography, and neurophysiology are the cornerstones of diagnosis, although their negativity cannot exclude FCD in symptomatic patients, especially in FCD type I which often is elusive. In MRI, the main finding is the irregularity of the cortical–subcortical signal, specifically reduction of cortical thickness and absence of clear demarcation between gray and white matters, which is strongly diagnostic for FCD. Epilepsy related to FCD is difficult to manage and until now there is not a clear direction for treatment's rules. FCD shows poor response to antiepileptic drugs (AEDs), and there is no evidence of some AED that has proved more efficacy than others in patients with FCDs. Considering genetical and pathophysiological recent acquisitions, mammalian target of rapamycin inhibitors may play a fundamental role in future treatment of FCDs, but nowadays, surgery still remains the main weapon, with 50% of patients who undergo neurosurgery.
* These authors contributed equally to this article.
Publikationsverlauf
Eingereicht: 11. Dezember 2023
Angenommen: 04. April 2024
Artikel online veröffentlicht:
11. Mai 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Barkovich AJ, Kuzniecky RI, Jackson GD, Guerrini R, Dobyns WB. A developmental and genetic classification for malformations of cortical development. Neurology 2005; 65 (12) 1873-1887
- 2 Blumcke I, Spreafico R, Haaker G. et al; EEBB Consortium. Histopathological findings in brain tissue obtained during epilepsy surgery. N Engl J Med 2017; 377 (17) 1648-1656
- 3 Lamberink HJ, Otte WM, Blümcke I, Braun KPJ. European Epilepsy Brain Bank writing group, study group, European Reference Network EpiCARE. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study. Lancet Neurol 2020; 19 (09) 748-757
- 4 Praticò AD, Falsaperla R, Ruggieri M, Corsello G, Pavone P. Prognostic challenges of SCN1A genetic mutations: report on two children with mild features. J Pediatr Neurol 2016; 14: 82-88
- 5 Crino PB. Focal cortical dysplasia. Semin Neurol 2015; 35 (03) 201-208
- 6 Najm IM, Sarnat HB, Blümcke I. Review: the international consensus classification of focal cortical dysplasia - a critical update 2018. Neuropathol Appl Neurobiol 2018; 44 (01) 18-31
- 7 Falsaperla R, D'Angelo G, Praticò AD. et al. Ketogenic diet for infants with epilepsy: a literature review. Epilepsy Behav 2020; 112: 107361
- 8 Blümcke I, Thom M, Aronica E. et al. The clinicopathologic spectrum of focal cortical dysplasias: a consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission. Epilepsia 2011; 52 (01) 158-174
- 9 Mellerio C, Labeyrie MA, Chassoux F. et al. 3T MRI improves the detection of transmantle sign in type 2 focal cortical dysplasia. Epilepsia 2014; 55 (01) 117-122
- 10 Pavone P, Praticò AD, Falsaperla R. et al. Congenital generalized hypertrichosis: the skin as a clue to complex malformation syndromes. Ital J Pediatr 2015; 41: 55
- 11 Praticò AD, Pavone P, Scuderi MG. et al. Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report. Cases J 2009; 2: 7394
- 12 Bartolini E, Cosottini M, Costagli M. et al. Ultra-high-field targeted imaging of focal cortical dysplasia: the intracortical black line sign in type IIB. AJNR Am J Neuroradiol 2019; 40 (12) 2137-2142
- 13 Pavone P, Praticò AD, Ruggieri M, Falsaperla R. Hypomelanosis of Ito: a round on the frequency and type of epileptic complications. Neurol Sci 2015; 36 (07) 1173-1180
- 14 Ho CSH, Dubeau F, Séguin R, Ducharme S. Prevalence of neuropsychiatric symptoms associated with malformations of cortical development. Epilepsy Behav 2019; 92: 306-310
- 15 Pavone V, Signorelli SS, Praticò AD. et al. Total hemi-overgrowth in pigmentary mosaicism of the (hypomelanosis of) Ito type: eight case reports. Medicine (Baltimore) 2016; 95 (10) e2705
- 16 Pavone P, Falsaperla R, Ruggieri M. et al. Clinical course of N-methyl-D-aspartate receptor encephalitis and the effectiveness of cyclophosphamide treatment. J Pediatr Neurol 2017; 15: 84-49
- 17 Falsaperla R, Perciavalle V, Pavone P. et al. Unilateral eye blinking arising from the ictal ipsilateral occipital area. Clin EEG Neurosci 2016; 47 (03) 243-246
- 18 Guerrini R, Duchowny M, Jayakar P. et al. Diagnostic methods and treatment options for focal cortical dysplasia. Epilepsia 2015; 56 (11) 1669-1686
- 19 Wang TS, Liu QZ, Liu M. et al. Clinical features and surgical outcomes in young children with focal cortical dysplasia type II. CNS Neurosci Ther 2020; 26 (02) 270-277
- 20 Pavone P, Falsaperla R, Ruggieri M, Praticò AD, Pavone L. West syndrome treatment: new roads for an old syndrome. Front Neurol 2013; 4: 113
- 21 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Rediagnosing one of Smith's patients (John McCann) with “neuromas tumours” (1849). Neurol Sci 2017; 38 (03) 493-499
- 22 Ruggieri M, Polizzi A, Marceca GP, Catanzaro S, Praticò AD, Di Rocco C. Introduction to phacomatoses (neurocutaneous disorders) in childhood. Childs Nerv Syst 2020; 36 (10) 2229-2268
- 23 Wu Q, Liu J, Fang A. et al. The dynamics of neuronal migration. Adv Exp Med Biol 2014; 800: 25-36
- 24 Vitaliti G, Praticò AD, Cimino C. et al. Hepatitis B vaccine in celiac disease: yesterday, today and tomorrow. World J Gastroenterol 2013; 19 (06) 838-845
- 25 Vitaliti G, Cimino C, Coco A, Praticò AD, Lionetti E. The immunopathogenesis of cow's milk protein allergy (CMPA). Ital J Pediatr 2012; 38: 35 Erratum in: Ital J Pediatr 2014;39:82
- 26 Naveed M, Kazmi SK, Amin M. et al. Comprehensive review on the molecular genetics of autosomal recessive primary microcephaly (MCPH). Genet Res 2018; 100: e7
- 27 Palano GM, Praticò AD, Praticò ER. et al. [Accidental ethyl alcohol intoxication in a 30-day-old infant. Clinical findings and neurological follow-up]. Minerva Pediatr 2007; 59 (03) 275-279
- 28 Chassoux F, Devaux B, Landré E. et al. Stereoelectroencephalography in focal cortical dysplasia: a 3D approach to delineating the dysplastic cortex. Brain 2000; 123 (Pt 8): 1733-1751
- 29 Fiumara A, Lanzafame G, Arena A. et al. COVID-19 pandemic outbreak and its psychological impact on patients with rare lysosomal diseases. J Clin Med 2020; 9 (09) 2716
- 30 Praticò AD, Leonardi S. Immunotherapy for food allergies: a myth or a reality?. Immunotherapy 2015; 7 (02) 147-161
- 31 Pratico AD, Salafia S, Barone P, La Rosa M, Leonardi S, Type II. Type II autoimmune hepatitis and small duct sclerosing cholangitis in a seven years old child: an overlap syndrome?. Hepat Mon 2013; 13 (12) e14452
- 32 Praticò AD, Ruggieri M. COVID-19 vaccination for children: may be necessary for the full eradication of the disease. Pediatr Res 2021; 90 (06) 1102-1103
- 33 Bast T, Ramantani G, Seitz A, Rating D. Focal cortical dysplasia: prevalence, clinical presentation and epilepsy in children and adults. Acta Neurol Scand 2006; 113 (02) 72-81
- 34 Praticò AD, Polizzi A, Salafia R. et al. Megalencephaly capillary malformation syndrome. J Pediatr Neurol 2018; 16: 328-337
- 35 Praticò AD, Mistrello G, La Rosa M. et al. Immunotherapy: a new horizon for egg allergy?. Expert Rev Clin Immunol 2014; 10 (05) 677-686
- 36 Dobyns WB, Guerrini R, Leventer RL. Malformations of cortical development. In Swaiman KF, Ashwal S, Ferriero DM, Schor NF. eds. Swaiman's Pediatric Neurology: Principles and Practice. 5th ed. Edinburgh: Elsevier Saunders; 2012: 202-231
- 37 Insausti R, Muñoz-López M, Insausti AM, Artacho-Pérula E. The human periallocortex: layer pattern in presubiculum, parasubiculum and entorhinal cortex. a review. Front Neuroanat 2017; 11: 84
- 38 Fauser S, Huppertz HJ, Bast T. et al. Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in a series of 120 patients. Brain 2006; 129 (Pt 7): 1907-1916
- 39 Barba C, Mai R, Grisotto L. et al. Unilobar surgery for symptomatic epileptic spasms. Ann Clin Transl Neurol 2016; 4 (01) 36-45
- 40 Kwon HE, Eom S, Kang HC. et al. Surgical treatment of pediatric focal cortical dysplasia: clinical spectrum and surgical outcome. Neurology 2016; 87 (09) 945-951
- 41 Lawson JA, Birchansky S, Pacheco E. et al. Distinct clinicopathologic subtypes of cortical dysplasia of Taylor. Neurology 2005; 64 (01) 55-61
- 42 Hildebrandt M, Pieper T, Winkler P, Kolodziejczyk D, Holthausen H, Blümcke I. Neuropathological spectrum of cortical dysplasia in children with severe focal epilepsies. Acta Neuropathol 2005; 110 (01) 1-11
- 43 Pirozzi F, Nelson B, Mirzaa G. From microcephaly to megalencephaly: determinants of brain size. Dialogues Clin Neurosci 2018; 20 (04) 267-282
- 44 Parrini E, Conti V, Dobyns WB, Guerrini R. Genetic basis of brain malformations. Mol Syndromol 2016; 7 (04) 220-233
- 45 Dubeau F, Palmini A, Fish D. et al. The significance of electrocorticographic findings in focal cortical dysplasia: a review of their clinical, electrophysiological and neurochemical characteristics. Electroencephalogr Clin Neurophysiol Suppl 1998; 48: 77-96
- 46 Panzica F, Varotto G, Rotondi F, Spreafico R, Franceschetti S. Identification of the epileptogenic zone from stereo-EEG signals: a connectivity-graph theory approach. Front Neurol 2013; 4: 175
- 47 Severino M, Geraldo AF, Utz N. et al. Definitions and classification of malformations of cortical development: practical guidelines. Brain 2020; 143 (10) 2874-2894
- 48 Di Giacomo R, Uribe-San-Martin R, Mai R. et al. Stereo-EEG ictal/interictal patterns and underlying pathologies. Seizure 2019; 72: 54-60
- 49 Wang DD, Deans AE, Barkovich AJ. et al. Transmantle sign in focal cortical dysplasia: a unique radiological entity with excellent prognosis for seizure control. J Neurosurg 2013; 118 (02) 337-344
- 50 von der Hagen M, Pivarcsi M, Liebe J. et al. Diagnostic approach to microcephaly in childhood: a two-center study and review of the literature. Dev Med Child Neurol 2014; 56 (08) 732-741
- 51 Lagarde S, Boucekine M, McGonigal A. et al. Relationship between PET metabolism and SEEG epileptogenicity in focal lesional epilepsy. Eur J Nucl Med Mol Imaging 2020; 47 (13) 3130-3142
- 52 Aronica E, Becker AJ, Spreafico R. Malformations of cortical development. Brain Pathol 2012; 22 (03) 380-401
- 53 Galanopoulou AS, Gorter JA, Cepeda C. Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target. Epilepsia 2012; 53 (07) 1119-1130
- 54 van der Poest Clement E, Jansen FE, Braun KPJ, Peters JM. Update on drug management of refractory epilepsy in tuberous sclerosis complex. Paediatr Drugs 2020; 22 (01) 73-84
- 55 Hauptman JS, Mathern GW. Surgical treatment of epilepsy associated with cortical dysplasia: 2012 update. Epilepsia 2012; 53 (Suppl. 04) 98-104
- 56 Bourdillon P, Rheims S, Catenoix H. et al. Malformations of cortical development: New surgical advances. Rev Neurol (Paris) 2019; 175 (03) 183-188
- 57 Praticò AD. COVID-19 pandemic for Pediatric Health Care: disadvantages and opportunities. Pediatr Res 2021; 89 (04) 709-710
- 58 Praticò AD, Giallongo A, Arrabito M. et al. SCN2A and its related epileptic phenotypes. J Pediatr Neurol 2021
- 59 Chassoux F, Landré E, Mellerio C. et al. Type II focal cortical dysplasia: electroclinical phenotype and surgical outcome related to imaging. Epilepsia 2012; 53 (02) 349-358
- 60 Cocuzza S, Marino S, Gulino A. et al. ENT involvement and orobuccal movements' disorders in Pandas patients: assessment and rehabilitations tools. Eur Rev Med Pharmacol Sci 2019; 23 (10) 4110-4117