Buscar en
Neurología (English Edition)
Toda la web
Inicio Neurología (English Edition) Double cortex syndrome in a male patient without lissencephaly
Journal Information
Vol. 35. Issue 2.
Pages 144-145 (March 2020)
Vol. 35. Issue 2.
Pages 144-145 (March 2020)
Letter to the Editor
DOI: 10.1016/j.nrleng.2017.12.003
Open Access
Double cortex syndrome in a male patient without lissencephaly
Síndrome de doble corteza en paciente masculino adulto sin lisencefalia
D. Rivero Rodríguez
Corresponding author

Corresponding author.
, C. Scherle Matamoros, D. Dicapua Sacoto, N. Maldonado Samaniego
Departamento de Neurología, Hospital Eugenio Espejo, Universidad San Francisco de Quito (USFQ), Quito, Ecuador
Article information
Full Text
Download PDF
Figures (2)
Full Text
Dear Editor:

Subcortical band heterotopia, also known as double cortex syndrome (DCS), is an infrequent disorder of cortical migration, characterised by a well delimited layer of grey matter within the white matter, between the cerebral cortex and the lateral ventricles. The introduction of magnetic resonance imaging (MRI) in clinical practice made it possible to identify and characterise this entity.1 Most of the reported cases are women; affected men generally present lissencephaly with more severe neurological involvement.2

Our patient is a 26-year-old man referred to our centre due to suspected refractory epilepsy. The patient had no relevant prenatal history; he was born to non-consanguineous parents after a full-term pregnancy without complications and his neurodevelopment was normal during his first year of life. He had no family history of epilepsy or intellectual disability. During his first years of education, he presented poor school performance with learning difficulties; a psychological evaluation diagnosed mild-to-moderate intellectual disability. At the age of 6, he began to develop seizures and episodes of disconnection progressing to loss of consciousness with movements in the entire body. Over the past 20 years, seizure frequency increased, and the patient developed myoclonic, generalised tonic–clonic, and atonic seizures. A clinical examination revealed such dysmorphic features as hypertelorism and wide nasal bridge. He was treated with multiple antiepileptic drugs: phenytoin, carbamazepine, clonazepam, clobazam, valproic acid, and lamotrigine in monotherapy, bitherapy, and polytherapy, never achieving adequate control (Figs. 1 and 2). We started rational polytherapy with lamotrigine at 300mg/day, valproic acid at 2.5g/day, and levetiracetam at 3g/day, achieving acceptable control with only 2 partial seizures in the following 6 months.

Figure 1.

T1-weighted MR images (inversion recovery) obtained in a 1.5T scanner; coronal slices (A-C) and an axial slice (D) showing a band of grey matter within the subcortical white matter, with no lissencephaly or achygyria/pachygyria.

Figure 2.

Waking electroencephalogram (10-20 international system, longitudinal bipolar montage). The recording shows several stages, with paroxysmal activity starting in the left occipital area, subsequently extending to frontal areas; the activity persists independently in occipital regions, especially in the left hemisphere, along the entire trace.


DCS is an infrequent disorder of cortical migration associated with mutations of chromosomes 17p13.3 (LIS1) and Xq22.3-q23 (DCX or XLIS). Mutations in the doublecortin gene (DCX) account for 85% of sporadic cases in women and 25% in men.1,3 This gene plays an important role in the coding of microtubule-associated proteins participating in neuronal migration during brain development; mutations in this gene cause severe damage to the structure of the cerebral cortex.4 The clinical characteristics justifying suspicion of DCS are the onset of epileptic seizures during the first decade of life, progressively becoming resistant to treatment, presence of multiple types of seizures, and intellectual disability.5 Subcortical band heterotopia is more frequent in women; male patients usually present lissencephaly or agyria/pachygyria complex predominantly involving frontal regions.2,6 These alterations were not observed in our patient. There are few reports of men with DCS with no lissencephaly or agyria/pachygyria. Mosaicism for DCX mutation is a possible explanation for the reduced severity of clinical manifestations in men.6 There is little evidence regarding the treatment of this condition when rational polytherapy fails. Although these patients present epilepsy with focal activity, surgery has shown discouraging results.7 It has recently been reported that bilateral stimulation of the anterior thalamic nuclei may help improve seizure control.8

A.J. Barkovich, R.I. Kuzniecky.
Gray matter heterotopia.
Neurology, 55 (2000), pp. 1603-1608
N. Bahi-Buisson, I. Souville, F.J. Fourniol, A. Toussaint, C.A. Moores, A. Houdusse, et al.
New insights into genotype-phenotype correlations for the doublecortin-related lissencephaly spectrum.
Brain, 136 (2013), pp. 223-244
C. Quélin, Y. Saillour, I. Souville, K. Poirier, M.A. N??uyen-Morel, L. Vercueil, et al.
deletion causes subcortical band heterotopia in males.
Neurogenetics, 13 (2012), pp. 367-373
H. Koizumi, H. Higginbotham, T. Poon, T. Tanaka, B.C. Brinkman, J.G. Gleeson.
Doublecortin maintains bipolar shape and nuclear trans-location during migration in the adult forebrain.
Nat Neurosci, 9 (2006), pp. 779-786
R.J. Leventer.
Genotype-phenotype correlation in lissencephaly and subcortical band heterotopia: the key questions answered.
J Child Neurol, 20 (2005), pp. 307-312
N.P. Poolos, S. Das, G.D. Clark, D. Lardizabal, J.L. Noebels, E. Wyllie, et al.
Males with epilepsy, complete subcortical band heterotopia, and somatic mosaicism for DCX.
Neurology, 58 (2002), pp. 1559-1562
A. Bernasconi, V. Martinez, P. Rosa Neto, D. D’Agostino, N. Bernasconi, S. Berkovic, et al.
Surgical resection for intractable epilepsy in «double cortex» syndrome yields inadequate results.
Epilepsia, 42 (2001), pp. 1124-1129
A. Franco, J. Pimentel, A.R. Campos, C. Morgado, S. Pinelo, A.G. Ferreira, et al.
Stimulation of the bilateral anterior nuclei of the thalamus in the treatment of refractory epilepsy: two cases of subcortical band heterotopia.
Epileptic Disord, 18 (2016), pp. 426-430

Please cite this article as: Rivero Rodríguez D, Scherle Matamoros C, Dicapua Sacoto D, Maldonado Samaniego N. Síndrome de doble corteza en paciente masculino adulto sin lisencefalia. Neurología. 2020;35:144–145.

Copyright © 2018. Sociedad Española de Neurología
Article options
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

es en pt
Política de cookies Cookies policy Política de cookies
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.