Focal cortical dysplasia

Harvey B Sarnat MD FRCPC MS (Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.)
Originally released November 28, 1994; last updated May 15, 2016; expires May 15, 2019

This article includes discussion of focal cortical dysplasia and cerebral cortical dysplasia. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Focal cortical dysplasias are cytoarchitectural abnormalities most likely representing malformations of cortical development. Ranging from known genetic abnormalities to spontaneous mutations, these abnormalities most frequently present with intractable epilepsy. The author of this clinical article reviews the most recent proposed classification scheme for these disorders and looks at some of the recent genetic findings.

Historical note and terminology

The term "cerebral cortical dysplasia" encompasses a spectrum of malformations of the cerebral cortex that arise during development and are associated with epilepsy in infants and children (Mischel et al 1995). Initially, cortical malformations were referred to largely by their gross characteristics (eg, lissencephaly, agyria or pachygyria, hemimegalencephaly, microgyria). As investigators discovered the range of microscopic cortical malformations that produce epilepsy but show no (or milder) gross abnormalities, additional terms such as "microdysgenesis" (Meencke and Janz 1984), "dysplastic cortical architecture" (Rorke 1994), "focal cortical dysplasia" (Taylor et al 1971), "generalized cortical dysplasia" (Marchal et al 1989), "synaptic dysgenesis" (Becker 1991), and "cerebral dysgenesis" (Sarnat 1992) were added to the literature. The term "focal cortical dysplasia" was first used to describe a specific malformation of the brain that consisted of disorganized cortex with enlarged irregular neurons and enlarged ballooned cells in some, but not all, cases (Taylor et al 1971), now corresponding to focal cortical dysplasia type 2. Dysplastic and megalocytic neurons were first identified by Crome and colleagues in 1957 (Crome 1957).

Neuropathological classification scale. A classification scale to unify terminology of malformations caused by abnormalities of cortical development with emphasis on focal cortical dysplasias associated with epilepsy was proposed by a group of epileptologists, neuropathologists, and neuroradiologists (Palmini et al 2004). Various classification schemes of cortical dysplasias have been proposed (Vinters et al 1993; Mischel et al 1995; Palmini et al 2004; Krsek et al 2009a; Spreafico and Blü;mcke 2010). A resulting 2011 classification scheme was published under the auspices of the International League Against Epilepsy (ILAE); it represents a consensus statement with contributions by multiple European, North American, Japanese, and Australian neuropathologists who have special interest and long experience in epilepsy surgery (Blümcke et al 2011), and has been validated by an international consortium of neuropathologists with experience in epilepsy (Coras et al 2012). This scheme has a built-in flexibility for future revisions as new data become available and interpretations evolve. It includes both focal isolated dysplasias of the cortex and also those associated with other lesions. It is expected that this scheme will become the template for uniform criteria in the neuropathological diagnosis of cortical dysplasias, analogous to the WHO (World Health Organization of the United Nations) classification of nervous system tumors, another consensus statement now accepted by neuropathologists throughout the world, who nearly always note the WHO grade when preparing reports describing primary cerebral neoplasms in surgical resections and autopsies. Another strength and modern approach of the new ILAE classification is that although based primarily upon neuropathological features, it also considers and incorporates aspects of neuroimaging and clinical aspects to be integrated with interdisciplinary correlations. Molecular, genetic, and immunocytochemical characterization of these cortical dysplasias will be added to the ILAE scheme. The temporal expression of neuronal proteins during cellular differentiation and the immunocytochemical demonstration of synaptogenesis are now better defined and often are altered in malformations, either as delayed, arrested, or precocious maturation (Ulfig 2002; Sarnat 2013; Sarnat 2014). The neuropathological classification shown in Table 1 should not be confused with other ILAE clinical and electroencephalographic classifications of epilepsies, including ICD coding for epilepsy (Jette et al 2015).

Table 1 summarizes the neuropathological criteria of focal cortical dysplasias. The principal difference between types 1 and 2 is that individual neurons are normal in morphology and size in type 1 and are dysplastic and megalocytic (enlarged) in type 2; both types exhibit abnormal cortical architecture with displaced and disoriented neurons and abnormal lamination. In type 2, subtype 2b includes balloon cells as well, large globoid cells of mixed cellular lineage that often express both neuronal and glial proteins, in addition to primitive proteins of early stages of differentiation, such as vimentin and nestin, also found in progenitor “stem” cells. Type 3 is not a distinctive or unique focal dysgenesis as are types 1 and 2, but represents type 1 associated with other lesions.

Table 1. 2011 ILAE Classification of Focal Cortical Dysplasias

Focal cortical dysplasia type 1 (isolated)

 

• 1a: Focal cortical dysplasia with abnormal radial cortical lamination
• 1b: Focal cortical dysplasia with abnormal tangential cortical lamination
• 1c: Focal cortical dysplasia with abnormal radial and tangential cortical lamination

Focal cortical dysplasia type 2 (isolated)

 

• 2a: Focal cortical dysplasia with dysmorphic neurons
• 2b: Focal cortical dysplasia with dysmorphic neurons and balloon cells

Focal cortical dysplasia type 3 (type 1 associated with principal lesions)

 

• 3a: Cortical lamination abnormalities in the temporal lobe associated with hippocampal sclerosis
• 3b: Cortical lamination abnormalities adjacent to a glial or glioneuronal tumor or any other cerebral tumor
• 3c: Cortical lamination abnormalities adjacent to a vascular malformation
• 3d: Cortical lamination abnormalities adjacent to any other lesion acquired during early life (eg, trauma, ischemic injury, infarct, encephalitis)

(Blümcke et al 2011)

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