Focal cortical dysplasia (FCD)

10 Ocak 2012 Sal 14:27

www.medscape.com
[CLOSE WINDOW]

Authors and Disclosures Sanjay Sisodiya

Department of Clinical and Experimental Epilepsy, University College London Institute of Neurology, Queen Square, London WC1N 3BG, UK. s.sisodiya@ion.ucl.ac.uk From Nature Reviews Neurology The New OrderClassifying Focal Cortical Dysplasias Sanjay Sisodiya Posted: 03/28/2011; Nat Rev Neurol. 2011;7(3):129-130. 2011 Nature Publishing Group Abstract and Introduction Abstract Focal cortical dysplasia (FCD) is a commonly encountered neuropathology in drug-resistant focal epilepsy; the bizarre pathological appearance of FCD reflects molecular disorder bridging neurodevelopment and neurodegeneration. A new classification stands to resolve discrepancies in FCD categorization and accelerate advances in fundamental understanding and clinical management of drug-resistant epilepsy.

Introduction
Drug resistance in epilepsy is a major clinical problem, affecting 30% of people with epilepsy. One of the more common structural changes in the brain associated with such epilepsy is focal cortical dysplasia (FCD), an intriguing neuropathology of unknown cause that was first described by Taylor and colleagues in 1971.[1] FCD is a common pathology observed in surgical resection specimens from patients with drug-resistant epilepsy. A somewhat broader range of conditions has become loosely and variably subsumed within the term FCD, leading to some confusion and lack of comparability between reports. In an important and thoughtful effort, an ad hoc task forceunder the auspices of the International League Against Epilepsy (ILAE)has generated a comprehensive classification of FCD subtypes to improve FCD characterization and provide a consensus framework for clinical use and further research.[2] Why is this new consensus FCD classification important, and have the ILAE task force succeeded? Surgical resection of an epileptogenic lesion is a potentially curative treatment for drug-resistant epilepsy. Evaluations for surgery constitute a well-honed multidisciplinary process, and should always include a preoperative MRI brain scan. One factor that generally supports surgical treatment, being associated with a high likelihood of successful surgical control of seizures, is the presence of a resectable focal lesion (such as hippocampal sclerosis, vascular malformation, low-grade glioneuronal tumor or FCD) on MRI. Nevertheless, seizure outcomes reported after resective surgery often vary considerably between centers and publications. Moreover, the reported underlying causes of epilepsy (identified via histological examination of the resected material) sometimes differ markedly between centers operating on comparable patients, without obvious explanations as to why. Patterns of reporting may be inconsistent for several reasons,[3] not limited to pathology reporting itself.[4] All this varied information renders informed, evidence-based decision-making a complex prospect for physicians and patients. For FCD, these problems are aggravated by a lack of understanding of the underlying disease processes and are compounded by systematic differences between centers in the nomenclature and definitions of such lesions. Clinicians cannot learn from the collective experience of FCD treatment until disease nomenclature and definitions are clear. Previous consensus statements or agreed systems of reporting have addressed some of the issues with FCD definitions. For example, a reasonably straightforward 2001 outcome scale has gained widespread acceptance as a measure of seizure outcome after surgery,[5] facilitating cross-center comparisons. Furthermore, the 2004 Palmini FCD classification system [6] has already proved useful.[7] The new classification is an advance on these systems in several important ways. The ILAE classification[2] retains previous categories of FCD (subtypes Ia, Ib, IIa and IIb), which are distinguished by their cortical laminar structure, cytoarchitectural disruption and cell composition, and also introduces, but does not illustrate, a new disease subcategory (FCD type Ic). Additionally, the kortikal displazi klinik Sayfa 1

also introduces, but does not illustrate, a new disease subcategory (FCD type Ic). Additionally, the system takes the essential step of collating and molding robust definitions of FCD histopathological characteristics, which can be applied readily in clinical practice, and outlines standards for tissue preparation to permit practical application of the definitions. Most of the existing subtypes are handsomely illustrated. Blmcke et al.[2] rightly consider the clinical feasibility and utility of these established FCD categories, noting that currently only clinical data can validate these classifications. With well-developed technology to host large image datasets online now available, the ILAE task force might consider whether more detailed, comprehensive, interactively searchable and anonymized neuropathological images could be made freely available for centers that lack expertise in epilepsy neuropathology. This development would broaden the appeal of the new classification. In addition, were the small expert cadre of epilepsy neuropathologists able to remotely review data from centers without specialist provision, a truly impressive global service would be achieved with potential benefits to all concerned and to the classification itself. The major advance of the 2011 reclassification[2] relates to pathological findings, which were previously difficult to categorize. The reclassification includes subtle pathological changes found in association with other epileptogenic lesions, which are now grouped into FCD type III, with further subclassification depending on the association observed. For example, FCD type IIIa (Figure 1) is specified as a broad range of cortical or subcortical abnormalities occurring with hippocampal sclerosis, while the less homogeneous category of type IIId is defined as altered cortical architecture or cytoarchitecture found adjacent to other lesions acquired during early life, such as lesions resulting from traumatic brain injury, perinatal ischemia or Rasmussen encephalitis.

Figure 1. Histopathological findings of FCD type IIIa. A temporal lobectomy specimen immunolabeled for the neuronal antigen NeuN (neuronal nuclei) showing malorientated neurons (brown staining) in layer II of the temporal neocortex. The specimen also shows hippocampal sclerosis. Scale bar 100 m. Abbreviation: FCD, focal cortical dysplasia. Courtesy of M. Thom, University College London Institute of Neurology, UK. FCD classification, especially type III, is based on morphological criteria. For FCD types I and II, basing classification on histological criteria seems reasonable, as improved homogeneity seems to be emerging in postoperative outcomes grouped by pathology.[7,8] Fundamental research into patterns of molecular disruption, especially in FCD type II, is nurturing a coherent theory of what goes awry in these lesions,[9] leading to important insights into development and degeneration in the human brain.[10] Less progress has been made in understanding FCD type I and much work remains to improve understanding of FCD type III. Many of the defining characteristics of type III are shared with type I, although this observation does not signify shared causation or biology. Indeed, the ILAE task force considers that some type III FCDs may be 'acquired' or secondary in some way to the 'principal lesion', such as hippocampal sclerosis. By contrast, most researchers consider FCD type II to be developmental in origin. Whether separation of type I and type III FCD leads to improved understanding and management of FCD remains to be determined. The consensus reclassification is, however, an important step towards this goal. With further clinicopathological correlative studies based on this new classification, we may conclude that FCD type III is not independently epileptogenic, but merely a reactive change or an epiphenomenon. Such testing of the classification is vital; otherwise, FCD type III may simply be accepted as an established entity without adequate justification. The 2011 consensus classification on FCD[2] does succeed in separating disease entities that had been prone to variable and confusing reporting, and provides an important new framework. The challenge ahead is for all centers capable of testing the framework to do so in a coordinated way. Increased collaboration within the scientific community augurs well for the success of such endeavors. Whether FCD type III is pathological and epileptogenic needs to be confirmed. Additional challenges exist, chief among which is improvement of preoperative identification and delineation of all types of FCD by neuroimaging. Several hypotheses have been postulated for the low probability of a favorable outcome in epilepsy surgery in the absence of a preoperatively identified lesion on MRI, including the presence of a nonstructural or multifocal cause, the lesion being not amenable to surgical resection, and the occurrence of an extensive region capable of causing seizures that has not been, or cannot be, fully resected. Substantial advances are necessary from other disciplines to address these key problems, and this consensus statement will provide the neuropathological 'gold

kortikal displazi klinik Sayfa 2

address these key problems, and this consensus statement will provide the neuropathological 'gold standard' against which other measures can be judged, especially for MRI. Blmcke and colleagues [2] are to be congratulated on their efforts. We should now look forward, in due course, to their own reevaluation of the new classification, which will be tested through the imaging, surgery and pathological study of drug-resistant epilepsy.
[ CLOSE WINDOW ]

References 1. Taylor, D. C., Falconer, M. A., Bruton, C. J. & Corsellis, J. A. Focal dysplasia of the cerebral cortex in epilepsy. J. Neurol. Neurosurg. Psychiatry 34, 369387 (1971). 2. Blmcke, I. 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 52, 158174 (2011). 3. Sisodiya, S. M., Fauser, S., Cross, J. H. & Thom, M. Focal cortical dysplasia type II: biological features and clinical perspectives. Lancet Neurol. 8, 830843 (2009). 4. Chamberlain, W. A. et al. Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development). Epilepsia 50, 25932598 (2009). 5. Wieser, H. G. et al. ILAE Commission Report. Proposal for a new classification of outcome with respect to epileptic seizures following epilepsy surgery. Epilepsia 42, 282286 (2001). 6. Palmini, A. et al. Terminology and classification of the cortical dysplasias. Neurology 62, S2S8 (2004). 7. Lerner, J. T. et al. Assessment and surgical outcomes for mild type I and severe type II cortical dysplasia: a critical review and the UCLA experience. Epilepsia 50, 13101335 (2009). 8. Tassi, L. et al. Type I focal cortical dysplasia: surgical outcome is related to histopathology. Epileptic Disord. 12, 181191 (2010). 9. Crino, P. B. Focal brain malformations: seizures, signaling, sequencing. Epilepsia 50 (Suppl. 9), 38 (2009). 10. Sen, A., Thom, M., Nikoli, M. & Sisodiya, S. M. The potential role of cyclin-dependent kinase 5 in focal cortical dysplasia. Dev. Neurosci. 30, 96104 (2008). Competing interests The author declares no competing interests. Nat Rev Neurol. 2011;7(3):129-130. 2011 Nature Publishing Group

Yaptrma kayna <http://www.medscape.com/viewarticle/738697_print>

kortikal displazi klinik Sayfa 3