Letter to the Editor |
Reply to ‘Mild forms of focal cortical dysplasia: how certain are we?’
Epilepsy Centre, University of Freiburg, Freiburg, Germany
Correspondence to: Dr med. Susanne Fauser, Epilepsy Centre, University of Freiburg, Breisacher Strasse 64, 79106 Freiburg, Germany E-mail: fauser{at}nz11.ukl.uni-freiburg.de
Received October 28, 2004. Accepted November 11, 2004.
We thank Dr Kasper for his interest in our study. We agree with him that classification of focal cortical dysplasias (FCD) is a matter of ongoing debate and we are grateful that Dr Kasper directs attention to this topic. There is a constant effort made by many involved groups to integrate new aspects into existing classifications and, in the future, new classifications may emerge which may gain general acceptance. In our study, we refer to the Palmini classification (Palmini and Lüders, 2002
; Palmini et al., 2004) in order to allow the outcome data to be compared with previously published studies.
As described in our paper under ‘Patients and methods’, dyslamination was the inclusion criterion for the diagnosis of FCD Type 1 and thus was observed in all of the patients classified as FCD Type 1. The term dyslamination applies to abnormalities of cortical laminar architecture, resulting probably from dysfunctional migration of post-mitotic neurons during corticogenesis. Coronal sections and knowledge of the location are essential to the neuropathological evaluation of the laminar architecture. Dyslamination was defined as a blurred transition between different cortical layers; most commonly seen in our patient group between layers III and IV or layers V and VI. In these zones, we observed a relatively homogeneous population of neurons and a moderately increased cell density. Occasionally, dyslamination was characterized by a numerical reduction of pyramidal neurons and granule cells, and clusters of misplaced neurons (e.g. an increased number of pyramidal neurons in layers I or II with abundant ectopic neurons in the white matter). The laminar disorganization was more prominent, together with cytoarchitectural abnormalities such as immature neurons (a population of neurons with a large nucleus and a thin rim of cytoplasm) and/or giant neurons (FCD 1b), dysmorphic neurons (FCD Type 2a) and balloon cells (FCD Type 2b). Various secondary features were observed in FCDs, such as a columnar neuronal arrangement, an indistinct junction between the grey and white matter, a thickening of the molecular layer with gliosis, oligodendroglial clusters and satellite cells around neurons of layers V and VI. These secondary features, however, were not decisive for the diagnosis of FCD Type 1. Apart from Dr Kasper's study (Kasper et al., 1999), oligodendroglial clusters are mentioned by Mitchell et al. (1999). Though this study found no histological differences between epilepsy patients with MRI alterations in the anterior temporal lobe and those without MRI alterations, it agrees with our study that oligodendroglial clusters are a common feature in patients with temporal lobe epilepsy.
As far as mild malformations of cortical development (mMCD) are concerned, the common finding of these patients was, as we described under the heading ‘Neuropathological examinations’, an increased number of neurons in the white matter. We interpreted the Palmini definition of MCD Type 2 as met, because it demands either aggregates of heterotopic white matter neurons or dysgenesis of the hippocampal formation. The latter was not present in our patient group. Some of the patients had additional signs such as heterotopic neurons in the molecular layer or a persistent subpial granular layer.
We agree with Dr Kasper that the above mentioned alterations may not be absolutely specific for mMCD. However, the patients included in this study suffered from focal epilepsy. We identified regional, or in patients with subdural recordings, focal seizure onset coinciding with areas characterized by mMCD. The majority of these patients became seizure free after surgical removal of this area. We merely included these few (n = 8) patients with mMCD to demonstrate that even these minor histological changes could be associated with a pharmaco-resistant epilepsy and that these patients have a similar good outcome after epilepsy surgery as patients with FCD Type 1. Omitting this small group would not influence the results of our statistics.
MRI findings in FCD were not the focus of our study. Independent from the discussion of whether dyslamination is visible in MRI or not, a removal of the tissue harbouring these dyslaminated areas led to a very favourable outcome in our patients. In this reply, we add an MRI scan of a patient diagnosed as FCD Type 1 (Fig. 1A). We agree with Dr Kasper that morphological changes associated with FCD Type 1 may easily be missed on visual inspection of the MRI. This is shown in the MRI (Fig. 1A), where a suspected zone of cortical thickening may appear ambiguous. To resolve these cases, voxel-based morphometry was used in several of the patients included on the study (Fig. 1B), and invasive recordings were used (Fig. 1C–E) showing congruence with MRI data (Kassubek et al., 2002; Wilke et al., 2003).
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MRI findings in dual pathology are mentioned in ‘Patients and methods’ under the paragraph ‘MRI’ and in the ‘Results’ section under the paragraph ‘Role of dual pathology’. Hippocampal sclerosis (HS) was detected by MRI in 21 out of 29 patients, whereas HS was not seen in any of the patients with extratemporal epilepsy. As hippocampal alterations were seen in eight patients of the temporal group only on a histological level, we cannot exclude the presence of histological hippocampal alterations in patients with extratemporal epilepsies. However, in contrast to the temporal group, there was no clinical evidence of epileptogenesis in the mesial temporal structures based on seizure semiology and ictal EEG data.
In summary, our data support the notion that the presence of dyslamination, both in the temporal lobe and in extratemporal areas, has some epileptogenic potential (supported by EEG recordings of seizure onset in these areas and on the outcome data presented). This finding is in agreement with another study in which epileptogenicity in dyslaminated areas without dysmorphic neurons or balloon cells could even be demonstrated by direct electrocorticographical and histopathological correlation (Boonyapisit et al., 2003).
References
Boonyapisit K, Najm I, Klem G, Ying Z, Burrier C, LaPresto E, et al. Epileptogenicity of focal malformations due to abnormal cortical development. Direct electrocorticographic-histopathologic correlation. Epilepsia 2003; 44: 69–76.[Web of Science][Medline]
Kasper BS, Stefan H, Buchfelder M, Paulus W. Temporal lobe microdysgenesis in epilepsy versus control brains. J Neuropathol Exp Neurol 1999; 58: 22–8.[Web of Science][Medline]
Kassubek J, Huppertz HJ, Spreer J, Schulze-Bonhage A. Detection and localization of focal cortical dysplasia by voxel-based 3-D MRI analysis. Epilepsia 2002; 43: 596–602.[CrossRef][Web of Science][Medline]
Mitchell LA, Jackson GD, Kalnins RM, Saling MM, Fitt GJ, Ashpole RD, et al. Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study. Neurology 1999; 52: 327–36.
Palmini A, Lüders HO. Classification issues in malformations caused by abnormalities of cortical development. Neurosurg Clin N Am 2002; 37: 1–17.
Palmini A, Najm I, Avanzini G, Babb T, Guerrini R, Foldary-Schaefer N, et al. Terminology and classification of the cortical dysplasia. Neurology 2004; 62 Suppl 3: 2–8.
Wilke M, Kassubek J, Ziyeh S, Schulze-Bonhage A, Huppertz HJ. Automated detection of grey matter malformations using optimized voxel-based morphometry: a systematic approach. Neuroimage 2003; 20: 330–43.[CrossRef][Web of Science][Medline]
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