Mild Malformation Of Cortical Development Research Articles

Incomplete resection of focal cortical dysplasia is the main predictor of poor postsurgical outcome

Focal cortical dysplasia (FCD) is recognized as the major cause of focal intractable epilepsy in childhood. Various factors influencing postsurgical seizure outcome in pediatric patients with FCD have been reported. To analyze different variables in relation to seizure outcome in order to identify prognostic factors for selection of pediatric patients with FCD for epilepsy surgery. A cohort of 149 patients with histologically confirmed mild malformations of cortical development or FCD with at least 2 years of postoperative follow-up was retrospectively studied; 113 subjects had at least 5 years of postoperative follow-up. Twenty-eight clinical, EEG, MRI, neuropsychological, surgical, and histopathologic parameters were evaluated. The only significant predictor of surgical success was completeness of surgical resection, defined as complete removal of the structural MRI lesion (if present) and the cortical region exhibiting prominent ictal and interictal abnormalities on intracranial EEG. Unfavorable surgical outcomes are mostly caused by overlap of dysplastic and eloquent cortical regions. There were nonsignificant trends toward better outcomes in patients with normal intelligence, after hemispherectomy and with FCD type II. Other factors such as age at seizure onset, duration of epilepsy, seizure frequency, associated pathologies including hippocampal sclerosis, extent of EEG and MRI abnormalities, as well as extent and localization of resections did not influence outcome. Twenty-five percent of patients changed Engel's class of seizure outcome after the second postoperative year. The ability to define and fully excise the entire region of dysplastic cortex is the most powerful variable influencing outcome in pediatric patients with focal cortical dysplasia.

Epilepsy surgery patients with cortical dysplasia

Cortical dysplasia is the most common substrate in pediatric and the second or third most frequent etiology in adult epilepsy surgery patients.1 The histopathology was first described less than 30 years ago,2 and we are still learning about the clinical features of this disorder. Early surgical series involved few patients or focused on MRI positive cases,3,4 and reported inconsistent predictors of therapeutic success. Only recently have single centers published surgical cohorts of over 100 patients.5,6 This issue of Neurology® publishes two studies that together report on 315 epilepsy surgery patients with cortical dysplasia: Krsek et al., a mostly pediatric cohort from Miami Children's Hospital, and Kim et al., a generally adult population from Seoul, Korea.7,8 Both centers have previously published on their cohorts.9,10 From these and other reports emerges a clearer image of the electro-clinico-pathologic characteristics of patients with cortical dysplasia. For example, most surgical patients have mild compared with severe forms of cortical dysplasia on histopathology. This is defined as mild malformations of cortical development (mMCD; 16%) or mild type I (59%) cortical dysplasia using the Palmini classification system …

Characteristics of MEG and MRI between Taylor's focal cortical dysplasia (type II) and other cortical dysplasia: Surgical outcome after complete resection of MEG spike source and MR lesion in pediatric cortical dysplasia

Cortical dysplasia (CD) has been classified as Taylor's focal cortical dysplasia (FCD type II) or other CD (FCD type I and mild malformation of cortical development) based on histological findings. The aims of this study were to determine whether MRI and magnetoencephalography (MEG) could distinguish between these two groups and to evaluate surgical outcomes. We evaluated the MRI features, MEG spike source (MEGSS) patterns (clusters or scatters) and postsurgical seizure outcomes of 27 children with CD. Thirteen patients had Taylor's FCD and 14 had other CD. MRI showed visible lesion in 22 (81%) patients. Tapering of abnormal white matter signals to the ventricles and cortical thickening were more prevalent in Taylor's FCD; focal hypoplasia and white matter atrophy were more prevalent in other CD. MEG showed spike sources in 26 (96%) patients. Taylor's FCD showed clustered MEGSSs in 6, both clustered and scattered MEGSSs in 5 and scattered MEGSSs in 2; other CD demonstrated clusters in 2, cluster and scatter in 10 and scatter in 1. Eleven (85%) of 13 patients who had complete resection of clustered MEGSSs achieved Engel class I outcome, but 4 (44%) of 9 patients with incomplete resections achieved class I. Fifteen (88%) of 17 patients who had complete resection of MRI lesions achieved class I, but 1 (33%) of 3 patients with incomplete lesionectomy was class I. There was no difference in surgical outcomes between Taylor's FCD and other CD. Surgical outcome was the same in both groups following complete removal of areas containing clustered MEGSSs and MR lesions.

Clinical characteristics in focal cortical dysplasia: a retrospective evaluation in a series of 120 patients

Focal cortical dysplasias (FCDs) are increasingly diagnosed as a cause of symptomatic focal epilepsy in paediatric and adult patients. However, little is known about the clinical characteristics of epilepsy in these patients. In order to elucidate the clinical characteristics of their epilepsy, 120 pharmacoresistant patients including children and adults with histologically proven FCD were studied retrospectively. Age at seizure onset was analysed in the total group and compared between subgroups with different localization and different histological subtypes of FCD. The role of febrile seizures with respect to dual pathology was investigated. Seizure semiology was analysed focusing on initial seizure type and change of seizure semiology during the course of disease. Finally, transient responsiveness to antiepileptic drug therapy was studied. In the majority of patients, epilepsy began in the first 5 years of life. However, onset of epilepsy could also occur in the second or third decade until the age of 60. Age at epilepsy onset was not significantly different between temporal, extratemporal and multilobar localization of FCD. Patients without cytoarchitectural abnormalities (mild malformations of cortical development, FCD 1a according to Palmini) had significantly later epilepsy onset (P= 0.001) compared with patients with cytoarchitectural abnormalities (FCD 1b, 2a and 2b according to Palmini). In patients with additional hippocampal sclerosis (dual pathology) febrile seizures were significantly more frequently reported (P = 0.02) than in patients without dual pathology. Moreover, patients with dual pathology and febrile seizures significantly more frequently presented with severe hippocampal sclerosis (Wyler Grade 3-4) as compared with patients with dual pathology in the absence of febrile seizures (P = 0.03). First observed seizures were mainly tonic or generalized tonic-clonic. A change of seizure semiology seemed to be age-dependent and occurred between the age of >1 and 14 years. About 15.8% of the patients presented with status epilepticus during the course of disease. About 17% of the patients showed transient responsiveness (> or =1 year seizure freedom) to antiepileptic drug therapy either after initial therapy (50%) or later in the course of epilepsy (50%). Patients with FCD represent a heterogeneous group. Different age at epilepsy onset and transient responsiveness to antiepileptic drugs in approximately 17% of patients may reflect different dynamics in epileptogenicity of the underlying FCD. Dual pathology may be associated with different pathomechanisms in patients with and without febrile seizures.

Voxel‐based Morphometry Reveals Excess Gray Matter Concentration in Patients with Focal Cortical Dysplasia

Many patients with focal cortical dysplasia (FCD) continue to have seizures after surgical treatment. The usual explanation for the poor surgical outcome is the presence of residual dysplastic tissue missed by the preoperative neuroimaging investigation and therefore not resected during surgery. We apply a voxel-based morphometry (VBM) analysis to the magnetic resonance imaging (MRI) scans from patients with epilepsy and visually detected FCD to investigate whether (a) VBM is able to detect gray-matter concentration (GMC) abnormalities in patients with FCD, and (b) whether the extent of GMC abnormalities in the brain of these patients differs from the regions observed by using visual inspection. We studied 11 patients with visually detected FCD (eight of them with histologic confirmation of FCD). The GMC from each one of these patients was compared with the mean GMC from a control group of 96 normal healthy subjects by using an optimized VBM protocol. Ten of 11 patients showed statistically significant GMC excess, and among patients with GMC excess, only one showed GMC excess that was not exactly correspondent to the visually detected FCD. Seven patients exhibited excess in GMC extending beyond the area of visually detected FCD. This preliminary neuroimaging study suggests that (a) VBM can detect GMC excess in patients with FCD, and (b) GMC excess in these patients can extend to brain areas not visually defined as abnormal. Abnormal areas detected by VBM can possibly correspond to mild malformations of cortical development, supporting the notion that the surgical refractoriness observed in patients with FCD can be due to the incomplete resection of the dysplastic tissue.

Densities of parvalbumin-immunoreactive neurons in non-malformed hippocampal sclerosis-temporal neocortex and in cortical dysplasias

The changes in density of inhibitory parvalbumin-immunoreactive interneurons were quantitatively studied by immunohistochemistry in a series of human neocortical samples comprising the spectrum of malformations of cortical development (MCD) encountered in epilepsy surgery and the non-malformed hippocampal sclerosis-temporal neocortex in patients with refractory temporal lobe epilepsy. The highest relative density of parvalbumin-immunoreactive cells was obtained in the control samples ( n = 21). The number of parvalbumin-immunoreactive neurons was significantly decreased in non-malformed hippocampal sclerosis-temporal neocortex ( n = 73, 80.5% of control values). In a proportion of the latter samples as well as in two controls we observed patchy regions of absence of parvalbumin staining. The total counts of parvalbumin-immunoreactive cells in all the categories of MCD – “mild MCD” ( n = 25), focal cortical dysplasia type I ( n = 19) and type II ( n = 15) – were decreased representing 72.4%, 55.0% and 12.2% of control values, respectively. Significantly different parvalbumin-immunoreactive cell densities were demonstrated between the focal cortical dysplasia types IIA and IIB. In “mild MCD”, we observed a more pronounced decrease of parvalbumin-immunoreactive cells in the infragranular layers. No significant differences were revealed between the temporal and extratemporal examples of analogous MCD types. This study provides evidence for reduction of inhibitory parvalbumin-immunoreactive interneurons in the epileptic neocortex affected by MCD as well as in morphologically unaffected epileptic temporal neocortex, thus representing a possible mechanism for their epileptogenicity.

Mild forms of focal cortical dysplasia: how certain are we?

The study by Fauser and colleagues on subtypes of focal cortical dysplasia (FCD) and their impact on post-surgical outcome in focal epilepsies (Fauser et al ., 2004) focussed on reports of milder forms of FCD, i.e. focal cortical dysplasia type I (Type 1-FCD) and mild malformations of cortical development (mMCD) according to a recent classification system (Palmini et al ., 2004). These entities were compared with cases with dysmorphic neurons and balloon cells on histopathology (Type 2-FCD). The histopathological features used for tissue diagnosis and some of the clinical characteristics reported for Type 1-FCD and mMCD deserve comment. The issue of milder forms of FCD—in particular what tissue findings are needed for diagnosis and whether these categories are useful at all—are matters of ongoing debate in epileptology (Palmini and Luders, 2002; Palmini et al ., 2004). For the presumed milder FCD variants, the uncertainties were emphasized and the hope expressed that ‘the use of the proposed classification scheme in every day practice and for research purposes will refine and validate its usefulness’ (Palmini et al ., 2004). The large series presented by Fauser et al . (2004) missed an opportunity to clarify these classifications further since it diverges from the Palmini classification. It would have been useful for …

Focal cortical dysplasias: surgical outcome in 67 patients in relation to histological subtypes and dual pathology.

The purpose of this study was to assess whether the histological subtype of focal cortical dysplasia and dual pathology affect surgical outcome in patients with medically intractable epilepsy due to focal cortical dysplasia (FCD). We retrospectively analysed the outcome of 67 patients from 2 to 66 years of age at follow-up periods of 6 to 48 months after epilepsy surgery. Histological subtypes were classified according to Palmini and included a few cases with mild histological abnormalities corresponding to the definition of mild malformations of cortical development. The seizure outcome was classified according to Engel and evaluated at the last follow-up visit as well as at follow-up periods of 12 and 24 months after surgery. The outcome in patients with FCD and additional hippocampal pathology (dual pathology) was analysed separately. Distribution of histological subtypes differed in temporal and extratemporal localization, with a significantly higher extratemporal prevalence of FCD type 2. There was a tendency towards better postsurgical outcome related to the last follow-up visit in patients with more subtle abnormalities classified as mild malformations of cortical development (mMCD) (63% Engel Ia), FCD type 1a (67% Engel Ia) and FCD type 1b (55% Engel Ia) compared with patients with FCD type 2a (43% Engel Ia) and FCD type 2b (Taylor type) (50% Engel Ia). Considering the outcome at follow-up periods over 12 and 24 months, complete seizure-freedom was achieved significantly more often in patients with FCD type 1 and mMCD than with FCD type 2, and seizure reduction by less than 75% (Engel IV) occurred in more patients with FCD type 2a compared with the other subgroups. This tendency was seen in the whole patient group and in the extratemporal subgroup. Patients with dual pathology almost always had temporal lobe epilepsy; the outcome in this patient group was generally favourable (66% complete seizure-freedom at the last follow-up visit). The outcome remained almost constant with longer periods of follow-up. We conclude that patients with FCD type 1 and mMCD had a better outcome compared with those with more severe forms of cortical dysplasia. A higher incidence of FCD type 1 in temporal localization did not allow the effects of histological subtype and localization to be separated. A subanalysis of extratemporal FCDs, however, revealed a similar tendency for a better outcome with FCD type 1, suggesting that the histological subtype itself seems to be at least a relevant cofactor influencing postsurgical outcome.