Susanne Fauser

Enhanced visualization of blurred gray–white matter junctions in focal cortical dysplasia by voxel-based 3D MRI analysis

PURPOSE Focal cortical dysplasia (FCD), a frequent cause of partial epilepsy, is often associated with blurring of the gray-white matter junction in magnetic resonance images (MRI). To improve the recognition and delineation of FCD we developed a novel voxel-based image post-processing method for enhanced visualization of blurred gray-white matter junctions. METHODS Using standard algorithms of statistical parametric mapping software (SPM99) a T1-weighted MRI volume data set is normalized and segmented. The distribution of gray and white matter is analyzed on a voxelwise basis and compared with a normal database. Based on this analysis, a three-dimensional feature map is created which highlights brain areas with blurred gray-white matter transition. This method was applied to the MRI data of 25 epilepsy patients with histologically proven FCD. RESULTS In 18/25 patients the new feature maps clearly showed that the dysplastic lesions were accompanied by blurring of the gray-white matter junction. Combined with a formerly published method of voxel-based 3D MRI analysis, 21/25 FCD lesions were shown to be associated with either blurring or abnormal extension of gray matter beyond the normal cortical ribbon, including four cases with lesions not or incompletely recognized on conventional MRI. CONCLUSIONS The MRI post-processing presented here improves the visualization of FCD and may increase the diagnostic yield of MRI. Thereby, it provides a valuable additional diagnostic tool in the presurgical evaluation of epilepsy patients.

EEG and MEG source analysis of single and averaged interictal spikes reveals intrinsic epileptogenicity in focal cortical dysplasia.

Summary:  Purpose: Simultaneous interictal EEG and magnetoencephalography (MEG) recordings were used for noninvasive analysis of epileptogenicity in focal cortical dysplasia (FCD). The results of two different approach methods (multiple source analysis of averaged spikes and single dipole peak localization of single spikes) were compared with pre‐ and postoperative anatomic magnetic resonance imaging (MRI).

Focal cortical dysplasia type II: biological features and clinical perspectives

Focal cortical dysplasia (FCD) type II is an important cause of drug-resistant epilepsy. Clinical presentation is variable, and depends on age of onset of seizures and the location and size of lesion. As FCD type II cannot be diagnosed with certainty in the clinic, in vivo identification by use of MRI is important. Diagnosis will have a major effect on management of this pathology as it should prompt referral for specialist assessment. Drug treatment commonly proves ineffective, whereas appropriate surgical treatment can be curative in many cases. The dramatic cellular anomalies of FCD seen at histopathology indicate a widespread pattern of molecular disruption underpinning the structural disorganisation of the cortex. The cause for FCD has not been firmly established, and there are no explanations for its potent intrinsic ability to cause seizures. There seem to be both neurodevelopmental abnormalities and possible premature neurodegeneration in FCD. Understanding the coordination of the abnormal processes in FCD type II might help to promote improved detection in vivo, direct treatment strategies, and perhaps help explain the development, differentiation, and loss of brain cells, with broad implications for the epilepsies and other neurological disorders.

Long‐term seizure outcome in 211 patients with focal cortical dysplasia

Focal cortical dysplasia (FCD) is currently recognized as the most common cause of neocortical pharmacoresistant epilepsy. Epilepsy surgery has become an increasingly successful treatment option. Herein, the largest patient cohort reported to date is analyzed regarding long‐term outcome and factors relevant for long‐term seizure control.

Multi-focal occurrence of cortical dysplasia in epilepsy patients

This study describes the existence and the clinical and electrophysiological features of multi-focal cortical dysplasia in epilepsy patients. Five patients with intractable focal epilepsy are reported. All patients underwent invasive presurgical video-electroencephalography monitoring. Localization of dysplastic areas was based on high-resolution magnetic resonance scanning, surface and intracranial electroencephalography. Four patients underwent epilepsy surgery. Histological findings in focal cortical dysplasia (FCD) were classified according to Palmini. In addition, genetic examinations were performed in order to assess possible mutations in the genes for tuberous sclerosis complex. In four patients, FCDs were located in the same hemisphere. One case presented with bilateral FCDs. In three patients seizures arose from two separate dysplastic areas and in one patient, one lesion showed only interictal activity. In one further patient, seizures started exclusively from the hippocampus. In two of three patients with removal of the FCDs, the histological subtype was identical (Palmini type 2) and in one patient, histology differed between the lesions. All operated patients became seizure-free. In patients with FCD type 2, germ-line mutations in the tuberous sclerosis complex genes were not detectable. Dysplastic brain regions may not be restricted to a single brain region. Areas of FCD can have different degrees of epileptogenicity, ranging from electrographic silence to interictal epileptic discharges and initial involvement in seizure generation. Based on genetic analysis and clinical features, multi-FCD in this patient series was not likely to be related to tuberous sclerosis.

CD34-immunoreactive balloon cells in cortical malformations

Balloon cells are histopathological hallmarks of various cortical malformations, i.e., focal cortical dysplasia (Taylor’s type, FCD IIb), hemimegalencephaly (HME) or cortical tubers (tuberous sclerosis, TSC). Whether this intriguing cell type results from similar pathogenetic pathways remains to be shown. Here, we analyzed the immunohistochemical distribution pattern of the CD34 epitope in surgical specimens from 34 patients with FCD IIb, compared to that of 6 patients with TSC and 3 patients with HME. In normal brain, CD34 occurs only transiently during neurulation, but cannot be detected in mature neuroectodermal cell progenies. In contrast, 58% of our patients showed CD34 immunoreactivity within a subpopulation of balloon cells. Interestingly, CD34-positive balloon cells were confined to the white matter, but never observed in neocortical layers. Furthermore, balloon cells expressing neurofilament protein were also restricted to white matter, whereas GFAP-positive balloon cells were observed either in white or gray matter location. Clinical characteristics did not significantly differ between patients with CD34-positive versus CD34-negative lesions. No significant correlation was found between CD34 expression and genetic alterations of the TSC1 gene, which is affected in many FCD and TSC patients and which plays a role in the regulation of cell size. Further studies are warranted to clarify the restricted expression of CD34 in balloon cells of the white matter.

FDG-PET and MRI in potassium channel antibody-associated non-paraneoplastic limbic encephalitis: correlation with clinical course and neuropsychology.

Objectives –  We report a patient with potassium channel antibody‐associated non‐paraneoplastic limbic encephalitis (NPLE) in whom repeated fluorodeoxyglucose‐positron emission tomography (FDG‐PET) and magnetic resonance imaging (MRI) are correlated with epileptic activity and memory performance during the course of disease.

Noninvasive source localization of interictal EEG spikes: effects of signal-to-noise ratio and averaging.

Source localization using single current dipoles estimates equivalent centers of the spiking gray matter. The extent of the active cortex, however, is difficult to assess from scalp EEG because of the unknown individual volume conduction. The spatial scatter of dipole localizations of single spikes has been proposed as a measure of extent. Single spike localization, however, is strongly dependent on the signal-to-noise ratio (SNR), that is, the ratio of spike and background EEG amplitudes. On the other hand, averaging of all spikes yields only the localization of equivalent centers of activity. We investigated the influence of SNR and multiple subaverages on the estimation of spatial extent by comparing the localization scatter of 100 single spikes in 27 spike types of 25 epilepsy patients with 1000 different subaverages computed by random sampling and bootstrapping. Averaging increased SNR and therefore allowed for localization not only at the spike peak but also during spike onset when less cortex is active. In several subjects with known cortical lesions, the single spike scatter considerably exceeded the lesion. Single dipole scatter was highly correlated with SNR (r = −0.83, P < 0.0001) and was greatly reduced when analyzing multiple subaverages of 10, 25, 50, and 100 spikes. Thus, we found a dominant role of the SNR on the estimated extent and improvement by scatterplots based on the dipole localization of randomly sampled subaverages.

Spread of ictal activity in focal epilepsy.

Purpose: Latencies between seizure onset, propagation of ictal activity, and initial clinical symptoms and signs are critically important for the successful implementation of detection‐based intervention systems in the treatment of epilepsy. This study analyzes intracranial EEG‐recordings for temporal characteristics of ictal spread and its dependence on focus localization.

Outcome and predictors of interstitial radiosurgery in the treatment of gelastic epilepsy.

Background: Gelastic epilepsy due to hypothalamic hamartomas is usually a severe condition encompassing both epileptic seizures and an epileptic encephalopathy associated with behavioral and cognitive impairments. Here we report the effects of interstitial radiosurgery in the treatment of this generally pharmacoresistant epilepsy syndrome. Methods: Twenty-four consecutive patients (3–46 years of age, 7 women, mean age 21.9 years, mean duration of epilepsy 17.6 years) with gelastic epilepsy due to MR-ascertained hypothalamic hamartoma and a minimum follow-up period of 1 year were included in this evaluation. Treatment was performed by interstitial radiosurgery using stereotactically implanted 125I seeds. Effects of treatment on seizure frequency and possible side effects were assessed prospectively. Factors influencing outcome and side effects were analyzed statistically. Results: After a mean 24-month follow-up period following the last radiosurgical treatment, 11/24 patients were seizure free or had seizure reduction of at least 90% (Engel class I and II), in some cases only after repeated treatment. The duration of epilepsy prior to radiosurgery negatively influenced outcome. Treatment was well tolerated in most patients. Headache, fatigue, and lethargy were transient side effects associated with the development of brain edema extending from the implantation site in five patients. Four patients had a weight gain of more than 5 kg which was severe in two patients. The majority of those patients whose cognitive functions initially deteriorated showed subsequent recovery of cognitive functions, but episodic memory in two patients showed persistent decline at 1 year follow-up. Longer disease duration increased the risk for cognitive side effects, and larger hamartoma size and eccentric seed positioning increased the risk for radiogenic brain edema. Neither perioperative mortality nor neurologic impairments, visual field defects, or endocrinologic disturbances were encountered following treatment. Conclusion: Interstitial radiosurgery was efficacious in significantly improving gelastic epilepsy in about half of the patients treated in this series. Weight gain may occur as a side effect, whereas other severe side effects reported following microsurgical removal of the hamartoma were absent. The study results strongly suggest early causal treatment, as chances for seizure control are higher and the risk for cognitive side effects is lower in patients with shorter disease duration.