Frameless stereotactic functional neuronavigation combined with intraoperative magnetic resonance imaging as a strategy in highly eloquent located tumors causing epilepsy.

BACKGROUND: Intractable epilepsy due to tumors located in highly eloquent brain regions is often considered surgically inaccessible because of a high risk of postoperative neurological deterioration. Intraoperative MRI and functional navigation contribute to overcome this problem. OBJECTIVES: To retrospectively investigate the long-term results and impact of functional neuronavigation and 1.5-tesla intraoperative MRI on patients who underwent surgery of tumors associated with epilepsy located close to or within eloquent brain areas. METHODS: Nineteen patients (9 female, 10 male, mean age 41.4 ± 13.4 years, 11 low-grade and 8 high-grade glial tumors) were evaluated preoperatively using BOLD imaging, diffusion-tensor imaging tractography and magnetoencephalography. Functional data were implemented into neuronavigation in this multimodal approach. RESULTS: In 14 of 19 patients (74%), complete resection was achieved, and in 5 patients significant tumor volume reduction was accomplished. Eight of 14 (57%) complete resections were achieved only by performing an intraoperative image update. Neurological deterioration was found permanently in 2 patients. After a mean follow-up of 43.8 ± 23.8 months, 15 patients (79%) became seizure free (Engel class Ia). CONCLUSIONS: Despite the highly eloquent location of tumors causing intractable epilepsy, our multimodal approach led to complete resection in more than two-thirds of patients with an acceptable neurological morbidity and excellent long-term seizure control.

Electro-clinical-pathological correlations in focal cortical dysplasia (FCD) at young ages.

The prevalence of focal cortical dysplasia (FCD) in pediatric patients with focal epilepsy is not exactly known because authors of publications in which the etiologies of epilepsies are listed, but which are not dealing specifically with epilepsy surgery issues, tend to lump together the many kinds of malformations of cortical development (MCD), of which FCDs, because of their relative frequency, are the most relevant subtypes. Out of 561 patients with MCD (children and adults) operated at centers in Europe who do feed data into the "European Epilepsy Brain Bank," 426 (76 %) had FCD.

Frontal lobe epilepsy and mild malformation with oligodendroglial hyperplasia: Further observations on electroclinical and imaging phenotypes, and surgical perspectives.

OBJECTIVE: Mild malformation with oligodendroglial hyperplasia (MOGHE) is a recently described clinicopathologic entity, associated with drug-resistant epilepsy and extensive epileptogenic networks. Knowledge is accumulating about particular electroclinical phenotypes, correlations with imaging, and potential prognostic significance for surgical outcomes. The study adds relevant information by documenting the presence of a hyperkinetic frontal lobe seizure phenotype in adolescents and an epileptic encephalopathy phenotype in young children. METHODS: Five cases were subjected to a structured presurgical evaluation protocol, including EEG-FMRI, chronic and acute invasive EEG, subjected to frontal lobe surgery with postoperative follow-up between 15 months and 7 years. RESULTS: In the two adult cases, surface EEG demonstrated lateralized widespread frontal lobe epileptogenicity and hyperkinetic semiological features. MRI demonstrated cortical white matter blurring and deeper white matter abnormalities. EEG-FMRI suggested concordant frontal lobe involvement. iEEG demonstrated a widespread frontal lobe epilepsy network. The three young children demonstrated a diffuse epileptic encephalopathy phenotype, with nonlocalizing, nonlateralizing surface EEG, and "spasms" as the main seizure type. MRI demonstrated extensive frontal lobe subcortical gray and white matter abnormalities, consistent with MOGHE literature for this age, while EEG-FMRI, in 2/3, demonstrated concordant frontal lobe involvement. They did not undergo chronic iEEG, and the resection was assisted by acute intraoperative ECoG. All cases were subjected to extensive frontal lobectomies with Engel class IA (2/5), IB (1/5), and IIB (2/5) outcomes. SIGNIFICANCE: The study confirms the presence of frontal lobe epilepsy and epileptic encephalopathy phenotypes, in accordance with epilepsy phenotypes already described in MOGHE literature. Presurgical evaluation studies, including EEG-FMRI, can provide strong lateralizing and localizing evidence of the epileptogenic networks involved. All responded favorably to extensive frontal lobe resections, despite widespread epileptic activity recorded by surface and intracranial EEG pre- and postoperatively; an epileptic encephalopathy phenotype, in the first years of life, should not discourage such a resection.

Ultra-High-Field 7 T Magnetic Resonance Imaging Including Dynamic and Static Contrast-Enhanced T1-Weighted Imaging Improves Detection of Secreting Pituitary Microadenomas.

OBJECTIVE: A prospective preoperative evaluation of 7 T ultra-high-field magnetic resonance imaging (MRI) in patients with suspected pituitary microadenomas for both adenoma detection and intrasellar localization compared with 3 T MRI was carried out. MATERIALS AND METHODS: Patients underwent prospective preoperative standardized 3 and 7 T MRI. A distinct qualitative (lesion detection, intrasellar lesion location) and quantitative (lesion diameters, T1/T2 signal intensity ratio of the lesion to normal pituitary gland tissue) analysis was performed, along with an evaluation of image quality (IQ) regarding overall IQ, anatomical parameters, and artifacts; the findings of the qualitative analysis were compared with intraoperative findings and endocrinological outcomes. RESULTS: Sixteen patients (mean age, 43 ± 16 years; 13 women) with pituitary microadenomas were included. Using 7 T MRI allowed the detection of 15 microadenomas-3 more than 3 T MRI. In addition, 7 T MRI allowed more precise lesion localization with 93.75% (15/16) agreement with intraoperative findings, compared with 75% (12/16) agreement using 3 T MRI. Lesion diameters showed no significant difference between 3 and 7 T MRI. T1 and T2 signal intensity ratio between microadenomas and normal pituitary gland tissue were higher in 7 T MRI than in 3 T MRI. The overall IQ and the IQ of each anatomical parameter of 7 T MRI were rated higher than those of 3 T MRI. No significant differences in susceptibility or head motion artifacts were observed between 3 and 7 T MRI; however, 7 T MRI was more susceptible to pulsation artifacts. CONCLUSION: Ultra-high-field MRI surpasses 3 T MRI in pituitary microadenoma detection and enables more precise delineation with higher correlation with intraoperative findings. Thus, 7 T sellar imaging is a promising option-especially in previously magnetic resonance-negative patients with endocrinologically confirmed hormone oversecretion-and helps reduce the need for invasive diagnostics.

Combined Artificial Intelligence Approaches Analyzing 1000 Conservative Patients with Back Pain-A Methodological Pathway to Predicting Treatment Efficacy and Diagnostic Groups.

Patients with back pain are common and present a challenge in everyday medical practice due to the multitude of possible causes and the individual effects of treatments. Predicting causes and therapy efficien cy with the help of artificial intelligence could improve and simplify the treatment. In an exemplary collective of 1000 conservatively treated back pain patients, it was investigated whether the prediction of therapy efficiency and the underlying diagnosis is possible by combining different artificial intelligence approaches. For this purpose, supervised and unsupervised artificial intelligence methods were analyzed and a methodology for combining the predictions was developed. Supervised AI is suitable for predicting therapy efficiency at the borderline of minimal clinical difference. Non-supervised AI can show patterns in the dataset. We can show that the identification of the underlying diagnostic groups only becomes possible through a combination of different AI approaches and the baseline data. The presented methodology for the combined application of artificial intelligence algorithms shows a transferable path to establish correlations in heterogeneous data sets when individual AI approaches only provide weak results.

Validation of automatic MRI hippocampal subfield segmentation by histopathological evaluation in patients with temporal lobe epilepsy.

OBJECTIVE: The present study validates the results of automated hippocampal subfield segmentation with histopathology in epilepsy patients undergoing epilepsy surgery. METHODS: We performed an automated hippocampal subfield segmentation on presurgical three-dimensional, T1-weighted magnetization Prepared Rapid Acquisition of Gradient Echoes Magnetic Resonance Imaging (MRI) data of 25 patients with unilateral mesial temporal lobe epilepsy due to hippocampal sclerosis (HS), using Freesurfer Version 6.0. The resulting volumes of cornu ammonis (CA) subfields CA1, CA2/3, CA4 and the dentate gyrus (DG) were compared to the histopathological cell count. RESULTS: We found a significant correlation between histopathology in subregion CA2 and automated segmentation of subregion CA1 (p = 0.0062), CA2/3 (p = 0.004), CA4 (p = 0.0062) and the DG (p = 0.0054), between histopathology in CA3 and automated segmentation of CA1 (p = 0.0132), CA2/3 (p = 0.0004), CA4 (p = 0.0032) and the DG (p = 0.0037), as well as between histopathology in the DG and automated segmentation of CA1 (p = 0.0115), CA2/3 (p < 0.0001), CA4 (p < 0.0001) and the DG (p = 0.0001). The histopathological finding of HS type 1 could correctly be classified in all cases on MRI. SIGNIFICANCE: The present study shows significant correlations between histopathological evaluation and results of the automated segmentation of the hippocampus, thereby validating the automated segmentation method. As the differential involvement of different hippocampal subfields may be associated with clinical parameters and the outcome after epilepsy surgery, the automated segmentation is also promising for prognostic purposes.

The Role of KRAS Mutations in Cortical Malformation and Epilepsy Surgery: A Novel Report of Nevus Sebaceous Syndrome and Review of the Literature.

The rare nevus sebaceous (NS) syndrome (NSS) includes cortical malformations and drug-resistant epilepsy. Somatic RAS-pathway genetic variants are pathogenetic in NS, but not yet described within the brain of patients with NSS. We report on a 5-year-old boy with mild psychomotor delay. A brown-yellow linear skin lesion suggestive of NS in the left temporo-occipital area was evident at birth. Epileptic spasms presented at aged six months. EEG showed continuous left temporo-occipital epileptiform abnormalities. Brain MRI revealed a similarly located diffuse cortical malformation with temporal pole volume reduction and a small hippocampus. We performed a left temporo-occipital resection with histopathological diagnosis of focal cortical dysplasia type Ia in the occipital region and hippocampal sclerosis type 1. Three years after surgery, he is seizure-and drug-free (Engel class Ia) and showed cognitive improvement. Genetic examination of brain and skin specimens revealed the c.35G > T (p.Gly12Val) KRAS somatic missense mutation. Literature review suggests epilepsy surgery in patients with NSS is highly efficacious, with 73% probability of seizure freedom. The few histological analyses reported evidenced disorganized cortex, occasionally with cytomegalic neurons. This is the first reported association of a KRAS genetic variant with cortical malformations associated with epilepsy, and suggests a possible genetic substrate for hippocampal sclerosis.

Mesenchymal stem cells promote oligodendroglial differentiation in hippocampal slice cultures.

We have previously shown that soluble factors derived from mesenchymal stem cells (MSCs) induce oligodendrogenic fate and differentiation in adult rat neural progenitors (NPCs) in vitro. Here, we investigated if this pro-oligodendrogenic effect is maintained after cells have been transplanted onto rat hippocampal slice cultures, a CNS-organotypic environment. We first tested whether NPCs, that were pre-differentiated in vitro by MSC-derived conditioned medium, would generate oligodendrocytes after transplantation. This approach resulted in the loss of grafted NPCs, suggesting that oligodendroglial pre-differentiated cells could not integrate in the tissue and therefore did not survive grafting. However, when NPCs together with MSCs were transplanted in situ into hippocampal slice cultures, the grafted NPCs survived and the majority of them differentiated into oligodendrocytes. In contrast to the prevalent oligodendroglial differentiation in case of the NPC/MSC co-transplantation, naïve NPCs transplanted in the absence of MSCs differentiated predominantly into astrocytes. In summary, the pro-oligodendrogenic activity of MSCs was maintained only after co-transplantation into hippocampal slice cultures. Therefore, in the otherwise astrogenic milieu, MSCs established an oligodendrogenic niche for transplanted NPCs, and thus, co-transplantation of MSCs with NPCs might provide an attractive approach to re-myelinate the various regions of the diseased CNS.

Clinical relevance of source location in frontal lobe epilepsy and prediction of postoperative long-term outcome.

PURPOSE: To evaluate the value of magnetoencephalography (MEG) source localization in localization of epileptic activities and predicting surgical outcome in frontal lobe epilepsies (FLE). METHODS: Forty-six patients with presurgical MEG evaluation and intractable FLE surgery (28 male patients) were analyzed retrospectively with a mean follow-up of 5 years. Dipole analysis was performed for MEG source imaging (MSI). The localization of dipole clusters in relation to the dominant hemisphere, lesions, resection cavity and functional cortex were analyzed. The predictive value of MSI in respect to clinical outcome with long-term postoperative follow up was evaluated. RESULTS: Interictal focal epileptic activities were found in 82.6% (38/46) patients with monofocal activity 81.6% (31/38) and multifocal activities 18.4% (7/38). Seizure free rate was 47.9% at the mean follow-up of 5.0 ± 4.0 years (median 11.5, range 2-57). Seizure recurrence mainly occurred in the first 1 year after surgery. In the monofocal epileptic activity group, 58.1% (18/31) of the patients were seizure free, predicitng postoperative seizure freedom better than multifocal localization 0% (0/7) (p=0.028). Dipole clusters were completely resected in 70.9% of monofocal activity patients, which had higher seizure free rates compared to partial resection (p=0.002). In patients with surgery in the dominant hemisphere, seizure control was less likely (p=0.006). CONCLUSION: MSI contributes to the clinical prediction of postoperative outcome in FLE patients. MSI may non-invasively disclose early epileptogenic lesions, pointing to a resectable lesion, and it then facilitates shortcut route of presurgical evaluation.