Sabine Rona

Targeted next generation sequencing as a diagnostic tool in epileptic disorders

Purpose:  Epilepsies have a highly heterogeneous background with a strong genetic contribution. The variety of unspecific and overlapping syndromic and nonsyndromic phenotypes often hampers a clear clinical diagnosis and prevents straightforward genetic testing. Knowing the genetic basis of a patient’s epilepsy can be valuable not only for diagnosis but also for guiding treatment and estimating recurrence risks.

Proposal: Different types of alteration and loss of consciousness in epilepsy

There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.

Predictors of preoperative and early postoperative seizures in patients with intra‐axial primary and metastatic brain tumors: A retrospective observational single center study

Antiepileptic treatment of brain tumor patients mainly depends on the individual physicians choice rather than on well‐defined predictive factors. We investigated the predictive value of defined clinical parameters to formulate a model of risk estimations for subpopulations of brain tumor patients.

Vorschlag für eine neue patientenorientierte Epilepsieklassifikation

ZusammenfassungDer kürzlich erschienene Vorschlag der ILAE-Taskforce zur Epilepsieklassifikation ist ein multiaxialer, syndromorientierter Ansatz. Hierbei werden die Patienten unterschiedlichen und oftmals unzureichend definierten Kriterien zugeordnet. Die resultierenden Syndrome haben häufig keine ätiologische oder pathophysiologische Relevanz, überlappen und wechseln je nach Alter des Patienten. Wir schlagen einen 5-dimensionalen, patientenorientierten Ansatz zur Klassifikation der Epilepsien vor. Dieser Ansatz wendet sich von der Orientierung an Syndromen ab und basiert stattdessen auf dem methodologischen Ansatz der allgemeinen Neurologie, in dem einerseits das klinische Bild des einzelnen Patienten im Mittelpunkt steht und andererseits in jeder Dimension voneinander unabhängige und möglichst operationalisierbare Kriterien angewandt und schließlich zusammengeführt werden. Die Dimension dieser Klassifikation sind: (1) Lokalisation der epileptogenen Zone, (2) Semiologie der epileptischen Anfälle, (3) Ätiologie, (4) Anfallshäufigkeit und (5) sonstige relevante medizinische Faktoren. Diese Dimensionen enthalten alle für das Management eines Patienten notwendige Information und sind voneinander unabhängige Parameter. Alle Patienten können selbst beim initialen Patientenkontakt sinnvoll in das System eingeordnet werden, auch wenn noch keine apparativen Untersuchungen durchgeführt wurden. Die Information aller Untersuchungen (z. B. MRT, EEG) fließt zum jeweiligen Zeitpunkt der Klassifikation in die Zuordnung des Patienten ein und erlaubt mit jeder neu verfügbaren Information eine Zunahme der Präzision und Validität der Klassifikation.SummaryThe recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes – at least as defined by the ILAE Task Force – group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient management. All cases can be classified according to this five-dimensional system, even at initial encounter when no detailed test results are available. Information from clinical tests such as MRI and EEG are translated into the best possible working hypothesis at the time of classification, allowing increased precision of the classification as additional information becomes available.

Suggestion for a new, patient-oriented epilepsy classification

ZusammenfassungDer kürzlich erschienene Vorschlag der ILAE-Taskforce zur Epilepsieklassifikation ist ein multiaxialer, syndromorientierter Ansatz. Hierbei werden die Patienten unterschiedlichen und oftmals unzureichend definierten Kriterien zugeordnet. Die resultierenden Syndrome haben häufig keine ätiologische oder pathophysiologische Relevanz, überlappen und wechseln je nach Alter des Patienten. Wir schlagen einen 5-dimensionalen, patientenorientierten Ansatz zur Klassifikation der Epilepsien vor. Dieser Ansatz wendet sich von der Orientierung an Syndromen ab und basiert stattdessen auf dem methodologischen Ansatz der allgemeinen Neurologie, in dem einerseits das klinische Bild des einzelnen Patienten im Mittelpunkt steht und andererseits in jeder Dimension voneinander unabhängige und möglichst operationalisierbare Kriterien angewandt und schließlich zusammengeführt werden. Die Dimension dieser Klassifikation sind: (1) Lokalisation der epileptogenen Zone, (2) Semiologie der epileptischen Anfälle, (3) Ätiologie, (4) Anfallshäufigkeit und (5) sonstige relevante medizinische Faktoren. Diese Dimensionen enthalten alle für das Management eines Patienten notwendige Information und sind voneinander unabhängige Parameter. Alle Patienten können selbst beim initialen Patientenkontakt sinnvoll in das System eingeordnet werden, auch wenn noch keine apparativen Untersuchungen durchgeführt wurden. Die Information aller Untersuchungen (z. B. MRT, EEG) fließt zum jeweiligen Zeitpunkt der Klassifikation in die Zuordnung des Patienten ein und erlaubt mit jeder neu verfügbaren Information eine Zunahme der Präzision und Validität der Klassifikation.SummaryThe recent proposal by the ILAE Task Force for Epilepsy Classification is a multiaxial, syndrome-oriented approach. Epilepsy syndromes – at least as defined by the ILAE Task Force – group patients according to multiple, usually poorly defined parameters. As a result, these syndromes frequently show significant overlap and may change with patient age. We propose a five-dimensional and patient-oriented approach to epilepsy classification. This approach shifts away from syndrome orientation, using independent criteria in each of the five dimensions similarly to the diagnostic process in general neurology. The main dimensions of this new classification consist of (1) localizing the epileptogenic zone, (2) semiology of the seizure, (3) etiology, (4) seizure frequency, and (5) related medical conditions. These dimensions characterize all information necessary for patient management, are independent parameters, and include information more pertinent than the ILAE axes with regard to patient management. All cases can be classified according to this five-dimensional system, even at initial encounter when no detailed test results are available. Information from clinical tests such as MRI and EEG are translated into the best possible working hypothesis at the time of classification, allowing increased precision of the classification as additional information becomes available.

Nonlinear Correlations Impair Quantification of Episodic Memory by Mesial Temporal BOLD Activity

OBJECTIVE Episodic memory processes can be investigated using different functional MRI (fMRI) paradigms. The purpose of the present study was to examine correlations between neuropsychological memory test scores and BOLD signal changes during fMRI scanning using three different memory tasks. METHOD Twenty-eight right-handed healthy subjects underwent three paradigms, (a) a word pair, (b) a space-labyrinth, and (c) a face-name association paradigm. These paradigms were compared for their value in memory quantification and lateralization by calculating correlations between the BOLD signals in the mesial temporal lobe and behavioral data derived from a neuropsychological test battery. RESULTS As expected, group analysis showed left-sided activation for the verbal, a tendency to right-sided activation for the spatial, and bilateral activation for the face-name paradigm. No linear correlations were observed between neuropsychological data and activation in the temporo-mesial region. However, we found significant u-shaped correlations between behavioral memory performance and activation in both the verbal and the face-name paradigms, that is, BOLD signal changes were greater not only among participants who performed best on the neuropsychological tests, but also among the poorest performers. The figural learning task did not correlate with the activations in the space-labyrinth paradigm at all. CONCLUSIONS We interpreted the u-shaped correlations to be due to compensatory hippocampal activations associated with low performance when people try unsuccessfully to remember presented items. Because activation levels did not linearly increase with memory performance, the latter cannot be quantified by fMRI alone, but only be used in conjunction with neuropsychological testing.

Incipient preoperative reorganization processes of verbal memory functions in patients with left temporal lobe epilepsy

We previously reported nonlinear correlations between verbal episodic memory performance and BOLD signal in memory fMRI in healthy subjects. The purpose of the present study was to examine this observation in patients with left mesial temporal lobe epilepsy (mTLE) who often experience memory decline and need reliable prediction tools before epilepsy surgery with hippocampectomy. Fifteen patients with left mTLE (18-57years, nine females) underwent a verbal memory fMRI paradigm. Correlations between BOLD activity and neuropsychological data were calculated for the i) hippocampus (HC) as well as ii) extrahippocampal mTL structures. Memory performance was systematically associated with activations within the right HC as well as with activations within the left extrahippocampal mTL regions (amygdala and parahippocampal gyrus). As hypothesized, the analyses revealed cubic relationships, with one peak in patients with marginal memory performance and another peak in patients with very good performance. The nonlinear correlations between memory performance and activations might reflect the compensatory recruitment of neural resources to maintain memory performance in patients with ongoing memory deterioration. The present data suggest an already incipient preoperative reorganization process of verbal memory in non-amnesic patients with left mTLE by simultaneously tapping the resources of the right HC and left extrahippocampal mTL regions. Thus, in the preoperative assessment, both neuropsychological performance and memory fMRI should be considered together.

BOLD Signal in memory paradigms in hippocampal region depends on echo time

To evaluate the hypothesis that the entire hippocampus might be affected by susceptibility artifacts. Previous studies described susceptibility artifacts in the amygdala and the anterior hippocampus.

Face-name association task reveals memory networks in patients with left and right hippocampal sclerosis☆

We aimed to identify reorganization processes of episodic memory networks in patients with left and right temporal lobe epilepsy (TLE) due to hippocampal sclerosis as well as their relations to neuropsychological memory performance. We investigated 28 healthy subjects, 12 patients with left TLE (LTLE) and 9 patients with right TLE (RTLE) with hippocampal sclerosis by means of functional magnetic resonance imaging (fMRI) using a face-name association task, which combines verbal and non-verbal memory functions. Regions-of-interest (ROIs) were defined based on the group results of the healthy subjects. In each ROI, fMRI activations were compared across groups and correlated with verbal and non-verbal memory scores. The face-name association task yielded activations in bilateral hippocampus (HC), left inferior frontal gyrus (IFG), left superior frontal gyrus (SFG), left superior temporal gyrus, bilateral angular gyrus (AG), bilateral medial prefrontal cortex and right anterior temporal lobe (ATL). LTLE patients demonstrated significantly less activation in the left HC and left SFG, whereas RTLE patients showed significantly less activation in the HC bilaterally, the left SFG and right AG. Verbal memory scores correlated with activations in the left and right HC, left SFG and right ATL and non-verbal memory scores with fMRI activations in the left and right HC and left SFG. The face-name association task can be employed to examine functional alterations of hippocampal activation during encoding of both verbal and non-verbal material in one fMRI paradigm. Further, the left SFG seems to be a convergence region for encoding of verbal and non-verbal material.

Clinical application of advanced MR methods in children: points to consider

The application of both functional MRI and diffusion MR tractography prior to a neurosurgical operation is well established in adults, but less so in children, for several reasons. For this review, we have identified several aspects (task design, subject preparation, actual scanning session, data processing, interpretation of results, and decision‐making) where pediatric peculiarities should be taken into account. Further, we not only systematically identify common issues, but also provide solutions, based on our experience as well as a review of the pertinent literature. The aim is to provide the clinician as well as the imaging scientist with information that helps to plan, conduct, and interpret such a clinically‐indicated exam in a way that maximizes benefit for, and minimizes the burden on the individual child.