J. Parra

Dynamical diseases of brain systems: different routes to epileptic seizures

In this overview, we consider epilepsies as dynamical diseases of brain systems since they are manifestations of the property of neuronal networks to display multistable dynamics. To illustrate this concept we may assume that at least two states of the epileptic brain are possible: the interictal state characterized by a normal, apparently random, steady-state electroencephalography (EEG) ongoing activity, and the ictal state, that is characterized by paroxysmal occurrence of synchronous oscillations and is generally called, in neurology, a seizure. The transition between these two states can either occur: 1) as a continuous sequence of phases, like in some cases of mesial temporal lobe epilepsy (MTLE); or 2) as a sudden leap, like in most cases of absence seizures. In the mathematical terminology of nonlinear systems, we can say that in the first case the systems attractor gradually deforms from an interictal to an ictal attractor. The causes for such a deformation can be either endogenous or external. In this type of ictal transition, the seizure possibly may be anticipated in its early, preclinical phases. In the second case, where a sharp critical transition takes place, we can assume that the system has at least two simultaneous interictal and ictal attractors all the time. To which attractor the trajectories converge, depends on the initial conditions and the systems parameters. An essential question in this scenario is how the transition between the normal ongoing and the seizure activity takes place. Such a transition can occur either due to the influence of external or endogenous factors or due to a random perturbation and, thus, it will be unpredictable. These dynamical changes may not be detectable from the analysis of the ongoing EEG, but they may be observable only by measuring the systems response to externally administered stimuli. In the special cases of reflex epilepsy, the leap between the normal ongoing attractor and the ictal attractor is caused by a well-defined external perturbation. Examples from these different scenarios are presented and discussed.

Dynamics of epileptic phenomena determined from statistics of ictal transitions

In this paper, we investigate the dynamical scenarios of transitions between normal and paroxysmal state in epilepsy. We assume that some epileptic neural network are bistable i.e., they feature two operational states, ictal and interictal that co-exist. The transitions between these two states may occur according to a Poisson process, a random walk process or as a result of deterministic time-dependent mechanisms. We analyze data from animal models of absence epilepsy, human epilepsies and in vitro models. The distributions of durations of ictal and interictal epochs are fitted with a gamma distribution. On the basis of qualitative features of the fits, we identify the dynamical processes that may have generated the underlying data. The analysis showed that the following hold. 1) The dynamics of ictal epochs differ from those of interictal states. 2) Seizure initiation can be accounted for by a random walk process while seizure termination is often mediated by deterministic mechanisms. 3) In certain cases, the transitions between ictal and interictal states can be modeled by a Poisson process operating in a bistable network. These results imply that exact prediction of seizure occurrence is not possible but termination of an ictal state by appropriate counter stimulation might be feasible.

Electrical brain-stimulation paradigm for estimating the seizure onset site and the time to ictal transition in temporal lobe epilepsy

OBJECTIVE To explore and validate a novel stimulation and analysis paradigm proposed to monitor spatial distribution and temporal changes of the excitability state in patients with temporal lobe epilepsy (TLE). METHODS We use intermittent pulse stimulation in the frequency range 10-20Hz. A quantitative measure of spectral phase de-modulation, the relative phase clustering index (rPCI) was applied to the evoked EEG signals, measured from electrodes implanted in the hippocampal formation. RESULTS We found that in the interictal periods, high values of rPCI recorded from specific sites were correlated with the most probable seizure onset sites (SOS). Furthermore we found that high values of rPCI from certain locations correlated with shorter time intervals to the next seizure. CONCLUSIONS Our clinical findings indicate that although the precise moment of ictal transitions is in general unpredictable, it may be possible to estimate the probability of occurrence of some epileptic seizures. SIGNIFICANCE The use of the rPCI for probabilistic forecasting of upcoming epileptic seizures is warranted. rPCI measurements may be used to guide interventions with the aim of modifying local tissue excitability that ultimately might prevent ictal transitions.

Quantification of Unidirectional Nonlinear Associations Between Multidimensional Signals

In this paper, we present a rigorous, general definition of the nonlinear association index, known as h2. Proving equivalence between different definitions we show that the index measures the best dynamic range of any nonlinear map between signals. We present also a construction for removing the influence of one signal from another, providing, thus, the basis of an independent component analysis. Our definition applies to arbitrary multidimensional vector-valued signals and depends on an aperture function. In this way, the bin-related classic definition of h2 can be generalized. We show that upon choosing suitable aperture functions the bin-related intuitive definition can be deduced. Special attention is dedicated to the direction of the association index that in general is taken in only one sense. We show that for linearly coupled signals high associations are always bidirectional. As a consequence, high asymmetric nonlinear associations are indicators of nonlinear relations, possibly critical, between the dynamic systems underlying the measured signals. We give a simple simulated example to illustrate this property. As a potential clinical application, we show that unidirectional associations between electroencephalogram (EEG) and electromyogram (EMG) recorded from patient with pharmacologically intractable epilepsy can be used to study the cortical involvement in the generation of motor seizures

Photosensitivity and visually induced seizures: review

Purpose of reviewInterest in visually induced seizures has increased in recent years as a result of the increasing number of precipitants in our modern environment. This review addresses new developments in this field with special attention given to the emergence of new diagnostic, therapeutic and preventive approaches; it also emphasizes the importance of this condition as a public health issue. Recent findingsCurrent evidence indicates the presence of two different mechanisms of photosensitivity, one dependent on luminance changes and the other on wavelength. Both mechanisms may be active in the same patient, although one may be dominant. Magnetoencephalography studies revealed an enhancement in gamma frequency preceding the development of a paroxysmal response as well as underlying uncomfortable visual illusions, suggesting that a loss of control over high-frequency oscillatory processes may be involved in the genesis of both types of phenomenon. The genetics underlying this trait remain to be determined. More precise definition of different phenotypes should help in this search. Recognition of the risks posed by the audiovisual environment for induction of seizures in photosensitive individuals, who may not even be aware of their condition, will prompt further development of guidelines and devices designed to prevent the occurrence of seizures triggered by dangerous video sequences. SummaryPhotosensitive epilepsy constitutes a unique benchmark model in which to address important issues in human epileptogenesis. The scope of the health risks posed by the modern audiovisual environment is increasingly being recognized, and further development of guidelines and regulations to control exposure to provocative materials are warranted.

Magnetic source imaging in fixation-off sensitivity: relationship with alpha rhythm.

A patient in whom a variety of abnormal EEG findings can be elicited by elimination of central vision and fixation demonstrates fixation-off sensitivity. The underlying mechanisms of fixation-off sensitivity and its relationship with alpha rhythm remain unclear. To obtain a better understanding of this issue, we used a whole-head magnetoencephalograph to study an epileptic child with fixation-off sensitivity resulting in a 3-Hz, large-amplitude oscillation (300 microV) over the occipital regions on the EEG. Magnetic source localization revealed alpha activity around the calcarine fissure and surrounding parieto-occipital areas. Magnetic sources of abnormalities relating to fixation-off sensitivity, however, usually were located deeper in the brain, suggesting more extensively distributed sources, with involvement of the cingulate gyrus and the basomesial occipitotemporal region. Distributions of the sources of both types of activities show independent clusters but also an appreciable domain of overlap. Our findings indicate that abnormalities related to fixation-off sensitivity can emerge in thalamocortical networks, with larger and more anterior cortical distribution than those that generate alpha rhythm. Transition in the type of oscillation appears not only to depend on a change in cellular dynamics but also to be reflected in a different spatial distribution of the underlying neuronal networks.

Removal of epileptogenic sequences from video material The role of color

Background: After Pokémon viewing triggered an epidemic of seizures in Japan, many efforts have been made to design safety guidelines and systems to protect subjects with photosensitivity. The authors developed a new method based upon nonlinear diffusion techniques capable of filtering the epileptogenic content of a video sequence related to color without altering its spatial and luminance content. Methods: The authors showed to 25 photosensitive patients (18 women, mean age: 22 years) the original Pokémon sequence and a modified one in an ABBA protocol using two television (TV) sets (100 and 50 Hz). Results: Twenty-three patients had a photoparoxysmal response (PPR) according to Waltz classification with at least one of the scenes. The modified sequence triggered fewer and less severe PPRs than the original version in both TVs (p < 0.001). Original sequences elicited generalized PPRs in 56.5% of the trials for the 50 Hz TV and in 41.3% for the 100 Hz TV, whereas modified sequences elicited these responses in only 8.7% (50 Hz) and 4.3% (100 Hz TV) of the trials (p < 0.001). Sensitivity to the modified version on the 50 Hz TV correlated with pattern sensitivity (p < 0.05). Conclusion: Specific manipulations of the color modulation-depth could be enough to decrease dramatically the risk of triggering seizures in susceptible subjects exposed to provocative visual scenes. This new method can be implemented in protective devices able to filter out the epileptogenic video sequences in which color plays a fundamental role while leaving intact the spatial content, frequency, and average luminance.

Extensive intracranial involvement with multiple dissections in a case of giant cell arteritis

A 56-year-old man presented with weight loss, articular pain and minor neurological symptoms progressing over 1 month. Neurosonological evaluation suggested occlusion in intracranial segments of the left vertebral artery (VA) and of both internal carotid arteries (ICA) and hypoechoic halo sign in both superficial temporal arteries. The diagnosis of giant cell arteritis was supported by inflammatory markers and confirmed by biopsy. Despite early steroid initiation, he manifested fluctuant vascular deficits and became lethargic. Brain MRI indicated watershed infarcts and intracranial dissections of left VA and both ICA. The patient was stabilised with the association of prednisolone 2 mg/kg, methotrexate and oral anticoagulation. Since then he has been neurologically asymptomatic and control imaging showed only residual intracranial left VA stenosis, with no signs of temporal artery inflammation or new vascular lesions. This is to the best of our knowledge, the first reported clinical case with such an extensive intracranial involvement with multiple dissections.

Correlation-based alignment of multichannel signals and application to paroxysmal events

We propose a new group-theoretical approach to the problem of alignment of time events in multichannel signal recordings. Such an alignment is an essential phase in the classification of transients in electroencephalogram/magnetoencephalogram (MEG) signals. A common reference frame is reconstructed applying a time translation transformation based on delayed mutual correlation functions of the individual events. The method is applied to MEG data sets recorded from epileptic patients showing paroxysmal interictal discharges.

Intracranial Internal Carotid Artery Wall Calcification in Ischemic Strokes Treated with Thrombolysis

Background: Calcifications are an important element of atherosclerotic plaques and have been used as a marker of atherosclerosis and clinical outcome predictor in different vascular territories. CT-scan, performed in the acute ischemic stroke setting, can reliably detect intracranial arterial calcifications. Objectives: To investigate the association between intracranial internal carotid artery calcification and functional outcome, symptomatic intracerebral hemorrhage (sICH), recanalization, and death. Methods: We included 396 consecutive ischemic stroke patients submitted to recombinant tissue plasminogen activator treatment between January 2011 and September 2014. Admission CT-scans were reviewed to calculate the Total Carotid Syphon Calcification score. Patients were followed for up to at least 6 months post-stroke or until death. Outcome measures included evaluation of recanalization on the first 24 h (transcranial color coded Doppler or angio-CT), sICH, and assessment of functional outcome at 3 months after stroke (using modified Rankin scale). Results: Carotid artery wall calcification did not predict sICH, recanalization or any good outcome. However, it was a statistically significant predictor of death (OR 1.102, 95% CI [1.004–1.211], p = 0.042). Discussion: Intracranial carotid artery calcification does not increase the risk of thrombolysis-induced sICH. Patients with higher grade of carotid artery wall calcification may have a higher mortality rate.