Seizure prediction
Encyclopedia
Seizure prediction refers to the forecasting of epileptic seizures based on physiological
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

 parameters, particularly of the electroencephalogram
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...

 of epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

 patients.

Background

Epileptic seizures are events during which abnormal synchronization of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

 leads to manifest disturbances in perception
Perception
Perception is the process of attaining awareness or understanding of the environment by organizing and interpreting sensory information. All perception involves signals in the nervous system, which in turn result from physical stimulation of the sense organs...

, thinking, and behavior
Behavior
Behavior or behaviour refers to the actions and mannerisms made by organisms, systems, or artificial entities in conjunction with its environment, which includes the other systems or organisms around as well as the physical environment...

. About 0.8% of the world's population suffer from epilepsy which is characterized by recurrent epileptic seizures which occur without obvious external precipitant. So far, the mechanisms leading to the apparently “spontaneous” occurrence of seizures are incompletely understood. Genetic
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...

 make-up in determining the individual “seizure threshold”, intrinsic fluctuations in EEG
Electroencephalography
Electroencephalography is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain...

 dynamics, and external triggers are thought to play a role in the transition from the interictal state to a seizure.

The frequency of epileptic seizures may vary from many per day to a few within several years. Even if epileptic seizures are rare in a given patient, their unforeseeable occurrence overshadows the whole life. The sudden occurrence of seizures endangers the patients during many activities of daily life, often resulting in traumatic injuries
Trauma (medicine)
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...

 and even death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

 e.g. from drowning
Drowning
Drowning is death from asphyxia due to suffocation caused by water entering the lungs and preventing the absorption of oxygen leading to cerebral hypoxia....

. Furthermore, being suddenly overwhelmed by loss of control regarding thoughts and behavior may result in serious psychological problems like anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

, avoidance behaviour and depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

, and has social consequences like restrictions in driving and in pursuing certain professional careers. Furthermore, the unforeseeable occurrence of seizures poses diagnostic problems and presently necessitates a continuous long-term treatment with anticonvulsants to prevent their occurrence.
Seizure prediction could thus overcome one of the most disabling aspects of the disease by warning patients in time to avoid seizure-related risks. Asides it would open new avenues of specific, timely targeted and closed-loop treatments instead of long-term interventions mostly targeting interictal periods.

Physiology of seizure generation

Attempts towards seizure prediction assume that brain dynamics do not change abruptly but are preceded by gradual changes which can be extracted from analyses of appropriate physiological parameters. It has been advocated that such gradual transitions in brain dynamics can be expected only in epilepsies arising from circumscribed brain areas (“focal epilepsies”).
Presently, the underlying pathophysiology of interictal transitions is unknown, as are parameters best suited for the detection of preictal changes. In principle, electrophysiological or chemical changes in brain activity, measures of brain metabolism and perfusion are considered as possible indicators. Most work has been concentrated on the field potential recordings of neuronal activity
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

 obtained at the level of scalp EEG
EEG
EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...

, subdural or depth EEG. So far, truly prospective and statistically valid evidence that prediction of seizures is possible remains to be provided, and there is an ongoing contest for its prove.

Methodology of seizure prediction

EEG-based seizure prediction uses linear or non-linear measures derived from the EEG. Based on a moving-window analysis, time-profiles of derived features are calculated. For predictions, thresholding of derived features is used; alternatively, seizure propensities can be derived from target ranges of features.
Predictions have to be made for certain time periods (“seizure occurrence periods”, SOP) during which a seizure is assumed to occur. Furthermore, to distinguish predictions from detections, a minimum time interval between the derivation of a prediction and seizure onset has to be defined.
The performance of seizure prediction algorithms is measured by its sensitivity to correctly predict seizures to occur during a SOP, the number of false prediction, and the statistical prove of superiority compared to random predictions.

Current status of seizure prediction

Analyses performed in the 1990s focused on changes in the dynamics during time periods preceding seizures. Various methods, e.g.the largest Lyapunov exponent
Lyapunov exponent
In mathematics the Lyapunov exponent or Lyapunov characteristic exponent of a dynamical system is a quantity that characterizes the rate of separation of infinitesimally close trajectories...

, correlation density, dynamical similarity index, claimed to find characteristic preictal changes. When such changes were compared to fluctuations in interictal dynamics (as done on a first international database from 5 patients following the First International Seizure Prediction Workshop in Bonn, 2000), most methods could not prove the statistical significance of such changes,data mining using discrete finite automata have predicted seizures in rats by 6 seconds s,. Recent analyzes show that short time prediction (1 min) is possible with high accuracy if electrodes are located at the focal point where seizure develops. So far, evidence from retrospective analysis including limited interictal time periods suggest that some bivariate measures like phase synchronization are superior to random predictors, but have insufficient sensitivity and specificity for clinical applications. Improved performances can result with consideration of circadian variability in EEG dynamics, and by combining different measures in the analysis of characteristic preictal alterations.
The build-up of large databases containing recordings with sufficient duration and numbers of seizures is presently regarded as one important step to provide the growing number of research groups worldwide devoted to seizure prediction with adequate data for the development and analysis of new approaches for seizure prediction. Both the European Community (project “EPILEPSIAE”) and the NINDS (USA) support such multicentric databases.

External links

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