LITERATURE REVIEW ON SEIZURE DETECTION

PI: Asst Prof Justin Dauwels Post-Doc: Dr. Lalit-Garg Research Assistant: Abhishek Agrawal

Abstract
In this review, we explore different seizure types that have been clinically studied in the past. We also distinguish between epileptic and non-epileptic seizures. We explore different methods that are followed for seizure diagnosis.<to be edited>

LIST OF ABBREVIATIONS USED

SUDEP Sudden unexpected death in Epilepsy. CBC Complete Blood Count EEG Electroencephalogram MRI Magnetic Resonance Imaging

1. Introduction
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain"(1).Not all seizures come under the category of epileptic seizures. The medical syndrome of recurrent, unprovoked seizures is termed as Epilepsy(2). The external effect of an epileptic seizure that can be perceived can range from wild thrashing movement in the form of convulsions toa full body slump. However, not all epileptic seizures have such drastic consequences.Timely diagnosis and treatment may reduce the chance of recurrent seizures by as much as half(4).Studies(3-4) have revealed that about 4% of people will have an unprovoked seizure by the age of 80. Theprobability thatthese people will suffer from a second seizure is as high as 30-40%. Seizures are classified as per the location of the source of seizure in the brain (7). When the source of seizure inside the brain is localized orlimited to a fixed region, the seizure is termed as a partialor focal-onset seizure. On the other hand, when the source of seizure inside the brain is distributedor spread over a large region; the seizure is termed as a generalized seizure. Generalized seizures are further classified according to their impact on the body. We will discuss the detailed classification of seizure types in the second section of this review. An understanding of the word Consciousness in the context of epilepsy is crucial in understanding the symptoms and state of a person during and after an epileptic seizure. A cognitive state is defined as a mental state in which a person is open to reasoning and learning. Consciousness is an alert cognitive state in which a person is aware of himself and his situation. Any deviation from this state is termed as loss of consciousness. Study (5)points out that the signs and symptoms of an epileptic seizure depends on the type of seizure.Seizures are often associated with loss of consciousness or sudden involuntary movement of muscles. The onset of a seizure may result in a fleeting numbness in a part of the body, a brief of long term loss of memory, visual changes, or a sensation of fear and total state of confusion. A seizure can last for a period of a few seconds to Status Epilepticus. Status Epilepticus is a life threatening situation in which the brain is in a state of persistent seizure for duration of at least five minutes(6). The review has been divided into several sections for the purpose of exploring each aspect of epilepsy in detail. Below is a brief description of the various sections under which the review is classified: 1. Classification&Syndromes 2. Causes & Diagnosis 3. Statistical Relationship between Normal and Epileptic Seizures -

2. Classification& Syndromes
The primary cause of a seizure is abnormal electrochemical discharge or disorder in the brain. Each brain celleither excites or inhibits other brain cells through its discharges.When this excitation is beyond a certain threshold, then a seizure occurs(7).There are various classifications of epileptic seizures. We first describe the seizure types as per the region of abnormalelectrochemical discharge in the brain. To gain an understanding of this classification, it is important to know about the different regions of the brain. The figure below is a pictorial representation ofthe key regions of the brain:

Fig 1: Brain Regions The brain is divided into two hemispheres each consisting of four lobes: frontal, parietal, occipital and temporal. When a seizure occurs, the electrical activity proceeds through the motor area activating each muscle group or organ.The most susceptible part of the brain where seizure related abnormal electrical activity can happen is the temporal lobe. When the abnormal electrical activity happens in the motor area, a motor seizure is said to have occurred. The effect is reflected in the respective organ or part of the body controlled by that particular area. Similarly, other seizures are also named as per the occurrence of abnormal electrical activity for e.g. sensory perception seizure (region is sensory cortex), visual perception seizure (region is visual cortex). A cortex is the outermost layer of the frontal part of the brain. Seizure in deep temporal lobes often results in loss of consciousness, interruptions or senselessness during activity.

The next and the most widely accepted classification is based on the committee generated conventions of terminology related to seizures (7). Under this classification, we have three main categories in which all the seizure types and their consequences have been listed. They are:

1. Partial Seizures These seizures occursonly onone side of the brain. The symptoms arising
from it are localized to a single physical part of the body or a resulting consequence/action. For instance, twitching in arms or face. It may or may not be accompanied by a loss of memory. There are two further subdivisions in this category: a) Simple Partial Seizure It does not involve the loss of memory or consciousness. b) Complex Partial SeizureIt involves loss of memory or consciousness.

2. Generalized Seizures These seizures occur on both sides of the brain. The consequences
can be anywhere from eyelid fluttering or head nodding to sudden loss of consciousness. There are two further subdivisions in this category: a) Generalized/Primary Generalized the abnormal electrochemical activity is spread right from the seizure onset time. b) Secondary Generalized the abnormal electrochemical activity starts from a localized part of the brain and spread to the entire area.

3. Unclassifiable All the seizure types which (i) do not come under the above two categories
and (ii) for whom reliable scientific evidence on occurrence of abnormal brain activity has not been found come under this category. Now we describe the above categories in detail. 2.1.1 Partial Seizures

These are seizures which only affect one part of the brain at seizure onset (8-9). The consequences of simple partial seizures can be twitching, abnormal sensations in the body, abnormal visions, sounds or smell and distortions of perception.The person affected by this type of seizure should be able to recall the effects on his body during the period at which seizure occurs. If there is some confusion or a loss of consciousness, then the seizure type is comes under complex partial seizure. The consequences of partial seizures can range from effect on sensory (loss of perception), motor (twitching), sensory-motor organs to psychic (abnormal thoughts/perception) and autonomic (body heat rising, gastrointestinal illness, flushing) effects (10).

2.1.2

Complex Partial Seizures

These seizures primarily arise in the temporal lobes of the brain and hence were earlier called as temporal lobe seizures (also called psychomotor seizures or limbic seizures); see (7). These seizures may be preceded by a warning signal in the form of a heat or tingling sensation, nausea or distortion of sensory perceptions. The period, during which the complex partial seizure occurs, the patient suffers from automatisms (11). They are senseless and fragmented of activities such as lip smacking, mumbling meaningless phrases, walking around aimlessly etc. 2.2.1 Generalized/Primary Generalized Seizures There are primarily two types of generalized seizures which come under this category. They are Absence or petit mal and tonic-clonic or grand mal seizures. Absence seizures typically start in childhood but can persist till adulthood. The person suffering from Absence seizures can be identified as having staring spells with staring spells coupled with eyelid fluttering or head nodding. Tonic-clonic or grand mal seizures start with sudden loss of consciousness followed by muscle stiffening (tonic activity) and rhythmic jerking (clonic activity). The duration for which the patient experiences these symptoms can be between one to three minutes. 2.2.2 Secondary Generalized Seizures

Seizures that begin focally at one part of the brain and spread to the entire brain area are called secondary generalized seizures. When this happens, the consequence is a tonic-clonic seizure. The treatment drugs and protocols for secondary and primary generalized seizures are different. For instance, surgical methods can be used for secondary seizures as compared to primary as the location of they originate focally. Secondary generalized seizures can be further sub-divided into Atonic, Tonic or Myoclonic seizure types.An atonic seizure originates in people who have previously suffered from a brain injury. A myoclonic seizure is a single un-sustained or a sequence of random jerks. A tonic seizure is sudden stiffness of a muscle or a group of muscles which may or may not result in loss of consciousness or abrupt extension of arms or legs of the patient. 3.3.1 Syndromes of Epileptic Seizures

The above classification is not enough to probe into the causes, severity and prognosis of the seizures.There are three terms associated with the identification of the symptoms of the seizures. They are symptomatic, idiopathic and cryptogenic. Symptomatic implies that seizures have a known underlying cause; idiopathic implies that the seizures dont have an underlying cause and cryptogenic implies that a symptomatic cause is suspected but hasnt been found yet (7).<to be edited>

3. Causes and Diagnosis

3.1 Causes The causes of epilepsy are also called as etiologies in medical terminology. Based on whether the seizures are generalized or partial, focal or spread: we discuss thefollowing etiologies. 3.1.1 Causes for Focal Seizures Due to Brain Injuries An injury or malfunction of one or more parts of the brain results in focal seizures. Often it happens that the seizure occurs several years later after the injury has occurred. This delay is due to the reorganization of nerve fibers inside the brain at the injured area (7).The injuries arising from events like a fall or a blow to the head are too mild to cause of epilepsy. However a head trauma penetrating a brain injury can be a cause for epileptic seizures.The seizures from brain injuries can be diagnosed using an MRI scan. Due to Stroke and Brain Infections During a stroke, blood flow to a part of the brain stops killing many brain cells which may be a cause of subsequent epileptic seizures. Brain hemorrhage may also be an etiology for epilepsy. Another most common etiology for brain seizures is brain infection. These infections may be caused by certain viruses, fungi and parasites which are commonly present in eatables like pork or unclean fruits and vegetables (7), (12). Due to Vascular Malformations and Brain Tumors Blood flows into the brain through arteries and reaches to the brain cells through tiny vessels called capillaries. It flows out of the brain through the veins. Any malformation due to a birth defect or radiation stresses in the arteries/veins is called as ateriovenous and that in the capillaries are called cavernous malformation (7). Due to these malformations, sufficient oxygen may or may not reach out to the brain cells which may result in seizures. Tumors rarely are a cause of seizures. However in typical cases where the brain cells are irritated or suffocated due to presence of a tumor, a seizure ensues. 3.1.2 Causes for Generalized Seizures

Due to Metabolic Imbalances and Medical Reactions Certain generalized seizures arise due to metabolic imbalances but are never sustained or epileptic. For example, seizures may occur due to low oxygen level, low blood sugar, low blood calcium, alcohol or sedative medication withdrawal, certain recreational or prescription drug overdoses,

kidney or liver failure, hyperthyroid diseases. Certain over the counter prescription drugs also cause seizures. A complete list of those drugs are given in the appendix A. <to be edited> Due to Idiopathic/Genetic Causes and Photosensitive Seizures The seizures whose causes and treatment are unknown are called idiopathic seizures. About 60 % of all seizures are idiopathic seizures (7). Genetic disorders increase the probability of generalized seizure onset rather than themselves being the direct cause. Only a few of the gene defects that may be a cause of epileptic seizures have been identified. The hereditary risk associated with epilepsy is around 5-20 % provided the mother suffers from the disease. Photosensitive seizures are seizures caused by flashing lights or certain visual patterns. This is reflected in the EEG brainwave pattern of the patients suffering from epilepsy, when exposed to these lights. Audio-Visual games, TV Shows, public displays or events having these visual patterns can provoke seizures in susceptible individuals (13).The frequency of the light must be between 10 to 25 frames per second for provoking seizures. 3.1.3 Sudden Unexpected Death (SUDEP) in Epilepsy

Sudden Unexpected death has been the most common cause among deaths due to epilepsy.It is also a major cause of death among individuals with intractable epilepsy (14). The study (14) suggests that the deaths occur due to cardiac abnormalities during and between seizures.To verify this, electrocardiograph data was obtained from patients who were suffering from refractory (stubborn or unresponsive to treatment) epilepsy. The data revealed ECG abnormalities and arrhythmias during and after the occurrence of the epileptic seizure for a majority of the patients who were victims of SUDEP; see (15). Melatonin, a naturally occurring chemical compound occurring in plants, animals and microbes is found to reduce seizure frequency in both children and patients with intractable epilepsy (6). <Write-up about syncopes, arrhythmias and ion channels to be added> 3.2 Diagnosis of Epileptic Seizures There are various tools and techniques for diagnosis and prediction of seizures and epilepsy in patients. The most important of them are: (a) Medical History (b) Physical Examination (c) EEG Data Medical History It isone of the most important diagnostic tools in epilepsy. A record of prior episodes and history of seizures enables the doctor to do prognosis about the future occurrences of seizures in the patients (16).It serves as a foundation for treatment and medicine prescription and is even more important than physical examination of the patient (7). It is crucial that the patient give detailed information about what has happened before. In some cases, where the patient is not able to recall relevant information from his/her memory, assistance may be taken from the people who witnessed the seizure happening. A written record or a video may also serve as a good source of information

about the epileptic seizure in the patient. The following questions are important for the patient to answer when he/she is being diagnosed (16): Before the spell: Did you experience lack of sleep or unusual stress? Were you sick recently? Did you take any kind of medication, including over-the-counter medicines, alcohol, or illegal drugs? What were you doing immediately before the event (for instance, lying down, sitting, standing, getting up from a lying position, heavy exercise)?

During the spell: What time of day was it? Were you just waking up or falling asleep? How did it begin? Was there a warning? Did your eyes, mouth, face, head, arms, or legs move abnormally? Were you able to talk and respond appropriately? Did you lose control of your bladder or bowels? Did you bite your tongue or the inside of your cheeks?

After the spell: Were you confused or tired? Could you speak normally? Did you have a headache? Did your muscles ache?

EEG Data Analysis The electroencephalogram (EEG) measures electrical activity of the brain. A person who can read electroencephalogram data can predict the normal brain patterns (7).When a seizure occurs, an electrical pattern is elicited in the brain which is typical to a particular seizure type. The EEG data can help to predict the part of the brain from where the seizure originated. Thus, it can be used to classify seizure type in the brain. It is important to understand two terms to gain an understanding of the use of EEG data in epileptic patients: ictal and post-ictal. An ictal period is defined as the period during which the patient undergoes a seizure. A post-ictal period refers to the time duration after a seizure has occurred. It is difficult and impractical to capture and record of EEG data during the ictal period. Luckily, a majority of people who suffer from epileptic seizure show abnormal EEG patterns during the post ictal period; called as spikes. The spikes occur in the EEG of about 5 to 8 out of every 10 individuals suffering from epilepsy; see (7). Such spikes are also called as inter-ictal spikes.

<compiling material, more to be added in this section> Physical Examination The two major techniques used during physical examination of epileptic patients are blood tests and medical imaging (such as Magnetic Resonance Imaging or an X-Ray). Blood tests are carried out to check for infectious or chemical causes of seizures such as low blood sugar, calcium or oxygen, kidney or liver failure, allergies or drug and toxins in the blood (7). As part of the diagnostic protocol, a doctor may also ask the patient to undergo a complete blood count test (CBC).A CBC provides a standard to the doctor to establish a baseline for the identification of the abnormalities mentioned earlier. It also helps to assign and choose the anticonvulsant medications and monitor the possible drug induced side-effects that the patient might face in the future (18). Other physical tests such as an X-ray may be carried out to test the possibility of a structural abnormality in the brain such as a tumor, a blood clot, old stroke or a localized collection of pus; see (7).Another method which yields more detailed information about the brain is Magnetic Resonance Imaging (MRI). It uses energy changes in the magnetic field to produce two dimensional computer images of the brain; see (19). <currently working on this section>

4. Statistical Relationship between Normal and Epileptic Seizures

5. Treatment &Medication

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13. Graham Harding, Arnold J. Wilkins, Giuseppe Erba, Gregory L. Barkley and Robert S. Fisher. Photic- and Pattern-induced Seizures: Expert Consensus of the Epilepsy Foundation of America Working Group (pages 14231425), Epilepsia, Volume 46, Issue 9, pages 1423-1425. 14. Lear-Kaul KC, Coughlin L, Dobersen MJ, Sudden unexpected death in epilepsy: a retrospective study, Am J Forensic Med Pathol, 2005;26(1):1117. 15. Cai X, et al., Unique roles of SK and Kv4.2 potassium channelsin dendritic integration, Neuron, 2004;44(2):35164. 16. http://www.epilepsy.com/epilepsy/testing_medhistory 17. http://en.wikipedia.org/wiki/Electroencephalography 18. http://www.webmd.com/epilepsy/epilepsy-blood-test 19. http://www.epilepsy.org.za/facts/diagnostic.php