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Epilepsy is a neurological disorder that is responsible for a tremendous amount of agony, affecting people of various ages in more than 50 million individual throughout the whole world (Hermann et al., 2008). Majority of the cases are idiopathic while the rest may be due to certain provoked forms such as traumatic brain injury, metabolic derangements, drugs withdrawal, alcohol intake, cerebral infarction and central nervous system (CNS) infection (Davenport and Simpson, 2009). With regards to that, many researchers tend to find the exact problem for these epilepsy sufferers in which some relates it to possible associations between immunological markers while some believe viruses' plays a big role as latent infection to epilepsy.
The word epilepsy is derived from the Greek word for "attack". Ancient people once thought that those with epilepsy were being visited by demons or dark souls. However, in 400 B.C., the Father of Medicine, Hippocrates suggested that epilepsy was caused by excessive phlegm which leads to abnormal brain consistency or by other means is a disease of brain disorder. In 1870s, Fritsch, Hitzig, Ferrier, and Caton started to conduct modern experiments to investigate the etiology of epilepsy by recording and suggesting epileptic seizures in the cerebral cortex of animals. The investigation continued where in 1929, Berger, The Father of Electroencephalography discovered that electrical brain signals could be recorded from the human head by using scalp electrodes; which this discovery led to the use of electroencephalography (EEG) to study and classify epileptic seizures.
With the advancement of medical technology nowadays, the term epilepsy can be defined as a brain disorder characterized by the occurrence of at least 2 unprovoked seizures 24 hours apart, but some first presenting seizures will also be diagnosed as epilepsy when the seizure occurs in the setting of an interictal discharge (Badawy et al., 2009, Cavazos et al., , Davenport and Simpson, 2009). Seizures are actually the manifestation of abnormal hypersynchronous discharges of cortical neurons in which the clinical signs or symptoms depend on the location and the propagation pattern of the epileptic discharges in the cortex (Cavazos et al., , Duncan et al., 2006, Badawy et al., 2009, Davenport and Simpson, 2009).
Seizures are recognized to be such a common neurological disorder as it is prone to be imbalance due to the electric current excitation and inhibition and so, it is not surprising that the lifetime likelihood of experiencing at least one epileptic seizure is about 9%, and the lifetime likelihood of receiving a diagnosis of epilepsy is almost 3% (Cavazos et al., , Badawy et al., 2009).
The incidence of epilepsy in developed countries is around 50 per 100 000 people per year, and is higher in infants and elderly people (MacDonald et al., 2000, L. Forsgren, 2005, Duncan et al., 2006, Sander and Shorvon, 1996). Most studies in the United States, Europe and Asia have also reported overall prevalencies of 5 to 9 cases per 1000 persons annegers 2001.
Less wealthy people show a higher incidence, for unknown specific reasons (Heaney, 2002, Duncan et al., 2006) but it is believed that poor sanitation, inadequate health delivery systems, and non proper medication due to illness could contribute to that high rate which is usually above 100 per 100 000 people per year (Duncan et al., 2006). Childhood incidence has fallen over the past three decades in developed countries, which could be a result of adoption of healthier lifestyles by expectant mothers, improved perinatal care, and immunization programs (Duncan et al., 2006).
Epilepsy is a neuronal disorder with many possible causes as anything that disturbs the normal pattern of brain activity will lead to seizure and yet to recur. Sometimes seizures are related to provoked condition, such as in some medication use of antibiotics or antidepressants, withdrawal from certain drugs as alcohol or benzodiazepins, metabolic derangements as in cases of hyponatraemia, hypocalcaemia and hypoglycaemia, cerebral infections and cerebral infarction (Davenport and Simpson, 2009). In such cases, repeated seizures may not recur once the underlying problems are resolved. In some cases, the brain's attempts to repair itself after a head injury, stroke, or other problem may inadvertently generate abnormal nerve connections that lead to epilepsy (Hirose et al., 2000) (NINDS). Some types of epilepsy runs in families which suggest the influence of gene, but the genetic abnormalities is believed to play only a partial role, perhaps by increasing a person's susceptibility to seizures that are triggered by an environmental factor (Reid et al., 2009, Kaneko et al., 2002, Ranua, 2005) (NINDS). About half of all seizures have no known cause or idiopathic in which they are not linked to any infection, trauma or other identifiable problems (P. M. C. Callenbach, 2003, Ranua, 2005) (NINDS).
In 1981, the International League Against Epilepsy (ILAE) developed an international classification of epileptic seizures that divides seizures into 2 major classes: partial-onset seizures which begin in the focal area of cerebral cortex, and generalized-onset seizures that have an onset recorded simultaneously in both cerebral hemispheres (Cavazos et al.).
With advances in imaging and neurophysiology it has become evident that some generalised seizures have underlying focal pathologies and some partial epilepsies originate in large neuronal networks (Shorvon 2000) (Ranua, 2005). Therefore, a new classification based solely on symptomatology has been proposed in 1998 by Lüders and his team members (Ranua, 2005). The ILAE commission on classification than developed additional reports (Engel, 2006, Wolf, 2006) (Cavazos et al.), but no proposed new revisions to the 1981 classification have been made (Cavazos et al.).
188.8.131.52 Partial seizures
Partial seizures involves motor, somatosensory or special sensory, autonomic and psychic manifestations which arises in specific often small loci of the cortex in one hemisphere (Ranua, 2005). Partial seizures are further classified as simple partial seizures which occur without alteration of consciousness, complex partial seizures in which consciousness is impaired or lost, or secondarily generalized tonic-clonic seizures that evolved from partial seizures (Dodson 2004) (Cavazos et al.). Complex partial seizures, in their complete form, have three components; an aura is equivalent to simple partial seizure; altered consciousness in the form of memory loss and motor arrest and finally automatisms, which are involuntary motor actions (Ranua, 2005).
184.108.40.206 Generalized seizures
According to the ILAE classification (ILAE 1981) as stated by Jouni Ranua in his academic dissertation in 2005, generalized seizures are those in which the first clinical changes indicate initial involvement of both hemispheres, and these seizures can be categorized into 6 major groups of absence, tonic, clonic, myoclonic, tonic-clonic and atonic seizure.
In absence seizures, consciousness is lost and regained in an abrupt off-on pattern. Behaviour occurring at the onset may be perseverated, but more usually ceases instantly as the person begins to stare. The eyes may gaze straight ahead or deviate upward while the eyelids twitch faintly.
Myoclonic seizures consist of brief, arrhythmic, jerking, motor movements that last less than a second. If the evolve into rhythmic, jerking movements, they are classified as evolving into a clonic seizure.
Clonic seizures are represented by rhythmic, motor, jerking movements with or without impairment of consciousness.
Tonic seizures are defined as rigid violent muscular contractions of axial and limb musculature which typically last for 30 s or less. Tonic seizures end abruptly with variable to no postictal symptoms. Isolated tonic seizures seem to be most common during sleep.
The tonic-clonic seizure is usually knows as grand mal seizure. It is characterised by a sudden fall and dramatic, violent, involuntary shaking or muscular spasms of the limbs and body. On clinical evaluation, the only behavioral difference between these seizures and secondarily generalized tonic-clonic seizures is that this seizure is lack of aura. Convulsions rarely last longer than 60 seconds. Longer lasting seizures tend to be prolonged.
Atonic seizures produce sudden reduction or loss of postural tone affecting posture to varying degrees. When extensive, patient may fall and injure themselves.
220.127.116.11 Classification of epilepsies and epileptic syndromes
Epilepsy is called symptomatic if the underlying cause is known, cryptogenic, if there is a presumed pathologic brain process which cannot be detected by present means, and idiopathic in the case of independent, intrinsic epilepsies (Ranua, 2005) (Shorvon 2000). The ILAE classification of epilepsies and epileptic syndromes are as in Table 2 (ILAE 1989). Juvenile myclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy and epilepsy with generalised tonic-clonic seizures on awakening are the most common generalized epilepsies whereas temporal lobe epilepsies and frontal lobe epilepsies are the most common localisation related epilepsies (Ranua, 2005). This classification is based on the anatomic origin of seizures.
Type of seizures- majority seizure jenis mana
Type of epilepsy - jenis epilepsy banyak didapati
The Immune System
The immune system plays an important role in human as a defense against infectious diseases. It also by any other means protects the body from toxic agents and maintains the antigenic homeostasis in the body. It does this by eliminating cells perceived by the immune system to be foreign (Ranua, 2005). Individuals with deficit immune responses, if untreated, succumb to infections in early life (Chapel et al., 1999). However, deviation in the immune response can harm tissue structures in the form of autoimmune diseases (Ranua, 2005). To meet the aforementioned demands, the immune system has evolved into two parts: one responsible for immediate, relatively generic action against external agents which is the innate immune system, and another system that responds specifically to external threat that is the adaptive immune system and both are functionally intertwined (Birnbaum 1998)(Ranua, 2005).
The Innate Immune System
Innate immunity is conferred by all those elements with which an individual is born and which are always present and available at a very short notice to protect the individual from challenges by foreign invaders (Benjamini and Leskowitz, 1993). Cells participating in the innate immune system are polymorphonuclear leukocytes, macrophages, granulocytes, dendritic cells, natural killer cells and T cells (Ranua, 2005). All of these elements either affect pathogenic invaders directly or enhance the effectiveness of host reactions to them (Benjamini and Leskowitz, 1993). Natural killer cells recognise and destroy cells infected by certain viruses and parasites. Due to evolution of the defence mechanisms of pathogens, the human body has developed the adaptive immune system (Birnbaum 1998, Pette et al. 1999) (Ranua, 2005).
The Adaptive Immune System
T and B lymphocytes derived from primary lymphoid tissue (the bone marrow, fetal liver and spleen) and are the main cell components of the adaptive immune system (Ranua, 2005) Birnbaum 1998. Lymphocytes originate in primary lymphoid tissue and circulate through the secondary lymphoid organs (spleen, lymph nodes, gut-associated lymphoid tissue) (Blum and Pabst, 2007). Lymphocyte counts in peripheral blood are often used to evaluate the immune status on daily basis in medicine. B cells, on the other hand are unique as they are able to secrete antibodies or immunoglobulins.
In its defense against invading foreign substances, the body has evolved a variety of mechanisms, each dependant on a somewhat different property or function of an immunoglobulin molecule. Thus, when a specific antibody molecule combines with a specific antigen or a pathogen, several different effector mechanisms come into play. These different mechanism derive from the different classes of immunoglobulin (isotypes), each of which may combine with the same epitope but each of which triggers a different response (Benjamini and Leskowitz, 1993). IgM is phylogenetically the oldest class of immunoglobulin with the largest molecule. The major physiological role of IgM is intravascular neutralization of organism (especially viruses). IgG is a smaller immunoglobulin which penetrates tissue easily and is the only immunoglobulin that crosses the placenta to provide immune protection to the neonate. IgG presents in blood, lymph fluid, cerebrospinal fluid, and peritoneal fluid. There are four subclasses for IgG. IgA is the major mucosal immunoglobulin in saliva, mucus, sweat, gastric fluid and tears that neutralizes antigens entering via these mucosal routes. IgD presents in serum in trace amounts, probably because it is not secreted by plasma cells and because among immunoglobulins, it is uniquely susceptible to proteolytic degradation. Its presence in serum serves as a marker of the differentiation of B cells to a more mature form, but its exact function as a receptor for triggering or differentiation remains unknown. IgE is produced by plasma cells but taken up by specific IgE receptors on mast cells and basophils. IgE probably evolved as a way of expelling intestinal parasites by increasing vascular permeability and inducing chemotactic factors via mast cell degranulation (Chapel et al., 1999, Benjamini and Leskowitz, 1993, Ranua et al., 2005).
Natural Killer Cells
Helen Chapel and her team members through their book of Essentials in Immunology in 1999, stated that Natural killer (NK) cells has a resemblance of a large granular lymphocytes that are capable to kill target cells, even in the absence of any antibody or antigenic stimulation. NK cells are not immune cells in the strictest sense because, they are not clonally restricted, they show minimal specificity and they have no memory. Animals and rare patients with deficient NK cell function are said to have and increased incidence of certain tumours and viral infections (Chapel et al., 1999). It was found that a few patients with selective absence of NK cells and recurrent infections (particularly herpesvirus infection) (Stites et al., 1997). Therefore, NK cells are thought to be important in immune surveillance against tumours (Chapel et al., 1999).
Viruses In The Central Nervous System
Viruses are the most common agents to which the human being is exposed both pre-, peri-, and postnatally and may enter the central nervous system (CNS) by different ways. The particles present in the blood can enter by replication in the endothelial cells lining the vessels or may enter within lymphocytes and macrophages (Eeg-Olofsson, 2003). They can infect peripheral neurons from which there is an axonal or retrograde transportation towards the CNS, once within the CNS, the different cell types can be infected and an antigen presenting cell (APC) is established (Eeg-Olofsson, 2003). The herpes virus group is of special interest in relation to complications of the central nervous system (CNS), and herpes viruses are capable of establishing a latent infection and to reactivate under a variety of stimuli.
Herpes viruses are human pathogens and seroprevelances are reported to bemore than 50%in the general population . It is not currently known if hematotropic herpes viruses like HHV-6 and CMV can be present in the latent form in CNS . However, sequences of neurotrophic viruses like HSV-1 were amplified from CNS structures and the presence of HSV-1 in latent state has been detected in normal CNS  (Karatas et al., 2008).
Viruses from the herpes virus group are divided into the neurotropic or alpha- (herpes simplex virus type 1 - HSV-1, herpes simplex virus type 2 - HSV-2, varicella zoster virus - VZV), and the hematotropic or beta- (human herpes virus type 6 - HHV-6 and cytomegalovirus - CMV) with tropism to T-cells and other leukocytes, and gamma- (Epstein-Barr virus-EBV) infecting B-lymphocytes (Eeg-Olofsson, 2003).
Immune Defence Against Viral Brain Infections
The concept that the immune system plays a role in the epileptogenic process of some epileptic syndromes was first proposed about 30 years ago. Since then, numerous studies have reported on the existence of a variety of immunological alterations in epileptic patients. The finding of immune system activation in patients with a seizure disorder has lead to the suggestion that immune mechanisms may play a role in the pathogenesis of some forms of epilepsy.That immunological mechanisms may play role in the pathogenesis of seizure disorders was first proposed by Walker in 1969 . Karpiak et al.  studied seizure induction in rats by antibodies against brain gangliosides. Ettlinger and Lowrie  put forward the hypothesis that epileptic discharges could be the result of an autoimmune response to either an antigen released during tissue destruction, or an infective agent. Bartolomei et al.  (Eeg-Olofsson, 2003).
Several recent studies in humans and animals have suggested a linkage between seizure activity and changes in immune functions (Aarli, 2000; Bostantjopoulou et al., 1994; McNamara, 2002; Wang et al., 1989; Caksen et al., 2001; Duse et al., 1986; Eeg-Olofsson et al., 1985; Goldstein et al., 2002). (Bhatt et al., 2005)
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