Clinical Features of Epilepsy Secondary to Neurocysticercosis at the Insular Lobe

1.1 Background Neurocysticercosis is eradicable parasitic zoonoses of the brain if it is manages by public health sector and agricultural sector with the dedicated support of veterinarian doctors. Neurocysticercosis is the only zoonotic infection which has been considered as eradicable by the World Health Assembly. Therefore, we will focus on that, and other parasitic zoonoses causing epilepsy will be discussed in another chapter. In this chapter new aspect about insular epilepsy secondary to NC will be introduced as well. Like other pathological disorders, early diagnosis and treatment can significantly decrease morbidity and mortality rates of parasitic infections. Diseases that have their origins in infected animals, such as H1N1 influenza or SARS have highlighted the need for a better understanding of their origin on an affected animal. The ease and speed of modern travel facilitates the spread of diseases once confined to specific geographic areas, as recently occurred with the widely publicized H1N1 influenza. Animal migration and trade pose a similar threat, as was shown by the outbreaks in the United States of West Nile fever, and monkey-pox, two diseases haven’t previously known in the Western Hemisphere. Each of these examples highlights the need for accurate, up-todate information and ongoing research on those public health problems. (Carabin, personal communication, 2010) Pig farming has increased considerably during the past decade in Eastern and Southern Africa (ESA); especially in rural, resource-poor, smallholder communities where sanitation is poor. Hence, it is highly suspected that the frequency of epilepsy secondary to NC in the region may further increase in the foreseeable future. We see a lot of pigs affected by cysticercosis free of neurological signs but when there is a sign it can indicate the etiology of human’s disease. Let us to address it in a better way, for example pigs with NC do not suffer of epilepsy, however presence of cysticercosis of pigs (intermediate host) indicates that NC is the most likely cause of epilepsy of peoples living around, being yet another reason to support that health worker and agriculture worker should work together in this field. In places where there are not clinical health laboratory facilities and CT/MR images or simply patients have not free to these investigations and the prevalence of epilepsy is considerably high we do suggest to confirm diagnosis of cysticercosis on pig’s population by physical inspection of the tongue (Figure 1).

The other choice is to take blood samples from jugular veins ( Figure 2) and request ELISA for cysticercosis at the nearest veterinarian laboratory. It may help suspecting the etiological diagnosis of epilepsy in these patients and to support their treatment. Seems to be that measly pork meat has been described long ago according to this sentence found in ancient documents: In 384-323 BC, Aristotle said: When only a few measles are found the meat is sweet, but when numerous, the meat becomes watery and unpalatable." Eggs develop into larval cysts causing human and porcine cysticercosis. Risk factors for taeniosis include the consumption of undercooked infected pork meat and inadequate meat inspection. Risk factors of cysticercosis include free-range pig farming, poor sanitation, close contact of humans and pigs and inadequate hygiene of food handlers. (See graphic 1) Graphic 1. Shows the life cycle of T Solium cysticercosis and the path toward to NC. Graphic modified from by Prof. Carabin. (CWGESA) www.intechopen.com Cysticercosis is thus strongly associated with poverty and other socio-economic-cultural problems , 2005a, 2007Foyaca-Sibat & Del Rio, 2004, 2005a. In both humans and pigs, cysts migrate mostly to the subcutaneous tissue, skeletal muscle, the eye, and the central nervous system (CNS). Currently, NC is not only the major cause of acquired epilepsy in many developing countries, but is also of growing concern in northern/western countries due to globalization and immigration of infected people as before-cited. In South Africa, epilepsy secondary to NC is quite common in ECP particularly in the poor, former black homeland, rural areas of the former Transkei, where pigs are allowed to roam freely and sanitation facilities are inadequate or nonexistent. Pig keeping and pork consumption have increased significantly during the past decade especially in rural smallholder communities, primarily due to the lack of grazing land for ruminants and the recognition of farmers of a quicker and more impressive return on their investment from raising pigs contact of humans and pigs and inadequate hygiene of food handlers. Consumption of uninspected pork meat is undoubtedly a major source of human taeniasis. The transmission of T. solium to pigs, the essential partner in the pig-man-pig cycle, requires that pigs have access to human feces and that people consume improperly cooked pork. The major risk factors related to transmission of eggs to pigs can be summarized as follows: Extensive or free-range pig rearing Outdoor human defecation near or in pig rearing areas Use of pigs to scavenge and eat human feces ("sanitary policeman") Deliberate use of human feces as pig feed Connection of pig pens to human latrines ("pig sty privies"); Use of sewage effluent, sludge or "night soil" to irrigate and/or fertilize pig pastures and food crops Involvement of humans' carriers in pig rearing and care.
The diagnostic assessment for NC was proposed by Del Brutto et al., (2001), and we used an abbreviated set of these criteria for the definition of NC in our studies.  evidence of household contact with peoples with cysticercosis residence in a cysticercosis endemic area visiting an endemic area for cysticercosis For the present study, definite NC will be defined as: 1 absolute criteria or 2 major criteria or 1 major, 2 minor and 1 epidemiologic criterion; probable NC as: 1 major and 2 minor criteria or 1 major, 1 minor and 1 epidemiologic criterion or three minor and one epidemiologic criterion; and possible NC as: 1 major criteria or 2 minor criteria or 1 minor and 1 epidemiologic criterion. The pilot study conducted by us at the Nelson Mandela Academic Hospital consisted of asking 57 epilepsy patients with confirmed NC, 52 epileptic patients without NC and 61 patients from the dermatology and ophthalmology clinics to answer a questionnaire interview about epilepsy and pig raising and management. A very preliminary analysis suggests that, using dermatology and ophthalmology clinic patients as the reference group, the POR of owning pigs and having NC was 6.8 (95% CI: 2.1-21.7) and the POR for consuming pork compared to never consume pork and having NC was 2.1 (0.7-6.2). Using the epilepsy patients without NC as the reference group, the POR of consuming pork in those with NC was 14.2 (5.1-39.5) and of owning pigs was 17.5 (5.4-56.2). Why the association between owning pigs and NC was stronger when the epilepsy patients were www.intechopen.com used as a reference group needs further investigation, but it is possible that the NC and 2 the non-epilepsy groups came from rural areas whereas the epilepsy non-NC group came from more urban areas with less exposure to infected pigs. Further analyses will determine whether these results are confounded by the age of the patients or where they live (i.e. Persons who only had epilepsy may be more likely to live in more urbanized areas). We also participated in the pilot study conducted at the St-Elisabeth hospital from ECP in SA. We studied 433 consecutive patients consulting the outpatient clinic for suspected new-onset seizures or existing epilepsy cases. (Foyaca-Sibat et al., 2009) Of these, 281 were diagnosed as recurrent focal or generalized motor seizures due to secondary epilepsy. Each consenting participant was administered the questionnaire and asked to provide a blood sample for a serological analysis of antibodies to and antigens of the larval stage of T. solium. Additionally, each week for consenting, randomly selected patients with the confirmed diagnosis of seizures disorder were transported to Mthatha for a CT scan of the brain and EEG. Among these 281 patients, the prevalence of seropositivity of antibodies to the larval stage of T. solium was 33% (95% CI: 27%-38%) in the 273 tested. Serological antigens were available for 189 patients with confirmed seizures or epilepsy. In this group the prevalence of seropositivity to antigens to T. solium was 8% (95%CI: 4.5%-13%). Modified from the original one done by Prof. Carabin. A total of 92 patients with recurrent seizures and who also completed a questionnaire were referred to Mthatha for a CT-scan. Of these, 34 (37.0%, 95%CI: 27.1%-47.7%) had a definite diagnosis of NC, 14 of whom had active lesions visible on CT, 39 (42%) had no CT abnormality, and 19 (21%) had other, undefined non-NC calcifications. The age of the NC cases ranged from 5 to 67 years old whereas the epilepsy cases ranged from 5 to 76 years old. Antibody ELISA results were available for 33 of the 34 patients classified as probable NC and for all 39 without NC. The predictive value of a positive antibody test in identifying NC in persons with epilepsy was 60% (95% CI: 41%-77%). Serological results for antigen ELISA were available for 23 confirmed NC cases and 22 non-NC cases. The predictive value of a positive antigen test in identifying NC in persons with epilepsy was 67% (95% CI: 22%-96%). Thus, it is clear that serology alone cannot be used to diagnose NC in this population. HIV status was available from 50 patients with epilepsy. Among the 47 patients with antibody ELISA results available, the antibody seroprevalence of T. solium was 30.0% among HIV positive patients and 48.1% among HIV negative patients. Interestingly, among the 33 patients with antigen ELISA results, the antigen seroprevalence of T. solium was 16.7% among the HIV positive patients but only 9.5% among the HIV negative patients. Even though these results are based on a very small sample, it does suggest that HIV patients may be less able to mount a detectable antibody response to cysticercosis but might be more likely to be infected with active cysts. A total of 22 of these patients (13 HIV negative and 9 HIV positive) were referred for a CT-scan. Of these, five HIV negative and seven HIV positive patients had CT evidence of NC with two HIV negative and five HIV positive patients harboring active cysts. These very preliminary and imprecise results do suggest that there may be an association between NC and HIV infection. (Foyaca-Sibat et al., 2009)

Occipital lobe epilepsy secondary to neurocysticercosis
In our series patients presenting occipital lobe epilepsy usually is reporting www.intechopen.com

Structured visual hallucinations and moving colored shapes
Flashes light and transitory cortical blindness Forced blinking and eyelid flutter follow by horizontal gaze deviation.
Calcified NC with or without perilesional edema is the most common cause. This presentation is uncommon despite it has been underestimated importantly. It can be associated to insula epilepsy or other types of epilepsy mainly in multiple calcified NC. Seems to be that measly pork meat has been described long ago according to this sentence. The medication of choice is carbamazepine. Menon (2007) reported two young patients with symptomatic occipital lobe epilepsy due to discrete lesions of cysticercosis were misdiagnosed and treated for 2 years as migraine with visual aura. The patients suffered from frequent visual seizures often followed by migrainelike headache. Seizures manifested with colored and mainly circular elementary visual hallucinations of up to 1 minute duration. Headache, often severe and of long duration, was frequently associated with nausea, photophobia, and phonophobia. Both patients became seizure-free with appropriate treatment of the underlying disease and epileptic seizures.

Frontal lobe epilepsy secondary to neurocysticercosis
Clinical features of epileptic seizures may help to identify the specific frontal region of onset. (So, 1998;Kotagal & Arunkumar, 1998)

as follow:
Dominant hemisphere involvement= Prominent speech disturbances Supplementary motor area= Unilateral or asymmetric bilateral tonic posturing and facial grimacing, vocalization, or speech arrest; somatosensory aura; and complex automatisms such as kicking, laughing, or pelvic thrusting Primary motor cortex= focal simple motor seizures with clonic or myoclonic movements Medial frontal, cingulate gyrus, orbitofrontal, or frontopolar regions=Complex behavioural events (motor agitation and gestural automatisms) ; viscerosensory symptoms and strong emotional feelings; pelvic thrusting, pedalling, or thrashing, vocalizations, laughter, or crying. Dorsolateral cortex=-Tonic posturing or clonic movements often associated with either contralateral head and eye deviation, or less commonly, ipsilateral head turn Operculum= Swallowing, salivation, mastication, epigastric aura, fear, and speech arrest often associated with clonic facial movements and gustatory hallucinations.
This modality of seizures often bizarre and diagnosed incorrectly as psychogenic and can be associated to insular seizures. Despite calcified NC is the commonest cause no always locations of the lesions cause same clinical manifestations and quite often some lesions remain silent for years.

Nocturnal frontal lobe epilepsy
Patients presenting nocturnal occipital lobe epilepsy (NFLE) usually report Seizure clusters occurring only during sleep The history of similar events with other family members (Autosomal dominant) The frenetic or agitated appearance of onset and normal intelligent Dystonic posturing, jerking, bending, and rocking; difficult to distinguish from parasomnias www.intechopen.com With nocturnal frontal lobe epilepsy, seizures begin shortly after falling asleep or in the early hours before awakening with a gasp, grunt, hums, moan or word, and are followed by sudden thrashing movements. Patients remain conscious but can neither control the movements nor speak. Thrashing can be vigorous enough to throw the patient out of bed, which can result in possible injury. Nocturnal frontal lobe epilepsy is typically treated with carbamazepine and, in some cases, surgery. We did not identify this type of seizures in our series. If there is evidence of NC on imagenology then a diagnosis of NFLE is ruled out.

Parietal lobe epilepsy
Parietal lobe epilepsy is the least common of syndromes defined by the area of brain affected. Parietal seizures spread rapidly, producing a range of symptoms that are also seen with other syndromes. A few signs are typical but appear in less than half of children who have this syndrome. Among the symptoms are: Tingling, pricking or crawling sensations upon the skin The feeling of burning, itching or pain Pain occurs in the extremities and sometimes in the abdomen Patients can present an acute confusional state (delirium) and the commonest affected parts of the body are: upper limbs and face. Partial seizures are divided into two major categories, simple and complex. Simple partial seizures occur in full consciousness; complex partial seizures occur with impaired awareness that ranges from slight to complete unconsciousness. (Epileptic Foundation)

Mesial temporal lobe epilepsy
Seizures often begin with auras or conscious feelings of a rising sensation from the stomach and of fear One of the sensory perceptions may also be triggered Impaired awareness follows, typically with staring and movements of the lips, tongue or jaw Fumbling, picking or gesturing may also occur

Insular lobe
Remembering the lost island of Atlantis, this lobe remains hidden and lies submerged beneath the parietal, frontal, and temporal opercular cortices, buried under a tangled web of middle cerebral artery branches. The insula is not visible from the surface of the brain, it's the best protected region of the whole cerebral cortex, and the poorest studied region all over the brain; IL represents a remarkable challenge for further researchers among new generations of neurologists, neurophysiologists, neuroinmunologists, and neuropathologist among others. Some functions of the right insular lobe are a little bit known such as its role in taste perception its intensity and recognition for the ipsilateral tongue (rostrodorsal insula) and some functions of the left insular cortex for the intensity of the stimulus ipsilateral to the tongue and taste recognition bilaterally, gustatory mechanism, movements of the mouth, and oropharyngeal swallowing (anterior insular) are not well known neither, and almost nothing has been demonstrated about the role of the insular lobe over the amygdala complex and emotional behavior. The human IL is also considered as paralimbic cortex, because of its connections with limbic and sensorimotor cortices, the IL is believed to play a role in affective and attention aspects of human behavior as well. Paralimbic insular regions have functional specialization for behaviors requiring integration between extra personal stimuli and the internal milieu. Based on these connections, one might expect that lesions of the insular cortex may result in disorders of neglect .

Insula lobe epilepsy 3.1.1 Background
Insular lobe epilepsy (ILE) and insular lobe seizures (ILS) are still not included in the current classification for epileptic seizures, epilepsy or epileptic syndromes belong to "The International League Against Epilepsy" therefore most of neurologists, epileptologists, clinician pediatrician, and general practitioner do not include this entity in their list of differential diagnosis in patients presenting "aberrant" types of temporal lobe epilepsy (TLE), "stereotype" simple focal seizures and others. Insular seizures may mimic temporal, parietal or frontal lobe seizures and may coexist with seizures from other lobes. The electroencephalographic (EEG) studies of the insula lobe (IL) are not confident because it is the only cortical part of the brain that is not accessible at the surface of the cerebral hemisphere, because it is totally covered by the fronto-parietal and temporal opercula, therefore accuracy of EEG made by surface electrode is uncertain. The insula is one of the five cerebral lobes and its cortex is situated deep within each hemisphere. It is overlayed by the frontal and temporal neocortex and this explains how difficult it should be to get a reliable EEG sampling from the insular cortex and to define an "insular epileptic syndrome" as has been done with temporal lobe epilepsy. Adequate sampling from the insula can only be obtained by depth or subdural electrodes' implantation or acute intraoperative electrocorticography. Depth or subdural electrodes implantation of the insular faces some technical problems. There is substantial evidence that the insula is involved as a somesthetic area, including a major role in the process of nociceptive input. The role of the insula in some epileptic patients was recently investigated by means of depth electrode recordings made following Talairach's stereoelectroencephalography (SEEG) methodology. It appears that ictal signs associated with an insular discharge is very similar to those usually attributed to mesial temporal lobe seizures (Robles et al, 2009]) others authors reported: sensation of laryngeal constriction and paresthesiae, often unpleasant, affecting large cutaneous territories, most often at the onset of a complex partial seizure (five of the six patients) as a common presentation [ Isnard J, et al., 2004] while other said: the most common clinical feature associated with damage to the insula is the complex partial seizures with involvement of the visceral sensations (Duffau H, et al., 2002). Different authors reported ictal symptoms associated with insular discharges mainly made up of respiratory, viscerosensitive (chest or abdominal constriction), or oroalimentary (chewing or swallowing) manifestations.
Unpleasant somatosensory manifestation always opposite the discharging side, are also frequent and they concluded that Ictal signs arising from the insula occur in full consciousness; these are always simple www.intechopen.com partial seizures. Seizures arising from the temporal lobe always invade the insular region, but in approximately 10% of cases, the seizures originate in the insular cortex itself (Isnard, 2004;Guenot, 2008). In 2005, Isnard studied 50 patients using intrainsular electrodes and found that the clinical presentation of insular lobe seizures was a simple partial seizures occurring in full consciousness patient, beginning with a sensation of laryngeal constriction followed by paresthesiae that were often unpleasant affecting large cutaneous territories. These initial symptoms were eventually followed by dysarthric speech and/or elementary auditory hallucinations, and seizures often ended with focal dystonic postures. Four years later he studied 164 patients in whom 472 insular electrodes were implanted, he again found that clinical presentation of insular lobe seizures are that of simple partial seizures occurring in full consciousness, beginning with a sensation of laryngeal constriction followed by paresthesia that were often unpleasant on extensive cutaneous territories. These initial symptoms were eventually followed by dysarthric speech and/or elementary auditory hallucinations, and seizures often ended with focal dystonic postures. He was able to reproduce several of the spontaneous ictal symptoms in the six patients with insular seizures. (Isnard, 2009). Looking into other ways to check clinical features of IL due to focal lesions, we reviewed what happen in patients presenting NC on the IL. According to the publications made in the last decade, very little is known about NC on the IL (Foyaca- . It is important to highlight that it is a dangerous location of NC because apart from epilepsy other complications such as: autonomic dysfunction (Oppenheimer et al., 2001), neurogenic heart (Tamayo & Hachinski, 2003), electrocardiographic changes (Blumhardt et al., 1986) and sudden unexpected death in epilepsy [SUDEP] (Leestma, 1984;Mc Gugan, 1999;Langan Y, 2000) can occur The main aim of our study was to identify ictal manifestations in patients presenting focal lesions (NC) on the IL proved by imagenology. To our knowledge, it is the first time that results from ILE secondary to focal NC in a case-control study are reported in the medical literature.

Material and method 3.2.1 Participants and study area
This is an epidemiological descriptive study of patients diagnosed as NC from Umtata General Hospital and Nelson Mandela Academic Hospital (South Africa) from January 2004 to January 2010 who were selected for a case control study in the project Neurocysticercosis protocol. (Database, n=3015). All selected patients were included in group A or group B.

Inclusion criteria:
Group A: fulfilled the following selected criteria: Demographic and clinical data were obtained through interviews with the patients and their relatives. The differences between groups A and B were evaluated for statistical significance with the use of Statistical Package for the Social Sciences version 16.0 for windows (SPSS Inc., Chicago, Ill) All patients received 800 mg of albendazole and 40 mg of prednisone per os daily for a week as part of treatment for NC and 200mg of carbamazepine orally every 8 hour to control epileptic seizures. All images were acquired on the same CT scan and MR images using a three-dimensional T1-fast field echo sequence providing an isotropic voxel size of 1 mm 3 . Images underwent correction for no uniform intensity and were linearly registered into a standardized stereotaxic space. The interval between the first and last scan was 31 ± 21 months (range = 10 to 52).

Exclusion criteria
Epilepsy due to other causes Terminal diseases, serious psychological illnesses, active addictions to psychoactive substances Patients younger than 13 years old, pregnant ladies, patients on HAART No written consent.

Withdrawal criteria
Any event that may lead to a situation that discourages the intervention or that may prevent communication with the healthcare professional.

Ethical aspects
Written informed consent was obtained in the first assessment of eligible patients for participation. All patients received information on the study's objective and procedures in addition to ethical considerations, including and the participant's right to intimacy, anonymity, confidentiality, withdrawal, and information. Both investigators completed CITI training-course on the Protection of Human Research and sworn to the Hippocratic Oath and committed to respecting the norms of good clinical practice, as well as the requirements of the Helsinki Declaration.
Methods for patient selection and information processing was accepted by clinical governance at Mthatha General Complex, and approval From the University of Transkei, and Walter Sisulu University IRB and the respective Ethical Committees (UNITRA:0018/05, and WSU:0068/009) were obtained.

Results and comments
The total number of patients with ILE due to unilateral calcified and active NC on the IL in our database is 21 and its prevalence is 0.69%. Four patients (19%) from this group presented an associated ischemic stroke due to infectious vasculitis. Three of them were HIV-positive (See figure 5) Fig. 5. CT scan of the brain shows calcified and active NC, some ring enhancing lesion is seen. Hypodensity lesion secondary to ischemic stroke on the right frontal and insular lobes with partial compression of the right lateral ventricle is also observed.
Demographic features are summarized in Table 1  Patients with NC on the temporal lobe presented TLE or partial secondary to generalized motor seizures except one who complained of a sensation of laryngeal constriction, perioral parentheses and sense of levitation and later loss of consciousness and tonic-clonic secondary generalized seizures.
Source: Table 2 Graphic 1. Clinical features of insula lobe epilepsy We tried to correlate the location of the lesion and ictal manifestation considering NC lesion small enough to produce non additional damage on surrounding tissue avoiding situations reported by Roper et al. in 1993 andDuffau in 2003. They described insular epilepsy in patients presenting seizures involved visceral sensory hallucinations followed by motor automatism and motor seizures with somatic sensory hallucinations and then produced visceral motor effects. Unfortunately, they studied patients with mass lesion (low-grade astrocytoma) big enough to involve the temporal lobe region. In our series, lesions of NC active or calcified measured less than 15 mm in both groups to assure that no surrounding tissue was affected. Fortunately, we also had previous information about insular NC from a pilot study made five years back  and based on those results we refined our selecting criteria. Our prevalence of ILE is low because it is an uncommon epileptic disorder. Previous studies based on video ictal recordings, and direct electric insular stimulation of the insular cortex for presurgical evaluation of temporal lobe epilepsy described clinical features of ictal manifestation on IL eventually followed by dysarthric speech and focal motor convulsive symptoms no present in our series. Other clinical manifestation in our series including speech problems, neurogenic heart and sudden unexpected death were not included for statistical analysis at this time because were not considered in our objectives. Some patients became a little bit surprised when we asked for some symptoms that they did not expressed before because these symptoms did not recall attention from patients and relatives which may contribute to an underestimate prevalence of this type of seizures mainly in patients presenting it sporadically . A fully conscious patient with laryngeal discomfort, dyspnea, unpleasant perioral or somatic paresthesia, and dysarthric speech, followed by somatomotor symptoms, implies an insular onset and a good respond to antiepileptic treatment can help to confirm it. Antiparasitic treatment for NC at the IL should be prescribed with caution because the risk of developing complications such as: the neurogenic heart and/or SUDEP. One patient from this series died because subendocardic hemorrhage probable due to active and calcified NC on the right insula cortex documented by postmortem examination (See figure 6) Fig. 6. Lateral view of the right insular lobe fixed in formalin. One cyst with the scolex inside (in vesicualr stage) on anterior insula is seen, another cyst without scolex with turbid fluidfilled oval cysts and local inflammatory reaction on the middle-anterior (agranular) insula is observed. Left insula was normal and no other cysts were found all over the brain. Cause of death: SUDEP/Neurogenic heart (subendocardial hemorrhage)

Sudden unexpected death in epilepsy secondary to neurocysticercosis
Although largely neglected in earlier literature, sudden unexpected death in epilepsy (SUDEP) is the most important epilepsy-related mode of death, and is the leading cause of death in people with chronic uncontrolled epilepsy. Research during the past two to three decades has shown that incidence varies substantially depending on the epilepsy population studied, ranging from 0-09 per 1000 patients-years in newly diagnosed patients to 9 per 1000 patient-years in candidates for epilepsy surgery. (Tomson et al., 2008) By definition, the cause of death in SUDEP is currently unknown, but it is very probable that cardiac arrhythmia during and between seizures plays a potential role. It has been suggested on postmortem studies and interictal cardiac abnormalities observed (Falconer & Rajs, 1976;Leestma, 1989;Ryvlin et al., 2006;Stollberger & Finsterer, 2004). Several suggestions have been made concerning the mechanisms behind SUDEP, most involving speculations on the possible role of autonomic effects such as cardiorespiratory disturbances. Clinical and experimental studies have shown that physical activity can decrease seizure frequency, as well as lead to improved cardiovascular and psychological health in patients with epilepsy . Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: cold temperatures , certain seizure types (Foyaca- Kloster & Engelskojon,1999), early adulthood (Lesstma,1997) early onset of epilepsy (Nilsson, 1999), long duration of epilepsy (Walczak et al., 2001), uncontrolled TLE (Walczak et al., 2001;Speling et al.,1999), high seizure frequency (Lagan & Nashef, 2005), and higher numbers of AED (Nilsson et al.,2001) and. Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures, electrolyte disturbances, arrhythmogenic drugs or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role (Stollberger & Finsterer, 2004). An increasing number of reports about SUDEP secondary to NC are seen on the medical literature gradually (Holmes, 2010) more details about SUDEP can be found in the other chapters of this book. Mortality due to epilepsy is a significant concern. Patients with epilepsy have a mortality rate significantly higher compared with the general population. The standardized mortality rate (SMR) is shown to be 1.6-9.3 times higher in this group (Nouri, 2011). Based on our observations we consider that ILE can be differentiated from TLE if patients remain fully conscious during the attack. When epileptic activity spread from IL to temporal lobe or vice versa then clinical differentiation can be almost impossible to perform.
If the above-cited features are not keeping in mind, diagnosis of ILE never going to be made and cardiac complications or SUDEP may happen.
We have hypothesized that NC on the temporal lobe can cause ictal manifestations which can be spread to the IL leading to a combination of TLE and ILE but most symptoms from IL are masked by those from TLE even before patients become unconscious. Further investigation should be made to reach final conclusions. In our experience, this sequence of ictal symptoms: laryngeal constriction, perioral paresthesia, dysphagia, and sense of levitation look reliable enough to characterize insular lobe epileptic seizures secondary to NC. To our knowledge, it is the first time that results from ILE secondary to focal NC in a case-control studies are reported.

Acknowledgment
We like to express our gratitude to all veterinarian doctors working in this field particularly: Professors Rosina Tammi  The founder had no role in study design, data collection and analysis, decision to publish, or the preparation of manuscript. Finally, we wish to declare our eternal and deepest gratitude to our family, relatives, and colleagues for their unconditional and permanent support. Finally, we wish to declare our eternal, deepest love and gratitude to Lorna María Foyaca García, Thabo Humberto Jorge Foyaca Ibañez and Fátima Susana Adolfina Foyaca Ibañez, because without their love and unconditional support this chapter would not have been written.