Epilepsy: From pediatric to adulthood. Definition, classifications, neurobiological profiles and clinical treatments

Introduction and defi nition: “Epilepsy” from the Greek ἑπιληψία, “to be caught, hit by something” [1], is a neurological condition characterized by recurrent and sudden (at least two twenty-four hours apart) [2], physical manifestations of sudden loss of consciousness and violent convulsive movements of the muscles (the so-called “epileptic seizures”) [3,4]. We will, therefore, speak of “epilepsy” only when the cause of the seizure will be primary (and not secondary); in all other cases, in the clinical setting it is preferable to speak of “epileptic seizure” [5,6].


Introduction: Defi nition, classifi cations and symptomatic profi les
Introduction and defi nition: "Epilepsy" -from the Greek ἑπιληψία, "to be caught, hit by something" - [1], is a neurological condition characterized by recurrent and sudden (at least two twenty-four hours apart) [2], physical manifestations of sudden loss of consciousness and violent convulsive movements of the muscles (the so-called "epileptic seizures") [3,4]. We will, therefore, speak of "epilepsy" only when the cause of the seizure will be primary (and not secondary); in all other cases, in the clinical setting it is preferable to speak of "epileptic seizure" [5,6].
In ancient times, epilepsy was associated with religious experiences and demonic or divine possession. Known as the "sacred disease", it was widely described in the fi fth century BC. by Hippocrates of Kos, since epileptic seizures were thought to be a form of attack by demons, or that the visions experienced by patients were messages from the gods; the father of modern medicine himself, however, raised doubts about the divine nature of the phenomenon. However, this belief was more realistic and clinical in the Indian area, where there was already talk of "loss of consciousness". However, in most ancient cultures (and some modern cultures, in Africa and Asia), people with epilepsy were stigmatized, avoided, or even imprisoned, because they were considered dangerous, contagious, or cursed [7].

Etiological and statistical profi les
In the epilepsy hypothesis, the etiology is not known and the hypotheses can be multiple; the etiologies do not have a hierarchical order and the importance attributed to the etiological group in which the patient is framed can depend on the circumstance [8]: and G protein-coupled receptors. In homozygous twins, if one of them is affected, there is a 50% chance that the other will also be affected. In heterozygous twins, this risk drops to 15%.
However, these risks are greater in subjects with generalized seizures rather than with partial seizures and if both twins are affected, most of the time they have the same form of epileptic syndrome (70-90%). Other close relatives of a person with epilepsy present a fi ve times higher risk than that of the general population. Between 1% and 10% of those with Down syndrome and 90% of individuals with Angelman syndrome also suffer from epilepsy [9,10]. More or less known causes are certainly head injury, brain A key element of the concept is that improving epileptiform activity could potentially improve development. From a clinical point of view, this is a crucial aspect, often reported by families and doctors. In many of these severe genetic disorders, developmental disturbance is due to the direct effect of the genetic mutation, as well as that of frequent epileptic activity. There are several ways in which this can manifest itself. There may be a pre-existing developmental delay, which is complicated by stopping or regression when seizures appear or if prolonged seizures occur. In other cases, the developmental slowdown may occur in a child with normal development, in which developmental slowdown occurs before the onset of frequent epileptic activity at EEG. A wellknown example is the encephalopathy of Dravet syndrome, in which the slowdown or regression of development occurs between 1 and 2 years of age, at a time when epileptiform activity on EEG is typically not yet abundant. This suggests that both developmental defi cit and epilepsy are secondary to the mutation of the sodium channel subunit gene (SCN1A) which is found in over 80% of cases. In a third group, epilepsy may die out relatively early in the history of the child, but the developmental consequences may remain severe as observed in some patients with KCNQ2 encephalopathy or STXBP1 encephalopathy. These observations, which apply to many of the genetic encephalopathies, suggest the need to extend, where appropriate, the terminology and to include the term "development", to recognize that both aspects (genetic cause and epilepsy) can play a role in clinical presentation. These concepts are fundamental for understanding the pathological process for both families and doctors [8,11].
What is certain, however, concerns the study of the epileptic attack, how it occurs and what it causes, as it is universally recognized that it is the result of the excessive and abnormal activity of the neurons of the cerebral cortex [12][13][14].
It is estimated, according to statistical studies, that about 1% [15], of the world population can suffer from epilepsy (even if other data speak of 3%) [16,17] and that about 7-10% can be genetically predisposed the onset, at least once in their life, of epileptic seizures [18]. Epilepsy can, in serious cases, lead to death [19].

Neurophysiological aspects
From a neurobiological point of view, the discussion is more complicated. The electrical activity of the brain is normally not synchronous and is regulated by various factors both within neurons and in the cellular environment (these factors include the type, number and distribution of ion channels, changes to receptors and changes gene expression, while factors external to the neuron are related to ion concentrations, synaptic plasticity and regulation of the release of neurotransmitters by glial cells [20,21]; the epileptic seizure is, therefore, a paroxysmal (violent and exasperated) event through which epilepsy occurs, caused by the sudden, excessive and rapid discharge of a more or less extensive population of neurons that are part of the gray substance of the brain, according to the defi nition of John Hughlings Jackson). The aggregate of neurons affected by the discharge is thus defi ned as an "epileptogenic outbreak" [6].
The exact mechanism underlying epilepsy is not known in itself, but the pathophysiology at the cellular level is well known, however, it has not yet been established in what circumstances in the brain an excessive synchronization of neuronal activity occurs which then leads to epileptic attack. In cases of epilepsy, the resistance of the excitatory neurons to stimuli appears diminished during the period of a seizure. This can occur due to changes in ion channels or the improper functioning of inhibitory neurons. This then translates into a specifi c area from which epileptic seizures can develop. A further mechanism leading to epilepsy may be due to the "up" regulation of the excitatory neuronal circuits or the "down" regulation of the inhibitory circuits, following damage to the brain. These secondary epilepsies occur through processes known as "epileptogenesis". Impairment of the blood-brain barrier can also be a causative mechanism, as it would allow substances in the blood to enter the brain. There is evidence that epileptic seizures are not usually random events but are often caused by factors such as lack of sleep, stress, fl ashing lights, or sudden noises. "Epileptogenic threshold" is the term used to indicate the amount of stimulus needed for an attack to occur. In epileptic patients, this threshold appears much lower than in the healthy population. In epileptic seizures, a group of neurons begin to function abnormally suddenly, and synchronously. This causes a wave of depolarization, known as a paroxysmal depolarizing shift. Normally, after a neuron has had an electrical discharge, it becomes more resistant to other electrical discharges for some time. This is due in part to the effect of inhibitory neurons, to the electrical changes themselves within the neuron, and the negative effects of adenosine. Partial seizures originate in only one hemisphere of the brain, while generalized seizures begin in both. Some types of seizures can modify the structure of the brain, while others seem to have a lesser effect. Gliosis, neuronal loss, and atrophy of specifi c areas of the brain are related to epilepsy, but it is not clear if it causes these conditions or if they are the cause [22][23][24][25][26].

Epilepsy in adults
Generally, epileptic forms are classifi ed according to strict technical schemes, based on the symptoms and the results of clinical investigations. In adults [27].
"Seizure epileptic seizure": It is the most common form and represents about 60% of the total epileptic episodes: a) About 30% are "generalized" or "big bad" crises, that is, which originate from both hemispheres of the brain and can be "tonic convulsive crises" (motor manifestations with muscle hypertonus) and "clonic convulsive crises" (phases muscle contraction-relaxation cycles) or "mixed seizures"; b) The remaining 70%, on the other hand, start with a "simple partial seizure" (ie involving a small brain region and there is no loss of consciousness) or "complex partial seizure" (evolution of the simple partial seizure, capable of involve multiple brain regions of the same hemisphere, with associated loss of consciousness). Partial seizures (also called "focal") therefore only affect a cerebral hemisphere but can nevertheless develop into generalized epileptic seizures, tending to spread.
"Non-convulsive seizure attack": The remaining 40% of overall seizures are of this type. It is the "typical absence" or the "little evil", which presents itself as a decrease in the level of consciousness, with a duration of about twenty to thirty seconds. By schematizing as much as possible, synthetically and linearly, we distinguish the forms of seizure in adulthood [6,[28][29][30][31][32][33].
Typical absences: They are clinically characterized by a brief and isolated alteration of consciousness, with sudden onset and end. The subject abruptly interrupts the activity in progress, has a fi xed gaze, if called generally does not answer; after a period ranging from 5 to 40 seconds, it resumes its activity as if nothing had happened. This central nucleus can be accompanied by minor motor phenomena such as small perioral and/or ocular clones (myoclonic absences), postural tone reduction (atonic absences), gestural automatisms, or motor perseveration (absences with automatisms); sometimes by vegetative signs such as initial loss of urine. All these clinical variants are accompanied by a typical critical EEG consisting of a bilateral, synchronous and symmetrical discharge of tipwave complexes at a frequency of 3 c / s. Absences usually begin in the child and adolescent and regress between 15 and 20 years, but the adult may persist.

1)
Atypical absences: Longer lasting and frequently accompanied by tonic, atonic or myoclonic motor components, often asymmetric, they show to the critical EEG anomalies similar to typical absences, but at a lower frequency (2-2.5 c / s) and associated with rapid activities. This type of seizure is characteristic of epileptic syndromes with an unfavorable prognosis (for example, epileptic encephalopathies) with onset in childhood and generally persistent in adults.

2)
Myoclonic seizure: They are characterized by the appearance of an involuntary, sudden and short (<100 msec) contraction of a muscle or group of muscles with variable topography (axial, proximal, distal), generally bilateral and symmetrical. A less frequent variant is the "negative myoclonus", consisting of a sudden interruption of muscle tone. Both positive and negative myoclonias are fl eeting and are not accompanied by measurable alterations of consciousness. A very typical bilateral and synchronous discharge appears on the EEG consisting of several points followed by a slow wave (poly point-wave complexes). They are frequent in idiopathic generalized syndromes of the child, adolescent or young adult (juvenile myoclonic epilepsy); they hardly continue in the mature adult, where however they can be replaced by tonicclonic crises. They can be found in symptomatic generalized epilepsies (see below), where the prognosis is much darker.

3)
Tonic-clonic seizure: They are the most known epileptic seizures in the collective imagination: known as "convulsions" and "the great evil", they are for many patients and the public sequential paroxysmal activation and affects the entire cortex, the structures of the brain stem that underlie wakefulness and muscle tone and culminates in a generalized muscle contraction and a coma. Neuronal and muscular energy consumption is very high, and combined with apnea it leaves a condition of neuronal exhaustion and general debilitation.

4) Clonic crises, tonic crises, falling spasms, atonic crises:
They are fragments of the tonic-clonic seizure and paradoxically indicate in many cases a more serious neurological condition, in which plurifocal or diffuse damage to the brain seems to be an obstacle to the orderly reticulocortical sequence of the tonic- When it is verifi ed by an observer it is defi ned as breakage or loss of contact. It can rarely go unnoticed and be denied by the patient, and emerge in the video-EEG recordings integrated by the interaction with the doctor or technician.
Despite the diagnostic diffi culties, the proposal to neglect the consciousness disorder as a classifi cation parameter does not agree with many clinicians, who are rarely considered satisfi ed if the therapy manages to prevent the seizure from ending with the loss of consciousness. Impairment of consciousness takes on greater clinical severity when it appears without warning at the beginning of the episode, since it does not allow for any defensive strategy. For this reason, it is appropriate to try to identify complex crises with loss of initial consciousness compared to those in which consciousness is compromised during the episode, after a focal phase with a clear conscience.
In crises with conscience disturbance, the emergence of automatisms (hence the defi nition of psychomotor crises) consisting of verbal, gestural, and mimic activities produced by the invasion of motor structures by epileptogenic discharge (critical automatisms) or by depression of consciousness is frequent (release automatisms).

1) Epilepsy of the temporal lobe:
The temporal lobe is the ideal terrain for the development of epilepsy, and the one where most adult epileptic seizures are structured. The main reason is its anatomical construction, the susceptibility of some areas to the lack of oxygen, and the almost unique possibility for the brain to generate new neurons. Last but not least, the considerable rearrangement that the medial temporal structures undergo in fetal development and the consequent greater frequency of malformative pathologies. The temporal lobe preserves the most archaic structures, those of memory (the fundamental building block to elaborate an individual story) and those of smell (the fi rst sensory approach to the knowledge of the environment), structures rolled upon themselves (such as the hippocampus) and parallel circuits (such as olfactory areas). The hippocampus is a vascular border area of the terminal vessels of the posterior cerebral, and like all border areas, it is more sensitive to ischemia. It also has one of the few areas (the subgranular zone of the dentate gyrus) where new neurons are generated in adulthood. All these are ideal conditions for building circuits that feed themselves by structuring repetitive discharges. The temporal lobe is divided into two areas that refl ect two evolutionary times: the medial, archaic portion, which contains the entorhinal and para-hippocampal cortex, the dentate gyrus and the actual hippocampus, consisting of three-layer bark (allogeneic) phylogenetically ancient, which underlies the functions of smell, memory, and emotions and regulates vegetative functions; and a lateral portion, which includes the three lower, middle and upper convolutions, consisting of phylogenetically more recent six-layer bark (neocortex), which underlies the functions of hearing and language. It is evident from what has been said that it is the medial portion, which contains the hippocampus, the one favored by epileptic discharges. The hippocampus can be called "the magic ring of epilepsy". There are therefore two major categories of temporal epilepsy, the medial and the lateral with many exchanges between them due to the territorial contiguity:

a)
Medial temporal epilepsy: The most frequent pathology, and by far the most common cause of epilepsy, is sclerosis of the hippocampus. It is formed following even brief phases of cerebral anoxia, an event at risk at birth, in the transition from placental to pulmonary circulation, when a delay in the expulsion phase of the fetus can interrupt the oxygenation of the blood for several minutes, and the hippocampus it is the fi rst structure to suffer. A second condition is the febrile seizures of the fi rst three years, in which the convulsive discharges favor the hippocampus and neighboring areas and where the energy consumption causes damage from hyperactivity (called glutamatergic due to the glutamate mediator involved). Loss of many neurons occurs and, in the following months and years, budding of new fi bers, the genesis of new neurons, and the formation of synapses and new recurrent circuits are activated. Other etiologies are benign tumors (astrocytomas, gangliocytomas, neuroepithelial dysembryoplastic tumors, known with the English acronym DNET), vascular malformations (cavernous angiomas) or cortex (focal dysplasias). The clinical manifestations are characterized by vegetative signs: the most common is the epigastric aura, an annoying sensation of pressure that rises from the stomach region towards the throat (the most frequent epileptic symptom ever); still salivation, nausea, pallor. Also, experiential signs (already seen, already lived, never seen, extraneousness, dreamy state, depersonalization), psychic (fear, anxiety, anger), sensory (strange fl avors and smells). Consciousness is generally compromised and oroalimentary (sucking, chewing, swallowing), gestural (mimic expressions, manipulations of objects), verbal (sounds or words), rarely outpatient, emerges. The most typical crisis evolves with epigastric aura, fear ("I am afraid that the seizure will come to me", reports the patient), confusion, chewing (movements of the jaw as with a candy in the mouth, which French epileptologists call "machonnement"). The prognosis is not good, since about one in three patients does not respond to medical treatments and becomes a possible candidate for surgical resection of the epileptogenic area. The early appearance of verbal automatisms is very important clinically and should always be investigated, as it denotes the rapid invasion of the centers of speech and makes surgical therapy more at risk.

b) Lateral temporal epilepsy:
The causes are the same as for the medial temporal form. Hippocampal sclerosis does not constitute the main etiology, as in the medial form, but is still present since in some cases tissue sclerosis also involves lateral structures from where the clinical seizure starts. The manifestations are acoustic, dizzying, experiential, and cognitive sensory; moreover, in some cases, the seizure starts with epigastric sensations dating back.

5) Hypothalamic hamartoma epilepsy: The hypothalamus
is an area located in the center of the brain, around the third ventricle responsible for autonomic and endocrine regulation functions. It develops an exclusive and characteristic form of epilepsy that appears in the hamartomas (malformative tumors consisting of neuronal and glial tissue) of this area and has as its main characteristic an unmotivated and sudden laugh seizure (the so-called gelastic seizure) or, even if very rarely, a seizure of sudden crying (diacritic seizure). This epilepsy can sometimes have a catastrophic evolution, with the appearance of a fall seizure or an evolution towards an encephalopathy.

6)
Other syndromic entities: A particular form of frontal epilepsy affecting the rolandic regions is Kojewnicow syndrome, also called continuous Epilepsia partialis, characterized by sub-continuous clones affecting the contralateral hemisome, expression of motor focal evil state. The form is often secondary to malformative lesions (cortical dysplasias). Another nosographic entity that can be assimilated from a clinical point of view to the previous one is Rasmussen encephalitis (or syndrome), an immune-mediated pathology with the presence in the blood of antibodies directed towards the glutamate receptor (antibodies antiGlu3). It is characterized by the association of continuous partial epilepsy, hemiparesis, cognitive disorders, and resonance fi nding of progressive cerebral hemiatrophy. More frequent in childhood, in addition to antiepileptic drugs, it requires immunomodulating treatment (plasmapheresis, IV Ig, steroids) and, in resistant and rapidly progressing cases, surgical therapy (often hemispherectomy).

The seizure seizure and the difference with the epileptic seizure
From the classic "epileptic seizure ", however, it is necessary to distinguish the so-called "convulsive seizure": with the latter term we want to indicate violent and involuntary contractions affecting some voluntary skeletal muscles (without loss of consciousness) and are caused by other conditions: abscesses brain; withdrawal seizure (alcohol withdrawal, drugs, drugs); encephalitis; fever (we speak of febrile seizures, especially in children); meningitis; brain tumors; metabolic problems (hypoglycemia, hyponatremia, and hypoxia); tetanus infection; hyperuricemia. About 5-8% of epileptics experience seizures that are often triggered by specifi c events; this condition is known as refl ex epilepsy. Those who suffer from this particular disorder have seizures that are activated only by specifi c stimuli. The most common triggers can be fl ashing lights and sudden noises. In some types of epilepsy, seizures occur more frequently during sleep and sometimes almost exclusively [29,[34][35][36].

The non-epileptic seizure
Finally, we can also speak of "non-epileptic seizures" if caused by external agents such as electroconvulsive therapy (TEC, the common "electroshock"), or convulsive drugs. Sometimes it can be even diffi cult to differentiate them from syncope, hysterical seizure, and simulation or from other pathologies that are actually at the origin of the epileptic seizure, as in the case of Bourneville tuberous sclerosis, West Syndrome, Lennox Syndrome-Gastaut, Down syndrome or Landau-Kleffner syndrome [29]. Epilepsy. The term "Unknown Epilepsy" is used to describe patients who have Epilepsy but the clinician is unable to defi ne whether the Epilepsy Type is focal or generalized due to lack of suffi cient information. This could be due to different reasons:

The recent revision of the classifi cation of epilepsies
EEG not available or non-informative EEG (for example because normal). If the Type-Types of Seizure are unknown, then the Type of Epilepsy may also be unknown for similar reasons, although the type of seizure and type of epilepsy may not always be in agreement. For example, the patient may have had several symmetric tonic-clonic seizures without normal focal and EEG characteristics. So the onset of the seizures is unknown and the patient has epilepsy of an unknown type [8] .
The third level is the diagnosis of "Epileptic Syndrome". Lastly, the "state of epileptic illness" deserves a separate mention: the epileptic seizure usually lasts no more than two to three minutes; when this does not happen and is prolonged considerably or repeated cyclically, we will speak of a "state of epileptic evil", and also here we will speak of partial forms or generalized forms. It is a condition capable of creating serious brain injuries to the patient, until death [6].

Epilepsy in children and adolescent
However, epileptic syndromes can also arise and occur in children and adolescents. Let's see them in detail [37]:

e) Epilepsy with focal migrant crises: Condition with
features not yet well-defi ned onset in the fi rst weeks of life.
Rapidly worsening epilepsy with focal or multifocal crises characterized by variable ("migrant") localization of the prevalent outbreak. Pharmacoresistant form with a negative prognosis.

Childhood-onset epileptic syndromes a) Infantile spasms (ISs or West syndrome):
Age of onset generally between 4 and 6 months (more rarely they can occur in the late neonatal period or after 12 months). The crises are represented by the typical spasms in clusters that occur mainly in waking; spasms can be in fl exion or extension; a focal brain alteration can cause asymmetric spasms. The period of spasms is associated with a psychomotor regression with a reduction in visual attention and interaction and an increase in irritability. Depending on the etiology, "symptomatic" (about 90%) or "presumed symptomatic" forms are distinguished; genetically determined forms have been described (CDKL5 gene in females and ARX gene in males). West syndrome is defi ned by the combination of spasms with a very characteristic EEG pattern, called "hypsarithmia". The most effective therapies are represented by the administration of adrenocorticotropic hormone (ACTH), or by high doses of oral corticosteroids or, in the case of symptomatic infantile spasms of tuberous sclerosis, by vigabatrin.

b) Benign myoclonic epilepsy of childhood (BMEI):
Rare condition (represents about 1% of idiopathic generalized epilepsies). Debut between 4 months and 3 years of life. Myoclonic seizures mainly involve the head, eyes, upper limbs, diaphragm, and more rarely the lower limbs (in this case they can cause occasional falls); myoclonic seizures can occur in isolation or short clusters. Normal psychomotor development. Male / female ratio = 2: 1. Normal intercritical EEG; myoclonic seizures have an EEG correlation of tip-wave or poly pointwave discharges. The drugs used for treatment are valproic acid or other broad-spectrum antiepileptics.

c)
Severe myoclonic epilepsy of childhood (SMEI or Dravet syndrome): It probably represents 1-3% of epilepsies with onset in the fi rst year of life; typically onset between 5 and 12 months with recurrent episodes of epileptic state during fever (often focal / lateralized seizures). The types of seizures that can occur are clonic seizures associated with fever, myoclonic seizures, atypical absences, and complex focal seizures. Before the onset, psychomotor development is normal; from the second year of life, different types of crises occur with the prevalent myoclonic component (especially starting from 18 months). Heat (fever or even a hot bath) is a trigger for crises. The intercritical EEG shows generalized, focal or multifocal anomalies, and can detect photosensitivity. Family history of epilepsy and / or febrile seizures in 15-25%; in about 70% of cases there is a mutation in the SCN1A gene. The most effective drugs are valproic acid and clobazam in association with stiripentol; carbamazepine and lamotrigine worsen critical symptoms. A clear regression of psychomotor development typically occurs about a year after the onset of the seizure.

f) Landau-Kleff ner syndrome (LKS):
Also known as acquired epileptic aphasia, it is a rare, rapid-onset condition (in a previously normal child), characterized by symptoms that make the affected child appear "as if he were deaf"; a fl uctuating and rapidly progressive course develops a disturbance in the understanding of language with the impossibility of decoding the meaning of some sounds (auditory agnosia, e.g. impossibility in understanding the meaning of a ringing telephone) and an expressive aphasia; other cognitive and behavioral problems may be present. The age of onset is between 3 and 8 years with a male / female ratio of 2:1. Generalized tonic-clonic crises, atypical absences, and focal motor crises can occur. The EEG shows frequent epileptic discharge especially during sleep and at the level of the temporal regions. It is an epileptic encephalopathy in which brain functioning is compromised by epileptic activity. The drugs most commonly used for treatment are corticosteroids and benzodiazepines; some children undergo epilepsy surgery.

g) Epilepsy with continuous wave-points in sleep or electric epileptic state in sleep (CSWS, ESES):
The term electrical Epileptic State in Sleep (ESES) is synonymous with continuous wavespikes in sleep (CSWS); there is an overlap between epilepsy with continuous wave-spikes in sleep (CSWS) and Landau-Kleffner Syndrome (LKS) (the fi rst is defi ned by EEG characteristics, while the second by clinical aspects); many children with LKS have a form of CSWS or a similar condition; LKS can be considered a type of CSWS with a temporal epileptogenic focus and consequent language regression. CSWS is characterized by the triad: continuous wave-spikes occupying more than 80% of slow-wave sleep, epileptic seizures, and cognitive-behavioral regression. The age of onset is typically between 4 and 6 years (range 1-11). Memory defi cits, regression in cognitive functions, and hyperactivity may be present. Males are more affected than females. The fi rst paroxysmal event is generally a generalized seizure in sleep (in some cases focal or focal crises with secondary generalization can occur which may have characteristics similar to the BECTS form). The evolution of this type of epilepsy is characterized by the possible appearance of other crises such as typical and atypical absences, myoclonic absences, clonic and atonic crises, generalized tonic-clonic crises. The treatment is based on the use of various antiepileptic drugs (especially benzodiazepines, valproic acid, ethosuximide or levetiracetam) and corticosteroids; carbamazepine can worsen critical symptoms; some children undergo epilepsy surgery.

h) Lennox-Gastaut syndrome (LGS):
This condition defi nes a relatively rare and serious form of epilepsy characterized by the presence of tonic crises (always present element) or even atonic and atypical absence crises; in general, there is an identifi able symptomatic cause (in 30% of cases there is an "alleged symptomaticity"). The EEG is characterized by the presence of diffuse slow wave-points and rapid activity paroxysms. The prognosis for cognitive development, behavioral characteristics, and seizure control is negative.

i)
Epilepsy with occipital paroxysms (CEOP form of Gastaut): Age of onset with a peak between 7 and 9 years. The seizures are characterized by brief visual symptoms without alteration of the state of consciousness and post-critical symptoms which include headache, nausea, and vomiting; some crises continue with versive type movements, sensory disturbances, automatisms, clones that are interesting to an emilate or widespread. This form of epilepsy compared to the Panayiotopoulos form has a slightly worse prognosis as regards the disappearance of the seizures. The EEG has characteristics similar to what is found in the form of Panayiotopoulos and presents as a characteristic element of epileptiform anomalies at the level of the occipital regions that are suppressed by opening the eyes ("fi xation-off sensitivity") and activated by sleep.

Adolescent onset epileptic syndromes a)
Juvenile Absence Epilepsy (JAE): Age of onset with a peak at 12 years, typically near the pubertal period. Unlike the EWC there are few episodes of "absence" per day and the degree of impairment of the state of consciousness seems less even if the electrical anomalies tend to have a prolonged duration. About 80% of patients will have generalized tonic-clonic crises while 15% will also experience myoclonic crises (less intense than those that occur in juvenile myoclonic epilepsy). The EEG shows generalized anomalies consisting of 3 Hz wave-point complexes, often induced by hyperventilation; photosensitivity is unusual. Many patients respond to valproic acid treatment although the prognosis for the disappearance of long-term seizures is less good than for EWC.

b)
Juvenile Myoclonic Epilepsy (JME): Debut between 12 and 18 years. The seizures are generalized and myoclonic tonic-clonic, and typically occur immediately after waking up; consciousness is preserved during myoclonic crises; generalized tonic-clonic crises are often preceded by a series of growing myoclonic crises; absence crises occur in about a third of cases. A story of objects falling from the hands while preparing breakfast is typical. Excessive tiredness, lack of sleep, and alcohol are potential trigger factors. The EEG typically shows discharges of poly points followed by irregular slow waves at a frequency between 1 and 3 Hz; absence seizures have a correlated EEG of poly point-wave complexes at 4-6 Hz which slow down to 3 Hz (these epileptic discharges are much less regular than what is seen in the absence of epilepsy of the child or the epilepsy of absences of the youth). The antiepileptic drugs generally used are valproic acid, clonazepam, and levetiracetam; lamotrigine can cause an increase in myoclonic seizures but is effective in combination with valproic acid; carbamazepine treatment is contraindicated. The prognosis regarding seizure control is good but it is generally not recommended to stop anti-epileptic treatment due to the high risk of recurrence of crises in the absence of therapy.

Diagnostic profi les
The diagnosis of epilepsy is typically formulated based on the description of the convulsive event and the circumstances in which it occurred, using an electroencephalogram and neuroimaging techniques for further study [38].
An Electroencephalogram (EEG) can help to show brain activity suggestive of an increased risk of experiencing convulsions (even during sleep), while resorting to biomedical imaging techniques, such as computed tomography and magnetic resonance imaging, it is recommended after a fi rst non-febrile seizure to detect structural problems of the brain [39]. In particular [7]: in the Electroencephalogram (EEG) of an adult in normal conditions and a waking state, the alpha frequency represents the fi rst and most common recordable signal. There is talk of an alpha wave, alpha rhythm, and alpha EEG: or occurs only occasionally. This is not necessarily a symptom of serious brain disorders. The alpha rhythm can be recorded more precisely by electrodes placed in the posterior area of the skull where the brain region is located, which receives and processes signals from the retina. Considering the univocal relationship between the opening and closing of the eyes and the appearance of the alpha rhythm, it has been ascertained that the phenomena that concern the alpha are infl uenced by the stimuli that reach the brain passing through the retina and the optic nerve. When an individual psychically and physically in a state of rest opens his eyes, the voltage of the alpha rhythm is lowered and sometimes completely disappears. Normally, if the eyes remain open, it does not return regularly but appears occasionally for some time. In many individuals, the alpha rhythm can disappear if they undertake a mental activity such as that of making calculations. Although normally we speak of an alpha rhythm, it must be specifi ed that a more careful observation of the traces can identify different brain areas from which it is possible to record as many alpha rhythms. The differences between these, however, are so small that they can safely speak of an alpha rhythm. Beta rhythm is often observed in the body of some forms of brain activity for which intense concentration is required.
If, for example, the patient is performing calculations, the replacement of the alpha rhythm with the beta rhythm frequently occurs.

3) Delta rhythm:
The frequency of this electroencephalographic rhythm varies from 0 to 3.5 waves per second. In normal individuals, the frequency is never lower than two waves per second. The voltage is low and never exceeds 50 microvolts. This rhythm occurs irregularly, usually with isolated waves. The delta rhythm is usually recorded by electrodes located above the temporal lobes of the brain. The delta activity varies from individual to individual and often shows great differences even in the same individual if the electroencephalogram or EEG is recorded at different times.

4)
Theta rhythm: This rhythm is characterized by waves having a frequency ranging from 4 to 7 per second, while for the voltage it generally does not exceed 50 microvolts. The theta rhythm presents itself with irregularities and is almost always recorded using electrodes placed above the temporal lobes of the brain.

Clinical treatments
Epilepsy is usually treated through the daily intake of drugs, prescribed after the occurrence of a second seizure treated mainly in the hospital setting. During fi rst aid, it is essential to put people with an active tonic-clonic seizure in the lateral safety position to help prevent inhalation of fl uids in the lungs.
Putting your fi ngers in your mouth or inserting a tongue depressor is not recommended as it may cause vomiting or cause the rescuer to be bitten. The interventions should aim to avoid trauma, however, precautions for the spine are generally not necessary. If an attack lasts longer than 5 minutes or there are two attacks within an hour without a return to a normal level of consciousness in between, there is a belief that there is a medical emergency known as a "state of illness epileptic".

Conclusions
Epilepsy often has negative effects on social and psychological well-being. These effects may include social isolation, stigmatization or a real state of disability, poor academic performance, and on average lower occupations, but also learning diffi culties, attention disturbances, and socialization problems. All aspects that deserve to be adequately addressed with the help of a psychotherapist, supported by the clinical staff. Progress in research is giving encouraging signals and new, less and less invasive, targeted therapies are passing the test of scientifi c reliability. It is assumed, in the recent future, that attention will be increasingly focused on the well-being of patients and their defi nitive recovery.