Epilepsy and epileptic seizures - Symptoms

Epileptic seizure is a sudden developing stereotyped episode, characterized by a change in motor activity, sensory functions, behavior or consciousness, and is associated with a pathological electrical discharge of neurons in the brain. Epilepsy is a condition manifested by repeated spontaneous seizures. Consequently, epileptic seizure is a separate episode, whereas epilepsy is a disease. A single seizure does not allow to diagnose epilepsy, just like a series of seizures, if they are caused by provoking factors, for example, alcohol abstinence or a brain tumor. Diagnosis of epilepsy requires that seizures be spontaneous and repetitive.

[1], [2], [3], [4], [5], [6], [7]

Symptoms of epileptic seizures

Symptoms of epileptic seizures depend on several factors, the most important of which is the localization of that zone in the brain, where a pathological electrical discharge occurs. Cortical zone, controlling movement and sensitivity, has the form of a strip and is located along the border of the frontal and parietal lobes. In this case, the part that controls the movement is rostral (in the projection of the frontal cortex), and the part that ensures the perception of somatosensory afferentation is more caudal (in the projection of the parietal lobe). If you move from the top of this area laterally and downwards, then the zones of the representation of the trunk, proximal part of the hands, hands, fingers, face, lips are successively located in it. The area of the language representation is located laterally in this motor-sensory strip and lower than the others. Epileptic excitation during a fit can spread along this zone, sequentially activating each of the muscle groups for a few seconds or minutes (Jackson's march). Broca's motorized speech zone is usually located in the left frontal lobe in front of the motor strip, and the Wernicke speech recognition area is in the parietal-temporal region. Visual perception is provided by the posterior poles of the occipital lobes. Focal epileptic activity in these regions causes a disorder of the corresponding function or a distortion of the corresponding aspect of perception.

Deep divisions of the temporal lobes are the area of the brain that is especially important for the development of epileptic seizures. The temporal lobes include the amygdala and the hippocampus, the most epileptogenic structures of the brain, which are most involved in the pathogenesis of epilepsy in adults. For this reason, the amygdala and the hippocampus involved in the regulation of emotions and memory processes are important targets in the surgical treatment of epilepsy.

If a pathological electrical discharge occurs in the frontal cortex, the patient develops a motor attack, if the sensory cortex is a pathological sensory perception, if in the visual cortex there are flashes of light and elementary visual sensations. Seizures generated in the deep structures of the temporal lobe are manifested by the arrest of activity, mnestic processes, consciousness, and the appearance of automatisms. If epileptic activity spreads to all regions of the brain, a typical generalized tonic-clonic seizure occurs with loss of consciousness, tonic torso strain and twitching in the limbs.

Epileptic seizures are due to an electrochemical pathological process in the brain. Since neurons either activate or inhibit neighboring cells, most epileptic syndromes are caused by a disbalance between these two actions. Although, apparently, almost all neurotransmitters and neuromodulators in the brain are involved in the pathogenesis of epilepsy, glutamate acid and GABA play a particularly important role, since the first is the main stimulating mediator, and the second is the main inhibitory mediator of the brain. The mechanism of action of some antiepileptic drugs is associated with the blockade of glutamatergic stimulating transmission. Although inhibition of glutamatergic transmission leads to the elimination of seizures, it can simultaneously cause a number of undesirable side effects that limit the use of these drugs. GABA, which is the most potent inhibitory mediator, can also be a target for antiepileptic drugs, and a number of drugs with a similar action are allowed for use in epilepsy.

For a long time there has been a lively discussion on whether epileptic seizures are the result of dysfunction of the entire central nervous system or only a limited group of neurons. At the same time, data that indicate the systemic nature of the disorder are more convincing. In the pathogenesis of seizures, anatomical, physiological and neurochemical brain resources are involved that ensure the spread of excessive hypersynchronous neuronal discharge from the epileptic focus, where intracellular registration reveals paroxysmal depolarization shift (PDS).

Braking effects in the brain have selective sensitivity to certain factors. The inhibitory circle - polysynaptic structure, formed by interconnected interstitial neurons, uses GABA or other inhibitory neurotransmitters. These pathways are more sensitive to pathological influences (such as hypoxia, hypoglycemia or mechanical trauma) than excitatory monosynaptic pathways. If the exciting synapses function normally, and the inhibitory synapses do not function, an attack occurs. If the damage is severe enough and, along with the inhibitory ones, the exciting systems suffer, then seizures cease, and then a coma develops or a lethal outcome occurs.

Braking neurons in the brain is not a single process, but rather a hierarchy of processes. The brake post-synaptic potential (TPMS) generated by the GABAd receptor is the most important part of it. As already mentioned, this receptor has selective sensitivity to damage and GABAA receptor antagonists, such as penicillin, picrotoxin, or bicuculline. Some neurons also have GABA-receptors, the agonist of which is the antispastic agent baclofen. Although several antagonists of GAMKg receptors have been developed, none of them are used in clinical practice. GABA-receptors appear to be especially important for the generation of a wave-one of the EEG signs of peak-wave absense epilepsy. The third level of inhibition is formed by calcium-dependent potassium channels, which mediate post-flare hyperpolarization. An increase in the intracellular level of calcium activates the potassium channels that remove potassium from the cell, which leads to hyperpolarization, which persists from 200 to 500 msec. The fourth level of inhibition is provided by activation of metabolic pumps using ATP as an energy source. These pumps exchange three intracellular sodium ions for two extracellular potassium ions, which increases the negative intracellular charge. Although such pumps are activated by an intense neuronal discharge and serve to restore the balance of ions inherent in the equilibrium state, they can lead to prolonged hyperpolarization of the cell, which lasts for many minutes. The existence of this hierarchy is important, because the violation of one of these inhibitory processes does not eliminate other mechanisms that can take over the defense of the brain from excessive excitation.

Petit mal is an exception to the rule that seizures result from the weakening of inhibitory influences, as they probably result from the amplification or hypersynchronization of inhibition. That is why absences are characterized by a lack of behavioral activity, rather than involuntary excessive or automated actions observed with other types of seizures.

During the absence of an electroencephalogram, repeated sequences of peaks and waves are recorded. Three forces are required to maintain this picture: an exciting stimulus that generates a peak; a stimulus stimulating the wave; and a pacemaker supporting the rhythm. It is assumed that the peak is due to glutamate-mediated EPSP (excitatory postsynaptic potential), wave-to GABA-mediated TPSP, and rhythmicity to changes in calcium channel activity in some thalamic nuclei. These representations serve as a basis for the search for new approaches to the treatment of absences.

There is no simple explanation why most seizures terminate spontaneously, as the ability of neurons to discharge continues even after the seizure ceases. The development of a special postictal condition predetermining the cessation of a seizure may be due to several factors, including hyperpolarization of neurons, probably related to the functioning of metabolic pumps and a reduction in cerebral perfusion, which leads to a decrease in the activity of neuronal circles. Excessive excretion of neurotransmitters and neuromodulators due to discharges during a seizure may also contribute to the development of the postictal state. For example, it is believed that endogenous opioid peptides released during a seizure inhibit brain function after paroxysm, since the antagonist opioid receptors naloxone exerts a wake-up effect on rats stunned after an electroconvulsive fit. In addition, adenosine released during the seizure, activating the adenosine A1 receptors, may partially block the subsequent stimulating synaptic transmission. Nitric oxide is the second mediator that affects the condition of blood vessels and neurons in the brain, and may play a role in the development of the postictal state.

The physiological mechanisms responsible for the development of the postictal state are crucial for the cessation of epileptic seizures, but at the same time they can also be the cause of postictal disorders, which in some patients are more disruptive than seizures themselves. In this regard, the development of treatment methods aimed at reducing the duration of the postictal state is of great importance.

Since epilepsy is characterized by recurrent seizures, a full explanation of the mechanisms of development of this disorder must take into account chronic changes in the brain, which are the condition for the onset of these seizures. Repeated seizures can be caused by a wide range of brain lesions, including perinatal hypoxia, craniocerebral trauma, intracerebral hemorrhages and ischemic strokes. Often seizures do not occur immediately, but several weeks, months or years after brain damage. Several studies have been conducted, which examined changes in the brain after injury, leading to the development of chronic hyperexcitability of brain structures. A useful model for studying this process was a hippocampus, a chemically exposed kainic acid (neurotoxin with a relatively selective effect), or excessive electrical stimulation, which caused a selective loss of some neurons. Cell death leads to overgrowth of axons (scoring) of other neurons that come into contact with deafferented cells. A similar process takes place in the motor units and leads to the appearance of fasciculations. From this point of view, some seizures can be considered as a kind of "fasciculation of the brain" caused by the reorganization of neurons. The goal of such a reorganization, of course, is not the production of a seizure, but the restoration of the integrity of neural circles. The price that one has to pay for this is an increase in the excitability of neurons.

It is known that epileptic seizures do not occur simply in any one region of the brain, but rather in circles formed by interacting neurons that behave like abnormal networks. Removing a specific area of the brain can nevertheless lead to the cessation of certain types of seizures. The mechanism of the therapeutic effect of such a surgical intervention can be compared with cutting a telephone cable that interrupts a telephone conversation even when the interlocutors are at a great distance from each other.

Some areas of the brain, apparently, are particularly important in the generation of epileptic seizures. Nonspecific thalamic nuclei, especially the reticular nucleus of the thalamus, are key to the generation of peak-wave absences, and the hippocampus and amygdala located in the medial parts of the temporal lobes are used to generate complex partial seizures. Prepiriform bark is known as the zone responsible for the occurrence of temporal seizures in rats, cats and primates. In rats, the reticular part of the black substance facilitates the spread and generalization of epileptic activity. In humans, the cortex of the large hemispheres is the most important structure that generates epileptic seizures. In this case, focal seizures usually occur as a result of damage or dysfunction of the new cortex (neocortex) or the ancient and old cortex (archcortex and paleocortex) in the medial parts of the temporal lobes. Although the main manifestations of seizures are associated with the neocortex, the subcortical systems are also involved in the pathogenesis of the seizure, although the structures and pathways involved in the development of seizures are not exactly known.

Fundamental studies change the traditional ideas about the mechanisms of the development of epilepsy, especially focal seizures. Nevertheless, many questions remain unanswered, including: what systems are involved in the mechanism of development of generalized seizures, how seizures begin and end, what processes lead to the formation of an epileptic focus after brain damage, what role is played by the hereditary predisposition to the development of seizures , what explains the coincidence of some forms of epilepsy to certain phases of the development of the brain, why the abnormal electrical excitability manifests itself in different types ripadkov.

Classification of epileptic seizures

Since seizures are classified mainly on the basis of a terminology agreement developed by an expert committee, and not on the basis of any fundamental provisions, the classification scheme will undoubtedly change as knowledge about epilepsy grows.

Epileptic seizures are divided into two broad categories: partial (focal) and generalized. Partial epileptic seizures are generated in a limited area of the brain, which leads to the appearance of focal symptoms, for example, twitching in the limbs or face, sensitivity disorder and even memory changes (as, for example, in temporal seizures). Generalized seizures result from the involvement of the entire brain. Although some experts believe that these seizures are generated in deep brain structures that are widely projected onto the cortical surface and as a result of the manifestation of dysfunction of different parts of the brain occur almost simultaneously, the true mechanisms of development of generalized seizures remain unknown.

Partial epileptic seizures are divided into simple partial (without loss of consciousness or memory) and complex partial (with loss of consciousness or memory). Simple partial epileptic seizures can be manifested by twitching, pathological sensations, visual images, sounds, smells, distortion of perception. If epileptic activity extends to the autonomic structures, there is a sensation of tidal or nausea. With all types of simple partial seizures, the patient remains conscious and remembers everything that happens to him. If the patient is confused or he can not remember what happened to him during the seizure, then the fit is defined as a complex partial.

[8], [9], [10], [11], [12], [13], [14]

International classification of epileptic seizures (simplified version)

Partial epileptic seizures (generated in a restricted area of the brain)

• Simple (without disturbance of consciousness or memory):
  • sensory
  • motor
  • sensorimotor
  • mental (pathological ideas or altered perception)
  • vegetative (sensation of warmth, nausea, tidal, etc.)
• Complex (with a violation of consciousness or memory)
  • with aura (forerunners) or without aura
  • with automatisms or without automatisms
• Secondary generalized

Generalized epileptic seizures (generated by an extensive brain area)

• Absenses (petit mal)
• Tonic-clonic (grand-mall
• Atonic (drop-fits)
• Myoclonic

Unclassified epileptic seizures

Complex partial epileptic seizures were previously referred to as psychomotor, temporal or limbic seizures. Complex partial seizures can begin with an aura, a harbinger of a seizure, which is often manifested by the sensations of "already seen" (deja vu), nausea, warmth, crawling, or distorted perception. However, about half of patients with complex partial seizures do not remember the aura. During a complex partial seizure, patients often perform automated actions - they fumigate around themselves, lick their lips, take off their clothes, aimlessly hang around, repeat pointless phrases. Such senseless actions are called automatisms - they are observed in 75% of patients with complex partial seizures.

Generalized epileptic seizures are divided into several categories. Absensives, formerly referred to as petit mal (small seizures), usually begin in childhood. They are short-term bouts of loss of consciousness, accompanied by a stiff look, twitching of the eyelids or a nod of the head. Absenses can be difficult to distinguish from complex partial seizures, which are also accompanied by stasis, but absences usually last a shorter time than complex partial seizures, and are characterized by a faster recovery of consciousness. In the differential diagnosis of these types of seizures, EEG is useful (see below).

Generalized tonic-clonic epileptic seizures, formerly known as grand mal, begin with a sudden loss of consciousness and tonic tension of the trunk and limbs, followed by rhythmic clonic twitching of the limbs. The patient produces a cry, caused by contraction of the respiratory muscles with closed vocal cords. Fit (ictus) typically lasts 1 to 3 minutes, followed by a postictal (postictal) condition characterized by lethargy, drowsiness, confusion, which can last for hours. The postictal period can occur after any seizure.

Epileptic activity, arising in a certain zone, can spread to the entire brain, causing a generalized tonic-clonic seizure. It is important to distinguish between true (primarily generalized) large convulsive seizures from partial seizures with secondary generalization, since these two types of seizures may require the use of different antiepileptic drugs. Moreover, with secondary generalized tonic-clonic seizures, surgical treatment is possible, while in primary generalized tonic-clonic seizures it is not performed, since there is no explicit source (epileptic focus) that could be removed.

Atonic epileptic seizures usually occur after brain damage. When the atonic seizure suddenly decreases muscle tone and the patient can fall to the ground. In some cases, patients are forced to wear a helmet, which prevents serious damage to the head.

Myoclonic seizure is characterized by a short-term rapid twitching or a series of twitchings, usually less coordinated and organized than with a generalized tonic-clonic seizure.

An epileptic status is a seizure or series of seizures that continue, without interrupting the restoration of consciousness and other functions, for more than 30 minutes. Epileptic status is an urgent condition, as it can lead to damage to neurons and to somatic complications. There are several types of epileptic status, corresponding to different types of epileptic seizures. The status of simple partial seizures is known as epilepsia partialis continua (constant partial epilepsy). The status of complex partial seizures and absences is indicated by several terms, including as an unconvulsive status, peak-wave stupor, status of absences, epileptic twilight state. Recommendations for the diagnosis and treatment of epileptic status have been developed by a special working group on epileptic status.

A patient may have several types of seizures, one of which can go into the other as electrical activity spreads through the brain. Usually, a simple partial fit goes into a complex partial, and that one into a secondary generalized tonic-clonic seizure. In some cases, antiepileptic drugs increase the ability of the brain to limit the spread of epileptic activity.

In adults, most often (more than 40% of cases) there are complex partial seizures. Simple partial ones are detected in 20% of cases, primary generalized tonic-clonic seizures - in 20% of cases, absences in 10% of cases, and other types of seizures - in 10% of cases. In children, absences are more common than in adults.

Classification of epileptic syndromes

Classification of epileptic seizures does not carry information about the patient's condition, causes, severity, prognosis of the disease. Hence the need for an additional classification scheme that allows to qualify epileptic syndromes. This is a more voluminous classification, which includes not only a description of the type of seizures, but also information about other clinical features of the disease. Some of these epileptic syndromes are described below.

Infantile spasms / Vest syndrome

Infantile spasms occur in children aged 3 months to 3 years and are characterized by sudden flexion spasms and a high risk of mental retardation. During flexion cramps, the child suddenly unbend limbs, the body tilts forward, a scream is issued. The episode lasts a few seconds, but can be repeated several times per hour. With EEG, gypsarhythmia with high-amplitude peaks and disorganized high-amplitude background activity is revealed. Early active treatment can reduce the risk of developing persistent mental retardation. Although valproic acid and benzodiazepines are considered drugs of choice, their effectiveness is low. Of the new drugs, the most promising results were obtained with the use of vigabatrin and felbamate, as well as lamotrigine and topiramate.

Lennox-Gasto syndrome

The Lennox-Gasto syndrome is a relatively rare condition (with the exception of epileptological centers, where it constitutes a significant proportion of patients with treatment-resistant seizures). It manifests itself in the following characteristic features:

1. polymorphic seizures, usually including atonic and tonic seizures;
2. variable mental retardation;
3. EEG changes, including slow peak-wave activity.

Although the syndrome usually begins in childhood, adults can suffer from it. The Lennox-Gastaut syndrome is very difficult to treat, only 10-20% of patients have satisfactory results. Since seizures are almost always multifocal, surgical treatment with this disease is ineffective, although collosotomy can reduce the degree of suddenness of a seizure and prevent injuries. In spite of the fact that valproic acid, benzodiazepines, lamotrigine, vigabatrin, topiramate and felbamate can be useful in this condition, the results of treatment are often unsatisfactory.

Febrile epileptic seizures

Febrile epileptic seizures are provoked by fever and are usually manifested in children between the ages of 6 months and 5 years of tonic-clonic seizures. Febrile seizures should be distinguished from seizures caused by more serious diseases, such as meningitis. Febrile epileptic seizures often frighten parents very much, but usually have a benign character. Although they are considered as a risk factor for the subsequent development of complex partial seizures, there is no conclusive evidence that preventing febrile seizures reduces this risk. In most children with febrile seizures, epilepsy does not subsequently develop. In this regard, the advisability of prescribing antiepileptic drugs that can have an adverse effect on the child's learning and personality is being questioned. To prevent febrile seizures, phenobarbital is usually used. But it is effective only with daily intake, as the seizure usually occurs immediately after the body temperature rises. Prolonged daily intake of phenobarbital leads to hyperactivity, behavioral disorders and learning in a significant percentage of children. Many pediatric neurologists believe that treating febrile seizures is more adversely affected than episodic seizures that may never recur, and are advised to refrain from treatment. Several trials with febrile seizures of other antiepileptic drugs did not yield encouraging results. Thus, the problem of treating febrile seizures remains controversial.

Benign epilepsy of childhood with central-temporal peaks

Benign epilepsy of childhood with central-temporal peaks (benign Rolandic epilepsy) is a genetically determined disease, usually manifested in childhood or adolescence (from 6 years to 21 years). Rolandova is called the area in the brain, located in front of the border of the frontal and parietal lobes. Seizures that are generated in this zone are manifested by twitches and paresthesias in the face or hands, sometimes turning into secondary generalized tonic-clonic epileptic seizures. In this condition, the EEG usually reveals pronounced peaks in the central and temporal regions. Seizures often occur when falling asleep. The term "benign" is used not because seizures may manifest as minimal symptoms, but because of a very favorable long-term prognosis. With age, seizures almost always regress. The use of antiepileptic drugs is not necessary, but with frequent or severe seizures use means effective for partial seizures (most often carbamazepine).

Juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is the most common cause of generalized seizures at a young age. In contrast to benign epilepsy with central-temporal peaks, there is no age-related regression of these seizures. UME is a genetically determined epileptic syndrome, usually starting in older children and adolescents. In some family cases, a pathological gene was found on chromosome 6. With JME, morning myoclonus (twitching of limbs or head) and episodic generalized tonic-clonic convulsions are usually observed. EEG with JUME usually reveals generalized complexes "peak-wave" frequency of 3-6 / s. High efficacy of antiepileptic agents, including valproic acid and benzodiazepines, is characteristic. If these funds are intolerant, lamotrigine and topiramate can be used.

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