Help for patients with epilepsy

Epilepsy (epileptic disease) is a chronic brain disease of various etiologies, which is characterized by repeated unprovoked attacks of impaired motor, sensory, autonomic, mental or mental functions resulting from excessive neural discharges. Epileptic disease includes only repeated and spontaneous seizures (with the exception of reflex forms, for example, photosensitive epilepsy, reading epilepsy).

Epilepsy is a large group of nosologically independent forms with strictly defined clinical manifestations, treatment and prognosis. Epileptic syndromes are defined as independent forms of epilepsy, characterized by a limited age of onset of seizures, the presence of a special type of seizures, specific changes in the EEG, patterns of course and prognosis. Over the past decades, it has become apparent that only a specialist with specialized knowledge in various fields of medicine and neuroscience can provide effective care for patients with epilepsy. Therefore, since the 60s. XX century in many countries of Western Europe and America, epileptology has emerged as an independent clinical discipline at the intersection of neurology, psychiatry, neurosurgery, neurophysiology, neuroradiology, neuropsychology and clinical pharmacology. An epileptologist, in most cases, is a neurologist (less often a psychiatrist) – a doctor with special knowledge in the diagnosis, therapy and rehabilitation of people with epileptic paroxysms. 

The prevalence of epilepsy in the general population of Western Europe and the USA is 5-10 cases per 1000 population, while febrile seizures occur in 3-5% of the population of these countries. According to a number of epidemiological studies conducted in Western Europe, 2-5% of the population is likely to develop at least one afebrile paroxysm. Epilepsy is more common in men and in populations with low living standards. In the United States (1990), during a full examination of patients with epilepsy, it was found that 8% of patients are constantly in specialized institutions, 33% are monitored by specialists and need systematic administration of anticonvulsants, 26% are observed by general practitioners and receive treatment periodically, and 33 % are in prolonged remission. 

Manifest epileptic paroxysms in 70% of patients under the age of 20 years. The average duration of the active course of epilepsy reaches 10 years, and in 50% of patients, the period of active attack lasts about 2 years. The incidence of epilepsy depending on age has a certain dependence. So, epilepsy, which occurs with absences and myoclonic paroxysms, occurs mainly at the age of 15 years, and generalized tonic-clonic and partial forms of epilepsy are more often observed at the age of 15 to 45 years. In 14-37% of children with epilepsy, mental retardation is detected. In 10-20% of patients with epilepsy, dementia develops, in 1-8.2%, epileptic psychoses occur, and in 30-60% of patients a variety of nonpsychotic disorders form. Mortality of patients suffering from epilepsy exceeds the general population indicators by 4 times, in its structure sudden death is 10-17%. Other causes of death directly attributable to epilepsy include status epilepticus, an accident during a seizure, and suicide.

The main mechanisms of epileptogenesis are a decrease in GABA-ergic inhibition and an increase in glutamatergic excitation. An imbalance between the processes of inhibition and excitation in the brain leads to the development of secondary changes in neurons, their metabolism. Changes are characterized by proliferation of axons and damage to dendrites, induction of growth factors of nerve tissue and hormones-modulators, modification of ionic and cellular receptors, channels. The current classification of epilepsy and epileptic syndromes was adopted by the International League for the Fight against Epilepsy (ILAE) in 1989 (New Delhi). Unlike previous classifications, which were based on localization (the topic of the outbreak) or etiological (genuinic, post-traumatic, etc.) principles, the New Delhi classification reflects general pathological ideas and considers epilepsy as a polyetiological disease with monopathogenesis. Localization, etiology, age of onset of seizures, nature of dominant seizures, and features of the course and prognosis are used as classifying signs underlying it. It should be emphasized that the “Classification of epilepsy …” New Delhi (1989), is not identical and does not replace the well-known Classification of epileptic paroxysms (Kyoto, 1981). If the course of epileptic syndromes is described in the Delhi classification, then only one, but the leading symptom of the epileptic process – paroxysms is systematized in the Kyoto classification. 

It is advisable to clarify some key concepts of these classifications. Symptomatic forms are understood as epileptic syndromes with a known etiology and verified morphological disorders (tumors, scars, dysgenesis, etc.). With idiopathic epilepsy, there are no symptoms of organic damage to the central nervous system, structural changes in the brain according to neuroimaging data and information about patients with epilepsy among the patient’s blood relatives. In this case, the idiopathic form is considered as an independent, genetically determined disease. The cryptogenic form includes syndromes that do not meet the criteria for idiopathic and symptomatic epilepsy.

International Classification of Epilepsies, Epileptic Syndromes and Similar Diseases (New Delhi, 1989)
1. Localization-related forms.
1.1. Idiopathic (age-dependent onset) forms (in accordance with ICD-10 G 40.0).
Benign epilepsy with central temporal lobes (Rolandic).
Childhood epilepsy with occipital paroxysms.
Primary reading epilepsy.
1.2. Symptomatic forms.
Chronic progressive epilepsy of Kozhevnikov (G 40.5).
Attacks characterized by specific methods of provocation (G 40.1).
Other forms of epilepsy with a known etiology or organic changes in the brain (frontal, temporal, parietal, occipital) (G 40.1).
1.3. Cryptogenic forms (G 40.2).

2. Generalized forms of epilepsy.
2.1. Idiopathic with age-dependent onset (G 40.3).
Benign family cramps of newborns.
Benign convulsions of newborns.
Benign myoclonic epilepsy of infancy.
Absence childhood epilepsy (pycnolepsy).
Absence of juvenile epilepsy.
Juvenile myoclonic epilepsy.
Epilepsy with generalized attacks of awakening.
Other generalized forms of epilepsy.
Forms characterized by specific methods of provocation.
2.2. Cryptogenic and / or symptomatic forms (G 40.4).
West syndrome (infantile spasm).
Lennox-Gastaut syndrome.
Epilepsy with myoclonic-astatic seizures.
Epilepsy with myoclonic absences.
2.3. Symptomatic forms (G 40.4).
Early myoclonic encephalopathy.
Early infantile epileptic encephalopathy with a flash-inhibition pattern (Otahara syndrome).
Other symptomatic generalized forms of epilepsy.
3. Forms of epilepsy that do not have a clear classification as partial or generalized (G 40.8).
Cramps of the newborn.
Severe myoclonic epilepsy of early childhood.
Epilepsy with continuous peak waves during slow sleep.
Acquired epileptic aphasia (Landau-Kleffner syndrome) (F 80.3).
4. Specific syndromes.
Febrile seizures.
Seizures that occur only due to acute metabolic, toxic disorders (G 40.5).
Status epilepticus (G 41).
Currently, in connection with the new economic and political situation in Western Europe, the ILAE Commission on European Affairs has developed uniform requirements (standard) for the organization, financing, level and volume of medical care provided to patients with epilepsy. Requirements are mandatory in any European country and are intended for epileptologists, for organizations and persons involved in the management and financing of care for patients with epilepsy.

ILAE REQUIREMENTS 1.
General Diagnostic Principles
Epileptic seizures and syndromes are classified according to ILAE recommendations. The criteria for the diagnosis of epilepsy are repeated spontaneous seizures and characteristic changes in an EEG study. The classification of seizures is carried out in accordance with the Classification of epileptic paroxysms (Kyoto, 1981). The minimum requirement for diagnosis is a subjective description of seizures by the patient, consistent with information received from witnesses.
Classification of syndromes according to the International Classification of Epilepsies, Epileptic Syndromes and Similar Diseases (New Delhi, 1989). Diagnostics is based on the ratio of clinical and electroencephalographic data. Additional information on hereditary burden, genetic type and neurological status, data on intravital imaging of the brain are necessary to determine the etiology of epileptic syndrome. Anamnestic information and initial examination. An anamnesis is collected based on the patient’s stories and the information of family members. Clinical structure, duration, frequency and other characteristics of the attack are detailed. Mandatory information about the stages of psychophysical development, previous diseases, social, family, professional status of the patient, information about the presence of any hereditary burden, information about previous treatment. The etiological features of the disease, concomitant neurological and mental disorders, as well as side effects of ongoing anticonvulsant therapy are identified.

Stages of medical care. The first medical help for patients with epilepsy is provided by an ambulance doctor, a doctor – specialist in anticonvulsants, a neurologist or an epileptologist. Patients with treatment-resistant seizures, side effects and complications associated with anticonvulsant therapy should contact an epileptologist or a specialist center as soon as possible . Further therapy is carried out under the supervision of a physician with practical experience in treating at least 300 patients with epilepsy annually.

2. Diagnostic procedures
2.1. Electroencephalographic study

2.1.1. A routine electroencephalographic study is performed for all types of seizures and involves the simultaneous registration of at least 12 EEG channels. Additional channels are used to monitor heart rate, respiration, muscle activity, eye movement, etc. Basic EEG recording is performed for at least 20 minutes. Hyperventilation, photostimulation, and sleep tests require longer EEG recordings. Provocative procedures (hyperventilation, photostimulation) make it possible to evaluate the effect on the EEG of some stimuli. Hyperventilation is performed (if not contraindicated) for 5 minutes, with continuous recording for 1 minute. Two-stage hyperventilation is allowed: at first 3 minutes, and after 5-10 minutes – repeated hyperventilation for 2 minutes. Photostimulation is a prerequisite when conducting an EEG study. Paroxysmal EEG patterns can be fixed at the time of the test and at the end of the test.

2.1.2. Outpatient EEG monitoring consists in the long-term recording of brain activity during the patient’s daily activities and during sleep. EEG monitoring is carried out using surface electrodes and portable recording devices. EEG signals are recorded and stored on a magnetic cassette tape. Laboratory EEG monitoring is carried out with immediate reproduction on paper and can be transmitted by cable or telemetry. Long-term recording of EEG or telemetry are considered as necessary studies in epileptological centers.

Indications for EEG monitoring:
diagnosis of “suspicious” clinical symptoms,
unclear etiology of paroxysmal symptoms,
evaluation of treatment effectiveness with therapeutic resistance
2.1.3. EEG recording using implanted electrodes is carried out to clarify the localization of the epileptogenic focus before surgery. These studies are allowed only in specialized centers. As a rule, sphenoidal electrodes are used, with which it is possible to register epileptic activity in the temporal lobes of the brain.

2.2. Methods of neuroimaging.
In contrast to EEG studies, neuroradiological methods can neither confirm nor deny the diagnosis of epilepsy. They are not informative for the purpose of actually diagnosing epilepsy, but are intended to establish the etiology of the disease and to manage the preoperative period.

Indications for compulsory computed tomography (CT) or nuclear magnetic resonance imaging (NMR) imaging.
debut of epilepsy before the age of 1 year or after 20 years of age;
any forms of partial epilepsy; the
presence of focal neurological syndromes or a decrease in intelligence in patients;
progressive course of the disease; the
presence of epileptic status; occurrence of attacks shortly after confirmed traumatic brain injury;
persistent local changes on the EEG;
therapeutic resistance of attacks
2.2. 1. CT is informative regarding tumors, cerebral calcifications, ischemic foci and bone deformities. In addition, CT is recommended for children under 2 years of age.

2.2.2. NMR imaging is informative with respect to hippocampal sclerosis, cortical dysplasias, microdisgenesis, heterotopia, as well as minor superficial damage to brain tissue.

2.2.3. If dubious morphological sites are found, as well as the absence of any morphological changes, the appropriate clinic requires special tomographic techniques: single-photon emission or positron-emission tomography (angiography mode). Single photon emission tomography is informative for extra hippocampal seizures. Another indication for this study, as well as positron emission tomography, is the preoperative period in patients in whom the localization of the lesion could not be established using EEG, CT or NMR imaging. Informativeness of angiography in patients with epilepsy is low. The main goal of angiography is to objectify circulatory disorders in arteriovenous malformations or tumors before surgery, as well as to assess cerebrovascular disorders as a possible cause of epilepsy.

2.3. Laboratory research methods
2.3.1. Diagnosis of the etiology of epileptic syndromes and the period of selection of anticonvulsants (scope of examinations): a
detailed (with platelet and hematocrit counting) clinical blood test, assessment of lymphocyte vacuolization;
clinical analysis of urine;
determination of blood chemistry parameters (electrolytes, calcium, magnesium, iron, glucose, folic acid, vitamins B12, B6, blood coagulability, protein, urea, lactic acid, ammonia, creatinine, amylase, ceruloplasmin, bilirubin, transaminases, gamma-glutamintransferase, alkaline phosphatase, thyroid hormones, prolactin, porphyrin, immunoglobulins);
serological tests for viruses or syphilis.

2.3.2. Screening studies (the goal is the diagnosis of congenital and acquired metabolic disorders). The intermediate metabolism is studied: ketone bodies, carbohydrates, mucopolysaccharides, amino acids, organic acids, purines, pyrimidines, polyunsaturated fatty acids, leukocyte enzymes.

2.4. Other diagnostic methods (carotid and basilar dopplerography; 24-hour ECG monitoring; passive tilt test, cerebrospinal fluid analysis; biopsy of the skin, muscles, liver, bone marrow and brain; carotid sinus irritation methods; genetic study with karyotyping, DNA analysis , etc.).
With therapy-resistant epileptic syndromes, a neuropsychological examination and consultation with a psychiatrist is necessary.

2.5. Non-psychotic psychiatric disorders and formulation of a functional diagnosis of epilepsy. Non-psychotic psychiatric disorders are observed in 30-60%, and according to some reports – in 90% of patients, and consist in personality changes resulting from the chronic course of the epileptic process. In terms of their severity, they can range from specific personality reactions to pseudo-psychopathies in concentric, paranoid, hypochondriac, hysterical and asthenic types.
The construction of a functional diagnosis for epilepsy, taking into account non-psychotic psychiatric disorders, can be shown by the example: Epileptic disease, idiopathic, with frequent (1-2 times per month) secondary-generalized tonic-clonic seizures and focal motor paroxysms. A progressive course with pronounced and persistent personality changes in a concentric type.
The construction of a functional diagnosis has not so much academic value as it is a necessary condition for an adequate assessment of the degree of social adaptation of a patient.

3. Principles of drug therapy
The main goal of the pharmacotherapy of epilepsy is to prevent the development of seizures without the occurrence of acute or chronic side effects of antiepileptic drugs. The choice of drug is determined by the nature of the attack and the type of course of the epileptic syndrome. Treatment should always begin with one first-choice antiepileptic drug indicated for this form of epilepsy. The dose of the drug is increased weekly until a therapeutic effect, a higher dose or side effects occur. Also used: diazepam, gabapentin, topiramate, oxcarbazepine and tiagabin. In epileptological centers specializing in the field of clinical trials, experimental anticonvulsants are used: zinisamide, lozigamon, levetiracetam, remacemide, styripentol.
The following parenteral preparations are recommended for relief of epileptic status: diazepam, lorazepam, chlonazepam, phenobarbital, lignocaine, pentobarbital, chloromethiazole chloral hydrate.
Therapeutic control. Express methods for determining the concentration of a drug substance are necessary when using: phenytoin, carbamazepine, valproate, phenobarbital, ethosuximide and primidone.

4. The principles of surgical treatment of epilepsy.
Any neurosurgical intervention, the main purpose of which is to reduce the frequency of epileptic seizures, can be regarded as surgical. Surgical treatment is indicated for pharmacologically resistant epilepsy. Types of surgical interventions: excision of epileptogenic brain tissue, cortical topectomy, lobectomy, multilobectomy, hemisperectomy, certain operations such as amygdalgippocampectomy, callosotomy, as well as functional stereotactic intervention, other procedures such as multiple dissection under the pia mater with surgery, for example, surgery and vagal stimulation.
Indications for various surgical procedures. Removal of epileptogenic brain tissue – with therapeutically resistant focal seizures. Hemispherectomy – with an extensive unilateral cerebral morphological defect. Callosotomy (palliative procedure) – therapeutically resistant generalized tonic-clonic seizures, accompanied by falls and injuries. Functional stereotactic procedures (partial amygdaltomy and surgical interruption of seizure distribution pathways) – with some (still unspecified) types of pharmacoresistance.

Preoperative assessment includes clinical and encephalographic confirmation of the focal zone of epileptogenesis with the determination of localization and anatomical size according to NMR imaging. In generalized seizures, EEG monitoring data confirm the generalized activity and determine the mechanisms of distribution of the epileptic focus. If necessary, epileptic activity is recorded from intracranial electrodes. Minimum requirements for the stage of preoperative assessment of patient status. Team of specialists: an epileptologist, a clinical neurophysiologist, a specialist in the surgical treatment of epilepsy, a neuropsychologist and an EEG technician trained in an epilepsy surgery program. It is advisable to include a nurse, psychiatrist and social worker in the group. During a preliminary examination of persons who may undergo surgery, neuropsychological, electrocorticographic studies and daily EEG monitoring are required. A unit organized in this way can carry out at least 25 surgical procedures per year.

5. The principles of organization of epileptological care.
The work of a clinical psychologist. An epileptological clinic should have at least one adult and pediatric psychologist. They are obliged to provide the patient with guidance, determine the amount of reversible intellectual-mnestic disorders, deficiency of cognitive functions and identify ways of rehabilitation. Surgical centers are required to have two full-time clinical psychologists (adult and pediatric). Their functions include providing pre- and postoperative assessment of patients, as well as predicting the possible adverse effects of the operation on mnemonic functions. The auxiliary therapeutic measures of a clinical psychologist include the correction of concomitant anxiety-depressive disorders, teaching patients how to control seizures and managing non-epileptic seizures. In addition, he advises families who have experienced bereavement, and conducts psychotherapeutic work.

Rehabilitation. Epileptic illness often leads to negative social consequences, especially in the areas of family, school and professional activities. The Epileptological Clinic is obliged to carry out rehabilitation programs, which include assessing the level of psychological and social functioning of patients, training, social support and recommendations for further treatment. In addition, in patients who are operated on, there may be a need for neurological and neuropsychological rehabilitation of the resulting intellectual-mnestic disorders.
Providing antiepileptic care. In the EU countries, direct access to any stage of the epileptological service is guaranteed: to an epileptologist, to a regional specialized multidisciplinary group consisting of an adult and pediatric epileptologist, a patronage nurse, a clinical psychologist, a social worker and a general practitioner. Patients have access to a highly qualified neurophysiologist, laboratory tests, therapeutic drug control, neuroimaging methods, a surgical treatment program for epilepsy, and a special evaluation unit for intermediate care. Patients are entitled to counseling services, including advice on planning for conception and upcoming pregnancy, to consult a psychologist specializing in epilepsy, have access to a helpline and to voluntary public organizations. The duties of the antiepileptic service include the publication of popular reference books on epilepsy, in which the information on the types of seizures, etiology of the disease, and new methods of diagnosis and treatment should be presented in an intelligible way.