RU2404777C1 - Method for treatment of drug-resistant epilepsy - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine, namely to dietology and neurology, and relates to treatment of drug-resistant epilepsy. For this purpose ketogenic dietary treatment is administered with monitoring of glucose level in blood and ketone bodies in urine. The first stage includes hungry phase with duration of not more than a day, which is interrupted as level of ketone bodies reaches 8-10 millimole/l or as glucose level in blood becomes lower than 3.5 millimole/l, independently on level of ketone bodies. At the second stage, high-fat cocktail is introduced during the day in three stages, having high ketogenic ratio of components. Then independently on level of ketone bodies, the third stage is started, including individual basis ketogenic food ration, at the same time, if therapeutic level of ketone bodies is not obtained at the first and second stages, at the third stage in daily ration 1-2 food intakes are substituted with high-fat cocktail, and in case ketonuria is not available in this case as well, basic food ration is recalculated with correction of its nutrition value.

EFFECT: mode of dietary treatment executed with account of individual metabolic features of patient, provides for increased efficiency of epilepsy treatment by elimination of drug-resistance and with reduction of side effects.

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Description

The invention relates to medicine, namely to dietetics, and can be used for complex and monotherapy of drug-resistant epilepsy using a ketogenic diet.

Epilepsy is one of the most common diseases of the nervous system. The frequency of the disease in the population of the child population is quite high and reaches 0.5-1% (Mukhin K.Yu., Petrukhin A.S. Idiopathic forms of epilepsy: systematics, diagnosis, therapy. M: Art Business Center, 2000. p. 318). Moreover, in more than 20% of cases, resistance to anticonvulsant therapy is noted. The significance of the problem is determined by the potentially serious consequences of the disease: impaired psychomotor skills and higher cortical functions, which leads to social maladaptation. If therapy with anticonvulsants is ineffective, alternative approaches are used, among which the leading role is played by a ketogenic diet (CD). The effectiveness of its effect largely depends on the ability to achieve and maintain a certain level of ketone bodies in the blood, as a result of which the anticonvulsant activity increases.

Known is the generally accepted pharmacological method of treating epilepsy by using anticonvulsant drugs (Aicardi J. Epilepsy in Children. 3rd ed. Lippincott Williams & Wilkins, 2002, p. 487). In accordance with the form of the disease, the patient is prescribed antiepileptic drugs, starting with the first choice drugs. The dose is increased to the maximum recommended therapeutic under the control of the level of the drug in blood plasma. With the ineffectiveness of the drugs of the first choice, drugs of the second, third and subsequent selection from the standard and their combinations are prescribed. With the failure of traditional drugs, they add the latest drugs with a fundamentally different effect compared to the main antiepileptic drugs adopted by WHO. If the tried and tested combinations are ineffective or are accompanied by severe and not correctable side effects (allergic reactions, impaired functional state of the liver, kidneys, heart, thrombocytopenia, etc.), the disease is classified as pharmacoresistant. “Resistant” refers to epileptic diseases in which anticonvulsants in doses that do not cause unacceptable side effects and complications do not give results with respect to the cessation or satisfactory reduction in the number and severity of seizures and psycho-cognitive and / or communicative disorders directly caused by epilepsy ( Zenkov L.R. Pharmacoresistant epilepsies. M.: MEDpress; 2003, p. 208).

In the case of pharmacoresistance of epilepsy, a ketogenic diet (CD) with a high fat content, protein adequate for growth and development, and a sharp restriction of carbohydrates is simulated, which imitates the metabolism similar to a starvation condition and allows long-term maintenance of a high level of ketosis, which provides an anticonvulsant effect. The ratio in the diet of fats to the sum of proteins and carbohydrates can be from 3: 1 to 4: 1. The stability of the level of ketone bodies is achieved by a uniform distribution of food throughout the day, as a rule - in 4 equivalent doses.

It is known that the fastest way to achieve a state of ketosis is starvation until a clinically significant level of ketone bodies is reached. In the future, ketosis is supported by a ketogenic diet. (Bergqvist AG, Schall JI, Gallagher PR, Cnaan A, Stallings VA. (2005) Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy. Epilepsia; 2004; 46: 1810-1819).

The disadvantages of the method include the high incidence of complications associated with metabolic disorders due to a sharp switch of energy metabolism from carbohydrate to lipid: hypoglycemia, dehydration, increased concentration of anticonvulsants in the blood and the side effects caused by this, as well as the psycho-emotional difficulties of patients with a long hunger break pediatric profile.

There is also known a method of treating epilepsy using a ketogenic diet, in which the state of ketosis is achieved by the progressive introduction of a ketogenic diet into the diet without a previous hungry pause. (Kim DW, Kang NS, Park JC, Kim HD. Benefits of the nonfasting ketogenic diet compared with the initial fasting ketogenic diet. Pediatrics; 2004; 114: 1627-1630).

However, difficulties arise in achieving optimal ketonemia, a necessary condition for achieving a clinical effect. The method is accompanied by significant and prolonged fluctuations in the level of ketone bodies, and as a result of this is accompanied by a prolonged feeling of hunger, which negatively affects the well-being of patients. This, in turn, causes a violation of the discipline of treatment, up to the refusal to continue the diet.

As the closest analogue, a method has been adopted for the treatment of pharmacoresistant epilepsies by prescribing a ketogenic diet according to the protocol of the Johns Hopkins Hospital, which occupies a priority position in the world on this issue. (Freeman JM, Kelley MT, Freeman JB. (2000) The ketogenic diet: a treatment for epilepsy, 3-d ed. New York: Demos Medical Publishing; 2000; 236). The protocol provides for a phased introduction of the diet, starting with a hunger pause, during which urine ketones and blood glucose are monitored. The duration of fasting can reach 72 hours. When the level of ketones in urine reaches a therapeutic value of 12-16, a high-fat milk drink with a ratio of fat to total protein and carbohydrate ratio of 5 to 1 is included in the diet, the formulation of which includes 40% cream, gelatin, soft high-fat low-carb cheese and water. The drink is prescribed for 1-2 days in divided doses in three doses, starting from the amount that provides 1/4 of 1/3 of the daily calorie intake, and reaching 1/4 of 2/3 of the daily requirement. Using the drink allows you to stabilize the level of ketone bodies. Then the patient is transferred to the main ketogenic diet.

However, the known method has several significant disadvantages. The frequency of development of complications of CD in the form of hypoglycemia and dehydration with this method is quite high 40-45% and 27-30%, respectively. The reason is the lack of recommendations in the protocol that take into account the individual metabolic characteristics of patients that affect ketogenesis.

The authors aim to achieve the necessary levels of ketone bodies in the urine of 12-16 mmol / l already at the first stage of the diet - during the fasting period, which leads to the need for a long observance of a hungry pause - up to 72 hours, and therefore a significant number of side effects: hypoglycemia, dehydration, increased concentration of anticonvulsants, psychological difficulties.

In this case, the correlation of the level of ketone bodies in urine and glucose in the blood is not taken into account. It is known that in some cases, against the background of starvation, hypoglycemia in the body develops much faster than the accumulation of ketone bodies to a therapeutic concentration, reaching a critical threshold. Low blood glucose values are not an indication for a known method to stop fasting and move on to the next step. The authors recommend monitoring the concentration of glucose in the blood only for the timely diagnosis and subsequent correction of hypoglycemia against the background of achieving the required level of ketone bodies in the urine by introducing sources of carbohydrates (fruit juice, glucose solution) into the body.

Correction of the hypoglycemic state by taking drinks containing carbohydrates (fruit juice, glucose solutions) inhibits ketogenesis, prolongs the duration of a hungry pause and the transition to the next stage, which in turn increases the risk of hypoglycemia, thus forming a “vicious circle” .

The increase in the concentration of anticonvulsants against the background of dehydration is accompanied (depending on the features of the anticonvulsants used) by various complications: nausea, vomiting, bronchorrhea, hepatopathy, thrombocytopenia, neuropathy (sedation and doubtfulness), which in some cases may require interruption of treatment. Correction of anticonvulsant therapy by reducing the dose to prevent side effects at the initial stages is impractical, since in the future, when expanding the diet, against the background of a changing metabolism, a regular decrease in the concentration of anticonvulsants occurs, which as a result may decrease below therapeutic values and provoke epileptic seizures.

The emerging problems also have economic consequences in the form of an increase in the length of hospital stay.

Thus, from the point of view of the practice of treating pharmacoresistant epilepsy, the existing recommendations for a ketogenic diet cannot be unambiguously considered rational, since they do not take into account the individual metabolic risk factor for the patient and can contribute to early complications of diet therapy in the form of hypoglycemia, dehydration and an increase in the concentration of anticonvulsants, which in some cases can become an obstacle to continuing treatment.

In addition, the cocktail recipe is not adapted to general international standards, including the Russian product range, which does not allow its widespread use in clinical practice.

The objective of the invention is to provide a method for the treatment of pharmacoresistant epilepsy, which allows to achieve a persistent clinical effect and reduce the incidence of complications.

The essence of the invention lies in the fact that a method of treating pharmacoresistant epilepsy is characterized by the fact that they carry out diet therapy based on a ketogenic diet, the algorithm of which is formed on the basis of clinical studies and is carried out in stages under the control of blood glucose and ketone bodies in the urine, performing correction at all stages with taking into account the individual metabolic risk, the first stage includes a hunger pause of no more than a day, during which every 3 hours the glucose level is determined PS in the blood and ketone bodies in the urine and when the ketone body level is 8-10 mmol / l or blood glucose is lower than normal - 3.5 mmol / l, regardless of the level of ketone bodies, the hunger break is interrupted, in the second stage, aimed at achieving or fixing the therapeutic level of ketone bodies - 12-16 mmol / l, the patient takes a high-fat cocktail with a high ketogenic ratio of components during three days for three doses, after which, regardless of the level of the patient’s ketone bodies, they are transferred to the third stage, including an individual basic an ethogenic diet aimed at stabilizing or achieving a therapeutic level of ketone bodies, and if this level is not achieved in the first and second stages, 1-2 meals are replaced with a high-fat cocktail in the daily diet, and in the absence of ketonuria in this case, the basic diet is recalculated with correction its energy value.

Using the invention allows to obtain the following technical result.

A high and persistent clinical effect is achieved, which is expressed in a reduction of 1.5 times the most common complications of the initial period of CD - hypoglycemia and dehydration.

When using the method, the number of side effects associated with an increase in the concentration of anticonvulsants is halved.

The number of refusals from the diet in the first week of its use was reduced by 20%.

The economic effect is expressed in the timely discharge of children from the hospital under supervision at home. The length of hospital stay was reduced from 8.9 ± 2.4 to 6.8 ± 2.2.

The method has wide functionality. It can be used to treat all forms of epilepsy that are resistant to anticonvulsant therapy, as well as for specific metabolic disorders - impaired glucose transport type I, deficiency of the dehydrogenase complex, congenital deficiency of phosphofructokinase, etc. in different age groups.

The technical result is achieved due to the developed diet therapy algorithm, which provides for differentiated tactics of its management taking into account the individual metabolic risk factor, which is reflected in the dynamics of blood glucose and ketones in the urine in order to reduce the risk of side effects and achieve a stable and pronounced clinical effect, which allows sparing, gradual, not only due to starvation, achievement of a clinically significant level of ketone bodies, taking into account individual characteristics patient, with a detailed correction at all stages of the diet, thus minimizing the risk of hypoglycemia, dehydration, increasing the concentration of anticonvulsants - the most typical complications of the diet, reducing the psychological burden on the patient and his relatives. As a result, the number of cases of premature refusal of treatment is reduced.

Accounting at all stages of diet therapy as one of the criteria for the value of blood glucose allows you to make timely and individual corrections in the tactics of diet therapy, including the use of high-fat cocktail, the composition of which is adapted to wide clinical practice.

The method is as follows.

A child with an established pharmacoresistant course is given diet therapy. A follow-up protocol is preliminarily developed, which includes a preliminary examination of the child with an assessment of:

- somatic, nutritional and neurological status (with analysis of the frequency of seizures in the last month and the concentration of anticonvulsants in the blood);

- clinical and laboratory parameters: clinical blood and urine tests, biochemical blood tests (total protein, albumin, urea, creatinine, cholesterol, triglycerides, beta-lipoproteins, electrolytes, alkaline phosphatase, glucose, ALT, ACT, amylase), urine biochemical tests (protein, glucose, phosphorus, calcium, oxalates, uric acid, amino nitrogen, creatinine, titratable acids, sodium, potassium, chlorides, anticrystalline ability of urine), study of the vitamin-mineral profile;

- clinical and instrumental examination: electroencephalography, video-EEG monitoring with registration of clinical-EEG patterns of the patient’s seizures, electrocardiography, ultrasound of the heart, abdominal organs and kidneys.

After conducting studies in accordance with the developed protocol, the patient is prescribed diet therapy based on a ketogenic diet aimed at achieving ketosis. The diet is based on clinical studies and is carried out in stages under the control of blood glucose and ketone bodies in the urine, correcting at all stages, taking into account the individual metabolic risk of hypoglycemia.

An individual diet is developed for the patient. The patient is selected a set of products and a 7-day menu-layout with a card index of dishes in accordance with age, body weight, and eating habits. When calculating the energy value of the diet, the patient's motor activity is taken into account. It is advisable for children with motor disabilities to reduce the number of calories.

Treatment is carried out by phased administration against the background of basic therapy with anticonvulsants (with or without) a ketogenic diet.

The first stage (1st day of observation) includes a hunger pause of no more than a day, during which every 3 hours the level of glucose in the blood and ketones in the urine are determined. During fasting, the intake of liquids with zero calorie is allowed.

A hunger pause is interrupted when the blood glucose level drops below normal - less than 3.5 mmol / L, regardless of the level of ketone bodies or when the level of ketone bodies in the urine reaches 8-10 mmol / L.

After stopping the hunger pause in the second stage, aimed at achieving or fixing the therapeutic level of ketone bodies - 12-16 mmol / l, the patient takes a high-fat cocktail with a high ketogenic ratio of components, starting from 1/3 of the calculated amount, for three doses per day for three doses. calories, with a gradual increase to 1/2 and 3/4 calculated on the intake of energy value.

The basis of the cocktail is high-fat dairy products. The ratio of fats to the sum of proteins and carbohydrates in a cocktail is 5 to 1. The number of ingredients is selected empirically in order to optimize the consistency and taste. Due to the high ketogenic ratio, the cocktail allows you to fix or achieve the required level of ketones in the urine, without increasing the risk of hypoglycemia.

After that, regardless of the level of ketone bodies, the patient is transferred to the third stage, including an individual basic ketogenic diet, aimed at maintaining the level of ketone bodies in the body, which provides ketonuria at values of 12-16 mmol / l or reaching this level.

If it is impossible to achieve high and stable indicators of the level of ketone bodies during treatment in the first and second stages (in particular, with the early termination of a hungry pause due to hypoglycemia, or when the standard cocktail regimen did not allow reaching the required level of ketone bodies), at the third stage of diet therapy one or two meals are replaced with a high-fat cocktail.

If in this case there is no stabilization of the level of ketone bodies (ketonuria) within 3 days, the basic diet is recalculated with a correction of its energy value.

At all stages, the clinical and biochemical parameters provided by the protocol are monitored, including the determination of the concentration of anticonvulsants.

With good tolerance of the diet and stability of somatic and neurological parameters, the patient is discharged from the hospital with an appointment and instructions for maintaining CD at home.

At home, the use of CD is carried out under the control of the child's well-being, the number and nature of seizures, his actual nutrition (food diary), the level of ketones in urine and blood glucose, urine output.

The method was tested on 30 patients: 6 girls and 24 boys aged 2 to 18 years, suffering from various forms of epilepsy resistant to anticonvulsant therapy. The result was a decrease in the frequency of complications of the ketogenic diet in the form of hypoglycemia and an increase in the concentration of anticonvulsants in the blood by 1.5 times, which ultimately contributed to an increase in the effectiveness of diet therapy.

Example. Child Nikita K, born in 1995 (6.5 years old), lives in Moscow. From the age of 5, she has been observed at the Scientific and Practical Center about cryptogenic partial (frontal lobar) epilepsy with focal seizures with impaired consciousness, a delay in psycho-speech development. Concomitant pathology - Ellers syndrome - Danlo type II, mitral valve prolapse I.

From the anamnesis it is known that the boy from 1 pregnancy, which proceeded with the threat of termination of an urgent rapid birth throughout the term. Birth weight 3200, height 51 cm. During the neonatal period, motor stereotypes were noted - head tilting, head movements from side to side. Until 7 months of age, it developed without features, at 7 months - the first episode of febrile seizures lasting up to 1 min, in connection with which he began to receive phenobarbital. At 9 months of age - a repeated episode with loss of consciousness, general atony lasting up to 40 minutes. When conducting an EEG study, epileptiform activity was identified, benzonal therapy was prescribed. Up to 2 years of age, 6 febrile episodes were recorded, about which from 1 year 9 months. received benzonal and clonazepam. For the first time at the age of 2 years, 8 months. there were attacks of febrile provocation in the form of "fading" with the eyeballs rising upwards against the background of impaired consciousness - a hypomotor state for 10 minutes with intact reactivity, if the attack lasted more than 10 minutes, then clones in the hands were noted against the background of complete loss of consciousness. The use of various anticonvulsants and their combinations - benzonal and suxilep, depakin-chrono and defenin, finlepsin, carbamazepine, topamax in mono-and polytherapy was ineffective. Valproic acid preparations showed disparity disorders. From 3 years old, the attacks of “fading” became shorter, but the frequency increased up to 25 times a day. In addition, generalized seizures appeared with an inverse component, the development of post-attack paresis in the right extremities, the frequency of which progressed from 2 times a month to weekly by four years.

The child developed with a gross delay in psycho-speech development: babble words from 1 year old, since then there has been no significant development of speech. Started walking from 1 year 1 month. Physical development was age appropriate.

The disease was accompanied by a violation of behavior in the form of violent affective reactions, sleep, fixation on ideas, objects (machines, numbers), elements of autism, and difficulties in social adaptation. It was difficult to use in the treatment of methods of pedagogical and speech therapy correction.

Due to the lack of effect of drug therapy in April 2002, the child was admitted to the NPC for an alternative treatment, a ketogenic diet. The results of a preliminary examination of contraindications to the use of the method were not revealed. Diet therapy was coordinated with the ethics committee and relatives of the child.

For the period of taking under observation - the condition of the child of moderate severity for the underlying disease. Seizures daily after 0.5-1 hour after falling asleep or 1-2 hours before waking up for 1-2 minutes with a frequency of 1-2 times per night. When an attack occurs, it opens its eyes, eyeballs are brought up and to the right, with tonic tension and raising arms up and twitching in the muscles of the hands, tonic tension in the legs, clonies in the lower facial muscles on the right, clonic blinking, rapid and noisy breathing, rarely urination. Motor disinhibited, affective behavior. Expressive speech, single words, poor vocabulary, echolalia. In the neurological status of the FMN - total muscle hypotension, areflexia, single diffuse myoclonus, a positive symptom of Hvostek on both sides. Ataxia, most likely, frontal genesis.

Gets quadrotherapy with anticonvulsants: clonazepam 3 mg / day, lamictal 150 mg / day, benzonal 250 mg / day, suksilep 375 mg / day without proper effectiveness. With the cancellation of benzonal, “fading” became more frequent, with a decrease in the dose of clonazepam, generalized tonic-clonic convulsions resumed. Against the background of a decrease in the dose of lamictal, seizures appeared during sleep with the institution of eyeballs up and to the right and raising hands up of the above character.

Nutritional status is satisfactory. Appetite saved. Proper physique, adequate nutrition. Weight 22 kg, height 116 cm. Skin of normal color, hyperelastic. Hypermobility of the joints. Heart sounds are sonorous, rhythmic, in the apex and at the V point - systolic murmur. The abdomen is soft, sensitivity is determined during palpation at the projection points of the gallbladder and pancreas. Liver +1.5 cm, the edge is tightly elastic. Chair - daily, decorated. There are no dysuric phenomena.

During video EEG monitoring, seizures in the form of “fading” were recorded, accompanied by the appearance in the EEG of discharges of generalized epileptiform activity.

EEG: moderate diffuse changes with outbreaks of beta activity in the anterior regions and outbreaks of generalized bilateral synchronous delta activity with the inclusion of complexes of acute-slow wave in the left frontotemporal region.

Ultrasound of the abdominal cavity: cholestasis, metabolic changes in the kidneys.

ECG: sinus respiratory arrhythmia. The vertical position of the electrical axis of the heart. Conductivity disorders in the right leg of the bundle of His.

The results of biochemical studies of blood and urine are presented in tables 1 and 2. In clinical analyzes of blood and urine pathology was not detected.

Table 1 Dynamics of biochemical blood parameters against the background of diet therapy Originally In a year After 2 years Total protein g / l 75,4 74.6 72.8 Albumin g / l 39 40 38 Urea mol / L 2.8 2.5 2.66 Creatinine μmol / L 58 59 60.8 Uric acid mmol / L 250 290 262 Cholesterol mmol / L 2.7 5.3 5.3 Bilirubin μmol / L 11.5 9.8 9.6 Triglycerides mmol / L 0.6 1.12 1,11 AST Unit / L 23.3 46 58 ALT Unit / L 42,4 28 thirty Alpha amylase 73 70 62 Alkaline phosphatase Unit / L 430 480 564.8 K mmol / L 4.65 4,56 Na mmol / L 141.52 141.1 Cl mmol / L 106.6 101 Calcium total mmol / L 2.6 2,3 2.1 Calcium ionized mmol / L 1,2 1.10 1,04 Glucose mmol / L 3 3,5 3.8

table 2 Dynamics of biochemical parameters of urine in the background of diet therapy Originally In a year After 2 years Protein g / day 0.01 0.02 - Glucose mm / day - - - Phosphorus mg / kg / day 21 1.14 fifteen Calcium mg / kg / day 0.3 2.24 1.9 Oxalates mg / day 17.6 11.5 7.2 Amino nitrogen mg / day 0 72 - Cystine 0 0 0 Uric acid mg / day - 131.6 296 Creatinine mg / day 469 167.9 418 Titratable acids mm / day 19.5 14.3 eleven Ammonia mM / day 42 42.8 33 pH 6.9 - 6.5 Na meq / day 57 20.6 70 K meq / day 25 8.3 28 Chlorides mm / day 76 - 99

The ketogenic diet corresponded to the formula (ratio of fats to the sum of proteins and carbohydrates) 4: 1. The energy value of the diet was 1430 kcal, the amount of protein 19.8 g / day, carbohydrates 16 g / day, fat 143 g / day. Meals 4 equivalent meals for.

The one-day menu is presented in table 3.

Table 3 Sample menu Nikita K, 6 years old, 1430 kcal Name of products and dishes The mass of food and dishes (g) Breakfast Curd Agusha fifty Butter 27 Cream 35% 24 Carrot eighteen Dinner Cabbage soup from St. vegetarian cabbage 150 Sour cream "Valio" fifteen Boiled meat (beef) 12 Refined vegetable oil 24 Fresh cucumbers 35 High tea Fat kefir 93 Cheese "Russian" 10 Refined vegetable oil thirty Dinner Boiled pink salmon 13 Cauliflower 85 Butter 82.5% twenty Refined vegetable oil eighteen The chemical composition of each meal Proteins, g / day 19.8 Fats, g / day 16 Carbohydrates, g / day 143 Energy value, kcal / day 1430

At the first stage of diet therapy, including a hunger break, by the middle of the first day of fasting, the level of ketone bodies in the urine of 6-8 mmol / l was reached, sedation and doubt caused by an increase in the level of barbiturates in the blood increased. At the same time, a drop in glucose level to 3.2 mmol / l was noted, in connection with which the hungry pause was stopped and the child was transferred to the next stage.

At the second stage, the patient is prescribed a ketogenic high-fat cocktail in the amount of 1/3 of the recommended single amount of energy. The cocktail recipe includes high-fat cream, butter, gelatin and water, providing a ratio of fats to the amount of proteins and carbohydrates of 5 to 1.

The glucose level increased to 3.4 mmol / l, ketones in the urine increased to 10 mmol / l and at night the child again received a cocktail in an amount providing 1/2 of a single calorie intake. At 7.00 the next day, the level of ketone bodies is 8, blood glucose is 3.2 mmol / l. The child is offered a cocktail in the amount of 3/4 of the calculated energy value.

The child is transferred to the third stage of dieting. The boy is offered half a standard meal for lunch, and a full ketogenic meal for lunch. Against the background of the diet, the level of ketone bodies in the urine stabilized by the end of the second day at 12-15, glucose in the blood above 4 mol / L.

After the child adapted to the high-fat diet, observation continued at home with regular monitoring of the child's condition. Clinical efficacy in the form of cessation of seizures was achieved by the end of the first day of a hungry pause at a level of ketone bodies in the urine of 8 mmol / L. Subsequently, ketone vibrations in the range of 10-15 provided a therapeutic effect.

The cessation of seizures was accompanied by positive EEG shifts (a decrease in the severity of diffuse changes in the electrical activity of the brain with a decrease in the power of the main types of electrical activity in the delta and theta range and a decrease in spike activity).

By 6 months from the beginning of diet therapy, distinct changes in the cognitive sphere and speech development were achieved: the child's socialization improved, interest in games, watching TV, phrasal speech (separate phrases) appeared. All this allowed the boy to begin attending an auxiliary school. At the same time, motor disinhibition, restlessness, and periodic aggressiveness remained.

Indicators of physical development did not go beyond the limits of normal fluctuations. Against the background of CD, by the end of the second year of treatment it was possible to halve the number of anticonvulsants (lamictal and suxilep were canceled).

According to instrumental examination methods (ultrasound of the abdominal cavity and kidneys, ECG) and the results of clinical studies of blood and urine, no negative dynamics were noted.

In the biochemistry of blood against the background of the diet, there is a tendency to increase the level of cholesterol in the blood, in the biochemistry of urine there is an increase in crystalluria.

Satisfactory tolerance of the diet at 100% effectiveness in the frequency of seizures was the basis for its implementation for 3 years. During this period, the diet was repeatedly corrected taking into account changes in mass and growth indicators. For the first 2 years, the patient received a basic diet of 4 to 1, then the ketogenic ratio gradually decreased over the third year.

However, against the background of cancellation, with a decrease in the ketogenic ratio to 3 to 1, seizures resumed in the form of right-sided phacio-brachial clones lasting from 10-14 seconds to 5-10 minutes, which required correction of therapy. In June 2005, Topamax was introduced into the treatment regimen, followed by dosage adjustment. As a result, 100% control over seizures was again achieved, which remains to date with anticonvulsant therapy with Topamax 300 mg / day, benzonal 225 mg / day and clonazepam 2 mg / day (with a child weighing 38 kg).

Problems remain in psycho-speech development: frontal psyche (disinhibition, there is no sense of distance), phrasal speech, poor. Intelligence reduced. At the same time, the child continues to study at the auxiliary school. The quality of life of the family in the dynamics of observation has improved.

Claims (1)

A method for the treatment of pharmacoresistant epilepsy, including the administration of anticonvulsants and ketogenic diet therapy, characterized in that the ketogenic diet algorithm is carried out in stages under the control of blood glucose and ketone bodies in the urine, correcting at all stages taking into account individual metabolic risk, the first stage includes a hungry pause of no more than a day, during which every 3 hours determine the level of glucose in the blood and ketone bodies in the urine and when the level of ketones is reached x bodies of 8-10 mmol / l or a decrease in blood glucose below normal - 3.5 mmol / l, regardless of the level of ketone bodies, interrupt a hungry pause, at the second stage, a high-fat cocktail with a high ketogenic ratio of components is administered in three doses in a day, after this, regardless of the level of ketone bodies of the patient, is transferred to the third stage, which includes an individual basic ketogenic diet aimed at stabilizing or achieving a therapeutic level of ketone bodies, and if this level is not reached in the first and second stages x in the daily diet, replace 1-2 meals with a high-fat cocktail, and in the absence of ketonuria, in this case, the basic diet is also recalculated with a correction of its energy value.