RU2314817C2 - Method for treating children for neurological injuries - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method involves administering drug therapy with Famvir, Cortexin and Viferon. Cytomegalovirus infection or herpetic infection in maternal milk being available, infancy age babies receive drug therapy with Famvir at a dose of 0.25, one pill tree times a day at the first stage in a 7 days long course combined with Viferon-2 in rectal suppositories containing 500000 IU twice a week in 1 month long treatment course at the first stage. Famvir, Cortexin are used in drug therapy at the second stage. Famvir is administered in a 8-10 days long course. The child younger than 2 months and one aged from 2 months to 2 years is treated with Famvir at a dose of 20 mg/kg of body weight per day. The dose of 10-15 mg/kg of body weight is given to 2-11 years old children. The children elder than 11 years receive dose of 20-25 mg/kg of body weight per day. After having finished Famvir therapy, Cortexin is administered to children of any age at a dose of 5 mg/kg of body weight per day in the amount of 5-10 intramuscular injections.

EFFECT: enhanced effectiveness in reducing static and motor speech functions disorders and motor and emotional disorders.

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Description

The invention relates to pediatrics and neurology and can be used to prevent the formation of neurological damage in children infected with cytomegalovirus, using therapeutic health-saving technologies and neurosonographic monitoring.

Treatment of children, especially children of the first year of life, infected in utero, is a very difficult and largely unresolved task.

Usually, neuroprotective, vasoactive, and metabolic drugs are used to treat neurological damage in children in their first year of life.

The use of the drug elkar in children with perinatal lesions of the central nervous system is known (J. Russian Bulletin of Perinatology and Pediatrics, vol. 50, 2005, No. 3, p. 36-41).

It is known to use ganciclovir, which is administered intravenously in a single dose of 5 mg / kg body weight for at least 1 hour, every 12 hours, in a course of 14-21 days ("CMVI as a problem of perinatal pathology ..." in J. "Russian Bulletin perinatology and pediatrics ”, t.48, 2003, No. 5, p.52-56).

It is known to use human immunoglobulin intravenously 3 ml every other day, 3-4 infusions (ibid.).

It is known to use tactivin 0.01% subcutaneously 2 μg per 1 kg of body weight 1 time per day, 9 injections according to the scheme (ibid.).

The use of viferon rectally in suppositories is known to be 150,000 ME 2 times a day (ibid.).

The considered source of information is considered as a prototype.

It is also known the use of such nootropic drugs as piracetam, pantogam, vasoactive drugs such as cavinton cinnarizine.

Known use in the complex treatment of neurological damage to complex therapy in combination with physiotherapy using drug electrophoresis and massage.

The disadvantages of the known methods of treating neurological damage to young children include

- ganciclovir is highly toxic. It has a pronounced myelosuppressive effect with the development of leukopenia and thrombocytopenia;

- Immunoglobulin preparations are contraindicated in patients with hypersensitivity to human immunoglobulin.

The objective of the proposed method is to increase the therapeutic effect by ensuring the cessation of productive viral replication and excretion, transferring the infection to the latency stage, and controlling the body's immune system to prevent the activation of infection.

To this end, a method for the treatment of neurological damage in children with diagnosed cytomegalovirus (CMV) or herpetic infection is proposed, including drug therapy, characterized in that famvir, cortexin and viferon are used as drug therapy, and for infants with CMV or herpetic infection in the mother’s milk at the first stage, they carry out drug therapy of the mother with famvir 0.25, one tablet three times a day, a course of 7 days in combination with viferon-2 in suppositories 500,000 ME rectally, d one time a week, a course of one month, and at the second stage, drug treatment is given to the child with famvir and cortexin, and famvir is prescribed in the course of 8-10 days, while a child aged up to two months and from two months to two years is prescribed 0.25 a dose of 20 mg / kg body weight per day, a child aged two to twelve years old - 10-15 mg / kg body weight per day, a child older than twelve years of age - 20-25 mg / kg body weight per day, after treatment with famvir to all children prescribe cortexin at a dose of 5 mg / kg body weight from 5 to 10 injections intramuscularly.

An analysis of neuropsychiatric disorders in children with CMV infection reveals:

high incidence of hypertension-hydrocephalic syndrome - 78%;

tremor of the chin and upper limbs - 70%.

Revealed:

the formation of affective and respiratory paraxisms - 20%;

polyfemorphic convulsions - 24%;

cranial nerve neuropathies - 64%;

hypomotor type of behavior - 44%;

delayed speech development - 60%;

mental retardation - 24%;

dissomnia - 60%;

meteorological dependence - 87%;

emotional lability - 70%;

hysteroid reactions and aggressiveness - 11%;

negativity - 17%;

violation of eating behavior - 28%;

autism - 7%.

The indicated percentages were taken on the basis of 100% of the examined patients.

At the Academic Medical Center “Family and Healthy Generation” (Yekaterinburg), 48 couples were observed in the “mother-child” system with CMVI.

Age of children: from 2 weeks to 14 months.

The first group (n = 66) included patients with indication of CMVI DNA in milk; in the second group (n = 30) - patients with the absence of CMVI DNA in milk; in the third group (n = 20) - healthy children.

It was revealed that patients from the first group more often form neuropsychic disorders in comparison with patients from the third group.

Table 1 gives a comparative description of neurosonographic changes in children with CMVI who are breastfed (with the excretion of DNA of herpes viruses in breast milk,%).

Table 1 Neurosonographic symptoms Milk PCR + n = 27 Milk PCR-n = 25 Control group n = 20 P1 P2 RZ Hemispheric expansion 63 56 10 <0.001 <0.001 > 0.05 Bone Marrow Diastasis 67 45 5 <0.001 <0.001 > 0.05 Vascular pulsation enhancement 67 24 5 <0.001 > 0.05 0.001 Transparent partition cavity 24 four 0 <0.002 > 0.05 > 0.05 Periventricular ischemia 33 17 0 <0.001 > 0.05 > 0.05 Periventricular Leukomalacia 44 twenty 0 <0.001 <0.02 > 0.05 Subependymal cysts 44 36 5 <0.001 <0.01 > 0.05 Plexus cysts 67 56 5 <0.001 <0.001 > 0.05 Dilation of the anterior horns of the lateral ventricles 44 36 0 <0.001 <0.001 > 0.05 Dilation of the posterior horns of the lateral ventricles 48 eighteen 0 <0.001 > 0.05 0.02 Asymmetric ventricular dilatation 37 eighteen 0 <0.001 > 0.05 > 0.05 Ventricular dilatation 56 48 0 <0.001 <0.001 > 0.05 Hyperechoic zones in the thalamus, “calcifications” 56 52 0 <0.001 <0.001 > 0.05 "Chords" in the lateral ventricles of the brain 7 0 0 > 0.05 > 0.05 > 0.05 Note. Groups of children are compared: P1 - receiving PCR + milk with a control group; P2 - receiving PCR-milk with a control group; P3-receiving PCR + and PCR- breast milk.

Table 2 shows the formation of statomotor functions in breast-feeding children with indication of herpes virus DNA.

table 2 Statomotor functions in children from 1 month to 1 year Milk Control group healthy children n = 20 P1 P2 P3 PCR + n = 44 GWH-n = 42 Holds his head M = 3.93 M = 3.01 M = 2.25 > 0.05 > 0.05 > 0.05 m ± 0.52 m ± 0.28 M ± 0.25 Sits down M = 9.42 M = 8.32 M = 6.58 <0.01 > 0.05 > 0.05 m ± 0.65 m ± 0.45 M ± 0.39 Rises M = 10.94 M = 10.05 M = 7.68 <0.001 <0.01 > 0.05 m ± 0.61 m ± 0.58 M ± 0.41 Walks M = 13.89 M = 12.31 M = 10.87 <0.001 <0.05 <0.05 m ± 0.62 m ± 0.52 M ± 0.38 Note. Groups were compared among themselves: P1 - children receiving PCR positive breast milk, and a control group; P2 - children receiving PCR negative breast milk, and a control group; P3 - children receiving PCR positive and PCR negative mother's breast milk.

Table 3 shows a comparison of the formation of speech functions in children with CMVI who are breast-fed (with the excretion of viruses in breast milk), (M + m).

Table 3 Stages of pre-speech development, month Milk Control group n = 20 P1 P2 P3 PCR + n = 44 GWH-n = 42 Walk M = 4.92 m ± 0.58 M = 3.62 m ± 0.34 M-2.03 M ± 0.24 <0.001 <0.01 > 0.05 Babbling M = 6.47 m ± 0.43 M = 5.86 m ± 0.38 M = 4.07 M ± 0.26 <0.001 <0.01 > 0.05 Pronounces syllables M = 10.81 t ± 0.27 M = 9.61 m ± 0.34 M = 7.02 M ± 0.24 <0.001 <0.05 <0.05 First words M-14.02 m ± 0.54 M = 12.65 m ± 0, b5 M = 9.42 M ± 0.53 <0.001 <0.01 > 0.05 Note. Groups were compared among themselves: P1 - children receiving PCR positive milk, and a control group; P2 - children receiving PCR negative milk, and a control group; P3 - children receiving PCR positive and PCR negative milk.

Table 4 shows the pathomorphism of neuropsychiatric disorders in children with herpes virus infection,%.

Table 5 gives a comparative description of statomotor functions in children with herpetic infection who received antiviral therapy (M ± m).

Table 5 Motor functions Received n / 35 viral treatment P / viral treatment not performed n = 77 Control group n = 20 P1 P2 P3 Holds his head M = 2.98 m ± 0.32 M = 4.01 m ± 0.05 M = 2.25 m ± 0.25 > 0.05 <0.001 <0.01 Sits down M = 7.25 M ± 0.43 M = 9.02 M ± 0.61 M = 6.58 M ± 0.39 > 0.05 <0.01 <0.05 Rises M = 9.03 M ± 0.31 M = 11.1 M ± 0.54 M = 7.68 M ± 0.41 <0.05 <0.001 <0.01 Walks M = 12.08 M ± 1.02 M = 15.4 M ± 1.21 M = 10.87 M ± 0.38 > 0.05 <0.01 <0.05 Note. Groups of children with congenital herpes virus infection were compared: P1 - received antiviral treatment with a control group; P2 - did not receive antiviral treatment with a control group; P3 - children with and without antiviral treatment.

The main group consists of patients with congenital herpes-viral mixed infection who received antiviral treatment with famvir (n = 35), in the other study group, patients underwent only traditional therapy, including a wide range of medications with nootropic and vasoactive effects, as well as physiotherapeutic methods using drug electrophoresis and massage (n = 77). Groups of patients who received antiviral and conventional therapy are compared with healthy children (n = 20).

The formation of rectifying and statokinetic reactions in children with congenital CMV and herpetic infections who have not received etiotropic treatment is formed reliably later in comparison with healthy children. Indicators of static-kinetic functions in children with herpes infection who received antiviral therapy with famvir in the first months of life did not significantly differ from the standards for healthy children.

In patients with congenital herpes virus infection who have not received etiotropic treatment, a lag in the skills of independently holding their heads, sitting down, getting up and walking is recorded. At the age of one year, the static-motor functions in patients of the study group against the background of basic therapy are 3 months late (p <0.05) from children who received antiviral therapy, and more than 4 months (p <0.01) compared with healthy peers.

The development of rectifying and kinetic reactions against the background of antiviral therapy in patients of the study group was compensated, there were no significant differences with the control group, the ability to stand up alone on a support was delayed by an average of one epicrisis period (p <0.05).

Table 6 gives a comparative description of speech development in children with herpes infection who received antiviral therapy (M ± m).

Table 6 Speech Functions Received p / viral treatment n = 35 P / viral treatment not performed n = 77 Control group n = 20 P1 P2 P3 Gulit M = 3.01 m ± 0.42 M = 4.1 m ± 0.62 M = 2.33 m ± 0.44 > 0.05 0.05 > 0.05 Babbling M = 5.22 m ± 0.31 M = 6.83 m ± 0.48 M = 4.87 m ± 0.26 > 0.05 <0.01 <0.05 Pronounces syllables M = 10.04 m ± 0.37 M = 12.25 m ± 0.42 M = 7.02 m ± 0.24 <0.001 <0.001 <0.001 Pronounces words M = 14.57 m ± 1.04 M = 22.21 m ± 1.05 M = 79.42 m ± 0.53 > 0.001 <0.001 <0.001 Note. Groups of children with congenital herpes virus infection were compared: P1 - received antiviral treatment with a control group; P2 - did not receive antiviral treatment with a control group; P3 - children with and without antiviral treatment.

In comparison, the stages of the formation of speech functions were analyzed in a group of subjects who received antiviral therapy and patients who did not receive etiotropic treatment with a control group. Conducting antiviral therapy in the early stages of the postnatal period contributes to the timely establishment of the stages of pre-speech development. In the group of patients treated with famvir, the reproduction of gulenia and babble is half an epicrisis period; no significant differences with healthy patients were detected.

Patients who received only traditional metabolic therapy at the recovery stage of treatment reliably later begin to walk (p <0.05) - for one epicrisis period. They are treated with a delay of two epicrisis periods in comparison with healthy children (p <0.01) and patients treated with famvir in a timely manner (p <0.05).

The process of formation of syllabic speech and comprehension of words progressively worsens in children with cytomegalovirus and herpetic infections.

In the group of herpetic infected children without antiviral therapy, during traditional treatment, there is an increasing lag in the formation of speech functions.

Patients of this group are roughly behind in psycho-speech development, the first syllables are pronounced after a year, which significantly distinguishes their development by 2 months from children treated with famvir (p <0.001), and by 5 months from patients without markers of infection (p <0.001) .

Maturation of higher cortical functions in children with congenital herpes infection occurs much later. The neurological "deficit" in the subjects who did not receive antiviral treatment is more pronounced in the temporal aspect of the formation of speech functions.

Children with herpetic infection, not treated with famvir, pronounce their first conscious words by the age of two years, being more than a year late in comparison with the speech functions of healthy children (p <0.001) and seven months compared with patients who received antiviral therapy with famvir (p < 0.001).

A comparative analysis of the research results confirms the neurotropic effect of DNA viruses, the progredity of neurological symptoms in children with herpes virus infection in the form of an increasing variety of neurological symptoms and an increase in the timing of static-motor and speech development.

The studies confirm the effectiveness of antiviral therapy with famvir in comparison with traditional neurological correction in the studied group of children.

The greatest clinical effect was found during combination therapy with antiviral drugs famvir and the aminopeptide regulator cortexin to reduce the number of patients with neurological disorders, and in some cases a complete recovery of the central nervous system was achieved.

Conducting antiviral therapy contributed to the restoration of neurological status in every second child by leveling hypertension-hydrocephalic syndrome, polymorphic seizures, hypermotor behavior, delayed speech and mental movements and hysteroid reactions.

In treated patients, symptoms in the form of tremor, affective respiratory paroxysms, neuropathy of the cranial nerves, inhibited behavior, meteorological dependence, autism are recorded 4-5 times less often.

Significant differences in motor functions in children with herpes infection who received antiviral therapy, compared with healthy children, were revealed by the syndrome of muscular dystonia (p <0.05). In 33% of children after treatment with famvir, the difference in muscle tone of the limbs remains; the use of combination therapy with famvir and cortexin most effectively levels muscle dystonia (15%).

Manifestations of extrapyramidal syndrome, characterized by a “gear wheel” symptom, tremor of the chin and extremities, athetoid and chaotic movements, decrease after treatment with famvir from 83 to 15%.

Combination therapy in combination with famvir and cortexin allows to achieve leveling of disabling motor disorders in the form of paresis, extrapyramidal hypertonicity.

Myatonic syndrome and pyramidal insufficiency persist in more than a third of patients treated with famvir; after combination therapy with famvir and cortexin, the number of patients with these disorders in neurological status decreased to 28%, in the control group - in 20% of children. The delay in the formation of statomotor functions in children decreased after treatment with famvir from 72 to 33%. Combination therapy with cortexin contributed to the restoration of statomotor functions in a larger number of patients; in 20% of children, static and motor dysfunctions persist.

Thus, the data obtained indicate the effectiveness of combination therapy. The use of famvir, which suppresses virus replication in the tissues and organs of the nervous system, in combination with the aminopeptide drug, cortexin, which has neuroimmunotropic regulation, helps restore motor functions in children with herpes infection (types I, II, V).

Table 7 gives a comparative description of neuropsychic disorders in children treated with famvir in combination with cortexin,%.

A comparative analysis of the neuropsychic status of children with herpes infection who received monotherapy with famvir and in combination with cortexin confirms the effectiveness of the etiotropic treatment with the antiviral drug famvir in combination with cortexin, a nootropic aminopeptide, immunomodulating and reparative action.

The highest efficacy of combined therapy was achieved by leveling affective-respiratory paroxysms, chin tremor and limb paresis. In the study group, symptoms after treatment are not recorded.

The use of famvir monotherapy in combination with cortexin restores the communicative functions in children, helps level out autistic forms of behavior.

Using the comprehensive method of antiviral and nootropic effects significantly improves the condition of patients, halving the number of patients in the study group with polymorphic epiparoxism from 11 to 5%; negativity in behavioral reactions from 10 to 5%; cranial nerve neuropathy from 20 to 10%; with a delay in speech development from 33 to 15%. The lag in the formation of higher mental functions in children decreased from 15 to 10% after combination therapy.

Manifestations of attention deficit disorder in the form of hypermotor behavior (15%), hyperkinetic symptom, obsessive movements 15%, (p <0.05); increased emotional lability (20%); meteorological dependence (25%) and parasomic dysfunctions 28%, (p <0.02) in children of the study group significantly decreased during combination therapy.

Significant differences in the relief of hypertension-hydrocephalic syndrome, a hypodynamic form of behavior, a change in the motivation of eating behavior; hystericality and aggressiveness were not obtained in children with herpetic infection when using complex therapy in comparison with famvir monotherapy.

An analysis of neuropsychic monitoring in children with CMVI and herpetic infections, in comparison with famvir and in combination with cortexin, proves the effectiveness of combination therapy with famvir and cortexin.

Table 8 gives a comparative description of motor functions in children during treatment with famvir in combination with cortexin,%.

Table 8 Syndromes No antiviral therapy n = 35 Antiviral therapy n = 27 Antiviral therapy + cortexin n = 25 Control group n = 20 P1 P2 P3 P4 Myatonic 72 43 28 twenty <0.001 > 0.05 > 0.05 > 0.05 Pyramidal insufficiency 83 33 28 twenty <0.001 > 0.05 > 0.05 > 0.05 Paresis of limbs 33 5 0 0 <0.001 > 0.05 > 0.05 > 0.05 Muscular dystonia 72 33 fifteen 10 <0.001 <0.05 > 0.05 > 0.05 Extrapyramidal 83 fifteen 0 5 <0.001 > 0.05 > 0.05 <0.05 Registration of statomotor functions 72 33 twenty fifteen <0.001 > 0.05 > 0.05 > 0.05 Note. Groups of children are compared: P1 - children who did not receive antiviral therapy, with a control group; P2 - antiviral therapy with a control group; P3 - antiviral therapy and cortexin with a control group; P4 - antiviral therapy with combination therapy.

The use of antiviral therapy in infants and young children made it possible to eliminate the lag of static-motor functions, halve motor impairment and reduce the formation of limb paresis by six times, and reduce the delay in the formation of expressive speech by half.

Claims (1)

A method of treating neurological damage in children with diagnosed cytomegalovirus (CMV) or herpetic infection, including drug therapy, characterized in that famvir, cortexin and viferon are used as drug therapy, and for infants with CMV or herpetic infection in mother’s milk the first stage, mother's drug therapy is performed with famvir 0.25, one tablet three times a day, 7 days in combination with viferon-2 in suppositories 500,000 ME rectally, twice a week, with a course of in a month, and at the second stage, drug treatment is given to the child with famvir and cortexin, and famvir is prescribed in a course of 8-10 days, while a child aged up to two months and from two months to two years is prescribed 0.25 mg / kg of weight body per day, a child aged two to twelve years old - 10-15 mg / kg body weight per day, a child older than twelve years of age - 20-25 mg / kg body weight per day, after treatment with famvir all children are prescribed cortexin in a dose of 5 mg / kg body weight from 5 to 10 injections intramuscularly.