RU2481786C1 - Method of predicting risk of neurological complications in case of chicken pox in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to neuroinfections. Assessment of anamnesis data, virological indices, fever reaction and spotty-papular rash appearance is carried out. EEG is additionally registered in the first three days from the moment of admission, leukocyte index of intoxication, presence of mixed hypervirus infection are determined. If hypoxy-ischemic affection of central nervous system, spotty-papular rash on the body from the first day of disease with its "additional appearance" during 5-7 days, fever to 39-40°C during first 3-5 days are present in child's anamnesis, reduction of index of main physiological rhythm less than 30%, increased paroxysmal activity in form of diffuse sharp waves and flashes of slow activity with amplitude more than 100 mcV during 3 days or at least on one of these days are detected on EEG, value of leukocyte index is 0.2-3 conv.units, mixed hyperviruses together with varicella zoster virus, virus of type 6 herpes and/or type I herpes simplex virus are detected, risk of neurological complications is predicted.

EFFECT: method makes it possible to increase reliability of predicting risk of neurological complications in case of chicken pox in children.

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Description

The invention relates to medicine, namely to neuroinfections, and can be used to predict the risk of neurological complications of chickenpox (VO) in children.

Chickenpox is an acute infectious disease caused by a DNA-containing virus from the Herpesviridae family - varicella zoster virus (VZV), transmitted by airborne droplets, characterized by fever, moderate intoxication and a widespread rash. By 10-14 years, almost all children acquire immunity to the VO virus.

The incidence of VO has a steady upward trend. According to the annual statistics for 2010, we can talk about the epidemic of HE both in the Russian Federation (2010 - 475.5 cases per 100,000 population) and in St. Petersburg (among children under 14 years old - 4709.7 per 100,000 children) , and in the Leningrad Region (among children under 17 years old - 3,551.0 per 100,000 children of the corresponding age). The frequency of VO in the structure of the total infectious morbidity for the analyzed period amounted to 1.6-2.8% (7000-9500 cases per year), and the share of children, of the total number of patients with VO, accounts for 94-95%. From 5 to 6% annually among patients with HE are adults. An increase in the incidence of VO is accompanied by an increase in the frequency of the severe course of the disease, requiring hospitalization of the patient. It is known that the main place in the pathogenesis of VO is the infectious and inflammatory process, in which, due to the pathology of the pathogen to the nervous tissue, the nervous system is involved. The epidemic increase in the incidence of VO has determined the widespread increase in neurological complications.

The frequency of neurological complications in VO ranges from 60-65% of cases. Neurological complications develop more often in children from 4 to 6 years. According to NIIDI (2009), it was found that the most common neurological complication of chickenpox was encephalitis syndrome (83.6%), syndromes of facial neuropathy (5.5%), serous meningitis (5.5%), and polyradiculoneuritis were less common 4.1%), subarachnoid hemorrhage (1 case out of 73). With HE, the development of spinal cord lesions in the form of transverse myelitis syndrome is possible. Acute cerebellitis most often develops in children aged 2 to 5 years.

The most severe consequences of neurological complications in VO cause particular concern for clinicians, which is why the prediction of severe neurological complications is relevant, especially in the acute phase of the disease, when it is possible to prevent an unfavorable outcome of the disease by correcting etiotropic and immunomodulating therapy.

Known methods for predicting the development of neurological complications [Chernova TM, Timchenko VN Chickenpox (lecture) // Materials of the conference "Old" and "new" infections in children in modern conditions "- St. Petersburg: Publishing house" ArtEgo ", 2011. - p.335-341], [Sorokina M.N. , Skripchenko N.V. Viral Encephalitis and Meningitis in Children: A Guide for Physicians. - M .: OJSC "Publishing house" Medicine ", 2004. - p.193]. Symptoms may occur from the first days of the rash, lethargy, headache, nausea, more often against the background of fever, 2-11 days from the onset of the disease or 3-8 days after the onset of rashes are significant for diagnosing the development of neurological complications (during these periods as a rule, a clinic of damage to the nervous system appears). Damage to the central nervous system, manifested by acute cerebellar ataxia and symptoms of irritation of the meninges, is diagnosed approximately 21 days after the appearance of the rash. With the development of convulsive syndrome in children for the purpose of differential diagnosis with epilepsy, a study of the bioelectric activity of the brain was carried out using electroencephalography (EEG). The prognosis for chickenpox encephalitis, especially with the cerebellar form, is usually favorable - complete recovery. With cerebral form, there may be residual consequences in the form of epilepsy, pyramidal and extrapyramidal disorders (15%). Mortality in encephalitis reaches 10%.

Methods are also known with an attempt to predict the course of the disease. [Infectious Diseases in Children: Textbook / Ed. V.V. Ivanova. M .: Medical Information Agency LLC, 2002. - p.224, Infectious Diseases: Textbook / Ed. Corr. RAMP MD, prof. V.V. Ivanova. - St. Petersburg: MIA Publishing House LLC, 2009. - p.312, Guidelines for infectious diseases in children. Ed. Corr. Academy of Medical Sciences of the USSR prof. S.D. Nosova. - M .: "Medicine", 1980. - p.238-240]. The prognosis for uncomplicated course, as a rule, is favorable - recovery occurs within 10-14 days. Fatal outcomes are observed only with the development of severe complications and in individuals with impaired immunity. Neurological complications are observed in debilitated patients and in the presence of concomitant diseases. They are characterized by a general vascular lesion of the central nervous system and are manifested by the following symptoms: headache, vomiting, anxiety, convulsions and severe disorders of consciousness. The prognosis is significantly worse than with brain damage (chickenpox encephalitis). Well-known sources provide data on the epidemiology, clinical picture and diagnosis of the infectious process. The methods are descriptive in nature and do not provide accurate prediction of the development of severe neurological complications of chickenpox in children, including a high risk of their manifestation

Closest to the proposed invention is a method for predicting the development of complications in HE by the presence of immunodeficiencies in the patient (both primary and secondary), the severity of the onset of the disease (fever up to 38.5 ° C and the appearance of a spotty-papular rash, new elements of which appear in jerks with an interval of 24-48 hours), data of virological diagnostics, which allows confirming the etiology of the disease (detect VZV by polymerase chain reaction - PCR or enzyme-linked immunosorbent assay - ELISA) [Infectious diseases: Uch Ebnik / Ed. Corr. RAMS doctor of medical sciences, prof. V.V. Ivanova. - St. Petersburg: LLC "Publishing House FOLIANT", 2002. - p.224].

However, this method has several disadvantages, as described above, is descriptive, because There are no clear time and other parameters. An increase in temperature to 38.5 ° C is not a criterion for predicting the development of NO, since HE is characterized by a significant increase in temperature. Neurological complications of VO in children, as a rule, are ascertained by clinical symptoms, which significantly prolongs the duration of therapy and the patient’s hospital stay. The method does not provide forecast accuracy.

The technical result of the present invention is to increase accuracy by evaluating quantitative parameters in the acute period of the disease.

This result is achieved by the fact that in the known method, including the assessment of anamnestic data, virological parameters, febrile reaction and rash of a maculopapular rash, according to the invention, the child additionally records the EEG in the first 3 days from the moment of admission, determines the leukocyte intoxication index, the presence of mixed herpes virus infection and in the presence of a child’s history of hypoxic-ischemic damage to the central nervous system, maculopapular rash in all parts of the body from the first day of height drinking with “pouring” it for 5-7 days, fever 39 ° -40 ° C for the first 3-5 days, if the EEG has a decrease in the index of the main physiological rhythm of less than 30%, increased paroxysmal activity in the form of diffuse acute waves and outbreaks of slow activity with an amplitude of more than 100 μV for 3 days, or at least on one of these days, the leukocyte index is in the range of 0.2-3 cu, detection of mixed herpes viruses along with varicella zoster virus (VZV) herpes simplex virus type 6 (VH 6) and / or herpes simplex virus type 1 (VH 1) predict high cue risk of neurological complications.

Having been professionally involved in the treatment of VO in children for many years, we often noted the occurrence of severe neurological complications. While registering various parameters (complex, clinical, laboratory, and others), we found those that were associated with a high risk of severe neurology, including death.

This has prompted us over the past 2 years to carefully monitor such indicators and evaluate their time parameters, to which we referred them, indicated by us in the distinctive part of the claims, the combination of which, in our opinion, is necessary and sufficient to predict a high risk of occurrence neurological complications.

So we noted the prognostic significance of the anamnestic data - the premorbid background of the child, namely, the presence of a hypoxic-ischemic lesion of the central nervous system (HIP of the central nervous system) in the perinatal period, showed that the blood-brain barrier and cortical neurons are damaged as a result of hypoxia and ischemia, which is a predictor development of the complicated course of the infectious process in patients with chickenpox. It was also established that it is precisely these children that are most likely to develop autoimmune processes. So, in 62% of cases (34 out of 55 children) who were admitted to the hospital with a diagnosis of VO and subsequently had a clinic of damage to the nervous system, they were registered at the neurologist with a diagnosis of central nervous system hypertension.

We also found that the most unfavorable in terms of the prognosis of neurological complications in HE in children with a hypoxic-ischemic genesis in the central nervous system lesion is the detection of a decrease in the basic physiological rhythm index of less than 30% in the electroencephalogram (EEG), increased paroxysmal activity in the form of diffuse acute waves and flashes of slow activity with an amplitude of more than 100 μV for 3 days from the date of receipt, or at least one of these days. It is proved that the detected changes on the EEG indicate marked violations of the bioelectrical activity of the brain and are prognostically significant criteria. We have shown that in order to detect such changes in the EEG, daily registration is required for 3 days or at least one of these days. This, as a rule, indicates a high risk of subsequent neurological complications. We found empirical indicators of a decrease in the index of the basic physiological rhythm of less than 30% and increased paroxysmal activity in the form of diffuse sharp waves and flashes of slow activity with an amplitude of more than 100 μV.

We have discovered and proved the high prognostic value of a complex indicator of the functional activity of blood cells. It was found that a decrease in the compensatory-functional activity in relation to the detoxification activity of blood cells causes an increase in the pathogenicity factors of herpes viruses in the blood, their penetration through the blood-brain barrier and affects the functional activity of the brain, leading to a disturbance in rhythm. We found that the LII index is in the range of 0.2-3 cu reflects the barrier function of blood. The index parameters in these limits during the period of maximum viremia indicate tolerance, i.e. decreased functional activity of blood cells in relation to pathogenicity factors of viruses. It was shown that in 67% of patients with neurological complications in VO, the values of LII were in the range of 0.2–3 conventional units, which was regarded as the presence of a defect in the immune system in these patients.

The authors found that mixed herpes viruses, having lymphotropicity, in particular, to T and B lymphocytes, cause suppression of immunocompetent cells, and this is a factor aggravating the development of the infection process in VO.

We found that with VO complicated by involvement of the nervous system in the pathological process, ELISA detects antibodies to both VZV and in combination with antibodies to other herpes viruses (type 6 HS and / or type 1 HSV).

We noted that in children with VO who had a maculopapular rash from the first day of the disease with subsequent “pouring” within 5-7 days, the immune system was unable to quickly localize and stop the infection process. This played a significant role in predicting neurological complications. In children with VO who had neurological complications, in 61.7% of cases from the first day of the disease, a maculopapular rash was observed with "rash" for 5-7 days.

Hyperthermia up to 39-40 ° C for 3-5 days indicates the central genesis of fever associated with damage to the central thermoregulatory organs located in the diencephalic region of the hypothalamus, which is also a prognostically significant indicator.

This method is as follows.

During the initial clinical and neurological examination of a child with VO in the infectious boxing department of the hospital, he assesses the presence of a hypoxic-ischemic lesion of the central nervous system (CNS central nervous system) in the perinatal period. Hypoxia and ischemia in the perinatal period lead to the destruction of the glial and neuronal components of the brain, which affects its bioelectric activity. To establish the depth of damage to the structures of the brain, it is necessary to conduct an electroencephalographic study. The presence on the EEG of a decrease in the index of the basic physiological rhythm of less than 30%, increased paroxysmal activity in the form of diffuse sharp waves and flashes of slow activity with an amplitude of more than 100 μV for 3 days, at least on one of these days, indicate an unfavorable morphological background for development severe neurological complications in VO. High fever numbers (39-40 ° C) for 3-5 days also indicate perinatal damage to the central structures of thermoregulation as a result of hypoxia and ischemia. However, these parameters are insufficient to predict the risk of neurological complications. The immunological reactivity of the organism is also evaluated. So, the presence of a maculopapular rash from the first day of the disease with rash within 5-7 days indicates a defect in the patient’s immune system and proves that the child’s body is not able to adequately respond to massive viremia. At the same stage of forecasting, it is recommended to calculate LII. The values of the index within 0.2-3 srvc. units indicate a low functional activity of blood cells against viruses, which is a prognostic factor in the development of neurological complications in VO. The combination of the above conditions significantly increases the possibility of predicting the risk of developing neurological complications in HE, however, for a 100% prognosis, it is necessary to detect in the blood of children, along with VZV mixed herpes viruses, type 6 HS and / or type 1 HSV, each of which is a powerful immunosuppressor, and when mixed, they lead to an immunological disruption of the immune cells of the body. Thus, only a comprehensive assessment of anamnestic, clinical and laboratory criteria, their time parameters, the combination of which, in our opinion, is necessary and sufficient to predict a high risk of neurological complications.

We developed a method for predicting neurological complications of VO in children was tested in 55 children aged 1 month to 17 years, who were admitted to the hospital for different periods of the disease.

A method for predicting the risk of neurological complications of VO in children can be confirmed by the following examples:

Example No. 1. Patient S., 5 years old, was admitted to the clinic NIIDI on the 3rd day of illness, with a diagnosis of VO, moderate form. Case history No. 42895.

From the anamnesis of life, it is known that a girl in the first year of life was observed by a neurologist with a diagnosis of perinatal hypoxic-ischemic damage to the central nervous system. Among the diseases - pertussis at 1.5 years, pneumonia at 3 years, as well as acute respiratory infections with a frequency of 3-4 times a year. She was vaccinated by age. Based on the history, the child was regarded as threatened by the development of neurological complications.

Sick for 3 days. From the first day of the disease, there was an increase in body temperature to 39 ° C, after 6 hours the first elements of a maculopapular rash appeared.

Upon admission, the body temperature was 39 ° C, which lasted for the first 3 days, headaches, the presence of abundant spotty-papular, with an addition of 6 days. According to the clinical analysis of blood leukocyte intoxication index was 1.6 srvc. units In order to confirm the possibility of the development of neurological symptoms, an electroencephalographic study was carried out for 2 days. On admission EEG, a decrease in the index of the basic physiological rhythm of 25%, increased paroxysmal activity in the form of diffuse sharp waves and flashes of slow activity with an amplitude of 110 μV were revealed.

In a blood test by ELISA, antibodies to VZV, to herpes simplex virus (HSV) type 1 were detected. Based on clinical and laboratory data, the child was regarded as highly threatened by the development of neurological complications. In addition to etiotropic therapy, antiviral therapy was carried out: the patient was prescribed viferon-1 1 suppository after 12 hours with a course of 5 days. After 4 days, the patient showed a positive trend.

Thus, the above clinical observation confirms the high prognostic value of the earliest possible comprehensive assessment of clinical and medical history data in predicting the risk of developing neurological complications, which contributes to the timely correction of therapy and, as a result, the absence of neurological manifestations and a significant reduction in the patient's recovery period.

Example No. 2. Patient I., 1 year 5 months. The medical history No. 46291. He was hospitalized in the hospital on the 1st day of VO disease with a diagnosis of chickenpox, severe, uncomplicated. A child under 1 year old was observed by a neurologist with a diagnosis of perinatal hypoxic-ischemic damage to the central nervous system. 3 weeks before the present disease, VO suffered acute left-sided purulent otitis media, purulent meningitis.

He became acutely ill with an increase in body temperature to 39 ° -40 ° C, the appearance from the first day of the disease of an abundant spotty-papular rash (rashes continued for 5 days). Since the child had a central nervous system HIP in the perinatal period, recently undergoing neuroinfection, from the onset of VO disease a hyperthermic reaction to 40 ° C, it was decided to conduct an electroencephalographic study on the first day of admission with the aim of predicting the risk of neurological complications as early as possible. EEG revealed a decrease in the index of the main physiological rhythm of 28%, increased paroxysmal activity in the form of diffuse sharp waves and flashes of slow activity with an amplitude of 120 μV.

LII amounted to 2.8 conv. units Using ELISA, antibodies to VZV, HSV 1 and HSV type 6 were determined. When identifying prognostically significant criteria in a child, recombinant alpha-2-interferon (viferon) was used for 7 days as part of the etiopathogenetic therapy. The patient was discharged after 10 days without a neurological deficit.

Thus, a timely (from the first day of the illness) comprehensive assessment of prognostically unfavorable factors of damage to the nervous system during HE allowed us to predict the risk of developing neurological complications and, with the help of early complex therapy, prevent their development as much as possible and accelerate the child’s recovery without residual effects.

Example No. 3. Patient E., 6 years old. He was hospitalized on the first day of the disease with a diagnosis of chickenpox, severe. The medical history No. 44257.

A boy up to 1 year of age was under the supervision of a neurologist with a diagnosis of GUI of the central nervous system. Pace delays of psychomotor development up to 2 years were noted.

He became acutely ill with an increase in body temperature up to 40 ° C during the day, with headache, nausea. Since there was a combination of several prognostically unfavorable factors (history of central nervous system hyperactivity), an abundant maculopapular rash throughout the body from the first day of illness, fever 40 ° C, EEG was performed on the day of admission to the hospital, during which a decrease in the index was detected the main physiological rhythm, which amounted to 22%, an increase in paroxysmal activity in the form of diffuse sharp waves and flashes of slow activity with an amplitude of 115 μV.

Using ELISA, antibodies to both VZV and type 1 HSV and type 6 HBV were detected in the patient's blood. LII amounted to 0.2 srvc. units Rashes continued for 5 days. For 4 days, febrile body temperature was maintained up to 40 ° C. A comprehensive assessment of the history and laboratory examinations of the proposed method allowed us to predict a high risk of neurological complications. However, the mother of the child refused further treatment in the hospital.

On the 13th day from the onset of VO disease, complaints appeared about gait changes, fatigue, leg pain, choking with drinking, hypomimia, and slight asymmetry of the face. The child was again hospitalized. Neurological status showed signs of damage to the cranial nerves, a decrease in muscle strength to 3-4 points and tendon reflexes, radicular symptoms were moderately expressed. As a differential diagnosis with encephalitis, an EEG study was carried out, as a result of which pronounced diffuse changes in the bioelectric activity of the brain were recorded. Paroxysmal activity was not detected. On the basis of clinical and laboratory data, the diagnosis was made: chicken pox, severe, complicated by axonal demyelinating polyneuropathy. The patient was in hospital for 25 days and was discharged with improvement. During the follow-up study, 2.5 months after the onset of the disease, a neurological deficit was observed in the form of hyporeflexia of tendon reflexes of the legs.

The given case indicates the need in each case of the disease IN to conduct a comprehensive assessment of the anamnesis data, as well as clinical and laboratory prognostic data in the specified method. And the lack of timely measures for the prevention of neurological complications in HE can lead to their development and contribute to prolonged disability of children.

Thanks to the application of the method proposed by the authors, it was possible to prevent the development of neurological complications in children with HE, and to improve the outcome of the disease by increasing the percentage of children who recovered completely without neurological abnormalities, reduce the frequency of formation of residual neurological deficit, and reduce the length of hospital stay.

Chickenpox leads to significant economic and intangible costs. Even a mild, uncomplicated case of chickenpox can last for 14 days and entail significant financial losses. It should be noted that in 2008 the total economic damage in the Russian Federation from chickenpox alone amounted to 5770 billion rubles, and taking into account the increase in the incidence and severity of the course of VO, this figure increases every year. In this regard, a method for predicting the risk of developing neurological complications in children with HE is necessary from an economic point of view and has great medical and social significance.

Claims (1)

A method for predicting the risk of neurological complications of chickenpox in children, including the assessment of anamnestic data, virological indicators, a febrile reaction and a rash of maculopapular rash, characterized in that the child additionally records EEG in the first 3 days from the time of admission, the leukocyte intoxication index is determined, the presence of mixed herpesvirus infection and in the presence of a child’s history of a hypoxic-ischemic lesion of the central nervous system, a maculopapular rash on the body with per day of the disease with “pouring” it over 5-7 days, fever up to 39-40 ° C during the first 3-5 days, when the EEG detects a decrease in the index of the basic physiological rhythm of less than 30%, increased paroxysmal activity in the form of diffuse acute waves and flashes of slow activity with an amplitude of more than 100 μV for 3 days, or at least on one of these days, a leukocyte index of 0.2-3 cu, detection of mixed herpes viruses along with varicella zoster virus, herpes virus Type 6 and / or herpes simplex virus type 1 predict risk neurological complications.