RU2570385C1 - Method of predicting depression in patients with brain contusion in remote period - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: quantitative content of brain-derived neutrophic factor is determined in patient's blood serum within first two days after trauma moment. If its value is lower than 300 pg/ml, high risk of development is predicted, if index value is from 300 pg/ml, low risk of depression development in remote period of brain contusion is predicted.

EFFECT: acceleration and simplification of method with high accuracy.

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Description

The invention relates to medicine, in particular to neurology, neurotraumatology, and in particular to laboratory diagnosis of traumatic brain injury, and can be used to objectively predict the development of depression in patients with brain contusion.

The search for objective prognostic criteria for determining the outcome of a traumatic brain injury (TBI) is one of the urgent problems of neurology and neurosurgery. Psychovegetative syndrome is the most common consequence of the traumatic effect, regardless of severity [Likhterman L.B. Neurology of traumatic brain injury. M., 2009 .-- p. 73-74]. Particular attention in this regard is occupied by depression (clinically manifested or masked), which is one of the main maladaptive factors in the long term TBI. Predicting the development of depressive syndrome in the acute period will allow you to start timely therapy and prevent the development of clinical manifestations of depression.

Closest to the claimed is a method for predicting the development of depression in the early stages in patients with mild traumatic brain injury (Moskalenko S.N. Diagnostic capabilities of complex mapping in the prognosis of depression and short-term memory impairment in patients with mild traumatic brain injury: abstract. ... candidate of medical sciences: 14.00.13 / Sergey Nikolaevich Moskalenko. - M., 2009). The authors propose to study motor thresholds, amplitude-time characteristics of evoked motor potentials and acoustic stem evoked potentials, to record and spectrally-coherent analysis of electroencephalography after 3 weeks, and also to determine the presence of depression on the Hamilton scale 2 months after a mild TBI. At the same time, in patients at risk of developing depression 3 weeks after a mild head injury, an increase in the frequency of the alpha rhythm, the phenomenon of splitting of the main peak of the alpha rhythm, various variants of interhemispheric and intrahemispheric asymmetry are observed, which are most pronounced in the anterior parts of the right hemisphere.

The disadvantage of this method, in our opinion, is its complexity, duration (2 months). To implement the method requires expensive equipment and specially trained personnel.

Effect: acceleration and simplification of the method with high accuracy.

A method for predicting depression is achieved by determining the concentration of cerebral neurotrophic factor (MNF) in the patient’s blood serum during the first two days after an injury and, with its value up to 300 pg / ml, a high risk of development is predicted, and with a value of 300 pg / ml or more, a low risk the development of depression in the long term brain contusion.

The method is as follows.

5.0 ml of blood was taken from a vein in a patient within two days after an injury from a vein into a glass centrifuge tube in the morning on an empty stomach. Serum is obtained by centrifugation at 1000 rpm for 10 minutes. The separated serum can be stored for 3 hours at room temperature, up to 12 hours at 4-8 degrees, and for a long period at -20 degrees and below.

Essential reagents: enzyme immunoassay for the quantitative determination of human brain-derived neurotrophic factor (BDNF in the English literature BDNF - brain-derived neurotrophic factor) in serum, plasma, tissue homogenates and in cell culture supernatants ) concentration in cell culture supernates, serum, and plasma, 2009, R&D Systems, Inc., Quantikine; Maroder M. et al. J. Immunol., 1996. - 157. - 2864; Wolf D.E. et al. J. Biol. Chem. - 270. - 2133]. The principle of the test system for determining the MNF protein is based on a quantitative enzyme-linked immunosorbent assay of the sandwich type. Monoclonal antibodies to MNF are applied to the microplate cells. Standards and samples are introduced into the cells and the MNF present in them binds to the antibodies. Second anti-MNF antibodies labeled with the enzyme are introduced into the cells. Subsequent washing removes the unbound conjugate of antibodies to the enzyme, after which a solution of the enzyme substrate is added to the cells. The color intensity is proportional to the number of MNFs bound in the first step of the analysis. The color reaction is stopped and the absorbance of the cells is read. The optical density is determined at a wavelength of 450 nm. The concentration of MNF is calculated by extrapolating the obtained data to a calibration graph constructed according to the analysis with a series of Standards, expressed in pg / ml, and with a value of up to 300 pg / ml, a high risk of development is predicted, and with a value from 300 pg / ml, a low risk the development of depression in the long term brain contusion.

This method was tested in the examination of 56 patients with traumatic brain injury of mild to moderate severity (36 men and 20 women) aged 18 to 60 years in the first 2 days after injury and in the long term. The control group consisted of 15 healthy individuals, comparable by sex and age.

Case Studies

Example 1. Patient N., 45 years old, a secondary education, works as a freight forwarder (case history No. 3751), was admitted to the neurotraumatology department 1.5 hours after an everyday injury (beaten on the way to work). Objectively: the condition is serious, conscious, dynamic, inhibited, executes commands with a delayed reaction. Pupils are equal, live photoreactions, horizontal nystagmus on both sides, poorly monitored objects. There are no meningeal symptoms. Reflexes are alive, on the right are increased. In the Romberg position is not inspected due to the severity of the condition, the coordinator tests are not performed. There are no sensitive, pelvic disorders. A radiograph of the skull revealed a linear fracture of the parietal bone on the right. CT of the brain revealed a fracture of the bones of the arch and base of the skull, contusion-hemorrhagic foci of the left temporal and left frontal lobes, and contusion of the right frontal lobe. Subarachnoid hemorrhage. Diagnosis: brain contusion of moderate severity, subarachnoid hemorrhage, fracture of the bones of the arch and base of the skull. The study of the quantitative content of MNF in blood serum on the second day after the injury in patient N. was 396.5 pg / ml. A follow-up examination (in the distant period): complaints of recurring headaches of a pressing nature, decreased memory, attention, dizziness with changing weather. The status of focal neurological symptoms was not detected. Montgomery-Asberg Depression Testing - 5 points; Hospital Depression Scale - 1 point, which indicates the absence of depressive syndrome.

Example 2. Patient M., 22 years old, an incomplete higher education, works as a salesperson (case history No. 2676), was admitted to the neurotraumatology department a day after a personal injury (falling in the bathroom), did not lose consciousness, there was no vomiting. Objectively: the state is relatively satisfactory, in consciousness, available to productive contact, executes commands. There are no meningeal symptoms. Hematoma of soft tissues of the occipital region on the right. The skin is pale. Pupils are equal, photoreactions are alive, horizontal nystagmus when viewed to the right, objects are poorly monitored. Reflexes are living, equal. In the Romberg position is unstable, coordinator tests are not performed with intent. There are no sensitive, pelvic disorders. A radiograph of the skull revealed a linear fracture of the occipital bone on the right. Diagnosis: brain contusion of mild severity, a fracture of the occipital bone on the right. The study of the quantitative content of MNF serum on the second day after the injury in patient M. was 147.6 pg / ml. A follow-up examination (in the distant period): complaints of periodically almost constant headaches of a bursting and oppressive nature, increased irritability, decreased memory, low mood, general weakness, and increased fatigue. In the neurological status, focal symptoms were not detected. Montgomery-Asberg Depression Testing - 25 points, corresponding to clinically severe depression.

Example 3. Patient N., 42, a secondary education, at the time of the injury he didn’t officially work anywhere (medical history No. 1103), he was admitted to the neurotraumatology department a few hours later (he cannot be more specific) after a household injury (fell on the street). The fact of loss of consciousness cannot be clarified. Objectively: a state of moderate severity, conscious, disoriented, excited, executes commands. Pupils are equal, live photoreactions, horizontal coarse nystagmus on both sides, objects are poorly monitored. Stiff neck muscles 5 cm. Tendon reflexes reduced. In the Romberg position is unstable, dysmetria when performing a finger-nasal test on both sides. There are no sensitive, pelvic disorders. A radiograph of the skull revealed a linear fracture of the occipital bone on the right. ECHO-ES displacement of the median structures did not reveal. Diagnosis: brain contusion of moderate severity, a fracture of the occipital bone on the right. The study of the quantitative content of MNF in serum on the second day after the injury in patient N. was 288.0 pg / ml. A follow-up examination (in the distant period): complaints of headaches in the back of the head, general weakness, fatigue, increased irritability, anger. The status determines a slight instability in the Romberg position, a high reflex background. Montgomery-Asberg Depression Testing - 16 points, Depression Hospital Rating - 12 points, which indicates the presence of clinically severe depression.

Example 4. Patient V., 28 years old, secondary education, works as a glazier (case history No. 3451), was admitted to the neurotraumatology department 2 hours after the injury (fell from the stairs at work, lost consciousness). Objectively: the condition is serious, stunning, dynamic, performs commands with a slow reaction. Pupils are equal, live photoreactions, horizontal nystagmus to the right, does not monitor objects. There are no meningeal symptoms. Reflexes are lively, pathological foot reflexes on both sides. In the Romberg position is not examined due to the severity of the condition, coordinator tests are not performed. CT of the brain revealed a fracture of the bones of the arch (frontal and occipital) skull, multiple contusion-hemorrhagic foci on both sides. Subarachnoid hemorrhage. Diagnosis: brain contusion of moderate severity, subarachnoid hemorrhage, fracture of the bones of the cranial vault. The study of the quantitative content of MNF of blood serum on the second day after the injury in patient B. was 668.4 pg / ml. Examination in the long term: complaints of recurring headaches and dizziness due to changing weather and emotional stress, periodically sleep disturbance (difficulty falling asleep). The status of focal neurological symptoms was not detected. Testing on the Montgomery-Asberg Depression Scale - 2 points; Hospital Depression Scale - 1 point, which indicates the absence of depression.

Claims (1)

A method for predicting depression in patients with brain contusion in the distant period, which consists in the fact that the quantitative content of cerebral neurotrophic factor is determined in the patient’s blood serum within the first two days from the injury, and with its value up to 300 pg / ml, a high risk of development is predicted , and with a value of 300 pg / ml or less, there is a low risk of developing depression in the long-term period of brain contusion.