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INVENTION
Russian Federation Patent RU2213967

METHOD OF DIAGNOSIS AND SEVERITY OF FLOW craniocerebral INJURY

METHOD OF DIAGNOSIS AND SEVERITY OF FLOW craniocerebral INJURY

Name of the inventor: PRSPs DB .; Kozel AI .; GK Popov .; DB Giller
The name of the patentee: Chelyabinsk State Institute of Laser Surgery
Address for correspondence: 454021, Chelyabinsk, Pobedy 287, Chelyabinsk State Institute of Laser Surgery, Director A.A.Kozelyu (for Goloshapova)
Starting date of the patent: 2002.07.22

The invention relates to medicine, in particular to neurosurgery, neurology and immunology, and can be widely used in the diagnosis of the severity and course of cranial traumas. The method provides an effective diagnostic severity and course of traumatic brain injury. Carry out a study of ferritin in the cerebrospinal fluid and blood of the patient and increase of its level in the blood up to 170-190 ng / ml CSF and 30-50 ng / ml, with its subsequent normalization to 8-14 days diagnose mild degree of traumatic brain injury with a favorable course disease without complications, with an increase in blood levels of ferritin to 200-210 ng / ml CSF to 200-220 ng / ml with the normalization of his blood values ​​for 8-14 days and 15-21 days in the cerebrospinal fluid to diagnose moderate traumatic injury with a favorable course of the disease without complications and with an increase in blood levels of ferritin to 460-500 ng / ml CSF to 280-350 ng / ml and maintaining this level for 8-14 days with the normalization of its values ​​to 28-32 days diagnosed with severe traumatic brain injury with a favorable course of the disease without complications, while during the accession of inflammatory complications of extracranial localization with mild to moderate levels of ferritin in the blood rises to a value equal to or above 465 ng / mL, and in the CSF coincides with this value or becomes less than 465 ng / ml, with severe severity ferritin level in the blood rises to a value equal to or more than 510 ng / ml and in CSF coincides with this value or becomes less than 510 ng / ml and at flow accession inflammatory complications of intracranial localization of ferritin levels in the cerebrospinal fluid is greater than the value of ferritin levels in the blood, and it is more than 465 ng / mL for mild to moderate and more 510 ng / ml in severe degree.

DESCRIPTION OF THE INVENTION

The method relates to medicine, in particular to neurosurgery, neurology and immunology, and can be widely used in the diagnosis of traumatic brain injury, more particularly for determining the degree of severity and course.

It is known that on the severity of traumatic brain injury in the dynamics are judged on a combination of indicators immunoreactivity of the body and the concentration in the blood and cerebrospinal fluid of toxic substances, in terms of state gematolikvornogo and the blood-brain barrier of cerebral blood flow, expression of hormonal disorders, the nature and extent of violations of functions of internal organs (see para. AP Romodanov. "Modern aspects of diagnosis and complex treatment of closed head injury in the acute period," the magazine "Questions of neurosurgery. NN Burdenko", Issue 5, 1989, p. 35 -37).

However, all of the above techniques do not reveal the severity of traumatic brain injury in the early stages of their occurrence. Furthermore, these methods may not give a complete picture of the severity of the disease, in particular do not indicate joining inflammatory complications and their localization.

Known method for determining the severity of a traumatic brain injury which is carried out by determining in the cerebrospinal fluid of malondialdehyde (MDA) and the diene conjugates (DC) (see patent RU 2146060, IPC:. G 01 N 33/92, 33/48, published on 02.27.2000. g).

When the concentration of MDA and DC respectively not more than 3.7 and 3.4 times diagnose mild injury of the brain in the range of increase in MDA and DC 3,8-10,5 times - in 3,5-9,0 time - the brain injury of moderate severity, increased levels higher than the 10.6 times for the MDA and 9.1 times for the DC indicate a brain injury severe.

According to the authors, this method can improve the accuracy and reduce the time of determining the severity of traumatic brain injury.

However, the known method does not allow to identify at an early stage of craniocerebral injury complications inflammatory connection, and their location and that does not provide a complete picture of the disease, and consequently the efficiency of the data at the designated disease treatment.

Thus, the technical result to be solved by this invention is to increase the efficiency of diagnostic method the severity of traumatic brain injury by determining its flow, in particular by determining the presence of inflammatory complications of various localization, or the possibility of their accession to this disease.

This technical result is achieved in that, which includes the study of cerebrospinal fluid of the patient, according to the invention is determined in the cerebrospinal fluid and the patient's blood ferritin level and increasing its level in the blood up to 170-190 ng / ml in the known method of diagnosis the severity and course of traumatic brain injury and in the cerebrospinal fluid of 30-50 ng / ml, with its subsequent normalization to 8-14 days diagnose mild degree of traumatic brain injury with a favorable course of the disease without complications, increased blood levels of ferritin to 200-210 ng / ml CSF to 200-220 ng / mL with the normalization of its values ​​in the blood for 8-14 days and 15-21 days in the cerebrospinal fluid to diagnose moderate traumatic brain injury with a favorable course of the disease without complications, and the rise in blood ferritin to 460-500 ng / ml CSF to 280-350 ng / ml and maintaining this level for 8-14 days with the normalization of its values ​​to 28-32 days diagnose severe traumatic brain injury with a favorable course of the disease without complications, while during the accession extracranial inflammatory complications localization of mild to moderate severity ferritin level in the blood rises to a value equal to or above 465 ng / ml, and in the cerebrospinal fluid matches this value or becomes less than 465 ng / ml, with severe severity ferritin level in the blood rises to values equal to or more than 510 ng / ml and in CSF coincides with this value or becomes less than 510 ng / ml and at flow accession inflammatory complications intracranial localization of ferritin levels in the cerebrospinal fluid higher than the values ​​of ferritin levels in the blood, namely more than 465 ng / ml with mild to moderate and more 510 ng / ml in severe degree.

The authors have experimentally established that the definition of ferritin levels in the cerebrospinal fluid and blood of patients with traumatic brain injury not only increases the reliability of establishing the severity of traumatic brain injury (mild, moderate or severe), but also at an early stage to establish the presence or absence of inflammatory complications various locations, attached to the disease, ie, determine for traumatic brain injury.

According to the authors, this is due to the fact that it is ferritin, being a universal regulator of physiological functions and the body's defenses, is detected in the cerebrospinal fluid and blood before all the other traditional tests.

And since it ferritin plays an important role in protecting cells from the toxic effect of excess iron, adaptation to hypoxia in acute traumatic brain injury, provides a change of physiological regulation systems of the body, activates the intracellular defense mechanisms play an important role in protecting against the damaging effects of cells, particularly from oxygen deficiency and apoptosis, it serves as a basis to believe that it is the value of ferritin levels in the cerebrospinal fluid and blood should be used to determine the severity and course of traumatic brain injury, in particular by determining the presence or absence of connection of inflammatory complications of various localization.

The authors of the experiment with a high degree of significance (p <0.05) revealed that it declared values ​​of ferritin in the blood and cerebrospinal fluid and the normalization of the timing of their show, and in the early stages of one or other of the severity and course of traumatic brain injury, in particular accession or absence of inflammatory complications of various localization.

Additionally, the authors found that the stated period of normalization of ferritin in the cerebrospinal fluid and blood of a patient can judge with high confidence about the effectiveness of the designated patient treatment.

The method is as follows.

The patient in the acute period of craniocerebral trauma is performed sampling of cerebrospinal fluid and blood. Fence liquor is carried out the traditional method during a lumbar puncture. Blood sampling was carried out from a peripheral vein conventional technique.

After a preliminary centrifugation of blood and cerebrospinal fluid chemiluminescent method on an automated fluorescent analyzer IMMULITE DPC (the company DIAGNOSTIC PRODUCT CORPORATION, USA) studied the levels of ferritin in serum and cerebrospinal fluid (CSF) of the patient with traumatic brain injury.

According to the results of this study in a patient in the early period determined by the severity and course of traumatic brain injury, such as addition or absence of inflammatory complications of various localization.

Increasing levels of ferritin in the patient's blood to 170-190 ng / ml (at a rate of 109,7 ± 42 ng / ml) and CSF to 30-50 ng / ml (normal 2,3-5,5 ng / ml) with further its normalization to 8-14 days indicates mild traumatic brain injury with a favorable course of the disease without complications.

Increasing the level of ferritin in the blood up to 200-210 ng / ml CSF to 200-220 ng / ml with subsequent normalization of his blood values ​​for 8-14 days and in the cerebrospinal fluid in 15-21 days indicates moderately severe traumatic brain injury with favorable course without the associated complications.

Increased blood levels of ferritin to 460-500 ng / ml CSF to 280-350 ng / ml, maintaining this level for 8-14 days and normalization of its values ​​to 28-32 days suggests heavy severity of traumatic brain injury with a favorable over without joining inflammatory complications.

Raising the level of ferritin in the blood to a level equal to or above 465 ng / ml for traumatic brain injury of mild to moderate severity and are equal to or above 510 ng / ml for traumatic brain injury, severe, suggests joining inflammatory complications.

In this case, if the values ​​of ferritin levels in the cerebrospinal fluid are the same or less than these values ​​(ie equal to or less than 465 ng / ml for traumatic brain injury of mild to moderate severity and are equal to or less than 510 ng / ml for traumatic brain injuries severe degree), it testifies to joining of inflammatory complications of extracranial localization (pneumonia, nephritis, septic wounds, etc.).

If the values ​​of ferritin levels in the cerebrospinal fluid higher than the specified values ​​of ferritin in the blood (ie, if the value of ferritin in the CSF over 465 ng / ml for traumatic brain injury of mild to moderate severity and more 510 ng / ml for head injuries severe degree), it testifies to joining of inflammatory complications of intracranial localization.

Normalization ferritin values ​​in the blood and cerebrospinal fluid in the inventive timing indicates the effectiveness of the prescribed treatment as the most traumatic brain injury, and inflammatory complications, and exceeding these terms demonstrates the need to continue intensive care as the most traumatic brain injury, and inflammatory complications, which confirms the effectiveness of the method.

Method confirmed examples.

Example 1. Patient B., 41 years old. He entered the clinic after a work-related injury. Preliminary diagnosis: closed brain injury. Bruising of the brain, presumably mild. Hypertensive syndrome. Syndrome of vegetative-vascular dystonia. Assigned medication, appropriate mild traumatic brain injury.

On admission, the patient was investigated ferritin levels in the cerebrospinal fluid and blood. On the fourth day the level of ferritin in the blood was 172 ng / ml, in the cerebrospinal fluid of 32.3 ng / mL. On the 10th day the level of ferritin in the blood was 102 ng / ml CSF - 5.4 ng / ml. The patient confirmed the diagnosis: Traumatic brain injury is mild, favorable course of the disease without the attachment of inflammatory complications. After the treatment, corresponding to a given degree of severity, the patient was discharged on the 18 th day.

Example 2. Patient X., 60 years. He admitted to the hospital after a road accident. Preliminary diagnosis: closed brain injury, presumably severe degrees of severity. Left-hand hemiparesis syndrome, hypertensive syndrome. On admission, the patient was investigated ferritin levels in the blood and cerebrospinal fluid. The content of ferritin on day 4 in the blood was 480 ng / ml in the CSF 350 ng / ml at day 14 the level of ferritin in the blood was 440 ng / ml in the CSF 290 ng / ml, on the 30th day level ferritin in blood was 107 ng / ml, in the cerebrospinal fluid of 5.6 ng / mL. The patient confirmed the severity of traumatic brain injuries - severe degree, suitable for connection without inflammatory complications.

After drug treatment, corresponding to a given degree of severity, the patient was discharged on the 40th day.

Example 3. Patient P., 73 years. He admitted to the hospital after a road accident. Preliminary diagnosis: An open head injury. Fracture of the base of the skull to the left. Brain Contusion pre severe. Hypertensive syndrome cochle-vestibular syndrome. The syndrome of right-sided hemiparesis, sensory aphasia.

On admission, the patient was investigated ferritin levels in the blood and cerebrospinal fluid. On the 14th day after traumatic brain injury, the patient noted a deterioration in growth of aphasic disorders, deepening hemiparesis. According to clinical data, and computed tomography of the brain was performed differential diagnosis between encephalitis and complication of vascular origin (cerebral infarction). When lumbar puncture obtained colorless transparent liquor: Protein 280; 2/3 cell count. (The patient had complete sanitation of hemorrhagic CSF to the 10 th day of the disease). To clarify the diagnosis determined ferritin blood - 680 ng / ml CSF - 1500 ng / mL. The patient is suspected intracranial inflammatory complications - meningoencephalitis. In the dynamics of the patient through the day there was a temperature of 38 o C. At repeated lumbar puncture in a day in the cerebrospinal fluid protein appeared to increase in 2050, and neutrophilic pleocytosis up to 360/3.

Earlier, the emergence of high ferritin levels in the cerebrospinal fluid and blood serum, the value prevailing at the cerebrospinal fluid has helped to clarify the diagnosis in a timely and appropriate to appoint anti-inflammatory and antibacterial therapy.

After treatment on the 30th day, the level of ferritin in the blood was 110 ng / ml in the CSF 5.0 ng / mL. The patient was discharged from the hospital 2 months later.

Example 4. Patient E., 59 years old. He admitted to the hospital after an industrial accident. Preliminary diagnosis: closed brain injury. brain injury, pre-severe. Hypertensive syndrome. Coma 1 tbsp. Started appropriate diagnosis treatment. On the third day the patient noted a deterioration in growth of hemiparesis, the deepening of human consciousness to coma 2 tbsp., Body temperature rise to 38 o C increase in leukocytosis in peripheral blood up to 15.5 × 10, noted the weakening of breathing in the lower divisions light. It is suspected connection inflammatory complications. Were examined. In the R-thorax grams per day revealed no deterioration in the pathology. To clarify the diagnosis in addition to traditional methods of survey investigated the levels of ferritin in the blood and cerebrospinal fluid. The serum ferritin level was 1500 ng / ml CSF 502 ng / mL. Increased blood levels of ferritin values ​​over its index in the cerebrospinal fluid, the deepening of neurological symptoms attributed to the addition of extracranial inflammatory complications - bilateral lobar pneumonia. Antibiotic therapy is begun. After 2 days the diagnosis is confirmed on the R-grams. After treatment at 32 th day of ferritin level in the blood was 107.7 ng / ml CSF - 5.4 ng / ml. After the treatment the patient was discharged from the hospital 2 months later.

CLAIM

A method of diagnosing the severity and course of traumatic brain injury, including the study of cerebrospinal fluid of the patient, characterized by determining a patient's blood and CSF ferritin level and increase in the blood level to 170-190 ng / ml CSF and to 30-50 ng / ml, with its subsequent normalization to 8-14 days diagnose mild degree of traumatic brain injury with a favorable course of the disease without complications, increased blood levels of ferritin to 200-210 ng / ml CSF to 200-220 ng / ml with the normalization of its values blood for 8-14 days and 15-21 days in the cerebrospinal fluid to diagnose moderate traumatic brain injury with a favorable course of the disease without complications, and the rise in blood ferritin to 460-500 ng / ml CSF to 280-350 ng / ml and maintaining this level for 8-14 days with the normalization of its values ​​to 28-32 days diagnose severe traumatic brain injury with a favorable course of the disease without complications, while during the accession of inflammatory complications of extracranial localization with mild to moderate level of ferritin blood rises to a value equal to or above 465 ng / ml, and in the cerebrospinal fluid matches this value or becomes less than 465 ng / ml, with severe severity ferritin level in the blood rises to a value equal to or more than 510 ng / ml, and CSF coincides with this value or becomes less than 510 ng / mL, and in the flow of the accession of inflammatory complications of intracranial localization of ferritin levels in the cerebrospinal fluid exceeds the value of the levels of ferritin in the blood, and it is more than 465 ng / mL for mild to moderate and more 510 ng / ml at severe.

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Publication date 02.04.2007gg