The method of differential diagnosis of encephalopathy

 

(57) Abstract:

The invention relates to medicine, in particular to gastroenterology, Hepatology, neurology and General medicine, and can be used for differential diagnosis of encephalopathy. The method consists of determining the concentration and qualitative composition of short-chain fatty acid fraction WITH2-C6with isomers in serum, where the relative content of acetic, propionic and butyric acids (C2WITH3WITH4in total the content WITH2-C4; the percentage of isovalerianic and isocaproate acids in the total content of C2-C6with isomers and values of the ratio of its6/ISOs5are support differential diagnostic criteria Genesis encephalopathy. The method allows high accuracy to verify Genesis encephalopathies in each case, regardless of the number of objective reasons: the seriousness of the patient, it is impossible to conduct additional studies with a low cost of research and a significant reduction in time to produce results, that allows to start pathoetiology, neurology and General medicine, and can be used for differential diagnosis of encephalopathy.

In some cases, the Genesis of encephalopathy accompanying diseases such as cirrhosis of the liver, cerebral atherosclerosis and other hard to diagnose, or in connection with latent clinical symptoms, either due to a severe state of the patients and reduced level of consciousness, when it is impossible to establish the basic pathology that led to the development of encephalopathy, which in turn affects the timing of pathogenetic therapy.

Under portosystemic encephalopathy (PSE) is a potentially reversible disorder of brain function resulting from chronic liver failure and portal systemic shunting of blood (W. Sherlock diseases of the liver and biliary tract", Chapter 7, "Hepatic encephalopathy", S. 100-119, "GEOTAR MEDICINE", Moscow, 1999).

Under "dyscirculatory encephalopathy (DE) refers to a syndrome of diffuse brain damage due to chronic cerebral vascular insufficiency and (or) repeated episodes of acute disorders of cerebral circulation. Diagnosis of DS is based on clinically who I am. Methodical recommendations. Edited Yakhno N.N, S. 32, Moscow, 2000).

Currently, diagnosis of encephalopathy is carried out mainly in the analysis of clinical symptoms. However, be aware that the initial stage of the disease often occur without symptoms. The major manifestations of encephalopathy are astheno-vegetative disorders, reflecting the mental status of the patient, and motor abnormalities that underlie clinical classifications (Diseases of the liver and biliary tract. Standartization of nomenclature, diagnostic criteria and prognosis. Editorial committee Carol M. Leeve et al. - New York Raven Press, 1994, 205 p. Encephalopathy. Methodical recommendations. Edited Yakhno N.N., S. 32, Moscow, 2000).

However, the clinical manifestations are not strictly specific for the encephalopathy of various origins.

Additional laboratory and instrumental methods of diagnosis of encephalopathy have different sensitivity and specificity, as well as various labor-and cost studies.

Determination of the level of ammonia in the blood is used to diagnose PSE.

The disadvantage of this method is that the ammonia level does not correlate with the stage of PSE. reduces the specificity of this study in relation to PSE (Sanjay Sandhir, MD, Frederick L. Weber, Jr. MD "Portal-Systemic Encephalopathy", Current Practice of Medicine, p. 103-108, N2, 1999 Jan.). In addition, the method has a high cost of research.

Electroencephalography is used to diagnose PSE and TE.

The main disadvantage of this method is that changes in the EEG are not specific and can also be detected by such conditions as uremia, hypercapnia, deficiency of vitamin B12or hypoglycaemia (Podymova C. D. "Heptagenia encephalopathy". Russian journal of gastroenterology, Hepatology, Coloproctology. N1, 1998, S. 88-91). The sensitivity of this method in identifying the various stages of encephalopathy low (30%) (Naginsky M. Y. "Latent hepatic encephalopathy: how to help the patient". Clinical perspectives in gastroenterology, Hepatology. N1, 2001, S. 10-17).

The method of evoked potentials brain occupies a small place in the definition of subclinical encephalopathy and is more of a scientific interest. Its sensitivity varies from one study to another (in average, 80%) (W. Sherlock diseases of the liver and biliary tract", Chapter 7, "Hepatic encephalopathy", S. 100-119, "GEOTAR MEDICINE", Moscow, 1999).

Psichari are different psychometric tests. Their sensitivity in detecting subclinical stage is 70-80%. However, it is proved that the test time increases with age and decreases with the years of formal education (Sanjay Sandhir, MD, Frederick L. Weber, Jr. MD "Portal-Systemic Encephalopathy", Current Practice of Medicine, p. 103-108, N2, 1999 Jan.). Additionally, there is no uniformity in the evaluation of test procedures: the European and national data often differ, low reproducibility of the tests and the trend towards learning (Syutkin C. E., Volokhov R. Y., Ivannikov Acting "Identify latent hepatic encephalopathy in patients with liver cirrhosis of different etiology and severity". Russian medical journal, 9 so, N12, 2001, S. 10-11). It should also be noted that psychometric tests are used in various fields of medicine (neurology, urology and others) and are not strictly specific to PSE or TE.

The Genesis of encephalopathy is determined by the primary disease, but in some cases described above, it is impossible to verify underlying pathology.

Thus, none of the listed methods can not be used as a differential diagnostic test encephalopathy due to low specificity of the study.

The invention is based on the identified logical fact, namely, that in determining the concentration and qualitative composition of short-chain fatty acids (KJC) (short-chain fatty acids (fraction C2-C6 with isomers) include C2-acetic acid, C3-propionic, ISO-isomaltol, C4-oil, ISO-valeric, ISO-isocaproate and C6-Caproic acid.) fractions WITH2-C6with isomers in serum:

- when portosystemic encephalopathy is a change in the relative content of acetic, propionic and butyric acids (C2WITH3WITH4), manifested in the increase in the percentage of propionic within 8,2-9,0%, oil 4,9-5,4% acid and reducing the percentage of acetic acid the OIC acid in the range of 4.4 to 5.8% in the total content of C2-C6with isomers and values of the ratio of its6/ISOs5equal to 0.92-1,94 when compared with normal levels (p<0,05);2WITH3WITH4), where the percentage of acetic acid is in the range from 89,6 up to 91.2%, propionic from 6.5 to 7.4% and oil - from 2.5 to 2.9% (p>0.05 with respect to the norm); the increase of the percentage of isocaproate acid in the range of 11.0-12.6% in the total content of C2-C6and the values of the ratio of its6/ISOs5equal to 4,4-6,82 (p<0.05 with respect to normal).

These changes occur together.

Normal indicators of the relative content of acetic acid are in the range from 89,6 down to 91.3%, propionic from 6.6 to 7.6% and butyric acid from 2.5 to 2.9% in the total relative content2-C4; the share of isovalerianic acid is 1.7-2.1 percent, isocaproate acid - 0.7-1.3% in the total content of C2-C6and the values of the ratio of its6/ISOs5- 0,32-0,74.

We also noted an increase in total who priori encephalopathy (up to 0,885 mg/l) compared with normal (up to 0,197 mg/l), and mutual improvement relative to the total content of isocyclic: when portosystemic encephalopathy ranging from 10.9 to 12.5% and with dyscirculatory encephalopathy - from 13.8 15.4% compared with normal levels (from 3.3 to 4.7%).

Marked changes may indicate the presence of encephalopathy, but not reflect its Genesis.

Finding a natural change these settings depending on the Genesis encephalopathy allows you to use these indicators as a differential diagnostic criteria.

The result that can be achieved with the implementation of the method is high accuracy verification Genesis encephalopathies in each case, which leads to timely and evidence-based appointment pathogenetic funds for the treatment of patients.

In our work studies were performed in 60 patients with chronic hepatitis b cirrhosis liver syndrome portosystemic encephalopathy and 30 patients with cerebral atherosclerosis syndrome dyscirculatory encephalopathy.

The method is as follows.

The patient to clarify the Genesis encephalopathy produce blood from ve content of short-chain fatty acids, determine the relative content of acetic, propionic, butyric acids in the total content of C2-C4relative content and isovalerianic isocaproate acids in the total content of C2-C6calculate the ratio of the content isocaproate acid to isovalerianic acid. The results of the study conclude that the Genesis encephalopathy (as described above).

Discussion the obtained data. Change profiles C2-C4 chronic hepatitis b cirrhosis of the liver may be associated with functional failure of the hepatocyte (liver cell failure) at the given pathology.

Propionic acid is one of the intermediate substrates oxidation of fatty acids used for the synthesis of cholesterol and is involved in the formation of propionyl COA and/or methylmalonyl-COA in the liver, with regulatory functions in lipid metabolism of the host organism. Butyric acid is involved in the biosynthesis of fatty acids and partially cholesterol. A higher proportion of propionate and butyrate by cirrhosis of the liver may be associated with lower utilization of these acids for the synthesis of cholesterol, which is not observed when sohraneny the correlation coefficient between the relative content of propionic and butyric acids with cholesterol, when cirrhosis is equal to r=0.83 and r=0.84, respectively. In patients with TE, given the increased level of cholesterol mainly due to-fractions (LDL-low density lipoprotein), also would be expected to change the profile propionic and butyric acids, which were not detected. In our opinion, this is due to the implementation of two interacting reasons for this disease: on the one hand, with the increase of cholesterol synthesis in intact liver function and, on the other hand, violation of the feedback mechanism regulating the reduction of cholesterol synthesis by the liver in high concentrations in the serum.

In the course of our work we observed increased levels of isocyclic in both groups studied. As is known, the main pathogenetic model PSE is "hypothesis glia", in which the main role in the damage of brain cells is given endogenous neurotoxins and neurotransmitters (ammonia, mercaptans, GABA -, medium - and short-chain fatty acids and others). This assumes that the FLC and KGC have a direct toxic effect on the cells of astroglia. However, we have identified increased levels of isocyclic in groups of patients with encephalopathy rozliczyc depolarizing effect on the membranes of astrocytes and are synergisti other neurotoxins.

Found increased concentrations of isovalerianic acid in the blood of patients with liver cirrhosis syndrome PSE can be explained as follows. The literature describes cases of isovalerianic acidemia - inherited disease caused by a defect isovaleryl-COA dehydrogenase and characterized by a variety of neurological symptoms and impaired consciousness up to coma (Byszewski A. W., Tursunov O. A. Biochemistry for the doctor. Ekaterinburg: publishing house "Ural worker", 1994, S. 383, Cohn R. M., Roth, K. S. Biochemistry and Disease. Williams and Wilkins. A Waverly Company. Baltimore. 1996). Given the increased concentration of isovalerianic acid in the blood of patients with PSE and the absence of this phenomenon in a group of patients with TE, we cannot exclude the acquired defect isovaleryl-COA dehydrogenase and/or a decrease in its synthesis (the production of enzyme by the cells in the affected liver) in these patients.

Also noteworthy friendly increased levels of propionic acid and the level of isovalerianic acid in patients with PSE. On the one hand, this can be attributed to a single biochemical process: as a result of the metabolism of isovalerianic acid through a series of transformations forms a propionic acid that contributes is the train due to a defect and/or decreased production of the enzyme propionyl COA-carboxylase, might also explain the high content of propionic acid in patients with PSE.

The observed increase in concentration isocaproate acid in the blood of patients with dyscirculatory encephalopathy is connected, apparently, with disturbance of lipid metabolism characterized by increased levels of triglycerides (the correlation coefficient level isocaproate acids and triglycerides r=0,81). CZK with an even number of carbon atoms (CnH2nABOUT2where n is an even number) can participate in the biosynthesis of long-chain fatty acids, neutral fats (mono-, di - and triglycerides), diphosphatidylglycerol and others, which together with hypercholesterolemia discussed as a possible, but not yet received evidence of the pathogenesis dyscirculatory encephalopathy (encephalopathy. Methodical recommendations. Edited Yakhno N.N. Moscow, 2000, S. 32.).

The obtained data are discussed in the light of biochemical processes allow you to get closer to a more precise understanding of the pathogenesis of encephalopathy in liver pathology (portosystemic encephalopathy and cerebral atherosclerosis (encephalopathy), in exact markers.

Below PR is th way which is not limited to them.

Example 1

Patient B., 62 years. Diagnosis: ischemic heart disease: Angina, 2 functional class. Hypertension stage 2, aggravation. Generalized atherosclerosis atherosclerotic cardiosclerosis, atherosclerosis of the aorta and lower extremity vessels, cerebral atherosclerosis. Dyscirculatory encephalopathy stage 2.

Upon receipt complained of dizziness that occurs when the rotation of the head, headache, memory loss, insomnia.

From the anamnesis it is known: About 25 years, suffering from hypertension and coronary heart disease. Constantly monitored by a cardiologist and a neurologist, takes antihypertensive and neuroprotective drugs.

At survey: the state is relatively satisfactory, clear consciousness, no edema, vesicular breathing, wheezing no heart tones are muffled, rhythmic, HR=80 / min, BP=140/90 mm RT. century, the abdomen is soft, painless, physiological functions in normal, meningeal signs, FMN no abnormalities, tremor +.

The results of the survey: 1) complete blood count: HB - 122 g/l, er. - 3,7110, leukocytes - 8,010, five - 1, SJ - 67, E. - 2, l - 19, m - 11, the platelet - 38610, ESR - 12 mm/h; 2) an overall field of view; 3) in the biochemical blood tests show increased levels of total cholesterol (7.2 mmol/l) and triglycerides (2,31 mmol/l), the other indicators are within normal values. 4) ECG: sinus rhythm, right, HR=87 per minute, EOS - deviation to the left, LV hypertrophy, diffuse changes of a myocardium; 5) chest x-ray: lung fields clear, the structural roots, sines free, the movable diaphragm, the left ventricle hypertrophied, aorta sealed. Conclusion: the atherosclerosis of aorta; 6) Doppler ultrasound of the carotid arteries: stenosing process in the system right internal carotid artery, the blood circulation of blood flow in both vertebrate arteries. Changing hemodynamics with a decrease in BFV in the left internal carotid artery; 7) the Study of the fundus of the eye: optic disc pale pink color, border, clear, arteries narrowed veins are moderately dilated, tortuous, field of vision within normal limits; 8) ultrasound of the abdominal organs, kidneys and thyroid gland: Conclusion: chronic pyelonephritis, indirect signs of dystonia and dyskinesia of the colon, diffuse changes of a thyroid gland; 9) Psychometric testing: the communication test numbers Reagan patient was performed in 63 seconds (considering the age of coefficients is euda cerebral diffuse changes in EEG in the form of pronounced spilled irritation of the cortex.

The study CZK in peripheral blood serum: marked unchanged relative content of acetic acid (C2) - 90%, propionic acid (C3) - 7.2% and butyric acid (C4) - 2.8% in the total content C2-C4; increased isocaproate acid (ISOs) - 12.4% in the total content C2-C6; the value of the ratio ISOs/ISOs=6,01. These figures indicate dyscirculatory encephalopathy.

Treatment using anti-hypertensive, vasoactive and neuroprotective funds with a positive effect.

Example 2

Patient A., aged 52. Diagnosis: Chronic hepatitis nutritional etiology of moderate activity in the stage of cirrhosis. Class child-Pugh. Portal hypertension stage 2 (spleen, varicose expanded veins of an esophagus 2 tbsp.). Hepatic cell failure (hypolipemic and hypocholesterolemia). Portosystemic encephalopathy stage 1.

Upon receipt complained of weakness, fatigue, decreased performance, heaviness in the right hypochondrium, insomnia at night.

From the anamnesis it is known that sick since 1999, when a sudden jaundice was hospitalized in To the Yeni. Since that time, annually held stationary examination and treatment, irregularly takes hepatoprotective drugs, verospiron. Abusing alcohol.

At survey: the state is relatively satisfactory, clear consciousness, no edema, vesicular breathing, wheezing no heart tones are muffled, rhythmic, pulse rate=76 min, AD=120/70 mm RT. century, the abdomen is soft, painless, liver enlarged, edge rounded, sensitive to palpation, spleen not palpated, physiological functions in normal, meningeal signs, FMN no abnormalities, tremor +.

The results of the survey: 1) complete blood count: HB - 123 g/l, er. - 3,6610, leukocytes - 7,510, five - 1, SJ - 69, E. - 1, HP - 20, m - 9, platelet - 35210, ESR - 15 mm/h; 2) urinalysis: St.-yellow, full transparency, 1014, protein and glucose is absent, an epithelium flat - 2-3, leukocytes - 2-4 in the field of view; 3) biochemical analysis of the blood was reduced albumin levels (33,0 g/l) and total cholesterol (3.8 mmol/l), as well as increasing concentrations of ALT (106,8 u/l), ACT (TO 124.4 u/l), GGT (316,9 u/l), the remaining parameters within normal values; 4) ECG: sinus rhythm, right, HR=80 min, EOS - normal position, diffuse changes of microdesign, the heart and large vessels without features; 6) ultrasound of the abdominal organs, kidneys: Conclusion: hepatomegaly due to the left lobe of the liver with diffuse changes of the liver, portal hypertension, splenomegaly; 7) Esophagogastroduodenoscopy: Conclusion: varicose expanded veins of an esophagus 2 tbsp., peptic esophagitis, cardia insufficiency, superficial gastritis; 8) Psychometric testing: test connection numbers Reagan patient was performed for 53 seconds (taking into account the age factor), which corresponds to stage 1 of PSE; 9) EEG: focal pathology of bioelectric potentials in the cerebral cortex have been identified, there are diffuse cerebral EEG changes in the form of pronounced spilled irritation of the cortex and effects of bilateral synchronous paroxysmal activity from the deep divisions of the cerebral hemispheres.

The study CZK in peripheral blood serum: increased percentage of propionic acid (C3) - 8,9%; butyric acid (C4) of 5.0% and a decrease in the percentage of acetic acid (C2) - 86.1% of the total content C2-C4; increased isovalerianic acid (ISOs) - 5.5% in the total content C2-C6; the value of the ratio ISOs/ISOs=1,45. D. treatment using hepatoprotective, enzyme funds blockers aldosterone and duphalac (lactulose).

Example 3

Patient F., 63 years old, was taken by ambulance from the street with a referring diagnosis: Chronic hepatitis nutritional etiology in the stage of cirrhosis. Portal hypertension, ascites. Hepatic cell failure. Portosystemic encephalopathy stage 3.

Complaints at admission was not charged due to the severity of the condition and the severity of lower intelligence.

The history of the disease it is impossible to collect.

Data of inspection: a serious condition, the spoor. The patient is lethargic, the inspection does not respond, responds only to loud voice. Pale skin, swelling of the feet and lower legs, breathing vesicular weakened in the lower divisions, no wheezing, heart tones are muffled, rhythmic, HR=90 / min, BP=150/100 mm RT. Art., belly increased in volume due to ascites (relaxed). Liver and spleen not palpable because of ascites. S/m tapping negative. Muscle tone is increased, tremor +.

The results of the survey: 1) complete blood count: HB - 98 g/l, er. - 2,5110, leukocytes - 9,010, five - 2, SJ - 66, E. - 2, HP - 20, m - 10, platelet - 28610, ESR - 22 mm/h; 2) a General analysis of urine: dark yellow, full transparency, 1012, is th, HR=90 min, EOS - deviation to the left, LV hypertrophy, diffuse changes of a myocardium; 4) chest x-ray: lung fields clear, the structural roots, sines free, diaphragm movable, LV the hypertrophied heart, aorta sealed. Conclusion: the atherosclerosis of aorta; 5) Research CZK in peripheral blood serum revealed an unchanged percentage of acetic acid (C2) - 90.3 per cent, propionic acid (C3) - 7.1% and butyric acid (C4) - 2.6% in the total content C2-C4; increase of the percentage of isocaproate acid (ISOs) - 12.3% in the total content C2-C6; the value of the ratio ISOs/ISOs=6,7. These results may indicate dyscirculatory encephalopathy.

In accordance with the results of the study CZK civardi blood diagnostic concept was modified and submitted to the following: cerebral vascular accident by ischemic type?

Hypertension stage 2, aggravation. IHD: Angina 2 options. class. Generalized atherosclerosis: vascular heart, brain, aorta. Dyscirculatory encephalopathy stage 3. Insufficiency of blood supply to 3 phase.

In the future, this diagnosis was confirmed through the second fluid; 7) ECHO-AG: marked shift of median structures of the brain to the left; 8) Doppler ultrasound of the carotid arteries: stenosing process in the system right internal carotid artery, the blood circulation of blood flow in both vertebrate arteries. Changing hemodynamics with a decrease in the rate of blood flow in the right internal carotid artery; 9) the Study of the fundus of the eye: optic disc pale pink color, border, clear, arteries narrowed veins are enlarged, twisted, field of vision within normal limits; 10) ultrasound of the abdominal organs, kidneys: Conclusion: chronic pyelonephritis, chronic cholecystitis; 11) In the biochemical analysis of blood marked increase in the concentration of total cholesterol (7.4 mmol/l) and triglycerides (2,33 mmol/l), other indicators do not differ from normal values.

The treatment of the patient was conducted in the Department of neurology with a positive effect.

The reliability of the method was confirmed by comparison with other diagnostic tests (psychometric testing, EEG). Sensitivity and specificity studies CZK in serum for the diagnosis of PSE (including support for PSE parameters) is 94% and 92%, respectively, and TE (considered diagnostic markers TE) - 90 and 93% solstone 78 and 81% for PSE, 80, and 82% for DE).

Thus, the proposed method of differential diagnosis of encephalopathy allows to achieve high accuracy verification Genesis encephalopathies in each case, does not depend on the number of objective reasons: the seriousness of the patient, it is impossible to conduct additional research at a low cost research and considerable reduction of time to obtain results, which in turn allows for a timely start of pathogenetic therapy.

The method of differential diagnosis of encephalopathy, which consists in determining the concentration and qualitative composition of short-chain fatty acid fraction WITH2-C6with isomers in serum of portosystemic encephalopathy shows the change in the relative content of acetic, propionic and butyric acids (C2WITH3WITH4), manifested in the increase in the percentage of propionic within 8,2-9,0%, oil in the range of 4.9-5.4% of the acids and the decrease in the percentage of acetic acid within 86,8-85.6% in the total content of C2-C4; increase of the percentage of isovalerianic acid in the range of 4.4 to 5.8% in total,92-1,94 when compared with normal; these changes occur together, discirculatory encephalopathy shows the same relative content of acetic, propionic and butyric acids (C2WITH3WITH4), where the percentage of acetic acid is within 89,6-91,2%, propionic 6.5 to 7.4% and oil 2,5-2,9%; increase of the percentage of isocaproate acid in the range of 11.0-12.6% in the total content of C2-C6and the values of the ratio of its6/ISOs5equal to 4,4-6,82; these changes occur in conjunction.

 

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