SEROTONIN AND AMYOTROPHIC LATERAL SCLEROSIS.

Selective degeneration of motoneurons is the pathological hallmark of amyotrophic lateral sclerosis (ALS). Does serotonin (5-HT) play a role in progression or development of disease is under the research. The topic of the present paper is pressing as there is no data available regarding the spread of amyotrophic lateral sclerosis. It is also noteworthy that previous studies have indicated that the pathogenesis of ALS is closely linked to 5-hydroxytryptamine (5-HT). The clinical research was conducted in Georgia. During the last five years, 60 patients from different parts of Georgia have been studied, searched, and examined by us. Including from Samegrolo, Kartli, Adjara, Abkhazia, Guria, Kakheti regions. The Georgian Neurologists Corps participated and helped us in finding patients. Brain MRI and electromyography were also performed. 60 patients with different forms of ALS participated in the study, including 34 (56.66%) men and 26 (43.33%) women. Their age ranges from 30 to 81 years. The study was conducted after obtaining the written consent of the patients, taking into account the ethical requirements for the study. We also compared the results of the serotonin level of patients with amyotrophic lateral sclerosis with a control group of 20 people (aged 18 to 50 years) who had no neurological disease in past medical history. Patients of the first group, with LMN damage, are observed with decreased amount of serotonin (61.3) %, compared to other pairs, followed by patients of the upper neuron and bulbar syndrome groups, the level of serotonin in the control group is quite high. Thus, the level of serotonin in the group of patients with bulbar events is higher than in the other groups. Low serotonin requires further investigation. According to our research, the longer the anamnesis of amyotrophic lateral sclerosis patients is, the lower the level of serotonin is observed. It should also be taken into account that a low level of serotonin may be due to the presence of depression, which requires additional research. We speculate that 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.

RISK FACTORS OF AMYOTROPHIC LATERAL SCLEROSIS IN GEORGIA.

Objective - to identify risk factors in patients diagnosed with Amyotrophic Lateral Sclerosis in Georgia directed to The First University Clinic of TSMU and P. Sarajishvili Institute of Neurology. Totally 53 patients, aged 24 to 82 years, were investigated with Amyotrophic Lateral Sclerosis (ALS), defined by "Gold Coast " criteria. We have used the Questionnaire for Environmental Exposures, Toxins, and Neurological diseases developed by Dartmouth-Hitchcock Medical center to identify risk factors, and categorized patients according to the place of settlement and environmental hazards. The control consisted of age and sex matched 50 healthy individuals. The brain was visualized by MRI (1.5T), and Electromyography (EMG) was performed on all patients. ALS risk was higher among those ever holding a job in mechanics, painting, or construction (p<0.05), head trauma or concussion that caused a "blackout" or loss of consciousness was associated with a higher risk of ALS (p<0.01). Demographically more ALS cases were found in Tbilisi and Imereti, compared to other regions (p<0.05). According to our research on Georgian ALS cases, several occupational jobs, Head trauma is associated with developing ALS in Georgia, Research is needed to identify environmental risk factors attributing to higher rates of ALS in Tbilisi and Imereti.

[OUTCOMES OF SURGICAL TREATMENT OF COMPLEX PATHOLOGY OF THE ASCENDING AORTA, AORTIC ARCH, DESCENDING THORACIC AORTA, THROUGH THE "ELEPHANT TRUNK" HYBRID METHOD].

Complete prosthetic surgery of the ascending aorta, aortic arch branches, and descending aorta in patients with aortic arch aneurysm, study and demonstration the possibility of the "elephant trunk" method. The paper describes the technology and demonstrates the results of the first 29 operations of ascending aorta, aortic arch, aortic arch branches and descending thoracic aortic prostheses performed by the staff of the Department of Aortic Pathologies of the Amusov State Institute during 2016-2020. All patients, underwent elephant trunk prosthesis surgery of the ascending aorta, aortic arch, aortic arch branches, and descending thoracic aorta as the first stage of reconstruction of aortic arch pathology. Most of the patients, except for three, underwent the second stage of surgery, endoprosthesis of the aortic arch and descending thoracic aorta through a vascular stent. In case of an aortic arch aneurysm or disruption of the anatomical integrity of blood vessels, restoration of the anatomical integrity of the aortic arch and aortic arch blood vessels or prosthesis of blood vessels in this basin can be performed through "elephant trunk" surgery. Optimization and improvement of preoperative diagnostics, surgical techniques, methods of protection of the brain, spinal cord and visceral organs, the use of hybrid / endovascular techniques allows treatment in case of complex damage to the ascending arch and descending thoracic aorta. The first completely satisfactory results of the performed operations were obtained, the hospital lethality was demonstrated within 10.3%.

CLINICAL CHARACTERISTICS OF ALS IN GEORGIAN PATIENTS.

Amyotrophic Lateral sclerosis (ALS ) is a fatal progressive neurodegenerative disease that affects the upper and lower motoneurons. .The disease is characterized by a plethora of neurological symptoms. There is a lot of information in the medical literature about ALS phenotypes, but the clinical diversity of ALS has not been studied in the Caucasus region and a unified clinical picture has not been conclusively established. In this regard, it is very important to study the symptoms among patients with ALS in Georgia. From 2018 to 2021, we examined 47 patients with ALS living in Georgia from different parts of the country, 23 - female, 24 - male, diagnosed based on clinical picture, electromyographic studies (AWAJI) and who met the EL ESCORIAL -Revised criteria. Also clinical symptom studies were conducted using the Mayo Clinic Laboratory Neurological Questionnaire. Cognitive changes were assessed using Addenbrooke's Cognitive Examination scale (ACE III) and the Frontal Behavioral Questionnaire, the patient's quality of life was assessed by ALSFRS-R. Patients were 26 to 84 years old, the age of onset of the disease was 58-60 years in men, 55-57 years in women. The bulbar type was observed in 21.3%, the upper limb type in 38.3% and the lower limb type in 40.4%. Frontotemporal dementia (FTD), diagnosed in 6 patients (12.7%). No reliable correlation was found between the forms of ALS and FTD. The results of the study showed that ALS is a multisystem disease and is not limited to damage to motoneurons. It is safe to say that ALS has characteristics of polysystemic degeneration, with the predominance of motorneuron damage. Therefore, we consider it advisable to screen all patients with ALS for additional symptoms with a focus on the examination of cognitive function, which ensures the proper management of the disease in the future.

ELEMENTAL CONTENT - GENERAL AND ORAL HEALTH OF CHILDREN.

Aim of study - to determine the composition of the essential macro and microelements in the hair and dental hard tissues and to study the influence of their imbalance on the general and dental health of the child. To assess the state of dental hard tissues, 375 children aged 3 to 12 years were randomly examined in Batumi. Monitoring of the examined children was carried out using standard indices provided by the World Health Organization. To determine the composition of the chemical elements in hair and dental hard tissues, according to the caries status 48 children were chosen from the examined 375 children. We used X-ray fluorescent spectroscopy method to study the qualitative and quantitative content of the chemical elements in the hair and dental hard tissues. The comparative analysis of the dental experience (dmft/DMFT) and the composition of chemical elements in dental hard tissues showed a statistically significant difference depending on caries status. The effect of some essential elements on the general health of the child has also been identified. The study into the composition of the essential macro and microelements in the hair and dental hard tissues revealed a high coefficient of correlation both with the mineralization of dental hard tissues and with the general health of the growing body.

[; SURGICAL TREATMENT OF TRANSPOSITION OF THE GREAT ARTERIES AND AORTIC ARCH HYPOPLASIA].

Aortic arch hypoplasia is a congenital anomaly of the development of the aortic arch, characterized by hemodynamically significant narrowing of one or more segments of the aortic arch. The combination of simple transposition of the great arteries (TGA) and obstruction at the level of the aortic arch is not very common. However, when transposition is combined with the VSD, Taussig-Bing anomaly, this combination is more common. The degree of obstruction at the level of the aortic arch may vary from discrete coarctation of the aorta, tubular hypoplasia of the aortic arch, to interruption. Despite the improvement in the results of surgical treatment of this pathology in recent years, the question of the stage of treatment remains debatable.; The objective of the study was to analyze immediate and long-term results of the correction of transposition of the great arteries and aortic arch hypoplasia.; From 2010 to 2019 at the "Amosov National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine" and "Scientific Center For Pediatric Cardiology and Cardiac Surgery of the Ministry of Health of Ukraine" 76 infants underwent repair of TGA and aortic arch hypoplasia. The study included only patients with two-ventrical physiology and subsequent two-ventrical repair. There were 49 (64%) male patients and 27 (36%) female patients. The mean age of patients was 1.1 ± 0.5 months, mean body weight was 3.7 ± 1.4 kg. The average body surface area was 0.23 ± 0.05 m². Patients were divided into two groups: group I involved 52 (68%) individuals - patients who underwent one-stage repair of TGA and aortic arch hypoplasia, group II included 24 (32%) patients with two-stage repair, consisting of aortic arch reconstruction and pulmonary banding at the first stage and correction of TGA at the second stage. Antegrade selective cerebral perfusion was performed in 24 (46%) patients during reconstruction of the aortic arch.; The in-hospital mortality rate was 5.3% (n= 4). In group I, in-hospital mortality was 3.8% (n=2), and was significantly lower compared to the group II - 8.3% (n=2), p<0.05. Eight patients (14.5%) had delayed sternal closure in the early postoperative period. The average long-term follow-up was 3.7±2.8 years (from one months to 9.1 years). One late death occurred in group II. Aortic arch restenosis developed in 11 (14.4%) patients: 7 (13.4%) patients in group I and 4 (16.6%) patients in group II. Right ventricle outflow tract and pulmonary artery obstruction occurred in 9 (11.8%) patients: in 2 (3.8%) patients from group I and in 7 (29.1%) patients from group II. In the long term follow-up there were no neurological complications and compression of the trachea.; Surgical treatment of TGA with aortic arch hypoplasia is effective in infants with good immediate and long-term results. The study indicates that one-stage repair has better immediate and long-term results, compared to two-stage treatment and may be the method of choice in the treatment of this complex pathology.

[THE ROLE OF ESSENTIAL MACRO- AND MICROELEMENTS IN THE DEVELOPMENT OF SOMATIC AND DENTAL DISEASES].

The purpose of our study was to monitor the prevalence and intensity of dental caries, to establish the relationship between general and dental health and the content of essential macro- and micronutrients in the hair and teeth of children and adolescents. A comprehensive epidemiological study was conducted according to the WHO methodology in 375 children aged 3 to 12 years. It was revealed that the prevalence of dental caries increases with age and amounts to 79.6% at the age of 3-6 years, with an intensity of 5.8; at 7-9 years old - 89.5% with DMF + DF - 6.3; at 10-12 years old - 95.6% with a DMF of 5.2. To establish the relationship between general and dental health and the elemental composition of the body in 47 children, the content of essential macro - and microelements was revealed in the hair and dental hard tissues. The established regularity of the content of chemical elements allows us to assume that elemental homeostasis has a significant effect on the human body, which may be impaired by inadequate supply or incompatibility of the elements. Determination of macro - and micronutrients in hair and teeth is an integrative test in the diagnosis of human health.

[BIOSUBSTRATES AS DENTAL HEALTH INDICATORS IN SCHOOL-AGE CHILDREN].

Lack of essential elements can lead to the development of general and dental diseases. To assess the level of microelements in the human body, the most informative biosubstrates are hair and dental hard tissues, in which the chemical elements are concentrated and fully reflect the quality of essential elements. We examined 34 6-12 years-old children to study the content of essential elements in biosubstrates, as in dental health indicators (in the period of formation and mineralization of most permanent teeth). The analysis was carried out by the X-ray fluorescence spectroscopy method. We studied 8 essential (Ca, Zn, K, Fe, Cu, Se, Mn, Cr) and 9 conditionally essential (S, Br, Cl, Co, Ag, V, Ni, Rb, Mo, Sr, Ti ) chemical elements in hair, and in the teeth - four essential (Ca, Zn, Mn, Fe) and three conditionally essential (Rb, Ni, Sr) trace elements. According to the study, in pupils, with compensated form of caries, was found minimal lack of essential chemical elements with the norm, and in children with decompensated form of caries - significantly low level of essential elements. In particular, the analysis of hair with the X-ray-fluorescence spectrometry method in second group children showed a significant lack of: Ca (0.8 times), Zn (1.2 times), K (1.5 times) Mn (1.8 times), etc. The low content of calcium (259025 ± 35224 ppm), iron (98.59±39.72 ppm), manganese (11.55±7.7ppm) was reported to be relatively low (p<0.05) in dental hard tissues. The exception was the zinc - its number exceeded the established norm by 28.1%, which should be explained by the fact that the zinc reduces the enamel penetration, and thus, transition of chemical elements from saliva to dental hard tissues. Thus, our study has showed that the composition of micro and macro elements in hair and dental hard tissues can be used as indicators of mineralization of dental enamel, dentine and alveolar bone. According to our results dental health changes are associated with the imbalance of chemical elements in biosubstrates.

UNUSUAL MANIFESTATION OF NEUROBORELIOSIS (CASE REPORT).

The paper reported the verified case of neuroboreliosis with unusual clinical presentation of Parkinsonism. Study aimed at establishing the significance of a precise differential diagnosis with substantial analysis of the symptoms of several diseases to avoid the false diagnosis and to conduct the opportune and adequate therapeutic management. We described the case of the diagnosed neuroboreliosis with clinical expression of Multiple Sclerosis (MS) and Parkinsonism. A 44 years old man was diagnosed as MS according to the McDonald's Criteria, who within two years developed typical clinical signs of Parkinsonism. Patient investigated neurologically, Brain contrast MRI (1.5 Tesla) was performed; Cerebrospinal fluid was researched for oligoclonal bands. Blood IgM and IgG were researched against Chlamidia pneumonie, Micoplasma pneumonie, Borrelia Burgdorferi, Herpes simplex 1/2, Cytomegalovirus by ELISA method. Clinically the patient expressed amimic face, oligobradikinesia, extrapiramidal rigidity in all limbs, resting tremor in upper limb fingers, horizontal nystagmus. Brain MRI showed multiple gadolinium enhanced demyelization lesions in periventricular and sub-cortical white matter. CSF oligoclonal bands were positive without dysfunction of blood-brain barrier. Blood IgM, IgG detected to be negative against Chlamidia pneumonie, Micoplasma pneumonie, cytomegalovirus, Herpes simplex ½, while the blood IgG was strongly positive against Borrelia burgdorferi, confirmed by followed Western blot test. Patient was stabilized by puls-therapy with 1 gr/intravenous Solumedrol (5 days) along with Rocephin treatment (2 gr /iv) for 21 days followed by long term treatment with Antiparkin (Carbidopa 250 mg, Levodopa 25 mg). MS and even Parkinsonism in suspicious cases should thoroughly be investigated for differentiation from chronic Neuroboreliosis.

Reversible cerebral vasoconstriction syndrome and migraine: sonography study.

RCVS is characterized by severe headaches with or without focal neurologic deficits and segmental constriction of cerebral arteries that resolves within 3 months. The primary clinical manifestation is recurrent sudden-onset and thunderclap headache. Diagnosis requires cerebral or magnetic resonance angiography (MRA) confirmation and ultrasound monitoring. Our purpose is to discover the difference of ultrasound data between RCVS and migraine. 61 patients (age range 17-60y., 41-female, 20-male) underwent sonography examination using Transcranial Dopplerography (TCD) and Transcranial Color-Coded Duplex Sonography (TCCD) methods. In 29 patients MRA examinations were performed. Group I- 27 patients with RCVS with typical acute-onset of severe headaches. Group II-34 patients- migraine in anamnesis, with 1-2 attacks monthly, control group -15 healthy persons. Ultrasound examinations were performed during 2 months with time intervals of 1-20, 21-40, and 41-60 days. Markedly in migraine group examinations were performed in interictal periods also. Group I-the mean maximum (MM) V(CS)-77,8 ± 14,7 cm/sec, V(MCA)- 127,5 ± 22.8 cm/sec, V(ACA) -115.7 ± 18.4, V(BA)- 74.7 ± 20.1. Lindegaard Index (LI) -3.1 ± 0.5. MRA revealed segmental cerebral artery vasoconstriction. The MCA was involved in 62.9%, the ACA- in 51.8%, the PCA- in 37% and the BAS- in 40.7% of patients. Group II- the MM V (CS)-72.8 ± 12.5 cm/sec, V (MCA)- 118,4 ± 26.7 cm/sec, V(ACA) -105.8 ± 17.6, V(BA)- 74.5 ± 18.1, averaged LI -2,9 ± 0.7. In the majority (61.7%) of this group revealed increased MM V in several cerebral arteries with different combination of involving vessels. No correlation was found between incidence side of pain and /or pain intensity. Both groups exceeded of controls -V (MCA) (63.2 ± 9.5 cm/sec), LI (2.1 ± 0.2), p<0.001) and revealed vasospasm. All data were calculated by nonparametric Binomial test. Obtained data showed no significant difference regarding the vasospasm degree between typical RCVS and migraine, whereas revealed that vasospasm in migraine is more determined to posterior circulation but in RCVS vasospasm has the more diffuse character. Despite the extensive knowledge concerning RCVS and migraine, many uncertainties still exist and further randomized controlled trials are needed for understanding the underlying pathophysiology factors.

Prognostic value of EEG in different etiological types of coma.

Study aimed at evaluation of prognostic value of standard EEG in different etiology of coma and the influence of etiological factor on the EEG patterns and coma outcome. Totally 175 coma patients were investigated. Patients were evaluated by Glasgow Coma Scale (GCS), clinically and by 16 channel electroencephalography. Auditory evoked potentials studied by EEG -regime for evoked potentials in patients with vegetative state (VS). Patients divided in 8 groups according to coma etiology. All patients were studied for photoreaction, brainstem reflexes, localization of sound and pain, length of coma state and outcome. Brain injury visualized by conventional CT. Outcome defined as death, VS, recovery with disability and without disability. Disability was rated by Disability Rating Scale (DRS). Recovered patients assessed by Mini Mental State Examination (MMSE) scale. Statistics performed by SPSS-11.0. From 175 coma patients 55 patients died, 23 patients found in VS, 97 patients recovered with and without disability. In all etiological groups of coma the background EEG patterns were established. Correspondence analysis of all investigated factors revealed that sound localization had the significant association with EEG delta and theta rhythms and with recovery from coma state (Chi-sqr. =31.10493; p= 0.000001). Among 23 VS patients 9 patients had the signs of MCS and showed the long latency waves (p300) after binaural stimulation. The high amplitude theta frequencies in frontal and temporal lobes significantly correlated with prolongation of latency of cognitive evoked potentials (r=+0.47; p<0.01). Etiological factor had the significant effect on EEG patterns' association with coma outcome only in hemorrhagic and traumatic coma (chi-sqr.=12.95; p<0.005; chi-sqr.=7.92; p<0.03 respectively). Significant correlations established between the delta and theta EEG patterns and coma outcome. Low amplitude decreased power delta and theta frequencies correlated with SND in survived coma patients (r=+0.21; p<0.001; r=+0.27; p<0.001 respectively). Standard EEG is the useful tool for elucidation of coma patients with a high probability to recover as well as those patients, who are at high risk of SND in case of recovery from coma state.

Non-convulsive status epilepticus in comatose patients (case reports).

Non-convulsive status epilepticus (NCSE) is relatively rare, but recognized condition observed in non-epileptic comatose patients. In coma state NCSE may be precipitated by stroke, severe electrolyte disturbance, acute intoxication, infection, traumatic brain injury and etc. All these critical disorders can cause coma themselves and without clinical EEG investigation it is impossible to attribute impaired consciousness to NCSE, while the condition can be responsive to anticonvulsant medication. The proper and rapid diagnosis of NCSE is challenging, because it can severely impact the patient and often is a treatable and completely reversible state. Case reports describe the state of three comatose patients affected by severe neurological disorders, who were diagnosed as NCSE after EEG investigation. Nor of these patients were noted to have the epileptic seizures and convulsions. The patients were treated with different anticonvulsive medications (Finlepsin, Levetiracetam, Depakin) and fully recovered from coma state. Frequently, physicians could not suspect presence of NCSE in patients with impaired consciousness because of sufficiently complicated underlying illness. Apparently, clinical EEG investigation is useful to be performed in all comatose patients.

The role of endogenous antiradical protective system in multiple sclerosis.

Present research aimed at investigation of the role of several inflammatory cytokines and free toxic radicals in Multiple Sclerosis (MS) course and disability progression as well as factors that can assist to the early transition of Relapse Remitting MS (RRMS) in Secondary Progressive MS (SPMS). Totally 22 MS patients, 14 RRMS and 8 SMPS have been investigated. Age at disease onset, disease duration, number of relapses and the Kurtzke Expanded Disability Status Scale (EDSS) scores were collected. Control comprised 10 healthy volunteers matched for age and sex. Brain was visualized by Magnetic Resonance Tomography (MRT- Siemens AVANTO-1.5-Tesla). Blood pro-inflammatory cytokines were detected by Enzyme Linked immunosorbent Assay (ELISA). Blood free toxic radicals and antioxidant enzymes were detected by Electron Paramagnetic Resonance Method (EPR). Statistics was performed using the SPSS-11.0. Blood pro- and anti-inflammatory factors (γ-Interferon, IL-6, IL-10) were elevated in MS patients against control. Increased blood IL-6 and IL-10 found in RRMS as compared to SPMS, while γ-interferon was higher in SPMS (p<0.000). Blood EPR specters of Lypoperoxiradical (LOO-) and superoxide anion (O2-) were increased in SPMS patients compared to RRMS and control. Blood EPR specters of antioxidant enzymes: superoxidismutase (SOD), catalase (CAT) and Glutathione reductase (GR) found elevated in RRMS against SPMS and control. Positive correlation was found between γ-interferon and EDSS (r=+0.52 p<0.05) in SPMS and negative correlation established between SOD and CAT and EDSS (r=-0.84 and r=-0.60 respectively, p<0.05) in RRMS. Multiple logistic regression toward the brain MRI Injury volume proved significance of C reactive protein, γ-interferon and CAT. Present research suggested that the state of endogenous protection system and blood content of antioxidant enzymes (CAT, SOD) in MS patients could play a significant role for early progression of RRMS in SPMS.

Dominated EEG patterns and their prognostic value in coma caused by traumatic brain injury.

Study aimed at investigation of dominated EEG patterns in traumatic coma of different severity and to elucidate their prognostic value for outcome of disease within month. A total of 53 coma patients with severe traumatic brain injury have been investigated. Exclusion criteria comprised the patients needing the neurosurgical intervention due to hemorrhage. Brain injury was visualized by conventional CT at admission. The level of consciousness was evaluated by Glasgow Coma Scale (GCS). Patients were divided in 5 groups according to GCS. Electrophysiological investigations were performed on 5th day from development of coma by application of 16 channel computer encephalography. Outcome of coma (death, vegetative state, recovery) was evaluated within month from disease onset. According to dominated EEG background activity patterns the 1st group (GCS=4) showed the delta EEG pattern in 50 % of patients, the beta EEG pattern- in 33.4% and the alpha EEG pattern - in 16.6%. The 2nd group (GCS=5) revealed the delta EEG in 40%, the beta EEG- in 6.7% and the theta EEG - in 53.3%. The 3rd group (GCS=6) showed the delta EEG pattern in 27.8% and the theta EEG pattern- in 72.2%. In 4th group (GCS=7) the theta EEG pattern found in 77.7% and the beta EEG pattern in 22.3%. The 5th group (GCS=8) revealed the theta EEG activity in 80% and beta EEG activity - in 20%. Positive correlation was found between the GCS and the frequency of theta EEG pattern (r=+0.62; p<0.05). Positive correlation was established between the frequency of delta EEG pattern, death and persistent vegetative state (r=+0.57 and r=+0.16 respectively, p<0.05) within month. Positive correlation was established between the frequency of delta EEG pattern and the size of brain injury (r=+0.3; p=0.04). Multinomial logistic regression revealed the significance of brain lesion size, GCS and EEG pattern for functional outcome of coma. In severe traumatic coma patients the delta EEG pattern is associating with deep coma state and predicts the poor functional outcome within month.

Treatment of experimental autoimmune encephalomyelitis by vitamin in animal model.

Study purposed to determine the effectiveness of vitamin treatment in experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis (MS) by comparing several blood serum inflammatory markers, neurological deficiency and histopathological changes in untreated and treated EAE animals. Eighteen, 9-13 week old, male Wistar rats were immunised by 100 µl MOG injection. Clinical signs of EAE scored by a masked investigator. After EAE exposition all rats were divided equally as untreated control and experimental group treated by vitamins (E, C, D3). Blood was obtained from all rats before and after immunization and on 7th day of treatment. ELISA method was used to detect the serum cytokine contents of IL-6, IFN-γ, IL-10. On 10th day of disease the rats were euthanized and transverse sections of spinal cord were divided in 16 areas with score of 1 for each area showing lymphocyte infiltration or demyelination. Mann-Whitney U-test was used for determining the level of significance of differences between sample means. On 7th day of treatment neurological deficiency stayed unchanged in control and was ameliorated in experimental group (p<0.05). Significant histopathological differences were found between control and experimental groups on 10th day of EAE. Serum levels of IFN-γ, IL-6 and IL-10 were elevated after exposition of EAE against healthy rats, while on 7th day of treatment the experimental group revealed the significant differences as compared to untreated control. Positive correlation was found between IL-6 and IFN-γ serum contents and neurological deficiency on 7th day of disease (r=+0.53, p<0.02 and r=+0.49; p<0.01).

Headaches and cerebral blood flow disturbances in patients with chronic nasal pathology.

Study aimed at research of cerebral blood flow and blood NO contents in patients with chronic non-surgical nasal pathology with accompanying headaches. Eighty five patients with non-surgical chronic nasal pathology with accompanying headaches were investigated. Patients were divided in two age categories: 1st group of 58 patients (18 to 55 years), and 2nd group of 27 patients (>55 years). Control consisted of 30 age-matched healthy individuals. CBF was studied by means of Transcranial Doppler Imaging in patients and control. Free blood NO and NO - complexes were measured by Electron Paramagnet Resonance (EPR) method. Statistics performed by SPSS-11.0. In both age categories of patients the mean blood velocity in middle cerebral artery, anterior cerebral artery, basilar artery of patients was significantly increased against control (p<0.05). Pulsation index (PI) found to be decreased compared to control. The blood free NO signals were non-significantly increased against control. The intensive EPR signals of HbNO and FeSNO were revealed in patients and no signals were detected in control. No differences were revealed between clinical groups regarding the blood EPR signals of NO and NO-complexes (p<0.5). Negative correlation was found between the PI and intensity of headaches (r=-0.37; p<0.01). Multivariate linear regression analysis found the significance of longevity of chronic nasal pathology, Pulastion Index and blood hemoglobin contents for Intensity of headaches (p<0.05). It is concluded that CBF disturbances in chronic nasal pathology may result in intensive headaches.

[Acute-phase proteins in patients with primary stroke and prodromal transient ischemic attacks].

A study aimed at investigating of the relationship between concentrations of several acute-phase proteins and clinical course and functional outcome of ischemic stroke in patients with and without prodromal transient ischemic attacks (TIA). Eighty-five patients with baseline moderate severity of stroke (NIHSS=12+/-3,5) have been stratified into 3 groups: 1st group - with first-ever stroke, 2nd - with prodromal TIA two or three months before stroke and 3rd - with prodromal TIA within 4 weeks before stroke. Brain lesions were evaluated on conventional MRI. Clinical course of disease and stroke outcome at 1 month were assessed by the NIHSS - by the Barthel index, respectively. A control group comprised 22 healthy people. Blood free radicals (NO, LOO-) and iron transporting proteins (oxidized ceruloplasmine, Fe3+ transferine), blood nitrate levels (NO2), activity of superoxiddismutase, activity of glutathione peroxidase have been studied. No significant between-group differences in regard to blood NO and LOO- contents, activities of blood erythrocyte antioxidant enzymes were found. Baseline levels of NO2 (p<0,05) and iron transporting proteins (p<0,01) were significantly higher in the 3rd group of patients and were correlated with better clinical course of stroke and better functional outcome (r=-0,31 and r=-0,37 respectively, p<0,05). It can be supposed that the elevated level of protective proteins in the 3rd group is caused by the development of ischemic tolerance.

Dopplerographic correlates of headaches accompanying the chronic nasal and nasopharyngeal pathology.

The present study aimed at research of cerebral blood flow in patients with chronic nasal and nasopharyngeal pathology with accompanying headaches before and after appropriate treatment. One hundred and six patients with chronic nasal and nasopharyngeal pathology, aged from 6 to 75 years, 57 male and 49 female have been investigated. According to the type of nasal and nasopharyngeal pathology patients were classified in 5 groups, and were divided in three age categories: 6 -18 years (39 patients), 19- 65 years (38 patients), 66-75 years (29 patients). Headaches were estimated by neurologist before appropriate surgical and conservative treatment, after treatment and 6 months later. Cerebral blood flow was studied before treatment, after treatment and 6 months later by means of Transcranial Dopplerography. Control consisted of 30 age-matched healthy persons. Chronic headaches were established in 63 patients (59%). In all age categories the mean blood velocity in middle cerebral artery, anterior cerebral artery, basilar artery was significantly increased against control (p<0.05), and pulsation index (PI) found to be decreased compared to control. After treatment blood flow velocity in the middle cerebral artery, anterior cerebral artery and in basilar artery in all age groups did not differ significantly from control (p<0.5), and PI was significantly elevated against previous data (p<0.05). Cephalic pains disappeared in 75% of treated patients and 25% noted the significant decrease in pain intensity and frequency. Treatment of chronic nasal and nasopharyngeal pathology can prevent the certain kind of cephalic pains, and improve the clinical course of accompanying headaches.

Probable role of immunological tolerance to ischemia injury in brain.

To address the issues of immunological tolerance to ischemia injury in the brain we have researched ischemic stroke patients with and without prodromal transitional ischemic attacks (TIAs) for several blood acute phase reactants involved in inflammatory reactions in respect to initial infarct size, clinical course of disease and functional outcome at 1 month. The study involved 54 ischemic stroke patients aged 45 to 70 years, 46 female and 38 male admitted within 24 hours of symptoms onset in neurological clinic of Georgian State Medical University during 2000-2006. Exclusion criteria comprised severe somatic pathology, liver and renal dysfunctions. Control subjects were aged-matched 15 healthy volunteers, who did not reveal any significant signs of cerebrovascular disease according to the anamnesis, clinical and instrumental investigations. Etiology of stroke was classified according to TOAST criteria. Patients were divided into three groups: the first group - 22 patients with first-ever stroke, the second -17 patients with prodromal TIAs from one to three months before stroke and the third - 15 patients with prodromal TIAs within 4 weeks before stroke. Initial neurological impairment assessed immediately after admission by NIHSS score. All three groups selected with the same initial severity of stroke with mean NIHSS score = 12+/-3.5; for evaluation of clinical course of disease patients were assessed by NIHSS on 7th day of stroke. In 48 hours from stroke onset the blood levels of (IL-1beta, IL-6, TNF-alpha, IL-10) were significantly elevated against control (p<0.05). At this time, no statistical differences were detected between groups regarding the initial blood levels of IL-1beta and TNF-alpha, while the level of IL-6 was significantly lower in the third group (p<0.05). Blood contents of IL-10 and TGF-beta1 found to be non-significantly elevated in the third group against two other groups, while blood TGF-beta1 was significantly increased compared to control. Significant positive correlation was found between IL-6 blood contents and clinical course of disease (r=+0.32, p<0.05). Multivariate logistic regression found the significance of initial blood IL-6 contents for probability of stroke functional outcome at 1 month. It can be supposed that relatively mild blood inflammatory response in third group can be related to occurring of immunological tolerance.

Proinflammatory reactants as determinants of stroke severity in elderly.

Investigations aimed at studying of peripheral blood levels of free nitric oxide (NO) and proinflammatory cytokines IL-1beta, IL- 6 and TNF-alpha in correlation with initial ischemic lesion size and neurological dynamics during a month of acute brain ischemia. Forty two patients aged 60-75 (26 male) have been investigated. Initial neurological status, later deterioration and functional outcome were evaluated using Glasgow Coma Scale (GCS), National institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI). Patients were divided into two groups: severe stroke (GCS15, BI<16, n=25) and a moderate/mild stroke (GCS>10, NIHSSor=18, n=17). The NO concentration was detected by spectrophotometric and Electron Paramagnetic Resonance (EPR) methods. Cytokine plasma levels were determined applying the Enzyme-Linked Immuno Sorbent Assay (ELISA). Statistical evaluation was performed by SPSS. Mean values calculated using the t-paired test. Pearson correlation ad multivariate logistic regression have been applied. In the first days of stroke onset the plasma levels of IL-1beta and TNF-alpha revealed the slight negative correlation toward the functional outcome, while the elderly patients found to have the significant negative correlation of IL-6 plasma levels toward the functional outcome (p<0.01). The NO plasma concentration within 48 hours after stroke onset more profoundly was reduced in aged patients, while in less severe cases and in relatively young patients it was significantly elevated (p<0.01). The high plasma level of IL-6 in the acute phase of stroke seems to be the strong predictor of poor outcome rather for aged, than for younger patients.