DOCTORATE THESIS THE STUDY OF CEREBRAL VASCULAR AND NEUROPHYSIOLOGIC CEREBRAL MANIFESTATIONS ON A GROUP OF PACIENTS SUFFERING FROM CHRONIC ETHANOLISM

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1 UNIVERSITY OF MEDICINE AND PHARMACY CRAIOVA MEDICINE FACULTY DOCTORATE THESIS THE STUDY OF CEREBRAL VASCULAR AND NEUROPHYSIOLOGIC CEREBRAL MANIFESTATIONS ON A GROUP OF PACIENTS SUFFERING FROM CHRONIC ETHANOLISM Abstract DOCTOR Dr. NICOLAESCU ADRIANA-ANA SCIENTIFIC SUPERVISOR Prof. Univ. Dr. SIMONA GUSTI 2010

2 THE STUDY OF CEREBRAL VASCULAR AND NEUROPHYSIOLOGIC CEREBRAL MANIFESTATIONS ON A GROUP OF PACIENTS SUFFERING FROM CHRONIC ETHANOLISM Key-words: Chronic Alcoholism, Strokes, Alcoholism, Psychic Disorders, Doppler Ultrasound Vascular Exploration, Vascular Hypertonic. In the first part of the thesis, there has been presented a short history of the problems related to anatomopsysiopatologic data of cerebral circulation, investigation methods, especially new methods, their interpretation taking into account clinical and paraclinical aspects, the study of alcoholism and its effects over organism, neurological and psychiatric manifestations of chronic ethanolism. The second part comprises personal research grouped into 4 chapters such as: material and methods, results, discussions and conclusions. Chapter Material and methods comprises: - The study of 250 pacients suffering from chronic ethanolism, clinically, neurophysiological and imagistically monitored, at 3 and 6 months of treatment and abstinence, the characteristics of groups of pacients according to: sex, age, origin, quantity of alcohol consumed, disease duration; - Complete neurological and psychiatric exam, using MALT test, imagistic actual exploration, such as Nuclear Magnetic Resonance, cerebral tomography, electroencefalography, cerebral vascular non invasive exploration, with DOPPLER ultrasounds;

3 - Statistic processing. For statistic analysis of data, I have used the Programme EPI Info2000 and SPSS, specialized in scientific statistic calculations. Registration and processing of pacients data has been made in Excel, DATA ANALYSIS Module. I have used Analysis Data Module of EPI Info 2000 programme, specialized in statistical tests, graphics and tables. Personal results are presented in chapter 6, grouping them as it follows: clinical and paraclinical parameters, during initial evaluation, evaluation after 3 and 5 months of treatment and abstinence, comparisons between imagistic parameters, clinical - paraclinical correlations both during initial evaluations and final evaluations. Correlations between DOPPLER vascular parameters and cerebrovascular Nuclear Magnetic Resonance, Correlations between Computed Tomography and Alpha Electroencephalogram ultrasounds. Correlation between consumed beverage and strokes, correlation between Computed Tomography modifications and vascular DOPPLER. Obtained results have been compared to actual data from specialized literature, resulting in similarities: major neurological clinical symptoms and pshychological symptoms in chronic ethanolism, have favourably evolved after 12 months of treatment and interruption of alcohol consumption, Electroencephalogram parameters (lower alpha rhythm and diminishing of amplitude direction) are similar to those in specialized literature, the aspect of eye fundus (hypertensive angiopathy), pulmonary radiological examination (interstitial pneumonia) correspond to specialized literature, electrocardiographic parameters and arterial pressure reflect modifications in chronic alcoholism as revealed by specialized literature (arterial systolic pressure lowers and diastolic arterial pressure grows) electroencephalographic modifications (left ventricular hypertrophy, left arterial hypertrophy, former ischemia or inferior ischemia); From numerous parameters of non invasive explorations I must underline the presence of unilateral and bilateral cortical atrophy during the examination of Computed Tomography and Craniocerebral Nuclear Magnetic Resonance, the reduction of cerebral irrigation amid a hypertonian cerebral circulation when

4 performing Doppler Cerebral Examination. There has been noticed a correlation highly significant statistically between the evaluation of resistance index and the type of atrophy observed when performing Computed Tomography and Nuclear Magnetic Resonance. As a result of the analysis, I have noticed that chronic ethanolism represents a risk factor for ischemic and hemorrhagic cerebral vascular accidents. There has been observed the presence of ischemic cerebral vascular accidents at 84% from the studied group, especially at the age group years old, and at men, while cerebral vascular accidents at 10% from examined ill persons, and at group age 40-49years old, especially in the case of men. Analysing the type of beverage in relation to AVC, I have noticed that ischemic cerebral vascular accidents have been produced especially at the consumers of alcoholic beverages. From precipitant factors and causative factors concerning the apparition of vascular accidents there must be noticed the flares of arterial pressure and the stress that have favoured at 5% form the pacients the production of ischemic vascular accidents and at 6% hemorrhagic vascular accidents.

5 Conclusions 1. The subjects of the research have been 250 pacients suffering from chronic alcoholism, 185 men (74%) and 65 women (26%) of years old; the average age being 54,4. Living environment has been predominantly rural (72%). 2. The largest number of alcohol consumers have been men, group age years old, from rural environment and those who have been consuming alcohol between 3 and 5 years. From the examined group, 44% have consumed between g. alcohol/day and 32% more than 250 g/day. 3. The group of pacients has been investigated clinically and paraclinically, using actual imagistic neurphysiologic noninvasive methods such as NMR and CT, cerebral vascular expolartion with Doppler ultrasound and using these parameters at the first hospitalization, at 3,6 and 12 months of treatment and interruption of alcohol consumption. 4. The distribution of pacients corresponding to every year has revealed a growth of 31,6% of the number of pacients suffering from chronic alcoholism from 2005 to 2008, explained by the lack od addresability towards hospitals during this period (the largest number of pacients belonging to rural environment), but also due to stress as a result of world crisis that has been affecting our country form 2008 to the present. 5. As a result of neurologic examination of the studied group, at first spitalization, there are several aspects that need to be mentioned: walk problems, walk and balance disorders, tactil disorders, painful superficial, vibratory, mioartrokinetic, stereognozy disorders, writing and speaking disorders, disorders that have evolved favourably, there have been reduced to 3 and 6 months, and 1 year after alcohol consumption, there have been present unsignificantly(2-4%). 6. As a result of the analysis on the studied group, there has been noticed that chronic etanolism represents a risk factor for hemorrhagic and ischemic strokes (CVA). Therefore there has been noticed the presence of ischemic strokes to 84% from the studied group, especially to the group age years and to men, while hemorrhagic strokes affectd only 10% from the examined patients at to the

6 group age years, especially to men. By analyzing the type of beverage in relation to vascular strokes, there has been noticed that ischemic strokes have been produced especially to alcohol consumers. From the precipitant factors that also favoured the aparition of vascular strokes, there must be mentioned arterial high pressure growths, and the stress that have favoured at 56% from the patients the production of ischemic CVA and to 6% of them hemorrhagic CVA. 7. From the analysis of psichiatric exam I have observed: the tremor, delirium, mental confusion, anxiety at 39% of pacients, at first examination; depressive disorders at 48% from pacients. The modifications have been reduced at more than a half following a year of treatment and abstinence. 8. From EEG analysis on a group of pacients suffering from chronic alcoholism I have noticed a reduction of alpha rythm incidence to 36%, the diminishing of trajectory aplitude at an alcohol consumption between 3 to 5 years. These modifications have been statistically corelated to the presence of bilateral cortical atrophy. 9. CT and NMR exam has evidenced the presence of unilateral cortical atrophy to 70% from pacients (men) and 18% women and bilateral cortical atrphy to 50% of pacients right at first examination, severe modifications, irreversible and preogressive modifications. 10. Cerebral vascular exploration with Doppler ultrasounds has evidenced a reduction of cerebral irigation on a hipertony background in cerebral circulation (evidenced by the growth of resistance index with 16% as opposed to witness group ( clinically healthy and nonconsumers of alcohol, from the same group age). These modifications have been significantly reduced after 1 year of treatment and abstinence. There must be underlined the presence of a significant statistical correlationbetween the growth of resistance index and the growth of diastolic arterial pressure. 11. ECG has evidenced morphologic modifications (HAS; HVS, anterior ischemia, lateral) to 60% from pacients in the case of a daily consumption of g. Of alcohol and rythm modifications (atrial fibrilation, paroxistic tachycardia) at 36% from pacients with a daily alcohol consumption higher 250 g. alcohol.

7 12. Pulmonary Xray has evidenced the presence of interstitial pneumonia and becterial pneumonia at 6%, respectively 4,8% from women and to 4% from men. 13. There has been remarked a highly significant correlation between the values of resistance index and the type of atrophy observed at CT. S Final Conlusion: - There has been developed a clinically and paraclinically complex study on a group of pacients suffering from chronic etanolism, focusing on cerebral vascular and neurophysiologic manifestations by using actual noninvasive methods such as NMR, CT, Doppler cerebral vascular exploration, a study that has not been mentioned by scientific research literature; - Doppler vascular exploration at chronic etanolism is scarcely mentioned the specialized literature and has evidenced important modifications of irigation; - Cerebral irigation methods evidenced have been highly corelated form a statistical point of view with the presence of cortical atrophy at NMR and CT exam, drawing attention on severe modifications, irreversible, and progressive modifications, in the case of chronic etanolism patients, even in incipient phases; - It is highly important to follow a new direction towards profilaxy and early diagnosis (by interdisciplinary colaboration of neuroligists, psychiatrists, psychologists, internists, family doctors) and a highly sustiained sanitary education in the rural environment.

8 E UROPEAN CURRICULUM VITAE Personal information First name(s) / Surname(s) NICOLAESCU, Adriana Ana Desired employment / Occupational field Work experience Nationality Romanian Gender Female Neuropsychiatry Dates 2000 until present Occupation or position held Neuropsychiatrist Name and address of employer Neuropsychiatry Hospital, Craiova Dates Occupation or position held Neuropsychiatrist Name and address of employer Hospital no 2, Craiova : Other specialties Family medicine specialt, Primary Neurologist, General Echography Specialist, Echo Doppler and Peripheral Doppler Specialist Education and training Name and type of organisation providing education and training Dates Promotion 1982 General Medicine Faculty of Craiova Name and type of organisation providing education and training Town Craiova Dates Theoretic Highschool of Calafat Name and type of organisation providing education and training Town Calafat Dates General School No 2

9 Town Calafat List of scientific works -S. GUSTI, A.GUSTI, M.COTEANU, M. ZĂVĂLEANU, A. NICOLAESCU, Studiul unor parametri vasculari Doppler cerebrali la un lot de bolnavi de cervicartroză, Reacţii neuropsihice şi cardiovasculare determinate de eustresul competiţional la un lot de voleibaliste ; Primul simpozion al Societăţii Naţionale de Neuroştiinţe, Investigarea Electrofiziologică a Sistemului Nervos, organizat de Societatea Naţională de Neuroştiinţe şi Universitatea de Medicină şi Farmacie CAROL DAVILLA, Bucureşti, 8 10 octombrie 2004; -S. GUSTI, T. RĂILEANU, A.GUSTI, A. NICOLAESCU, M. COTEANU, D.ENESCU BIERU, Studiul unor manifestări neuropsihice şi cardio vasculare determinate de stress-ul poluării sonore la un lot de muncitori, Al doilea Simpozion al Societăţii de Neuroştiinţe, Stress-ul. Investigare. Atitudine. Perspective, Iaşi, mai 2005; S. GUSTI, M. ŢAPU, A. GUSTI, M.COTEANU, A. NICOLAESCU, Corelaţii între modificările EEG şi vasculare cerebrale DOPPLER la un lot de bolnavi cu maladia Parkinson şi sindroame Parkinsoniene, Zilele U.M.F din CRAIOVA Prezent şi perspective, 35 de ani, Craiova, 3-4 iunie 2005; - T. RĂILEANU, S. GUSTI, A.GUSTI, M. COTEANU, A. NICOLAESCU, Evaluarea irigaţiei şi a activităţii electrice cerebrale la un lot de muncitori expuşi poluării sonore, A XXI-a Conferinţă Naţională a Societăţii Române de Ştiinţe Fiziologice, cu tema Actualităţi ale cercetării experimentale şi clinice în fiziologie, Oradea, Baile Felix, mai 2006; - S. GUSTI, A.GUSTI, A. NICOLAESCU, M. COTEANU, Manifestări vasculare cerebrale şi coronariene la un lot de persoane în vârstă, înainte şi după tratament, Zilele U.M.F din Craiova, Ediţia a XXXVI-a, Manifestări ştiinţifice, Craiova, 9 10 iunie 2006; - M. COTEANU, S. GUSTI, A.GUSTI, A. NICOLAESCU, ŢAPU. M, The study of the velocity DOPPLER cerebral vascular and EEG in a group of Alzheimer`s disease patients, 5th Forum of European Neuroscience, Vienna, 8 12 July 2006; - A. NICOLAESCU, A.GUSTI, S. GUSTI, M. COTEANU, ŢAPU. M, Aspects of cerebral irrigation, EEG and some vascular parameters to a lot of patients with chronic alcoholism, 5th Forum of European Neuroscience, Vienna, 8 12 July 2006; - T. RĂILEANU, A.GUSTI, M. COTEANU, A. NICOLAESCU, S. GUSTI, The study of cerebral circulation, EEG and vascular parameters in a group of

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