CONTRIBUTIONS IN THE THERAPY OF INTERVERTEBRAL DISCOPATHIES IN DOG Abstracts 1. OBJECTIVES OF THE RESEARCH Along thousands of years the dog has earned the title of man`s best friend. But who is this friend? Guardian of man, of his territories and goods, competitor in beauty shows, in races or agility contests, servant of people with sight or hearing deficiencies, policeman that detects dangerous substances or tracks down law-offenders, shepherd taking care of flock, aid in hunting, rescuer on land and in water (in earthquakes or fire), therapy for people with mental illnesses or prisoners, warrior who detect ammunition and ennemies and for most of us friend and family member, especially for those who know the joys of living in their company. We find him in myths and folklore, in religions and in cultural memorials, in movies and art, in cartoons and literature. In present, it is estimated that 400.000.000 dogs are living in the world, coming in all shapes, colors and sizes. This is why pet medicine has developed in the last 50 years to the extent of human medicine. Progresively, the connection between man and dog has made the owner aware of the fact that for a good life together it is necessary to take some prophilactic and treatment assistance. Among illnesses with dramatic manifestations in dogs, there is the intervertebral disk disease (IVDD). Although it is a disorder of the bony system, the clinical signs are neurological, caused by lesions on the spinal cord and nerves (traumas, compressions, iritations, local myelopathies and ischemia). The aggravating potential often leads to paralysis. IVDD affects all tissues in the region: disks, vertebrae, ligaments. Lesions between disks and vertebrae lead also to spondylosis deformans. Often not only local nervous syetem components are affected, but also muscles and organs in the abdominal cavity. From these facts and the present stage of research it was thought that it is necessary to make research in the following directions: - evaluating the incidence of vertebral column diseases in a canine population of western Romania; - establishing clinical, neurological and imagistic characteristics in diagnosis of IVDD (identifying clinical and neurological diagnosis elements to diferentiate IVDD of other spinal cord diseases, evaluation of radiological and clinical criteria to diagnose and localize IVDD and evaluation of utility of MRI exam in IVDD, establishing the best incidence, of MRI parameters and images relevant in diagnosis of IVDD in dog). - evaluating efficiency of IVDD treatment with Helleborus extract. The first part of the thesis contains embryology notions, followed by anatomic presentation of the regions (cervical, thoracic, lumbar and sacral) of the vertebral column; bones (vertebrae), muscles, ligaments, arteries, veins, nerves. For all the joints in the region bones forming them, shape, type, role and function were described. To understand the serious effects of compressions caused by IVDD, the spine and the spinal nerves were described, while the physiology of the vertebral column contains elements of biomechanics, structure and mobility. IVDD was described with its ethiopathogenesis, classification and characteristics,: age, breed, sex, nerve structures, effects of compressions and localizing the disease, history, general and neurological exam. In image diagnosis, there are methods used to determine causes of myelopathies and localizing of lesions. Basic imagistic techniques are radiography and myelography. Other methods (echography, scintigraphy, CT and MRI) are useful in diagnosis, but not so I accesible. The radiological exam part contains incidences used and pathological radiological marks sought in diagnosis and interpretation of pathological images. After notions of morpho-pathological and histo-pathological diagnosis, several diseases were described. There clinical signs prove the importance of diferential diagnosis: congenital diseases of the vertebral column (malformations of the vertebral body, perocomia, transitional vertebrae, vertebral block, hemivertebrae and caudal cervical spondylomyelopathy) and of the spinal cord (malformations like spina bifida, meningocel, myelomeningocel and spinal disraphy), degenerative diseases of the vertebral column (spondylosis deformans) and of the spinal cord (degenerative myelopathy and bony metaplasia of the dura mater), infectious diseases of the vertebral column (spondylitis and discospondylitis) and of the spinal cord, neoplastic diseases, nutrition diseases, traumatic diseases of the vertebral column (fractures and luxations) and of the spinal cord and also vascular diseases of the cord (diffuse haemoragic myelomalacia, ischemic myelopathy). After the description of prognosis and prophylaxy elements, treatment in IVDD was dealt with. The medical therapy consists of steroid or non-steroid anti-inflamatories, myorelaxants and tranquilisers and the surgical consists of decompression by laminectomy or hemilaminectomy and fenestration (profilactic method). In humans, artificial disks are last minute treatments. Restoring the function of a degenerated or disfunctional disk is done by biological reconstruction or arthroplasty Also some polimers can isolate the membranes of the lesioned cells and can protect neurons in cell cultures. Naturist treatment contains phytotherapy in which effects of Helleborus were described as well as the first aplications in human and veterinary medicine. Among other types of treatment, acupuncture, homeotherapy and medication with Alflutop were reffered to. As for physiotherapy, massage, hydrotherapy, electrotherapy, thermic agents and kynetotherapy were mentioned. 2. EPIDEMIOLOGY OF VERTEBRAL COLUMN DISEASES IN DOGS 2.1. MATERIALS AND METHODS Between 2004-2008 research were made on a population of 3693 dogs of different ages, sex and breed in the western part of Romania. Each dog was clinically examined, noting breed, age, sex, size, weight, housing and feeding. In those with vertebral column disorders, detailed neurological and radiological exams were made. The data obtained were noted in a file especially conceived for this study. Based on epidemiology and history, the character of the disease was mentioned (acute or chronic), conditions and clinical signs at the beginning and during the evolution of the disease. 2.2. RESULTS AND DISCUSSIONS The epidemiologic study made on 3693 dogs shows that 631 (17,08%) had one or more diseases of the vertebral column: 11,37% degenerative diseases, 3,03% traumatic, 0,62% congenital, 1,51% inflamatory and 0,54% neoplasic. After the neurological and radiological exam, the localisation of each disease was mentioned, resulting that the most affected segments of the vertebral column are thoracic (48,02%), lumbar (47,37%) and cervical (16,96%). Concerning correlation between localisation and type of affection, it is remarked that in these segments degenerative affections are predominant, with an incidence of 54,52%, 41,90% and 15%. In over 11,25% of the cases more that one affection and more localisations were diagnosed in the same dog, more frequently spondylosis deformans, spondylitis, discospondylitis and traumatic affections. The high percentage of affections localized in the thoracic region can be due to the great number of vertebrae compared to the ones in the lumbar region. Data concerning the dynamics of the incidence of vertebral column diseases in the last five years of study shows an annual growth of degenerative diseases, from 16,66% to II 24,28%. All the other types of affections (traumatic, congenital, inflamatory and neoplastic) had a random evolution and no correlation was made between them. The high incidence of IVDD in the canine population studied in the urban area in western Romania can be due to factors like feeding and housing that can be correlated especially with the incidence of degenerative diseases, the vulnerability of dogs to street accidents, as many roam unattended and the lack of owner`s interest in applying profilactic measures and in asking professional advice especially in the growth period of dogs. 1. Degenerative diseases. IVDD was diagnosed in 420 (66,56%) of cases, that is 11,37%, having the first place among vertebral column diseases. Radiologically and neurologically IVDD type 1 was diagnosed in 155 (36,9%) dogs while IVDD type 2 in 265 (63,09%) dogs, thoracic (54,52%) and lumbar (41,90%) segments being the most affected. In 132 of the dogs with IVDD (31,42%), spondylosis deformans was diagnosed. Incidence differs by breed. Thus in case of IVDD type 1, the most vulnerable are dogs of small and medium size and in case of IVDD type 2, most dogs are of large and medium dogs. These differences are due to liability of chondrodistrophic breeds (Dachshund, Peckingese, Bulldog, Beagle, Basset Hound) to IVDD in comparison to nonchondrodistrophic breeds. Distribution by breed shows that Shih-tzu breed (31,81%) is on the first place, followed by Basset Hound (25%) and Miniature Schnautzer (21,71%) in case of IVDD type 1, while in IVDD type 2, Dobermann (32,25%) comes first, then Boxer (30,85%) and Mioritic shepherd (30,64%). Concerning the age, differences can be seen in the two types of diseases. IVDD type 1 cases were recorded in dogs between 1-6 years, while IVDD type 2 in dogs over 5 years. In the first case, the highest incidence was at 3 years (29,03%), while in the second case at 8 years (24,52%). In IVDD type 1, clinical signs were accute in 32,9% of dogs. In IVDD type 2 clinical signs appear progressively and consist incoordination of pelvic limbs and then paresis and paralysis. Distribution of incidence by sex shows that IVDD type 1 was diagnosed in 43,57% females and in 56,42% males, while IVDD type 2 in 46,79% females and 53,2% males. In neutered dogs incidence was 30% lower. Regarding the relationship between incidence of IVDD and size, it is noticed that IVDD type 1 is predominant in small size dogs (81,29%, compared to 18,7% of medium ones and 0% of large ones). In IVDD type 2, incidence is obviously higher in large breed dogs (85,28%) than in small (1,88%) and medium (12,83%) sized breeds. Dogs of light weight proved to be vulnerable to IVDD type 1, while dogs over 20 kg to IVDD type 2. The study showed that 13,8% of the dogs were overweight, 80,71% had normal weight and 5,47% were underweight. In overweight dogs incidence is 25,6% higher. Housing conditions of the canine population in the study are in correlation with the vulnerability to the disease, thus the data obtained shows that the incidence of IVDD type 1 is significantly higher in dogs kept in apartments at floors and that climb stairs (76,77%), in comparison to those that live in houses or at ground floor (23,22%). In case of IVDD type 2, the phenomenon is reversed; only 17,73% climbed stairs until clinical signs appeared and 82,26% did not. Of the data presented it shows that 14,19% of the dogs with IVDD type 1 were fed industrial food, 58,7% industrial and cooked and 27,09% cooked food. Of the dogs with IVDD type 2, 67,54% got industrial food, 21,88% combined and 10,56% cooked. The dynamics of the incidence by age and by years of study, a strong correlation is noticed between incidence, type of IVDD and feeding and housing system of the dogs. The higher incidence in dogs fed with cooked food can be due to the lack of vitamins and minerals, as well as proteins and glicosaminoglicans (glucosamine and chondroitin-sulfate). It remains partially unaccountable the incidence in dogs with IVDD type 2 fed with industrial food, in which it is 64%, compared to 21,88% and 10,56%. The possible cause can be the long and cumulative effects of some emulgators in the food. Other causes: feeding this along many years as IVDD type 2 appears after 6-7 years and quantity is much biggger in large ogs III than in medium or small ones. It is also important that for financial reasons, often owners feed large dogs with bad quality food. Spondylosis deformans (SD). It was diagnosed radiologically in 6,37% of cases, 45,66% IVDD type 2 and 7,09% IVDD type 1. Out of the breed distribution, it is noticed that the highest incidence was in large and medium breeds over 9 years. Regarding sex, SD is predominant in females (52,89%) compared to males (47,10%). It is shown that housing affects 76% of the dogs kept at ground floors and only 27% of those kept in appartments (climbing stairs). This difference can be accounted for the fact that from the first category take part especially large and medium dogs in which the incidence of spondylosis was higher than in small breeds. The presence of the two diseases (IVDD and SD) in the cases studied can be justified by the fact that in both their ethio-pathogenesis there are nutritional and metabolic causes. Clinically, IVDD is expressed by neurological disorders (pain, contractions, functional deficits, while SD shows very discrete signs and only in evoluated stages. 2. Traumatic diseases were diagnosed in 3,03% of the cases examined and in 17,74% of the dogs with diseases of the vertebral column. 13 (11,6%) were located in the cervical, 43 (38,39%) in the thoracical and 79 (70,53%) in the lumbar region. Causes were: accidents (64,28%), falling from heights (18,75%), bites (14,28%) and hits (2,67%). Most of the dogs were of common breed (32,14%). Regarding the sex distributionof dogs with vertebral column trauma 69,64% were males while 30,35% females. 3. Congenital diseases were diagnosed in 0, 62%, representing 3,64% of the dogs with vertebral column diseases. Localisation was lumbar in 43,47%, cervical in 30,43% and thoracic in 26,08%. By radiologic exam five malformative entities were diagnosed: vertebral block (21,73%), hemivertebra (34,78%), caudal cervical spondylo-myelopathy (17,39%), atlanto-axial instabilitaty (17,39%) and myelo-meningocele (8,69%). 4. Inflamatory diseases. In dog with vertebral column, 8,87% were diagnosed with inflamatory diseases, representing 1,51% of all the dogs examined. 5. Neoplastic diseases were diagnosed in 0,54% of dogs examined and in 3,16% of dogs with vertebral column affections. 3. CONTRIBUTIONS IN ESTABLISHING DIAGNOSIS CRITERIA IN INTERVERTEBRAL DISK DISEASE 3.1. GENERAL CLINICAL AND NEUROLOGICAL EXAM 3.1.1. MATERIALS AND METHODS Research were made on 420 dogs in which by neurological and radiological exam IVDD was diagnosed. For each case a clinical and neurological file examination was filled out containing history data, general exam, neurological and radiological exam, diagnosis, prognosis and treatment. In the history part owners were asked about the following aspects: the moment and circumstances in which the first signs appeared, their evolution in time, if the dog had been already presented to the vet, if any treatments were given and which was the post-therapeutic evolution. Anterior episodes of the disease were noted as well as other diseases that the dog had suffered of. The clinical exam was concerned wih the following functions: cardio-vascular, respiratory, digestive and urinary. In the cardio-vascular system, heart rate, pulse, mucous membranes, capilary refill time and temperature were evaluated. In the respiratory system breathing rate and type were monitored. The digestive system was evaluated by appetite and digestive transit and in urinary system exam urinary transit was examined. The neurological exam consisted of: mental status, static and in moving exam, muscular system evaluation, positioning reflexes (placing, proprioceptive, extensor postural thrust, hemiwalking on thoracic and pelvic limbs, lateral walking on thoracic and pelvic limbs), superficial and deep pain perception and medular reflexes. IV By the degree of neurological deficit the dogs were divided in five categories: 1 pain (cervical, thoraco-lumbar) with no neurological deficit, walking possible; 2 - paresis (muscular instability), weak proprioception, ataxia; 3 - severe paresis, absent proprioception, walking possible only with assistance, ataxia; 4 - paraplegia with or without urinary bladder or defecation control, absent SPP (superficial pain perception), DPP (deep pain perception) present, the dog cannot walk; 5 - paraplegia without urinary bladder or defecation control, the dog cannot walk, SPP and DPP absent. 3.1.2. RESULTS AND DISCUSSIONS Cardio-vascular system and temperature. Heart rate disorders (tahicardia) were present in 23,22% of the dogs with IVDD type 1 and 11,69% of the dogs with IVDD type 2. The pulse was accelerated in 19,35% of the dogs with IVDD type 1 and in 15,47% of those with type 2. It is considered that tahicardia and accelerated pulse were due to pain and fear. Mucous membranes, capilary refill time and hidration degree were normal in all dogs. Regarding temperature, 6,45% of the dogs with IVDD type 1 presented hyperthermia and 1,93% fever. In dogs with IVDD type 2, 4,52% presented hyperthermia, 2,64% had fever and 1,5% were hypothermic. The 10 cases with fever led to the presumption that spondylitis (or discospondylitis) was associated to IVDD. Respiratory system. Respiratory disorders noticed in dogs with IVDD: tahipneea was noted in 25,16% dogs with IVDD type 1 and in 21,5% dogs with IVDD type 2. Bradipneea was noted in 1,88% of dogs with IVDD type 2. Tahipneea was correlated with the acute phase of the IVDD (type 1). In these dogs the percentage was higher due to pain that in this type has a rapid onset. In IVDD type 2 signs appear gradually and pain is not frequent. Most of the dogs with IVDD type 2 presented dispneea and abdominal breathing was present in 18,83% of the cases due to pain in the segments affected. Digestive system. Disorders were noted in 19,76% of the IVDD cases and were manifested by reduced appetite both in dogs with IVDD type 1 (14,83%) and with IVDD type 2 (8,67%). Fecal incontinence was manifestated by dilation, atonia or areflexia of the anal sphincter and noted in 20% of the dogs with IVDD type 1 and in 19,62% of dogs with type 2. Urinary system. It presented obvious changes in 110 of the 420 dogs. In dogs with IVDD type 1,10,32% presented retention and 21,29% incontinence, while in dogs with IVDD type 2, 7,92% presented retention and 15,09% incontinence, both being signs that appear sometimes in IVDD. They were noted in pacients with neurological deficits degree 4 and 5. Neurological exam A. Mental status. At the time of examination, 7,09% of the dogs with IVDD type 1 and 23,77% of the dogs with IVDD type 2 showed signs of depression. These were often noticed in older dogs in which neurological deficites appeared for many months and were accompanied by alteration of the general status due to complications. B. Static and movement exam. In static exam in dogs with IVDD type 1, 43,87% presented paresis (with trembling of limb muscles), difficulty in keeping the pasture, head oriented downwards, cifosis) and 34,19% presented paralisis. In 41,5% of the dogs with IVDD type 2, the followings were observed: difficulty in keeping the support on the four limbs, head oriented downwards, wide stance and cifosis. Of these 9,05% presented paralysis. The high percentage of paresis, noticed in dogs with IVDD type 2 was due to reduces dynamics of this type. On the other hand the high percentage of paralisis in dogs with IVDD type 1 was due to acute onset of spinal lesion. In 92,45% cases paralysis was flaccid, characterised by lack of muscular tonus. In 7,54% of the cases paralysis was spastic. In movement exam locomotory disorders were observed, manifested by ataxia and falling on the pelvic limbs and difficulty in sitting and standing up. They had a higher percentage (77,68%, 50%, and 84,29%) in dogs with IVDD type 2, due to gradual lesions of the motor tracts of the spinal cord. The other evaluated parameters (muscle trembles, wide stance, difficulty in climbing stairs, imposibility to jump and difficult walking) had higher percentages in IVDD type 2. Ataxia was correlated with disorders in the muscular tonus, more specifically the tonus is higher. V Voluntary movement was differenciated by reflex movement. 12,85% of the dogs with IVDD type 1 and 23,29% of those with IVDD type 2 managed to locomote by balancing their bodies out of reflex. In pelvic limbs the test was convincing when the dog was held up by the tail and forced to take steps. If limbs moved in the air, walking was voluntary. If not, it was considered to be motorized, which accounts for important spinal lesions, but not necessarily irreversibile. C. Evaluation of muscular system. A part of the dogs with IVDD showd disorders of the muscular tonus manifested by hypotonia or hypertonia. The latter was present only in dogs with IVDD type one due to lesions on upper motor neurons, as in severe medular compressions inhibition on the lower motor neurons dissapear. The region with the highest percentage of hypertonia was in the pelvic limb muscles. Muscle contractions were due to pain, too. Hypotonia which in our study was predominant in dogs with IVDD type 2 nostru, was due to upper motor neuron lesions. Both in dogs with IVDD type 1 and in those with type 2, most of the cases with moderate and avanced atrophy were registerd in the pelvic limbs (15,48% and 2,58% compared to 31,69% and 24,9%, probably due to the high percentage recorded in the thoraco-lumbar localisation of the IVDD. D. Positioning reflexes. They represent a sensitive indicator to neurological disfunctions, but cannot localise spinal lesions. Results show that there are no significant differnces in the two types of IVDD. In most dogs with IVDD type 2 (in which spinal lesions appear gradually), proprioceptive disfunctions appear before motory paralysis is installed. Excessive wear of nails is another confirmation of the proprioceptive deficit. E. Pain perception. In both types of IVDD disorders of pain perception were noticed in a higher percentage in pelvic compared to thoracic limbs, which shows that spinal lesions were predominantly located in the thoraco-lumbar region than in the cervical one. The dynamics of these values was coroborated with the time elapsed from the onset. DPP was absent in dogs with IVDD type 1 in a smaller percentage than in those with IVDD type 2. An important mark in evaluation of the neurological deficit and in specifying the affected segment is SPP which is diminuated/absent two segments caudally from the site of compression. F. Spinal reflexes. Comparing spinal reflexes tested in dogs with both types of IVDD, it was noticed that most disorders are in dogs with IVDD type 2. Also, in both cases cases with hyporeflexia are more frequent tan those with areflexia. All the testele mentioned above had a diagnostic value. Normal responses stood up for the integrity of the sensitive and motor pathways. The sensitive system is involved in transmitting information about pasture related to the central nervous system, while the motor one is involved in coordonation of responses. Deficits of postural reactions alowed specifications on the type and localisation of spinal compression. If only pelvic limbs were affected, and thoracic not, lesios were situated caudal to T2. If all were affected, lesions were situated cranial to T2. 3.2. RADIOLOGICAL EXAM 3.2.1. MATERIALS AND METHODS Research were made on 420 dogs in which clinically and neurologically IVDD was diagnosed. The goal was identify and describe radiological characteristics of the disease. Radiographies were made at Neurorad Radiology Centre and in the Faculty of Veterinary Medicine in Timişoara. In a part of dogs neuroleptanalgezia was used (acepromasine - ketamine or xylazine - ketamine). Incidences used were: latero-lateral in 269 dogs and ventro-dorsal in 151 (a total of 571 radiographies). Ventro-dorsal incidence was used in cases where the latero-lateral ones did not allow detailed localisation of the lesion. On each radiography 26 intervertebral spaces were examined in each dog (from axis to S1) and changes were noted. For differential diagnosis between IVDD and other clinically similar diseases, the radiographies were examined observing: shape, position and radioopacity of vertebra, their alignement, their bony tissue, the adjacent tissue, their symetry; the margins of the vertebral VI bodies; the distance between vertebrae or width of intervertebral space; intervertebral disk, possibile opacified (mineralizate) areas and their localisation. In coroboration with age, breed, siye, housing conditions and clinical and neurological exam, localisations of IVDD type 1 and 2 and SD were esteblished, as well as the degree of osteophytosis. 3.2.2. RESULTS AND DISCUSSIONS The analysis of results obtained after examining 570 radiographies of the vertebral column shows the importance of exposure parameters that have to be adapted to each animal fiecărui animal în funcţie de talia şi greutatea lui. As for incidence, in all cases latero-lateral exposure was used. This led to identification and radiologic description of vertebral column diseases, but in some cases ventro-dorsal exposure was used to emphasize changes in vertebral bodies and of joints. Thus in cases with IVDD modified and unequally narrowed/widened intervertebral spaces; mineralisation of disk material; displacement of disks in the intervertebral hole; narrowed spaces between articular facets; changes in the margins of vertebral bodies and of discal facets and bony proliferations (osteophytosis) of different degrees were identified. Between the two types of IVDD there are significant radiologic differences which allows establishing the differences between them. In IVDD type 1 mineralisation and discal displacement are predominant, while in IVDD type 2 changes in the intervertebral space an vertebral margins, sclerosis and bony proliferation as well as discal displacement without rupture of the annulus fibrossus were predominant. Concerning shape, position and radioopacity of vertebrae in dogs with IVDD type 1, in 8,38% cases position and alignement changes were noticed and in 3,22% cases radioopacity signs were noticed possibly due to mineral, vitamin and nutritional deficiencies, or to inflamatory processes. In dogs with IVDD type 2, 20,37% of the dogs showed vertebral deformations and 7,16% alignment changes. Changes in margins of vertebral bodies, characteristics for IVDD type 2, were associated with SD in 63,88% of the dogs. The radiological aspect of the intervertebral disks is hard to evaluate. Mineralisation of disks is a characteristic of IVDD type 1, while in IVDD type 2 fibrosis aspects are specific. Also some displaced mineralized areas were noticed. The number of affected intervertebral spaces varies from a dog to the other and by the type of IVDD. Generally more spaces are affected by IVDD type 2 than in IVDD type 1. Although narrowings of intervertebral spaces were different (equal or unequal, dorsal or ventral clippings) the general term of narrowed intervertebral spaces. Most spaces presented equal narrowings in both types of IVDD. Radiological investigations, coroborated with neurological ones, led to identification and localisation of the type of IVDD and of SD. The cervical localisation was present in 5,8% of the cases with IVDD type 1 and in 4,15% of the cases with IVDD type 2. The distribution of localisation does not vary within the two types, in both, C4–C5 being the most frequently affected. Regarding the correlation between cervical localisation and breeds, IVDD type 1 is predominant in small size breeds while type 2 is predominant in large breeds. The thoraco-lumbar localisation was diagnosed in 94,19% of the cases with IVDD type 1 and in 95,84% of those with IVDD type 2, T8-T9-T10-T11-T12-T13 and L1-L2-L3. disks being more predominantly affected. Regarding distribution by brees, the results show that IVDD type 1 is predominant in small breeds, while IVDD in large and medium breeds. IVDD type 1 was associated with SD in 10 cases while in IVDD type 2 in 111 cases. Discussion and interpretation of the results in the present study show radiological characteristics of discopathies related to type, localisation as well as vulnerability of different breeds to the disease. The high incidence in the last thoracic region was due to: the fact that this segment of the column is the most solicited and has a great mobility, the extradural space is more narrow in this region than in the cervical one, thus the discal materialul discal VII leads to a more rapid spinal compression. Also the number of thoracic and lumbar vertebrae is bigger than that of cervical ones (20:7). It was also remarked that between T1-T11 the incidence of IVDD localisations is smaller than between T11-T13 due to several anatomic features: the presence of the dorsal longitudinal ligament (situated on the floor of the spinal canal in the thoraco-lumbar area) and of the intercapitate ligament that extends from T1 to T11, transversally from the head of a rib to the head of the corresponding rib on the opposite side (above the spinal canal), ensuring together the stability of the column. The T11-T13 segment, not being strenghtened by the intercapitate ligament and the costal arch, becomes more mobile and vulnerable to mechanic solicitations, which explains the frequency of the IVDD in these region. Another observation that results from our study is that IVDD type 1 a smaller number of vertebrae are affected than in IVDD type 2. Regarding the association between IVDD and SD, it was observed that SD was present in 68,56% of the dogs with IVDD type 2 with thoraco-lumbar localization and in 5,81% in case of IVDD type 1. Corroborating the data from the neurological and radiological exam it is concluded that most cases with IVDD and different degrees of neurological deficit generated by spinal compression are confirmed radiologically. In all cases radiographies were indispensable to identify changes in intervertebral spaces and to establish the type of treatment. 3.3. MAGNETIC RESONANCE IMAGERY EXAM 3.3.1. MATERIALS AND METHODS The MRI exam was made at the Centre of Imagistic Diagnosis Neuromed in Timişoara. The machine used was a Siemens Harmony Magneton Maestra Class 1 T, year 2005. For study a German shepherd dog was chosen, aged 12, in which by clinical, neurological and radiological exam IVDD type 2 was diagnosed. To imobilise the dog general neuroleptanalgezic intravenous anesthesia was administered: xylazine (2 mg/kg) and ketamine (6 mg/kg). The anesthesized dog was laid on the scanning table in latero-lateral decubitus. The thorax and the limbs were fixed with belts to avoid any moving. The exposure lasted 30 minutes and 425 tomograms were made, slices being of 3-6,1 mm. Of these 9 were chosen for detailed examination of the bony and neurological tissue in the thoraco-lumbar region. The scanning was: axial (transverse), longitudinal (saggital) and coronar (craniocaudal), and relaxation times were T1 and T2. The status of the dog was permanently monitored from the command chamber. The antenna that captures the signal sends it to the computer where by the Fourrier transformance converts it into images. First the lesions suspected were localized in a sagital plan, then in a transverse plan. To select the relevant slices orientative images (called "scout") were made. On the MRI images the bony and neurological tissues of the vertebral column: disk, its degree of protrusion or extrusion (slight, moderated, advanced), its localization (letf, right or centered), the vertebral canal, the spine, the spinal nerves; the articular facets of the vertebrae; the adjacent soft tissues; the subarachnoid and epidural spaces; the quantity of epidural fat tissue (absent, reduced, normal or abundant); the degree of hydration of the intervertebral disk; the degree of spinal compression (light, moderate, advanced); localization of discal lesions (centre, right, left); the degree of compression on the spinal nerves (light, medium, advanced) and the size of the intervertebral disk (normal, enlarged, narrowed). 3.3.2. RESULTS AND DISCUSSIONS The MRI exam proves to be very useful in dogs, enabling detailed visualization of all tissual changes of the investigated body parts. The Siemens Harmony Magneton Maestra Class de 1T machine allowed using technical parameters adequate for emphasizing the qualitatively suitable images in dogs. In T1 images appear with low intensitz signal: air, compact bone, calcifications, necrosis and vessels with rapid flow. The cerebro-spinal fluid (CSF), the spine and the epidural fat tissue cannot be well differentiated between them, as they come in different VIII shades of grey. Normal intervertebral disks are of homogenous grey (medium intensity signal). In T2 images appear with low intensity signal (black): air, compact bone, calcifications and with high intensity signal (white): blood, normal intervertebral disks (more exactly the nucleus pulpossus), liquids, edemas and pathological processes like ischemia and tumors. CSF and epidural fat tissue are of shiny white, the images seem like myelographies. A special T2 image is stir, useful to supress the fat tissue in the skin. In the case taken into study 8 protrusions were diagnosed between C4-C5, C5-C6, C6-C7, T3-T4, T6-T7, L3-L4, L4-L5 şi L5-L6, and 3 disk extrusions localized between T8T9, L2-L3 and L6-L7. Although disk extrusion is not a characteristic of IVDD type 2, the three cases were probably due to the time elapsed since the protrusions. 4. CONTRIBUTIONS TO THE TREATMENT IN IVDD WITH HELLEBORUS EXTRACT 4.1. MATERIALS AND METHODS Research were made between 2003-2008 on 420 dogs of different breeds and sexes in which by clinical, neurological and radiological exam IVDD was diagnosed. Each dog taken into the study was identified and examined before and after treatment. The data obtained were registered into especially conceived examination files. The type of IVDD and the degree of neurological deficit were established, then the dogs were divided into five groups. The Helleborus extract was made at Exhelios Ltd. in Timişoara, having a concentration 2000 times bigger in active principles than the Boicil forte product, homologated and registered in Romania. The extractul was used by an original formula (Dr. S. Bolte) and was injected paravertebrally close to the affected disk. To perform the infiltrations the intervertebral spaces corresponding to the vertebral segments affected by IVDD were located by palpation, where after local antisepsy with betadine the needle was introduced in the direction of the disk and the extract injected. To establish the election spots, spinous or transverse processes and ribs were taken as reference points. Infiltraions were made bilaterally, the angle formed by the needle and the spinous processes being of 45 degrees. The needles varied in lenght according to the size of the dogs and the thickness of the muscular tissues they had to go through. The volume administered varied according to the number of affected disks, to the siye and weight of the dog. In one injection spot the volume was of 0,5 ml in dogs under 5 kg, 1 ml in dogs between 5-15 kg and 1,5 ml in dogs over 15 kg. The total volumul of extract was limited to 2-3 ml in dogs under 5 kg, 6-8 ml in dogs between 10-20 kg and 10-15 ml in dogs over 20 kg. The treatment was applied twice at 2 weeks interval in 392 of the cases with IVDD (149 with IVDD type 1 and 243 with type 2) and was repeated according to the evolution of the disease. By the protocol used dogs were divided into three lots. In lot 1 the treatment administered consisted in paravertebral infiltrations with Helleborus extract. In lot 2 treatment consisted in paravertebral infiltrations with Helleborus extract and vitamine B1 administered orally (10 mg/kg) for four weeks. In lot 3 (comparative) treatment consisted in oral administration of carprofen 4 mg/kg seven days and 2 mg/kg other seven days. In all dogs, physiotherapeutic methods were used (musculo-tendinous massages and reflexotherapy. Also, a part of the dogs were fed (according to financial possibilities of owners) Eukanuba Sensitive Joint diet (Iams Co.) and were given Artrostop (Walmark). Apart from these measures, owners were recommended to protect dogs of excessive efforts and to avoid climbing stairs and being overweight. The efficiency of the treatment was evaluated by neurological exams at 14 days from the last treatment, monitoring the dynamics of functional parameters. Also, each case was monitored by palpation for local reaction, post-injection, signs and duration of possible changes, as well as general reactions and dynamics of main functional parameters (cardio-respiratory and digestive). To evaluate possible adverse effects of infiltrations, lab exams were made to determine the main parameters of hepatic and renal profile in five dogs: ALP (DEA/DGKC1970, Roche, Hitachi 704), ALAT and ASAT (IFCC, Randox, Hitachi 704), IX Creatinine (PAP, Nobis, Hitachi 704), creatinin-kinaze (UV kinetics, activated NAC, Nobis, Hitachi 704), lactic-dehydrogenase (DGKG 1970, Roche, Hitachi 704) and hemoleucogram (impedance/ flux citometria, Diagon, Coulter STKS) in Bioanalitic lab in Timişoara. The blood was drawn before the administration of infiltrations, then in days 2 and 5. 4.2. RESULTS AND DISCUSSIONS The results obtained show that Helleborus extract has therapeutic effect in IVDD according to the moment of treatment and the degree of neurological deficit. The results of the study show that: - in dogs with pain and cervical and/or thoraco-lumbar muscle contractions, signs that appear in the beginning of the discopathy (degree 1), healing with no relapses in the following 12 months was obtained in over 89% of the cases; - in dogs with paresis, ataxia and weak proprioception (degree 2), healing was obtained in 79,67% of the cases, - in dogs with severe paresis, ataxia, absent proprioception and impossibility to walk (degree 3), healing was attained in 65,97% of the cases, - in those with paraplegia and loss of SPP (degree 4), healing was attained in 61,29%, - in those with paraplegia and/or tetraplegia and absence of SPP and DPP, healing was of 58,62%. There is a direct correlation between the degree of neurological deficit and the efficiency of the treatment. In dogs with degree 4 and 5, treatment was inefficient in 6,89% of the cases. The results analized generally show that out of the 392 of the cases treated with se intra and peridiscal infiltrations with Helleborus extract: 73,46% healed without relapse in the next 12 months, 9,18% improved (pain and muscle contractions disappeared), in 7,90% a slight motor neurological deficit remained with relapse after 12 months, in 5,86% a neurologic deficit remained, improvement consisting of regaining SPP, DPP and proprioception, walking possible, but difficult and ataxic, and in 3,57% it was inefficient. Coroborating the dynamics of neurological signs, efficiency of the treatment was maximum in 73,46% of cases, satisfying in 17,08% and absent in 9,43%. The efficiency was higher in cases where vitamine B1 was associated with the treatment. In this case complete healing was attained in 84,12% of the cases compared to cases in which B1 was not associated in which healing was of 73,46%. In this lot, too, it is observed that effeciency is correlated to the degree of neurological deficit, the moment when the diagnosis was established and the start of the treatment. In the lot where treatment consisted in Carprofen 14 days results show that the product improves pain in dogs with degree 1 and 2, but not the neurological signs. They are present along the duration of the treatment and sometimes accentuates after stopping it. Out of the 28 dogs given carprofen, in 7 (10,76%) cases digestive side effect (vomiting, inapetence) were noticed. The reason why carprofen was used in a very few cases is the controversy of studies reffering to its effects. In the statistic study performed regarding the therapeutic response of cases with IVDD type 1 and 2, results show that in IVDD type 2 complete healings without relapse in the next 12 months were more frequent than in IVDD type 1, regardless of the degree of neurological deficit. Clinically, after infiltrations, in 78,5% of the cases increase of pain and muscle contraction in the area near the site of inoculation and intensification of neurological signs were noticed in the first 2-4 days. In 64,8% of the dogs depression, anorexia and sometimes vomiting were noticed, signs that disappeared spontaneously in 24-48 hours. In the 392 cases studied there were no other side effects, general or local. At the exam made at 5-8 days and 14-20 days no local reactions were detected. The dynamics of the therapeutic effect varied in limited ranges from a dog to another. In most of the cases, at 3-6 days from infiltration SPP and DPP reappear, as well as proprioception and gradually in 15-30 days the dog regains his pasture and walking, which becomes normal in the following days. Clinically neurological signs disappear gradually, pain and muscle contraction (degree 1 and 2) disappear, the dog can bear superficial and X profound palpation in the affected vertebral segment. In dogs with paresis gradual improvement of the motor and sensitive reflex is remarked, ataxia disappears and locomotory dynamics normalizes. The dynamics of neurological signs disappearing is slow. From one interval to another dogs regain the withdrawal reflex at the stimulated limb, then the contraction of cutaneous muscles. Gradually, the dog can stand up and walk, first unstable, then more and more tonic and coordinated, being able to walk in the following 10-20 days. Regarding the efficiency of treatment correlated with localization of IVDD, results show that the percentage of recovery was higher in cases with thoraco-lumbar localization compared to the ones with cervical localization. This difference can be due to the fact that a more exact localization of election sites in the cervical area is more difficult and the injected extract does not get close enough to the disk affected and to the fact that in the cervical region the vertebral canal is wider, the disk being further from where the extract can be inoculated. The results of the necropsic exam performed at 4 days since infiltrations show changes in tissues that are characterized macroscopically by congestion and vasodilation associated by edema and the presence of a serous transsudate, lesions characteristics to inflamation. These changes were extended on 1,5-3 cm around the inoculation site. The inflamatory reaction explains the exacerbation of pain noticed in the first 72 hours after infiltrations. In all the dogs, the local exam performed by palpation and inspection of injection sites after seven days, there were no signs of inflamation or other disorders. The discolitic effect of Helleborus applied by an original protocol is demostrated by previous research in which it was established that after intratisular injections (intradermic, subcutanous, intramuscular or intratumoral) a process of necrolysis is produced. Its intensity varies according to the concentration and the purification degree of the extract. Regarding general effects, some dogs showed slight bradicardia, associated with bradipneea and gastro-intestinal hypermotility, signs that disappeared spontaneously after 412 hours. The lab investigations show no significant changes in the main hepatic, renal and hematologic profile. Also, no accidents or complications, no allergic or anafilactic reactions were registered in the 392 cases after injections, which certifies the security of the extract. The effect and the efficiency of the therapeutic protocol applied in IVDD on a large number of cases leads to the hypothesis that the Helleborus extract has a lytic action upon disks and peridiscal tissues, thus a process of tisulary distruction occurs, leading to decompression of the spine and/or spinal nerves and improving or disappearing of neuronal disfunctions. GENERAL CONCLUSIONS, ORIGINAL CONTRIBUTIONS AND RECOMMENDATIONS FOR PRACTICE The resultats of research that made the object of the doctoral thesis bring personal and original contributions: - the evaluation for the first time in our country of the incidence and types of diseases of the vertebral column in dogs; - identification of diagnosis characteristics in intervertebral disk disease; - evaluation of efficiency of treatment in intervertebral disk disease in dogs by intraand peridiscal infiltrations Helleborus extract by an original protocol and in national and international premiere; - conceiving prophylaxy measures and supplementary therapy in intervertebral disk disease in dogs. The results of research led to the following general conclusions: 1. The incidence of vertebral column diseases in a population of 3693 dogs from the western part of Romania is of 17,08%. Degenerative affections are predominant (11,37%), followed by traumatice (3,03%), inflamatory (1,51%), congenital (0,62%) and neoplastic (0,54%) ones. The incidence is in direct correlation with the breed, age, sex, height, housin and feeding conditions only in the case of the intervertebral disk disease, in the other types being random. XI 2. In degenerative diseases, the intervertebral disk disease is predominant; its incidence is 66,56% of the total of vertebral column diseases. Breeds with small size and weight, under five years, kept at floors and fed cooked food are vulnerable to intervertebral disk disease type 1, while breed of big size and weight, over six years, kept on the ground and fed industrial food are vulnerable to intervertebral disk disease type 2. 3. Incidence distribution on segments of the vertebral column shows that in 54,52% of cases intervertebral disk disease affected the thoracic segment, in 41,9% the lumbar one, in 15% the cervical one, and in 11,42% multiple localizations were diagnosed. In 31,42% of the cases SD was associated. Regarding breed distribution the most vulnerable were Shih-Tzu dogs (31,81%), followed by Basset Hound (25%), Miniature Schnautzer (21,73%), Poodle (21,49%), Cocker spaniel (21,42%) and Peckingese (21,05%) in intervertebral disk disease type one and Dobermann (32,25%), followed by Boxer (30,85%) and Mioritic shepherd (30,64%) in intervertebral disk disease type 2. 4. Neurological exam is compulsory and essential in dogs with intervertebral disk disease. If it is performed sistematically and thoroughly it supplies objective diagnosis and prognosis characteristics. Evaluating and establishing neurological functional deficits are the most important among these. The data of the neurological exam corroborated with imagery investigationslead to establishing the therapeutic outlines, particularir to each case, according to type, localization, evolution and complications related to the neurological deficits. To identify disks affected, an essential mark is represented by superficial pain perception which is diminuated or absent two segments caudally from spinal compression. 5. Radiological examination data confirm largely the data of the neurological exam. In 420 dogs with intervertebral disk disease on 571 radiographies the following aspects were identified: narrowing of the intervertebral space and mineralization of the disk in intervertebral disk disease type 1 and changes in intervertebral space and articular facets sclerosis and bony proliferation in intervertebral disk disease type 2. 6. Investigation by magnetic resonance imagery is clearly superior to other means of imagistic investigation (radiography, echography) and supplies detailed images of all the structures investigated. The Siemens Harmony Magneton Maestra Class de 1 T machine is useful in dogs and allows adapting of functional parameters to the anatomic characteristics of the dog and of the regions investigated. 7. The clinical study performed on 392 dogs with intervertebral disk disease show that treatment with Helleborus extract by an original protocol is an alternative to surgical treatment. The efficiency of the treatment is correlated with the duration of the disease and the neurological deficits. The results obtained show that healing without relapse was obtained in: 89,47% of dogs in incipient stages (degree 1); 79,68% of dogs with paresis, ataxia and diminished proprioception (degree 2); 65,97% of dogs with paresis, proprioceptive deficit, ataxia and assisted walking (degree 3); 61,29% of dogs with paraplegia/tetraplegia, absence of superficial pain perception (degree 4); 58,62% of dogs with paraplegia/tetraplegia, absence of superficial and deep pain perception (degree 5). 8. Analized generally the results of treatment by intra- and peridiscal infiltrations with Helleborus extract show that no matter the degree of neurological deficit spp. it is efficient and leads to complete recovery in 73,46% of cases, in 9,18% to improvement, in 7,90% to improvement with the remaining of neurological deficit degree 1, in 5,86% improvement with the remaining of neurological deficit degree 2. In 3,57% treatment was inefficient. Evaluating neurological sign dynamics it is obvious that in 73,46% efficiency is maximum, in 17,08% satisfactory and in 9,43% un satisfactory. 9. The efficiency of the treatment grows from 73,46% to 84,12% when it associated with vitamine B1 and proper housing and feeding. The treatment was more efficient in cases with intervertebral disk disease type 2 and in thoraco-lumbar localizations. 10. The Helleborus extract administered by original protocol has a therapeutic efficiency that can be compared to the one obtained by infiltrations with chemopapain, colagenase or ozone. Corroborating local effecs with healing dynamics it can be affirmed that even in the case of Helleborus therapy spinal decompression is produced by a process of discolisis, similar to the one produced by chemopapain or colagenase. XII 11. Helleborus extract used in concentrations and doses used on the dogs taken into study induces local postinjectional reactions characterized by congestion and vasodilation associated with edema and the presence of a serous transsudate and general reaction manifested by digestive disorders (vomiting, nausea), side effects that disappeared in 4-6 days from the treatment. No accidents or local/general complications were registered. 12. The results obtained by neurological and radiological exam on a well selected and numerous case load allows the recommendation of Helleborus extract therapy in practice as an efficient and secure alternative in intervertebral disk disease. 13. Therapy of intervertebral disk disease by Helleborus extract is an absolute premiere. The resultats obtained compel to continuation of research to discover the mechanism of action and to patent the therapeutic method and to homologate a product for veterinary use with the indication of being used in intervertebral disk disease. The results of the research corroborated with data from speciality literature allowed us to make supplementary recommendations and prevention measures, as well as treatment measures and special care for dogs with intervertebral disk disease. XIII