Diskospondylitis in a 3 year old Male Castrated Doberman Pinscher Nicholas Sherman Clinical Advisor: Dr. Estey Pre-clinical Advisor: Dr. Scrivani Senior Seminar paper Cornell University College of Veterinary Medicine February 12, 2014 Key words: diskospondylitis, spondylosis deformans, intervertebral disk, vertebrae. Abstract: A 3 year old male castrated Doberman Pinscher, presented to Cornell University Hospital for Animals’ (CUHA) Neurology Service for evaluation following a three month history of inappetance, severe weight loss and neck/ hind leg pain. Spinal pain was neurolocalized to both the cervical vertebrae (C1-C5) and lumbrosacral (L4-S3) region. Lateral spinal radiographs were consistent with progressive diskospondylitis (worst at L2-L3) and severe degenerative changes and spondylosis deformans. Sterilely collected blood and urine were submitted for culture and sensitivity. Both of which returned a result of Staphylococcus pseudintermedius. The patient was treated with intravenous fluids and antibiotics (Enrofloxacin and Cephalexin) in addition to oral pain medication (Gabapentin). His appetite and alertness improved dramatically and he was discharged for continued antibiotic and pain treatment at home. This paper will discuss the workup, treatment and monitoring of diskospondylitis in our patient. Definitions: Due to variability of spinal pathology, it is necessary to establish definitions that allow appropriate understanding of the disease processes. a. Vertebral osteomyelitis or spondylitis - infection confined to the vertebra (Lorenz, 2011). b. Infectious diskitis - infection confined to the intervertebral disk only (Lorenz, 2011). c. Vertebral physitis - inflammation confined to the physeal zones of the end plate (Lorenz, 2011). d. Diskospondylitis - refers to primary infection of the cartilaginous vertebral endplates with a secondary involvement of the disk. i. There is no differentiation of diskopondylitis and diskitis at diagnosis (Burkert, 2005). e. Spondylosis deformans - is a generalized disease of aging that is secondary to the degeneration of intervertebral disks. It is characterized by the formation of bony spurs or complete bridging to reestablish stability to the weakened joint. This is not an inflammatory process and is clinically insignificant (Greene, 2012). Case History: The patient, a 3 year old male castrated Doberman Pinscher, presented to Cornell University Hospital for Animals’ (CUHA) Neurology Service in August 2013 for evaluation following a three month history of inappetance, severe weight loss and neck/ hind leg pain. At the onset of his inappetance in May 2013, the patient was seen by his primary veterinarian, who obtained abdominal radiographs to rule out a gastric foreign body (none seen) as the cause of inappetance and a negative drawer to rule out a cruciate ligament rupture. A treatment trial of Amoxicillin and Carprofen was started to alleviate clinical signs. On the abdominal radiographs, bony changes were seen associated with the vertebrae which were diagnosed as spondylosis deformans at that time. The patient, again presented to his primary veterinarian in July 2013 after no improvement in his clinical signs was seen. Spinal radiographs were taken and reviewed by a radiologist who concluded abundant spondylosis deformans with suspected diskospondylitis and possible cervical spondylomyelopathy (Wobbler’s). No further diagnostics or treatments were performed at that time. Clinical Findings: On presentation, the patient was quiet, alert and responsive. His vital parameters were within normal limits (temperature=101.1F, pulse=110 bpm and respiration=20 bpm). The patient had diffuse muscle atrophy with a body condition score of 3 out of 9. His mucous membranes were pink but he had a prolonged capillary refill time (CRT) of approximately 3 seconds. Pulses were strong and synchronous with heart rhythm and rate. He had limited range of motion bilaterally in the stifle and hocks. Both stifles had medial buttress present. The patient had limited flexion of his neck in all directions. His complete neurologic exam revealed the following findings: Mental status: Depressed Attitude/Posture: Normal Conformation/Muscularity: Diffuse muscle atrophy Gait: Normal Cranial nerves: Normal Proprioception: Normal Spinal Reflexes: Normal withdrawals and patellar reflexes Nociception: Pain noted bilaterally on flexion of the hock and stifle, pain on palpation of his lumbar and cervical vertebrae. Neurolocalization: Cervical (C1-C5) and Lumbosacral (L4-S3) Given the clinical signs and spinal pain; multifocal lesions of the cervical and lumbosacral vertebrae were suspected. Differential Diagnosis: The differential diagnoses for a dog with spinal pain include: intervertebral disk disease (IVDD), cervical spondylomyelopathy (Wobbler’s), spinal cord neoplasia, vertebral body tumor, infectious/inflammatory, traumatic disk herniation or extradural spinal hemorrhage. Due to the several month history and multifocal distribution of lesions, infectious/ inflammatory was most likely. Infectious/ inflammatory causes of spinal pain include: diskospondylitis, vertebral osteomyelitis, physitis, infectious or non-infectious myelitis, polyarthritis or polymyositis. The other differentials are less likely to cause multifocal signs. Based on the fact that all of the clinical signs started at the same time it makes it unlikely that two disease processes were affecting the spine simultaneously. Spinal radiographs are beneficial in that they are able to identify and differentiate radiographic evidence of some of the differentials listed. The disease processes that one is able to visualize radiographicaly include: cervical spondylomyelopathy, diskospondylitis, vertebral osteomyelitis, physitis, bony neoplasia and vertebral fractures. Diagnostics: Imaging: In the case of diskospondylitis there are characteristic radiographic changes that allow the clinician to diagnose and monitor the disease. The first radiographic change is irregular vertebral endplate lysis with extension into the vertebral body. This is followed by collapse of the intervertebral disk space, sclerosis on the periphery of the endplate lysis and ventral enthesophyte production. If the collapse of the disk space is severe enough subluxation can occur (Thrall, 2013). An important attribute is that the lesions often are symmetric affecting the opposing margins of two vertebrae equally. Radiographic changes lag behind clinical signs by approximately 2-4 weeks (Dewey, 2008). The severity of radiographic changes to the vertebrae does not correlate with the severity of clinical signs (Shamir, 2001). It is estimated that 40% of dogs have multiple disk spaces involved at the time of diagnosis, the most frequent combination being thoracic and lumbar (Burkert, 2005). The primary sites of involvement are reported to be midthoracic (T3-4 thru T9-10), thoracolumbar junction (T12- Image 1. Lateral spinal radiograph (L1-2). Normal. 13 thru L2-L3) and lumbosacral junction (L7-S1) (Lorenz, 2011). Around 18% of cases of diskospondylitis that are diagnosed and subsequently started on a treatment regimen increase the number of disk spaces involved (Burkert, 2005). It is speculated that this is due to the lag time between the development of clinical signs and radiographic signs. Lateral spinal radiographs were taken by the primary clinician and sent to a radiologist who suspected diskospondylitis of T7-8, T9-10 and L2-3. Abundant spondylosis deformans was present in the thoracolumbar and lumbosacral regions. Repeat radiographs were performed when the patient presented to Cornell one month later. At that time, the vertebrae from T4-L2, had severe ventral bridging and non-bridging new bone at the intevertebral disk space with partial collapse of most disk spaces. The L2-3 disk space had extensive vertebral endplate lysis (worse Image 2. Lateral spinal radiographs (L1-3) at presentation. ventrally) with severe new bone formation both laterally and ventrally. These radiographs showed a progression of the disease in the one month time span. Diagnostic samples: Approximately 68% of dogs have a concurrent disease conditions at the time of initial evaluation. Typical concurrent conditions include: urinary tract infections, endocarditis, pyoderma/otitis, prostatitis, recent spinal surgery and other less common causes. By far the most commonly implicated concurrent condition is a urinary tract infection (Burkert, 2005). The pathogenesis of concurrent infections causing diskospondylitis will be discussed later in this paper. It is estimated that in approximately 50% of cases a microbial organism can be detected as the causative agent of diskospondylitis (Dewey, 2008). In the United States, bacterial organisms are the most prevalent organisms detected. Urine and blood are the most common samples collected and submitted for culture. Urine cultures are positive between 25-50% of the time while blood cultures are positive 45-75% of the time. It should be noted, that sterile urine cultures are easier to collect than blood and are submitted more frequently. The most commonly isolated bacterial organisms are: Staphylococcus spp, Brucella spp, Streptococcus spp and Escherichia coli, although numerous other organisms have been detected (Burkert, 2005). Brucella is most commonly isolated from intact, male, hunting dogs but it should always be on the differential list for a dog with spinal pain due to its zoonotic potential. Fungal diskospondylitis is more commonly seen with previously immunocompromised patients. The most commonly isolated fungal organism is Aspergillus but other possibilities include Fusarium and Paecilomyces (Greene, 2012). German shepherd dogs have been shown to have a higher incidence of Aspergillus diskospondylitis compared to other breeds (Berry, 1996). The patient’s complete blood count and chemistry profile were unremarkable. Blood was drawn in a sterile manner and submitted for a fungal serology, blood culture and sensitivity and both a Canine Brucella Slide AGGL and AGID II. Included in the fungal serology are Blastomyces AB (antibody), Coccidoides AB, Histoplasma AB, Aspergillus AB and Cryptococcus AG (antigen). In addition urine was collected via sterile cystocentesis and submitted for a urine analysis along with culture and sensitivity. The urine analysis on the patient indicated a cocci type organism was present. Cultures for both the urine and blood isolated Staphylococcus pseudintermedius. The Canine Brucella Slide AGGL/AGID II and fungal serology came back negative for any growth. Staphylococcus pseudintermedius is a facultative, anaerobic, gram positive, coagulase positive cocci that forms clusters. This bacterium is widely distributed amongst animals and is a common commensal of skin and mucous membranes (colonization rates of 31-68% in healthy dogs) (Greene, 2012). This commensal can become opportunistic if conditions are appropriate. Medical Treatment: In hospital, the patient was started on combination of broad spectrum IV antibiotics (enrofloxacin and cefazolin). Gabapentin, a pain medication geared specifically towards neuropathic pain, was given in addition to the NSAID (meloxicam) he was already on. Nitenypyram was given to treat the fleas present on him. These medications along with fluid therapy drastically improved his clinical signs. By the time of his discharge, three days later, he was bright, alert and responsive, euhydrated and had an improved appetite in addition to decreased spinal pain on neurologic exam. He was sent home on oral enrofloxacin and cephalexin for an antibiotic treatment. Meloxicam was discontinued three days after discharge and gabapentin was discontinued a few weeks later. Rationale for medical treatment: The duration of treatment with antibiotics is reported to be between 9-14 months (Dewey, 2008). Clinical signs are expected to resolve in 5-10 days, at that time pain management may be tapered or discontinued to as needed. Patients should remain on antibiotic regimens until radiographic healing has occurred. Radiographic healing can be quicker in dogs less than one year of age (Shamir, 2001). In 50% of diskospondylitis cases an organism is not isolated as the causative agent. In those cases, beginning a regimen of broad spectrum antibiotics such as a fluoroquinolone and 1st generation cephalosporin or beta-lactamase-resistant penicillin is appropriate. The reasoning behind the antibiotic selections comes from the understanding that Staphylococcus spp are the most frequently reported culprits of diskospondylitis (Dewey, 2008). Cephalexin and cefazolin are both 1st generation cephalosporin. They are bacteriocidal and act by inhibiting mucopeptide synthesis in the cell wall resulting in a defective barrier, this ultimately results in rupture of the cell due to osmotic pressure. These are not particularly effective against gram negative bacteria but excellent against gram positive anerobes. Enroflaxacin (Baytril) is a Fluoroquinolone antibiotic that is a concentration dependent bacteriocidal agent. It is primarily effective against gram negative bacteria but can work against some gram positive, and it acts on both stationary and growing bacteria. It works by inhibiting DNA-gyrase (a type II topisomerase), thereby preventing DNA supercoiling and DNA synthesis (Plumb, 2011). Treatment for patients diagnosed with Brucella infections often includes a combination of tetracyclines and aminoglycosides. While an azole antifungal, such as intraconazole, is the drug of choice for a fungal infection like Aspergillus (Dewey, 2008). Recheck Examinations: When monitoring spinal radiographs of patients with diskospondylitis, bone lysis is the only radiographic sign of the progression of the disease while sclerosis and bridging are seen as signs of recovery. Radiographic healing can be defined as an absence of the lytic focus, loss of sclerotic margins, smoothing of margins around the lytic focus, and replacement by bridging or fusion of the involved vertebrae (Shamir, 2001 and Burkert, 2005). Patients may have initial progression of lysis, following appropriate therapy, but then slowly resolve. Once radiographic healing has occurred and the disease appears quiescent, antibiotic therapy can be discontinued. The patient returned for recheck radiographs and neurologic exam four months after the start of treatment. The Image 3. Lateral spinal radiographs (L1-4) at 4 month recheck. owners reported that he was no longer on any pain medication and appeared to be non-painful. He had regained approximately 11kg and his owners were pleased with his improvement and recovery. There were no abnormalities noted on neurologic exam. Lateral spinal radiographs were taken. From T4-L3 it was noted that there was severe, bridging and new bone formation ventrally with partial collapse of the majority of the intervertebral disk spaces. At L2-L3 there appeared to be complete lytic involvement on the vertebral endplates (previously only ventrally). Some further lysis can be seen despite appropriate treatment. Overall the radiographs indicated healing diskospondylitis with progressive, severe, degenerative changes and spondylosis deformans of the thoracolumbar vertebrae. With this radiographic improvement and resolution of neurologic/clinical signs, it was deemed appropriate to begin the staggered withdrawal of antibiotics, and enrofloxacin was discontinued. Radiographic recheck exams are scheduled for every three months until complete radiographic healing has occurred. Prognosis With treatment for bacterial diskospondylitis, the prognosis is fair to good whether or not the causative agent is isolated. If there are severe neurological deficits at the time of presentation/ diagnosis the prognosis diminishes according to the severity of signs. For both Aspergillus and Brucella infections causing diskospondylitis the prognosis is poor. Even with appropriate treatment, life expectancy is only a few months (Lorenz, 2011 and Dewey, 2008). Discussion: The blood supply of the vertebrae, cartilaginous vertebral endplate and the disk itself is important in understanding the pathogenesis and treatment of diskospondylitis. Direct inoculation of the disk space is possible with spinal surgery, abcessation or a migrating foreign body but these causes of diskospondylitis are very rare. By far the most common route of infection is through hematogenous spread. The hematogenous infection often results from a concurrent infection such as a urinary tract infection, oral or heart valve infection. Urinary tract infections are often the most commonly implicated. Once in the blood stream the organism travels through the aorta to the segmental artery then the interosseous artery and finally to a capillary bed with reduced velocity that acts through diffusion to nourish and remove waste from the vertebral endplate and disk itself (these structures do not have a direct blood supply). This diffusion also allows the bacterium to seed the endplate and quickly move to and infect the disk itself. Due to the fact that there is not a significantly abundant circulation in this region it is difficult to achieve a high antibiotic concentration level and therefore results in treatment being protracted over several months (Thomas, 2000 and Shankar, 2009). Circulation also plays an important role in drug selection, such that they should have sufficient bone penetration, like a cephalosporin and/or quinolone. Retrospective studies have been performed to help determine the most common signalment of dogs that are diagnosed with diskospondylitis. They have determined that males are twice as likely to be diagnosed as females. As age increased the dogs became significantly more likely to be affected by diskospondylitis. Large purebred dogs such as Great Danes, Boxers and Doberman Pinschers seemed to be over represented. In summary: older, male, large breedpure bred dogs are most likely to be diagnosed with diskospondylitis (Burkert, 2005). These patients often have a history of unspecific clinical signs over several weeks, but can be acute in nature. Most commonly, animals diagnosed with diskospondylitis do not have any neurologic signs, but if they do they include: spinal pain, general proprioceptive deficits, hind limb paresis or tetraparesis in order of most likely to least likely. Summary: Diskospondylitis is a disease that requires a thorough history taking, physical exam and spinal radiographs. Fifty percent of the time an organism is cultured and the patient is treated according to the sensitivity panel. If an organism is not isolated empiric treatment with a combination of broad spectrum antibiotics is appropriate. Clinical signs often resolve quickly, but due to the pathogenesis of the disease and poor antibiotic penetration at the disk space, antibiotic treatment must be continued for several months. Serial recheck exams to monitor clinical signs and radiographic healing are recommended. With bacterial diskospondylitis the prognosis is often good. This patient was a large, male, purebred Doberman Pinscher with a several month history of inappetance. The physical exam and diagnostics revealed spinal pain and a staphylococcus spp. present in both urine and blood, while lateral radiographs revealed several vertebral endplates with lytic foci and signs of sclerosis and ventral bridging. Our patient responded well to IV fluids, IV/oral antibiotics and pain medication which resolved his clinical signs in approximately a week. 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