Causal Agent Investigation and Treatment of Dogs Diagnosed with Discospondylitis in a Brucella canis Endemic Region.

Discospondylitis is a well-recognized disease in dogs, but the relative prevalence of causal infectious agents and efficiency of relevant diagnostic tests are not well-established. Medical record review identified 117 dogs diagnosed with discospondylitis in our clinic over a 5-year period. In 32 dogs, discospondylitis was diagnosed as an incidental imaging finding; 24 of these dogs had concomitant neoplasia. A likely causal infection was identified in 45 of the remaining 85 dogs in which blood and urine cultures, serology for Brucella spp., and galactomannan fungal antigen testing were recommended. Ten dogs were diagnosed with Brucella canis, and ten were diagnosed with suspected fungal infection. Brucella suis serology was negative in all 35 dogs that were tested. Blood cultures were positive in 28 of 71 (39%) tested dogs, and urine culture was positive in 12 of 79 (15%). Cultures were positive from the lesion site of four of eight dogs that underwent surgery and one of the five dogs that underwent image-guided lesion sample collection. Subluxation secondary to discospondylitis was stabilized with metallic implants in four dogs. A similar proportion of known satisfactory treatment outcomes at last follow-up were recorded in dogs that had suspected fungal disease, other bacterial infections, or were Brucella-positive and in those dogs with imaging diagnosis only, although some individuals continued to receive anti-microbial agents or showed recurrent signs. These data support the value of blood culture in discospondylitis and suggest a relatively high prevalence of infection with Brucella spp. and suspected fungal infection.

Temporal and sequence-related variability in diffusion-weighted imaging of presumed cerebrovascular accidents in the dog brain.

Diffusion-weighted MRI (DWI) is often used to guide clinical interpretation of intraparenchymal brain lesions when there is suspicion for a cerebrovascular accident (CVA). Despite widespread evidence that imaging and patient parameters can influence diffusion-weighted measurements, such as apparent diffusion coefficient (ADC), there is little published data on such measurements for naturally occurring CVA in clinical cases in dogs. We describe a series of 22 presumed and confirmed spontaneous canine CVA with known time of clinical onset imaged on a single 3T magnet between 2011 and 2021. Median ADC values of < 1.0x10-3 mm2/s were seen in normal control tissues as well as within CVAs. Absolute and relative ADC values in CVAs were well-correlated (R2 = 0.82). Absolute ADC values < 1.0x10-3 mm2/s prevailed within ischemic CVAs, though there were exceptions, including some lesions of < 5 days age. Some lesions showed reduced absolute but not relative ADC values when compared to matched normal contralateral tissue. CVAs with large hemorrhagic components did not show restricted diffusion. Variation in the DWI sequence used impacted the ADC values obtained. Failure to identify a region of ADC < 1.0x10-3 mm2/s should not exclude CVA from the differential list when clinical suspicion is high.

Greater trochanter morphology and association with patient demographics, surgical factors, and post-operative stem position: a retrospective assessment of 150 cementless THRs in 135 dogs.

BACKGROUND: Total hip replacement (THR) in the gold standard surgical treatment for the canine hip. While it has been shown that greater trochanter morphology affects post-operative cementless stem position in humans, trochanter morphology and the effect on cementless stem position has not been extensively evaluated in dogs. The objective of this study was to classify greater trochanter morphology and identify potential associations between trochanter morphology and patient demographics, femoral canal geometry, surgical time, technique modifications, and post-operative stem position in client-owned dogs undergoing cementless THR. RESULTS: In this retrospective study, medical records and radiographs of 135 dogs undergoing 150 cementless total hip replacements from 2013 to 2020 were included. Trochanters were classified in the frontal plane using an ordinal grading system adapted from human THR. A Grade I trochanter denoted a trochanter positioned lateral to the periosteal surface of the lateral femoral cortex, whereas a Grade IV trochanter denoted a trochanter positioned medial to the anatomic axis of the femur. Associations between trochanter grade and other variables were examined using ANOVA, Kruskall-Wallis, or chi-squared tests. Significance was assumed at P ≤ .05. Trochanters were classified as follows: Grade I (44/150, 29.3%), Grade II (56/150, 37.4%), Grade III (44/150, 29.3%), Grade IV (6/150, 4.0%). Grade IV trochanters had lower anatomic lateral distal femoral angle (aLDFA; 91.0 ± 6.2°), angle of inclination (117.7 ± 10.5°), and canal flare index (1.53 ± 0.27). When compared to all groups, Grade IV trochanters were associated with longer surgical times (Grade IV: 227.0 ± 34.2 min; all grades: 183.2 ± 32.9 min) and technique modifications (Grade IV: 83.3%; all grades: 18%). Grade I trochanters had stems placed in valgus (- 1.8 ± 2.33°), whereas Grade II (0.52 ± 2.36°), III (0.77 ± 2.58°), and IV (0.67 ± 2.73°) trochanters exhibited varus stems. Depth of stem insertion was greater (11.2 ± 4.2 mm) for Grade IV trochanters. CONCLUSIONS: Trochanter grade was associated with post-operative stem alignment and translation in the frontal plane. Grade IV trochanters were associated with altered femoral geometry, increased surgical time, technique modifications, and stem insertion depth. Pre-operative greater trochanter classification may prove useful in identifying cases requiring prolonged surgical times or technique modifications.

Outcomes and Complications Associated with Acute Gunshot Fractures in Cats and Dogs.

OBJECTIVE: The aim of this study was to summarize outcomes and complications of gunshot fracture management in small animals. STUDY DESIGN: Review of cats and dogs with radiographically confirmed acute gunshot fractures, presenting data on signalment, fracture location, fracture management (surgical vs. non-surgical, type of surgical repair), fracture comminution, extent of soft tissue trauma, postoperative complication and overall outcome. A poor outcome was defined as patient death, major postoperative complication or limb amputation (both as primary treatment or secondary to postoperative complications). RESULTS: Ninety-seven animals with 137 acute gunshot-induced fractures were identified. There were 21 (15.3%) maxillofacial, 16 (11.7%) vertebral column, 8 (5.8%) rib, 56 (40.9%) distal long bone (below stifle/cubital joint) and 36 (26.3%) proximal long bone (at or above stifle/cubital joint) fractures. Overall, 20/37 cases with sufficient follow-up details incurred a poor fracture outcome. Extensive soft tissue trauma at the fracture site was associated with an increased likelihood of poor outcome. The most common poor outcomes were primary limb amputations (7 cases) and postoperative complications (3 osteomyelitis/surgical site infections, 4 delayed/non-unions). CONCLUSION: Gunshot fractures overall have high likelihood of poor outcome. Severe soft tissue injury is associated with complications. Mitigating poor outcome likely requires early aggressive wound management.

The impact of a surgical checklist on surgical outcomes in an academic institution.

OBJECTIVE: To determine the influence of a surgical checklist (SC) on morbidities and compliance with safety measures. STUDY DESIGN: Before-and-after-intervention study. SAMPLE POPULATION: Three thousand two hundred eighty-six dogs: 1375 dogs pre-SC and 1911 post-SC. METHODS: Completion of safety measures and occurrence of morbidity and/or mortality during hospitalization and up to death or 30-days postoperatively were recorded. RESULTS: Safety measures were more frequently completed post-SC, including oral confirmation of patient identity (467/1177 [40%] vs. 1911/1911 [100%]) and oral confirmation of surgical site (568/1175 [48%] vs. 1911/1911 [100%]). In addition, duration of anesthesia decreased from 241 to 232 min (t = 2.824; p = .005); a greater proportion of animals that were intended to receive antibiotics did so prior to incision (1142/1316 [86.8%] vs. 1656/1845 [89.8%] [χ2 = 6.70, p = .01]); and fewer dogs had unplanned return to the OR (32/1065 [3.0%], vs. 21/1472 [1.4%]) (χ2 = 7.52, p = .006). No difference in surgical site infection (adjusted odds ratio 1.02 [95%CI: 0.63-1.66]); morbidity, (adjusted odds ratio 1.00 [95%CI: 0.77-1.29]); or death within 30 days (adjusted odds ratio 1.15 [95%CI: 0.72-1.83]) was detected on multivariable logistic regression analysis. The checklist prevented one wrong-site surgery. CONCLUSION: Implementation of the checklist at our institution led to a decrease in anesthesia duration, increased administration of planned perioperative antibiotics before incision, increased completion of safety measures, and decreased unexpected return to the OR. IMPACT: Despite the lack of effect on morbidities, the use of SC is recommended to improve compliance with safety measures and potentially prevent rare catastrophic events.

Neurologic Causes of Thoracic Limb Lameness.

Although lameness of the thoracic limb typically is due to orthopedic disease, there are several important neurologic conditions that result in lameness. Neurologic diseases cause lameness due to disease of the nerves, nerve roots, spinal cord, or muscles. Common differentials include lateralized intervertebral disc extrusions, caudal cervical spondylomyelopathy (wobbler disease), brachial plexus avulsion, neuritis, and peripheral nerve sheath tumors. Many of these diseases compress or destroy the nerve roots of the cervical intumescence, resulting in non-weight-bearing lameness, or root signature. Advanced diagnostics, such as magnetic resonance imaging, are necessary in these cases to determine the underlying cause.

Assessment of Orthopedic Versus Neurologic Causes of Gait Change in Dogs and Cats.

Diagnosis of forelimb lameness may be challenging, as it not only can be due to multiple common orthopedic diseases but also may occasionally be caused by neurologic disease. A thorough orthopedic and neurologic examination is key to determining which disease category is the likely culprit. Deficits identified on the neurologic examination, such as proprioceptive deficits, changes in reflexes, and presence of spinal hyperesthesia, are key in identifying neurologic causes of forelimb lameness.

Extended durotomy to treat severe spinal cord injury after acute thoracolumbar disc herniation in dogs.

OBJECTIVE: To report recovery of ambulation of dogs treated with extended thoracolumbar durotomy for severe spinal cord injury caused by intervertebral disc herniation. STUDY DESIGN: Descriptive cohort. ANIMALS: Twenty-six consecutive paraplegic dogs presented with loss of deep pain sensation after acute thoracolumbar intervertebral disc herniation. METHODS: Each dog underwent routine diagnostic assessment and surgery for removal of extradural herniated intervertebral disc, followed by a four-vertebral body length durotomy centered on the herniated disc. Each dog was followed up until it was able to walk 10 steps without assistance or until 6 months after surgery. RESULTS: Sixteen of 26 dogs recovered to walk unaided (all but one also recovered fecal and urinary continence), and six dogs did not; four dogs were lost to follow-up. One dog was euthanized because of signs consistent with progressive myelomalacia. There was no evidence of detrimental effects of durotomy within the period of study. Using Bayesian analysis, we found a point estimate of successful outcome of 71% with 95% credible interval from 52% to 87%. CONCLUSION: Extended durotomy seemed to improve the outcome of dogs in our case series without increase in morbidity. CLINICAL SIGNIFICANCE: Extended durotomy appears safe and may improve the outcome of dogs with severe thoracolumbar mixed contusion and compressive injuries associated with acute intervertebral disc extrusion.

Analysis of outcomes following treatment of craniodorsal hip luxation with closed reduction and Ehmer sling application in dogs.

OBJECTIVE To describe outcomes for dogs after treatment of craniodorsal hip luxation with closed reduction and Ehmer sling placement and investigate potential risk factors for sling-associated tissue injury or reluxation of the affected hip at or near the time of sling removal. DESIGN Retrospective multicenter cohort study. ANIMALS 92 dogs. PROCEDURES Case information was solicited from 10 veterinary medical facilities through electronic communications. Data on patient demographic information, cause of injury, presence of concurrent injuries, details of Ehmer sling placement and management, and outcome at sling removal were collected. Data were analyzed for associations with outcomes. RESULTS 40 of 92 (43.5%) dogs had reluxation of the affected hip joint at or near the time of sling removal. Odds of reluxation occurring for dogs that had the initial injury attributed to trauma were 5 times those for dogs without known trauma (OR, 5.0; 95% confidence interval, 1.3 to 18.7). Forty-six (50%) dogs had soft tissue injuries secondary to sling use; 17 of these dogs had injuries classified as severe, including 1 dog that required limb amputation. Odds of severe sling injury for dogs that had poor owner compliance with home care instructions noted in the record, those that had the sling placed by an intern rather than a board-certified surgeon or resident, and those that were noted to have a soiled or wet bandage on ≥ 1 occasion were 12.5, 4.0, and 5.7 times those for dogs without these findings, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Placement of an Ehmer sling following closed reduction of a craniodorsal hip luxation had a low success rate and high complication rate.

Diagnostic Imaging of Discospondylitis.

Discospondylitis can affect dogs of any age and breed and may be seen in cats. Although radiography remains the gold standard, advanced imaging, such as CT and MRI, has benefits and likely allows earlier diagnosis and identification of concurrent disease. Because discospondylitis may affect multiple disk spaces, imaging of the entire spine should be considered. There is a lengthening list of causative etiologic agents, and successful treatment hinges on correct identification. Image-guided biopsy should be considered in addition to blood and urine cultures and Brucella canis screening and as an alternative to surgical biopsy in some cases.

Clinical Evaluation of the Feline Neurologic Patient.

Efficient, gentle, and safe handling of cats can result in complete neurologic evaluations and accurate neuroanatomic localizations. The clinic environment should facilitate the examination by providing a quiet and secure environment for the cat. When direct examination of a cat is not possible, the practitioner should fully use indirect methods of examination and video recordings of cat behavior or clinical signs. Direct examination of a cat should proceed in a logical order, where the most useful tests are performed early on in the examination.

Early Blockade of Matrix Metalloproteinases in Spinal-Cord-Injured Dogs Results in a Long-Term Increase in Bladder Compliance.

Spinal cord injury (SCI) is often accompanied by reduced bladder compliance, which contributes to adverse conditions including urinary tract infections and vesicoureteral reflux. Reduced compliance is, in part, attributed to extensive remodeling of the bladder wall, including the extracellular matrix (ECM). Here, we tested the hypothesis that blockade of matrix metalloproteinases (MMPs), known for their ability to remodel the ECM, improves bladder compliance in dogs with SCI. We first evaluated dogs with naturally occurring SCIs resulting from intervertebral disc herniation (IVDH). After characterizing the natural history of urological recovery by cystometry in healthy dogs (n = 10) and dogs with SCIs (n = 20), we conducted a randomized, double-blinded, placebo-controlled clinical trial in dogs with IVDH-associated SCIs to assess the efficacy of the broad-spectrum MMP inhibitor, GM6001, given within 48 h post-injury. The primary outcomes were bladder compliance, as measured by cystometry, and an ordinal gait score (Texas Spinal Cord Injury Score; TSCIS) at day 42 post-SCI. Dogs (n = 93) were randomized to receive either dimethyl sulfoxide (DMSO) or GM6001+DMSO. There were transient, but significantly (p = 0.023) greater, adverse events (31 of 42; 74%) in the GM6001-treated group relative to vehicle controls (22 of 46; 48%). Whereas there were no differences in TSCIS between treatment groups at day 42 (p = 0.9679), bladder compliance was significantly higher in dogs treated with GM6001+DMSO compared to controls (p = 0.0272). Further studies are needed to determine whether this inhibition results from a direct interaction with the bladder wall or indirectly through neural-based mechanisms.

The Effect of Sliding Humeral Osteotomy (SHO) on Frontal Plane Thoracic Limb Alignment: An Ex Vivo Canine Cadaveric Study.

OBJECTIVE: To determine the effect of sliding humeral osteotomy (SHO) on frontal plane thoracic limb alignment in standing and recumbent limb positions. STUDY DESIGN: Canine cadaveric study. SAMPLE POPULATION: Canine thoracic limbs (n=15 limb pairs). METHODS: Limbs acquired from healthy Labrador Retrievers euthanatized for reasons unrelated to this study were mounted in a limb press and aligned in a standing position followed by axial loading at 30% body weight. Frontal plane radiography was performed in standing and recumbent positions pre- and post-SHO. In the standing position, lateralization of the foot was measured pre- and post-SHO using a textured grid secured to the limb press base plate. Twelve thoracic limb alignment values (mean ± SD and 95% CI) were determined using the center of rotation of angulation (CORA) method were compared using linear mixed models to determine if significant differences existed between limb alignment values pre- or post-SHO, controlling for dog, limb, and limb position. RESULTS: Six of 12 standing or recumbent alignment values were significantly different pre- and post-SHO. SHO resulted in decreased mechanical lateral distal humeral angle and movement of the mechanical humeral radio-ulnar angle, radio-ulnar metacarpal angle, thoracic humeral angle, and elbow mechanical axis deviation toward coaxial limb alignment. In the standing position, the foot underwent significant lateralization post-SHO. CONCLUSION: SHO resulted in significant alteration in frontal plane thoracic limb alignment. Additional studies are necessary to determine if the changes reported using our ex vivo model occur following SHO in vivo.

Multi-Center Retrospective Evaluation of Screw and Polymethylmethacrylate Constructs for Atlantoaxial Fixation in Dogs.

OBJECTIVE: To evaluate outcome and adverse events following ventral stabilization of the atlantoaxial (AA) joint in dogs with clinical AA subluxation using screw/polymethymethacrylate (PMMA) constructs in a retrospective, multi-center cohort study. STUDY DESIGN: Historical cohort study. ANIMALS: 35 client-owned dogs. METHODS: Medical records from 3 institutions were reviewed to identify dogs with AA subluxation treated with ventral screw and PMMA constructs. Data on signalment, pre- and postoperative neurologic status, imaging performed, and adverse events were retrieved. Neurologic examination data were abstracted to generate a modified Frankel score at admission, discharge, and re-examination. Telephone interview of owners >180 days postoperative was conducted. RESULTS: Thirty-five dogs with AA subluxation treated with ventral screw/PMMA constructs were included. Most dogs were young (median age 1 year), small breed dogs with acute onset of neurologic signs (median duration 22.5 hours). Most dogs were non-ambulatory at the time of admission (median modified Frankel score 3). Adverse events were identified in 15/35 dogs including 9 dogs with major adverse events. Four dogs required a second surgery due to vertebral canal violation (n = 2) or implant failure (n = 2). Re-examination at 4-6 weeks postoperative reported 15/28 dogs with improved neurologic status and 19/28 dogs were ambulatory. Telephone follow-up was available for 23/35 dogs with 23/23 reported as ambulatory (median follow-up 390 days). CONCLUSIONS: Ventral application of screw and PMMA constructs for AA subluxation, as described here, is associated with clinical improvement in the majority of dog. Major adverse events are infrequent and the technique is considered relatively safe.

Outcome Following Surgical Correction of Grade 4 Medial Patellar Luxation in Dogs: 47 Stifles (2001-2012).

Grade 4/4 medial patellar luxation (MPL) is a complex disease of the canine stifle that often requires surgical realignment of the patella to resolve clinical lameness. Outcome following surgery remains poorly described. Medical records were retrospectively reviewed for surgical correction of grade 4 MPL. Signalment and exam findings, surgical procedures performed, complications, and clinical outcome were reported. Data was statistically analyzed for association with major complication occurrence and unacceptable function following surgery. Forty-seven stifles from 41 dogs were included. The surgical procedures most frequently utilized for patellar realignment were the combination of femoral trochleoplasty, tibial tuberosity transposition, and joint capsule modification. Median in-hospital veterinary examination was performed at 69 days (range 30-179 days) following surgery. Full function was reported for 42.6% of cases (n=20). Acceptable function was reported for 40.4% of cases (n=19). Unacceptable function was reported for 17% of cases (n=8). The overall complication rate was 25.5% (n=12), with revision surgery for major complications required in 12.8% of cases (n=6). Corrective osteotomies were associated with major complications (P < 0.001). In general, pelvic limb function improves following surgical correction of grade 4 MPL; however, a return to full function should be considered guarded.

Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury.

Spinal cord injury (SCI) affects thousands of people each year and there are no treatments that dramatically improve clinical outcome. Canine intervertebral disc herniation is a naturally-occurring SCI that has similarities to human injury and can be used as a translational model for evaluating therapeutic interventions. Here, we characterized cerebrospinal fluid (CSF) acute phase proteins (APPs) that have altered expression across a spectrum of neurological disorders, using this canine model system. The concentrations of C-reactive protein (CRP), haptoglobin (Hp), alpha-1-glycoprotein, and serum amyloid A were determined in the CSF of 42 acutely injured dogs, compared with 21 healthy control dogs. Concentrations of APPs also were examined with respect to initial injury severity and motor outcome 42 d post-injury. Hp concentration was significantly higher (p<0.0001) in the CSF of affected dogs, compared with healthy control dogs. Additionally, the concentrations of CRP and Hp were significantly (p=0.0001 and p=0.0079, respectively) and positively associated with CSF total protein concentration. The concentrations of CRP and Hp were significantly higher (p=0.0071 and p=0.0197, respectively) in dogs with severe injury, compared with those with mild-to-moderate SCI, but there was no significant correlation between assessed CSF APP concentrations and 42 d motor outcome. This study demonstrated that CSF APPs were dysregulated in dogs with naturally-occurring SCI and could be used as markers for SCI severity. As Hp was increased following severe SCI and is neuroprotective across a number of model systems, it may represent a viable therapeutic target.

Relationships between cerebrospinal fluid characteristics, injury severity, and functional outcome in dogs with and without intervertebral disk herniation.

BACKGROUND: Cerebrospinal fluid (CSF) is commonly acquired in dogs with intervertebral disk herniation (IVDH) and is a common method to assess inflammatory responses following spinal cord injury (SCI). OBJECTIVES: The purpose of the study was to describe relationships between cisternal CSF characteristics, behavioral measures of SCI, T2- weighted (T2W) hyperintensity on magnetic resonance imaging (MRI), and long-term outcome in dogs with IVDH. Diagnostic accuracy of CSF for differentiating IVDH from other myelopathies was also assessed. METHODS: The retrospective case series included 727 dogs, 443 with thoracolumbar IVDH, 103 with cervical IVDH, and 181 with other spinal cord diseases. Signalment, initial neurologic function, ambulatory function at long-term follow-up, T2W MRI, and CSF variables were recorded for dogs with IVDH. Signalment, etiology, and CSF data were retrieved for dogs with other myelopathies. Associations between CSF predictors, diagnosis, and outcomes were assessed. RESULTS: CSF total nucleated cell count (TNCC) increased with SCI severity (rho -0.256, P < .001) in dogs with IVDH, TNCC was significantly higher in the presence of T2W hyperintensity (P = .001) in dogs with thoracolumbar IVDH, but TNCC, RBC count, microprotein, and percent neutrophils decreased with increasing injury duration (rho -0.253, P < .001; rho -0.269, P < .001; rho -0.141, P = .004, and rho -0.356, P < .001, respectively). CSF characteristics were not accurate for differentiating IVDH from other spinal cord diseases. CONCLUSIONS: In dogs with IVDH, CSF TNCC, RBC count, microprotein, and percent neutrophils are correlated with clinical aspects of SCI such as injury severity and duration, but cannot differentiate IVDH from other etiologies.

Efficacy of a metalloproteinase inhibitor in spinal cord injured dogs.

Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0-4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0-8.0) or GM6001 (mean, 5; 95% CI 2.0-8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse secondary pathogenic events that emerge in the acutely injured cord.

Cerebrospinal fluid inflammatory cytokines and chemokines in naturally occurring canine spinal cord injury.

Canine intervertebral disk herniation (IVDH) is a common, naturally occurring form of spinal cord injury (SCI) that is increasingly being used in pre-clinical evaluation of therapies. Although IVDH bears critical similarities to human SCI with respect to lesion morphology, imaging features, and post-SCI treatment, limited data are available concerning secondary injury mechanisms. Here, we characterized cerebrospinal fluid (CSF) cytokines, and chemokines in dogs with acute, surgically treated, thoracolumbar IVDH (n=39) and healthy control dogs (n=21) to investigate early inflammatory events after SCI. A bioplex system was used to measure interleukin (IL)-2, -6, -7, -8, -10, -15, and -18, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), keratinocyte chemoattractant (KC)-like protein, IFN-γ-inducible protein-10, monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor alpha. Cytokine and chemokine concentrations in the CSF of healthy and SCI dogs were compared and, in SCI dogs, were correlated to the duration of SCI, behavioral measures of injury severity at the time of sampling, and neurological outcome 42 days post-SCI as determined by a validated ordinal score. IL-8 concentration was significantly higher in SCI cases than healthy controls (p=0.0013) and was negatively correlated with the duration of SCI (p=0.042). CSF MCP-1 and KC-like protein were positively correlated with CSF microprotein concentration in dogs with SCI (p<0.0001 and p=0.004). CSF MCP-1 concentration was negatively associated with 42-day postinjury outcome (p<0.0001). Taken together, these data indicate that cytokines and chemokines present after SCI in humans and rodent models are associated with SCI pathogenesis in canine IVDH.