Comparison of D-dimer concentration and thromboelastography for diagnosis of cerebrovascular accidents in dogs: A retrospective study.

BACKGROUND: Cerebrovascular accidents (CVAs) in dogs are diagnosed using magnetic resonance imaging (MRI). This modality is sometimes unavailable, and CVAs can resemble other lesions on MRI. D-dimer concentration and thromboelastography (TEG) are utilized in human medicine in addition to diagnostic imaging to support diagnosis of CVAs, but their use in veterinary patients has not been assessed. OBJECTIVE: Assess utility of blood D-dimer concentration and TEG in supporting the imaging diagnosis of CVAs in dogs. ANIMALS: Sixty-eight client-owned dogs with neurologic signs that had brain MRI and D-dimer concentration or TEG performed. METHODS: Multicenter, retrospective study. The incidence of abnormal D-dimer concentration or TEG was compared between patients with MRI evidence of CVA and a control population. Analysis methods included Fisher's exact test or Chi-squared test for association and comparison of independent proportions. RESULTS: Neither D-dimer concentration nor TEG was significantly associated with a CVA (P = .38 and .2, respectively). D-dimer testing was performed in a low-risk population and showed low sensitivity (30.8%; 95% confidence interval [CI], 10%-61%) and high specificity (86.4%; 95% CI, 64%-96%) for CVA diagnosis. Thromboelastography was performed in a high-risk population and showed moderate sensitivity (64.3%; 95% CI, 44%-81%) and specificity (66.7%; 95% CI, 24%-94%) for CVA diagnosis. Abnormal D-dimer concentration or TEG were not helpful in differentiating hemorrhagic from ischemic stroke (P = .43 and .41, respectively). CONCLUSIONS: Although blood D-dimer concentration or TEG alone are not diagnostic of CVAs in dogs, a positive D-dimer result supports additional testing for CVA.

Effects of trazodone administration on the neurologic examination in healthy dogs.

BACKGROUND: Trazodone is an anxiolytic used PO to decrease anxiety in dogs. Whether or not trazodone affects the neurologic examination in dogs has not been previously reported. OBJECTIVE: Investigate whether trazodone administration is associated with changes in the neurologic examination in healthy dogs. ANIMALS: Thirty-two healthy dogs between 1 and 6 years old with no previously diagnosed medical conditions and perceived by their owners as neurologically normal. METHODS: Baseline sedation and anxiety assessments and neurologic examination were performed on each dog, followed by trazodone administration (6.25-8.60 mg/kg PO). The sedation and anxiety assessments and neurologic examination were repeated 2.5 hours after trazodone administration. The examinations were performed by a single board-certified veterinary neurologist and were video-recorded. The videos were randomized and reviewed by a different neurologist, blinded to the previous evaluations, who scored the examinations. RESULTS: Seven of 32 (22%) dogs had worse scores on their neurologic examination after receiving trazodone, manifesting as new or progressive PR deficits. Although not clinically relevant, 18.7% of the dogs had consciousness levels that changed from bright, alert, responsive to quiet, alert, responsive after trazodone administration. No other changes were observed on neurologic examination. Sedation and anxiety scores were significantly different after trazodone administration compared to before (P < .001 and P < .001, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Most dogs did not have changes on neurologic examination after trazodone administration. However, approximately 20% of dogs had new or worsening PR deficits after receiving trazodone. Ideally, trazodone should not be given before neurologic examination in dogs.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Cerebrospinal fluid lactate concentrations in dogs with seizure disorders.

BACKGROUND: Cerebrospinal fluid (CSF) lactate concentrations increase after seizure activity in many human patients independent of the underlying disease process. The effect of seizure activity on CSF lactate concentration in dogs is unknown. HYPOTHESIS/OBJECTIVES: Cerebrospinal fluid lactate concentration is unaffected by seizure activity in dogs and is more dependent on the underlying disease process causing the seizures. ANIMALS: One-hundred eighteen client-owned dogs with seizure disorders. METHODS: Case series. Cerebrospinal fluid lactate concentration was determined using a commercially available lactate monitor. Seizure semiology, time from last seizure to CSF collection, number of seizures within the 72 hours preceding CSF collection, and clinical diagnosis were recorded. RESULTS: Dogs with focal seizures had higher CSF lactate concentrations than did those with generalized seizures (P = .03). No differences in lactate concentrations were found among dogs with single seizures, cluster seizures or status epilepticus (P = .12), among dogs with CSF collection at different time points after the last seizure activity (P = .39) or among dogs having different numbers of seizures within the 72 hours preceding CSF collection (P = .42). A significant difference (P = .001) was found in CSF lactate concentrations among diagnostic groups, and dogs with inflammatory and neoplastic disease had higher concentrations than did dogs with idiopathic or unknown epilepsy. CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid lactate concentration is minimally affected by seizure activity in dogs and increased concentrations are more likely associated with the underlying disease process.

Long-term postoperative pain evaluation in dogs with thoracolumbar intervertebral disk herniation after hemilaminectomy.

BACKGROUND: Chronic neuropathic pain is a common complication in people with spinal cord injury (SCI) but has not been investigated in dogs. OBJECTIVE: To determine the reliability of measuring spinal mechanical sensory thresholds (MSTs) in dogs and to compare MSTs of healthy dogs and dogs with SCI caused by acute thoracolumbar intervertebral disk extrusion after hemilaminectomy over a 1-year period. STUDY DESIGN: Prospective study. ANIMALS: Thirty-two healthy and 40 SCI dogs. METHODS: Dogs were divided into group 1 (healthy Dachshunds), group 2 (healthy dogs including several breeds), and SCI group. The MSTs were measured using algometry at an incision (thoracolumbar) and control site. Dogs in group 1 were tested once; those in group 2 were tested for 5 consecutive days; and SCI dogs were tested on days 7, 14, 28, 42, 180, and 365 postoperatively. The MSTs were compared among days in healthy and SCI dogs and between SCI and healthy dogs using mixed effect models. P < .05 was considered significant. RESULTS: At the incision site of SCI dogs, MST was significantly lower than in healthy dogs for 42 days postoperatively, but not subsequently. However, 4/27 dogs had control site MST below the reference range 1 year after surgery. CONCLUSIONS AND CLINICAL IMPORTANCE: Mechanical sensory thresholds normalize by 6 months after surgery in most dogs with SCI. Approximately 15% of SCI dogs may develop chronic neuropathic pain. Improving long-term pain assessment of SCI dogs is important for offering treatment options and advising owners.

Minimally invasive spine surgery in dogs: Evaluation of the safety and feasibility of a thoracolumbar approach to the spinal cord.

OBJECTIVE: To describe the safety and feasibility of a minimally invasive spine surgery technique to access the thoracolumbar vertebral canal in dogs. STUDY DESIGN: Prospective study. ANIMALS: Six healthy research dogs. METHODS: Dogs were placed under anesthesia for MRI to evaluate vertebral column and spinal cord integrity. Minimally invasive surgery was performed at multiple sites. Access to the vertebral canal was achieved by means of foraminotomy, discectomy, and lateral minicorpectomy by using minimally invasive access and a surgical microscope. Sequential neurological examinations, pressure algometry pain quantification, and creatine kinase levels were evaluated before and after surgery for 7 days. Magnetic resonance imaging, computed tomography, and histopathology were performed on day 6 postoperatively after animals were humanely killed to evaluate the impact of surgery on spinal cord, muscles, and bone. RESULTS: The vertebral canal was successfully accessed, and the ventral aspect of the spinal cord was identified at all sites. No neurological deterioration was observed. Postoperative pain was not different compared with baseline except in one dog on the day after surgery. CONCLUSION: Minimally invasive spine surgery was a safe and feasible technique to access the thoracolumbar vertebral canal and the ventral aspect of the spinal cord in dogs. Findings supported postoperative pain benefits. CLINICAL SIGNIFICANCE: Minimally invasive spine surgery is a valid surgical technique to access the thoracolumbar vertebral canal at single or multiple sites in dogs.

Cerebrospinal fluid lactate in dogs with inflammatory central nervous system disorders.

BACKGROUND: Cerebrospinal fluid (CSF) lactate is frequently used as a biomarker in humans with inflammatory central nervous system (CNS) disorders including bacterial meningitis and autoimmune disorders such as multiple sclerosis. HYPOTHESIS: Cerebrospinal fluid lactate concentrations are increased in a subset of dogs with inflammatory CNS disorders. ANIMALS: One hundred two client-owned dogs diagnosed with inflammatory CNS disease. METHODS: Case series. Cases were identified both prospectively at the time of diagnosis and retrospectively by review of a CSF biorepository. Cerebrospinal fluid lactate was analyzed with a commercially available, handheld lactate monitor. Subcategories of inflammatory disease were created for comparison (eg, steroid-responsive meningitis arteritis, meningoencephalitis of unknown etiology). RESULTS: Cerebrospinal fluid lactate concentrations were above reference range in 47% of dogs (median, 2.5 mmol/L; range, 1.0-11.7 mmol/L). There was no significant difference in lactate concentrations between disease subcategories (P = .48). Significant but weak correlations were noted between CSF lactate concentration and nucleated cell count (r = .33, P < .001), absolute large mononuclear cell count (r = .44, P < .001), absolute small mononuclear cell count (r = .39, P < .001), absolute neutrophil cell count (r = .24, P = .01), and protein (r = .44, P < .001). No correlation was found between CSF lactate concentration and CSF red blood cell count (P = .58). There was no significant association of CSF lactate concentration with survival (P = .27). CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid lactate concentrations could serve as a rapid biomarker of inflammatory CNS disease in dogs.

Time course and prognostic value of serum GFAP, pNFH, and S100ß concentrations in dogs with complete spinal cord injury because of intervertebral disc extrusion.

BACKGROUND: A noninvasive biomarker is needed to predict recovery from severe spinal cord injury (SCI) because of thoracolumbar intervertebral disc extrusion (TL-IVDE). Proteins released from neural and glial cells can be detected in the blood and show promise as prognostic tools, but their concentration is influenced by time after injury. HYPOTHESIS/OBJECTIVES: Serum concentrations of glial fibrillary acidic protein (GFAP), phosphorylated neurofilament heavy chain (pNFH), and S100ß will follow different time courses; measurement of combinations of these proteins will predict outcome. ANIMALS: Thirty-one dogs with TL-IVDE causing paralysis with no pain perception. METHODS: Prospective study. Serum samples were taken at presentation and intervals over 56 days and banked at -80°C. Glial fibrillary acidic protein, pNFH, and S100ß concentrations were measured using ELISA tests and plotted against time from onset of nonambulatory status. Outcome was established at 6 months. The association between biomarker concentration and outcome was examined using logistic regression, receiver operator characteristics curve analysis, and model development. RESULTS: Thirty-one dogs participated, 3/31 (10%) developed progressive myelomalacia and 19/31 (62%) recovered ambulation. Glial fibrillary acidic protein and S100ß concentrations rose for the first 1 to 3 days, and were undetectable by 14 and 28 days, respectively. Phosphorylated neurofilament heavy chain concentrations peaked at 14 days and were detectable at 56 days. Glial fibrillary acidic protein concentrations in the first 72 hours after onset of nonambulatory status predicted recovery with an accuracy of 76.7%-89% depending on sample timing. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum GFAP concentrations can be used to predict outcome in clinically complete SCI. A rapid inexpensive bedside test is needed.

Development of an International Canine Spinal Cord Injury observational registry: a collaborative data-sharing network to optimize translational studies of SCI.

STUDY DESIGN: Prospective cross-sectional cohort study. OBJECTIVES: The canine spontaneous model of spinal cord injury (SCI) is as an important pre-clinical platform as it recapitulates key facets of human injury in a naturally occurring context. The establishment of an observational canine SCI registry constitutes a key step in performing epidemiologic studies and assessing the impact of therapeutic strategies to enhance translational research. Further, accumulating information on dogs with SCI may contribute to current "big data" approaches to enhance understanding of the disease using heterogeneous multi-institutional, multi-species datasets from both pre-clinical and human studies. SETTING: Multiple veterinary academic institutions across the United States and Europe. METHODS: Common data elements recommended for experimental and human SCI studies were reviewed and adapted for use in a web-based registry, to which all dogs presenting to member veterinary tertiary care facilities were prospectively entered over ~1 year. RESULTS: Analysis of data accumulated during the first year of the registry suggests that 16% of dogs with SCI present with severe, sensorimotor-complete injury and that 15% of cases are seen by a tertiary care facility within 8 h of injury. Similar to the human SCI population, 34% were either overweight or obese. CONCLUSIONS: Severity of injury and timing of presentation suggests that neuroprotective studies using the canine clinical model could be conducted efficiently using a multi-institutional approach. Additionally, pet dogs with SCI experience similar comorbidities to people with SCI, in particular obesity, and could serve as an important model to evaluate the effects of this condition.

A randomized, blinded, prospective clinical trial of postoperative rehabilitation in dogs after surgical decompression of acute thoracolumbar intervertebral disc herniation.

BACKGROUND: Experimental evidence shows benefit of rehabilitation after spinal cord injury (SCI) but there are limited objective data on the effect of rehabilitation on recovery of dogs after surgery for acute thoracolumbar intervertebral disc herniations (TL-IVDH). OBJECTIVE: Compare the effect of basic and intensive post-operative rehabilitation programs on recovery of locomotion in dogs with acute TL-IVDH in a randomized, blinded, prospective clinical trial. ANIMALS: Thirty non-ambulatory paraparetic or paraplegic (with pain perception) dogs after decompressive surgery for TL-IVDH. METHODS: Blinded, prospective clinical trial. Dogs were randomized (1:1) to a basic or intensive 14-day in-house rehabilitation protocol. Fourteen-day open field gait score (OFS) and coordination (regulatory index, RI) were primary outcomes. Secondary measures of gait, post-operative pain, and weight were compared at 14 and 42 days. RESULTS: Of 50 dogs assessed, 32 met inclusion criteria and 30 completed the protocol. There were no adverse events associated with rehabilitation. Median time to walking was 7.5 (2 - 37) days. Mean change in OFS by day 14 was 6.13 (confidence intervals: 4.88, 7.39, basic) versus 5.73 (4.94, 6.53, intensive) representing a treatment effect of -0.4 (-1.82, 1.02) which was not significant, P=.57. RI on day 14 was 55.13 (36.88, 73.38, basic) versus 51.65 (30.98, 72.33, intensive), a non-significant treatment effect of -3.47 (-29.81, 22.87), P = .79. There were no differences in secondary outcomes between groups. CONCLUSIONS: Early postoperative rehabilitation after surgery for TL-IVDH is safe but doesn't improve rate or level of recovery in dogs with incomplete SCI.

The Effect of Electromagnetic Fields on Post-Operative Pain and Locomotor Recovery in Dogs with Acute, Severe Thoracolumbar Intervertebral Disc Extrusion: A Randomized Placebo-Controlled, Prospective Clinical Trial.

Spinal cord injury (SCI) attributed to acute intervertebral disc extrusions (IVDEs) is common in dogs and is treated by surgical decompression. Dogs with sensorimotor complete injuries have an incomplete recovery. Pulsed electromagnetic fields (PEMFs) reduce post-operative pain through anti-inflammatory effects and there is growing evidence for neuroprotective effects. This randomized, controlled clinical trial evaluated the effect of PEMF on post-operative pain and neurological recovery in dogs with surgically treated sensorimotor complete SCI attributed to acute IVDE. Sixteen dogs with surgically treated complete thoracolumbar SCI were randomized to receive PEMF (15 min every 2 h for 2 weeks then twice-daily for 4 weeks) or placebo starting immediately after diagnosis. The primary outcome was gait score at 2 weeks. Secondary measures of gait, pain perception, and proprioceptive function were evaluated at 2 and 6 weeks. Plasma glial fibrillary acidic protein (GFAP) concentration was measured as an SCI biomarker. Post-operative pain was quantified by measuring mechanical sensory thresholds (MSTs) at control and surgical sites. There was no significant difference in demographics or GFAP concentration between the two groups at trial entry. There was no difference in primary outcome or in secondary measures of gait, but proprioceptive placing was significantly better at 6 weeks and GFAP concentrations were significantly lower at 2 weeks in the PEMF group. MSTs were significantly higher in the PEMF-treated group. We conclude that PEMF reduced incision-associated pain in dogs post-surgery for IVDE and may reduce extent of SCI and enhance proprioceptive placing. Larger clinical trials are warranted.