Gwendolyn J. Levine

Description and repeatability of a newly developed spinal cord injury scale for dogs

The objectives of this study were to describe a new spinal cord injury scale for dogs, evaluate repeatability through determining inter-rater variability of scores, compare these scores to another established system (a modified Frankel scale), and determine if the modified Frankel scale and the newly developed scale were useful as prognostic indicators for return to ambulation. A group of client-owned dogs with spinal cord injury were examined by 2 independent observers who applied the new Texas Spinal Cord Injury Score (TSCIS) and a modified Frankel scale that has been used previously. The newly developed scale was designed to describe gait, postural reactions and nociception in each limb. Weighted kappa statistics were utilized to determine inter-rater variability for the modified Frankel scale and individual components of the TSCIS. Comparisons were made between raters for the overall TSCIS score and between scales using Spearmans rho. An additional group of dogs with surgically treated thoracolumbar disk herniation was enrolled to look at correlation of both scores with spinal cord signal characteristics on magnetic resonance imaging (MRI) and ambulatory outcome at discharge. The actual agreement between raters for the modified Frankel scale was 88%, with a weighted kappa value of 0.93. The TSCIS had weighted kappa scores for gait, proprioceptive positioning and nociception components that ranged from 0.72 to 0.94. Correlation between raters for the overall TSCIS score was Spearmans rho=0.99 (P<0.001). Comparison of the overall TSCIS score to the modified Frankel score resulted in a Spearmans rho value of 0.90 (P<0.001). The modified Frankel score was weakly correlated with the length of hyperintensity of the spinal cord: L2 vertebral body length ratio on mid-sagittal T2-weighted MRI (Spearmans rho=-0.45, P=0.042) as was the overall TSCIS score (Spearmans rho=-0.47, P=0.037). There was also a significant difference in admitting modified Frankel scores (P=0.029) and admitting overall TSCIS scores (P=0.02) between dogs that were ambulatory at discharge and those that were not. Results from this study suggest that the TSCIS is an easy to administer scale for evaluating canine spinal cord injury based on the standard neurological exam and correlates well with a previously described modified Frankel scale.

Naturally Occurring Disk Herniation in Dogs: An Opportunity for Pre-Clinical Spinal Cord Injury Research

Traumatic spinal cord injuries represent a significant source of morbidity in humans. Despite decades of research using experimental models of spinal cord injury to identify candidate therapeutics, there has been only limited progress toward translating beneficial findings to human spinal cord injury. Thoracolumbar intervertebral disk herniation is a naturally occurring disease that affects dogs and results in compressive/contusive spinal cord injury. Here we discuss aspects of this disease that are analogous to human spinal cord injury, including injury mechanisms, pathology, and metrics for determining outcomes. We address both the strengths and weaknesses of conducting pre-clinical research in these dogs, and include a review of studies that have utilized these animals to assess efficacy of candidate therapeutics. Finally, we consider a two-species approach to pre-clinical data acquisition, beginning with a reproducible model of spinal cord injury in the rodent as a tool for discovery with validation in pet dogs with intervertebral disk herniation.

Evaluation of brain tissue or cerebrospinal fluid with broadly reactive polymerase chain reaction for Ehrlichia, Anaplasma, spotted fever group Rickettsia, Bartonella, and Borrelia species in canine neurological diseases (109 cases).

BACKGROUND Vector-transmitted microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, Bartonella, and Borrelia are commonly suspected in dogs with meningoencephalomyelitis (MEM), but the prevalence of these pathogens in brain tissue and cerebrospinal fluid (CSF) of dogs with MEM is unknown. HYPOTHESIS/OBJECTIVES To determine if DNA from these genera is present in brain tissue and CSF of dogs with MEM, including those with meningoencephalitis of unknown etiology (MUE) and histopathologically confirmed cases of granulomatous (GME) and necrotizing meningoencephalomyelitis (NME). ANIMALS Hundred and nine dogs examined for neurological signs at 3 university referral hospitals. METHODS Brain tissue and CSF were collected prospectively from dogs with neurological disease and evaluated by broadly reactive polymerase chain reaction (PCR) for Ehrlichia, Anaplasma, Spotted Fever Group Rickettsia, Bartonella, and Borrelia species. Medical records were evaluated retrospectively to identify MEM and control cases. RESULTS Seventy-five cases of MUE, GME, or NME, including brain tissue from 31 and CSF from 44 cases, were evaluated. Brain tissue from 4 cases and inflammatory CSF from 30 cases with infectious, neoplastic, compressive, vascular, or malformative disease were evaluated as controls. Pathogen nucleic acids were detected in 1 of 109 cases evaluated. Specifically, Bartonella vinsonii subsp. berkhoffii DNA was amplified from 1/6 dogs with histopathologically confirmed GME. CONCLUSION AND CLINICAL IMPORTANCE The results of this investigation suggest that microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, and Borrelia are unlikely to be directly associated with canine MEM in the geographic regions evaluated. The role of Bartonella in the pathogenesis of GME warrants further investigation.

Cerebrospinal fluid myelin basic protein as a prognostic biomarker in dogs with thoracolumbar intervertebral disk herniation.

BACKGROUND Release of myelin basic protein (MBP) into the cerebrospinal fluid (CSF) is associated with active demyelination and correlates with outcome in various neurological diseases. HYPOTHESIS/OBJECTIVES To describe associations among CSF MBP concentration, initial neurological dysfunction, and long-term ambulatory outcome in dogs with acute thoracolumbar intervertebral disk herniation (IVDH). ANIMALS Fifty seven [corrected] dogs with acute thoracolumbar IVDH and 16 clinically normal dogs. METHODS Prospective case series clinical study. Signalment, initial neurological dysfunction as determined by a modified Frankel score (MFS), and ambulatory outcome at >3-month follow-up were recorded. Cisternal CSF MBP concentration was determined by an ELISA. Associations were estimated between CSF MBP concentration and various clinical parameters. RESULTS Dogs with thoracolumbar IVDH that did not ambulate at follow-up had a higher CSF MBP concentration (median, 3.56 ng/mL; range, 0.59-51.2 ng/mL) compared with control dogs (median, 2.22 ng/mL; range, 0-3.82 ng/mL) (P=.032). A CSF MBP concentration of >or=3 ng/mL had a sensitivity of 78% and specificity of 76% to predict an unsuccessful outcome based on receiver-operating characteristics curve analysis (area under the curve=0.688, P=.079). Affected dogs with a CSF MBP concentration>or=3 ng/mL had 0.09 times the odds of ambulation at follow-up compared with affected dogs with CSF MBP concentration<3 ng/mL when adjusted for initial MFS (95% confidence interval 0.01-0.66, P=.018). CONCLUSIONS AND CLINICAL IMPORTANCE These results would suggest that CSF MBP concentration may be useful as an independent prognostic indicator in dogs with thoracolumbar IVDH.

Associations of sex, breed, and age with cervical vertebral compressive myelopathy in horses: 811 cases (1974–2007)

OBJECTIVE To determine sex, breed, and age distributions in a population of horses with cervical vertebral compressive myelopathy (CVCM), compared with contemporaneous control horses. DESIGN Retrospective case-control study. ANIMALS 811 horses with CVCM and 805 control horses. PROCEDURES The Veterinary Medical Database was searched to identify horses with CVCM and contemporaneous control horses registered between July 1974 and August 2007. Admission date, admitting institution, sex, breed, age at the time of registration in the database, weight, and discharge status (alive, died, or euthanized) were recorded for each case and control horse. RESULTS On the basis of results of multivariable logistic regression analysis, geldings and sexually intact males had a significantly higher likelihood of having CVCM than females (odds ratio [OR], 2.0 [95% confidence interval, 1.5 to 2.6]; and OR, 2.4 [95% confidence interval, 1.8 to 3.2], respectively). Thoroughbreds, Tennessee Walking Horses, and Warm-bloods were overrepresented in the CVCM group, compared with Quarter Horses. Horses that ranged from < 6 months to < 7 years of age had significantly higher odds of having CVCM, compared with horses > or = 10 years of age. CONCLUSIONS AND CLINICAL RELEVANCE Sex, breed, and age predilections were detected in horses with CVCM. Improved understanding of these factors will aid clinical recognition of the disease in groups that may have a high prevalence of CVCM or were previously not recognized to be commonly affected. The results may also stimulate future investigations to further delineate etiopathogenesis, such as breed-related genetic causality.

Adverse effects and outcome associated with dexamethasone administration in dogs with acute thoracolumbar intervertebral disk herniation: 161 cases (2000–2006)

OBJECTIVE To determine complications and neurologic outcomes associated with dexamethasone administration to dogs with surgically treated thoracolumbar intervertebral disk herniation, compared with dogs not receiving dexamethasone. DESIGN Retrospective case series. ANIMALS 161 dogs with surgically confirmed thoracolumbar disk herniation. PROCEDURES Medical records from 2 hospitals were used to identify dogs that had received dexamethasone < 48 hours prior to admission (dexamethasone group dogs), dogs that received glucocorticoids other than dexamethasone < 48 hours prior to admission (other-glucocorticoid group dogs), and dogs that received no glucocorticoids (nontreatment group dogs). Signalment, neurologic injury grade, laboratory data, and complications were extracted from medical records. RESULTS Dexamethasone group dogs were 3.4 times as likely to have a complication, compared with other-glucocorticoid or nontreatment group dogs. Dexamethasone group dogs were 11.4 times as likely to have a urinary tract infection and 3.5 times as likely to have diarrhea, compared with other-glucocorticoid or nontreatment group dogs. No differences in neurologic function at discharge or recheck evaluation were detected among groups. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that treatment with dexamethasone before surgery is associated with more adverse effects, compared with treatment with glucocorticoids other than dexamethasone or no treatment with glucocorticoids, in dogs with thoracolumbar intervertebral disk herniation. In this study population, no difference in outcome was found among groups. These findings suggest that the value of dexamethasone administration before surgery in dogs with thoracolumbar disk herniation should be reconsidered.

Multicenter case-control study of signalment, diagnostic features, and outcome associated with cervical vertebral malformation-malarticulation in horses

OBJECTIVE To compare signalment of horses with cervical vertebral malformation-malarticulation (CVM) with that of control horses and to describe results of clinical examination, diagnostic imaging and necropsy findings, and reported outcome in horses with CVM. DESIGN Retrospective case-control study. ANIMALS 270 horses with CVM and 608 control horses admitted to 6 veterinary hospitals from 1992 through 2007. PROCEDURES Medical records of participating hospitals were reviewed to identify horses with CVM (ie, case horses) and contemporaneous control (non-CVM-affected) horses that were admitted for treatment. Signalment was compared between case horses and control horses. Results of clinical examination, laboratory and diagnostic imaging findings, necropsy results, and outcome were assessed for horses with CVM. RESULTS Case horses were younger (median age, 2 years) than were control horses (median age, 7 years). Thoroughbreds, warmbloods, and Tennessee Walking Horses were overrepresented in the CVM group. Gait asymmetry and cervical hyperesthesia were frequently detected in horses with CVM. Vertebral canal stenosis and articular process osteophytosis were commonly observed at necropsy; agreement between the results of radiographic or myelographic analysis and detection of lesions at necropsy was 65% to 71% and 67% to 78%, respectively. Of 263 horses with CVM for which outcome was recorded, 1 died and 172 (65.4%) were euthanatized. CONCLUSIONS AND CLINICAL RELEVANCE Odds of a diagnosis of CVM were greater in young horses and horses of specific breeds. Detection of gait asymmetry and cervical hyperesthesia were frequently reported in association with CVM. Accurate diagnosis of lesions associated with CVM by use of radiography and myelography can be challenging.

Broadly Reactive Polymerase Chain Reaction for Pathogen Detection in Canine Granulomatous Meningoencephalomyelitis and Necrotizing Meningoencephalitis

Background Granulomatous meningoencephalomyelitis (GME) and necrotizing meningoencephalitis (NME) are common inflammatory conditions of the central nervous system of dogs. Infectious pathogens, particularly viruses, are suspected to contribute to the etiopathogenesis of GME and NME. Hypothesis Broadly reactive PCR might aid in the identification of infectious agents in GME and NME. Animals Sixty‐eight client‐owned dogs evaluated by necropsy at 1 university referral hospital. Methods A mixed prospective/retrospective case‐control study was performed. Brain tissue prospectively collected at necropsy from GME, NME, and control cases was evaluated by broadly reactive polymerase chain reaction (PCR) for adenoviruses, bunyaviruses, coronaviruses, enteroviruses, flaviviruses, herpesviruses, paramyxoviruses, and parechoviruses. In addition, these tissues were retrospectively evaluated for the presence of mycoplasmas by PCR, culture, and immunohistochemistry (IHC). Results Brain tissue was collected from 11 GME and 27 NME cases and 30 controls. Viral nucleic acids were not identified in the 6 GME cases, 25 NME cases, and 2 controls evaluated by viral PCR. Mycoplasma canis was identified by Mycoplasma genus PCR in 1/5 GME and 4/25 NME cases and subsequently was cultured from 4/5 GME and 4/8 NME cases as well as 2/9 controls. The IHC did not detect M. canis in any of the 11 GME and 27 NME cases or 14 controls evaluated with strain PG14 polyclonal antiserum. Conclusions and Clinical Importance The negative results suggest that viral pathogens are not common in the brain tissue of dogs with GME and NME. Further investigation is warranted to determine the importance of M. canis in cases of GME and NME.

Associations between cerebrospinal fluid biomarkers and long-term neurologic outcome in dogs with acute intervertebral disk herniation

OBJECTIVE To examine associations between CSF biomarkers, initial neurologic dysfunction, and long-term ambulatory outcome in dogs with acute intervertebral disk herniation (IVDH). DESIGN Prospective clinical study. ANIMALS 54 dogs with acute thoracolumbar IVDH and 16 clinically normal dogs. PROCEDURES For each dog, variables, including CSF myelin basic protein (MBP), lactate, calcium, glucose, and total protein concentrations; nucleated cell count; and creatine kinase (CK) and aspartate aminotransferase activities, were measured. For dogs with thoracolumbar IVDH, initial neurologic function was characterized by use of a modified Frankel score (MFS; determined on a scale of 0 to 5, where 0 represented paraplegia with no deep nociception and 5 represented paraspinal hyperesthesia only). Long-term follow-up was assessed. RESULTS Among dogs with thoracolumbar IVDH, those with CSF CK activity ≤ 38 U/L had a 35-fold increase in the odds of long-term ambulation, compared with the odds in dogs with CSF CK activity > 38 U/L, adjusting for neurologic functioning at the evaluation. The CSF lactate, calcium, and glucose concentrations and aspartate aminotransferase activity were not predictive of long-term ambulatory outcome. Data analysis revealed that long-term functional recovery was > 98% for affected dogs, regardless of their initial MFS, when CSF CK activity was ≤ 38 U/L and MBP concentration was ≤ 3 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE In dogs with acute thoracolumbar IVDH, CSF CK activity and MBP concentration appeared to be prognostic indicators and, along with initial MFS, can be used to predict long-term ambulatory outcome.

Prospectively Recorded versus Medical Record‐Derived Spinal Cord Injury Scores in Dogs with Intervertebral Disk Herniation

BACKGROUND Validated spinal cord injury (SCI) scores have been established for veterinary species but are not uniformly used in practice. HYPOTHESIS/OBJECTIVES To determine the level of agreement of SCI scores at the time of admission versus those assigned from reconstructed medical records in a population of dogs with intervertebral disk herniation (IVDH). ANIMALS Eighty-six client-owned dogs with confirmed IVDH. METHODS Retrospective study. Medical records were reviewed for history, physical examination, neurologic examination, and recorded Modified Frankel score (MFS) and Texas spinal cord injury score (TSCIS) at the time of admission. Three raters, all board-certified neurologists, assigned MFS and TSCIS based on digitized abstracted medical records to each patient. These scores were then compared to the recorded score at the time of admission. RESULTS Actual agreement for MFS and TSCIS derived from medical records by the 3 raters compared to prospectively derived MFS and TSCIS was 77.9 and 51.2%, respectively. A kappa value of 0.572 (95% CI 0.450, 0.694; P < .001) and an ICC of 0.533 (95% CI 0.410, 0.646; P < .001) were calculated for MFS scores. A kappa value of 0.100 (95% CI 0.000, 0.222; P = .107), and an ICC of 0.503 (95% CI 0.377, 0.620; P < .001) were calculated for TSCIS scores. CONCLUSIONS AND CLINICAL IMPORTANCE Results showed that SCI scores recorded at the time of admission often do not agree with those retrospectively abstracted from medical records. Agreement was less when using the more complex TSCIS scale and therefore the MFS scale might be more appropriate for use in retrospective studies.