Magnetic Resonance Imaging in Dogs with Neurologic Impairment Due to Acute Thoracic and Lumbar Intervertebral Disk Herniation

Background: Magnetic resonance imaging (MRI) is a correlate to physical examination in various myelopathies and a predictor of functional outcome.
Objectives: To describe associations among MRI features, neurological dysfunction before MRI, and functional outcome in dogs with disk herniation.
Animals: One hundred and fifty-nine dogs with acute thoracolumbar disk herniation.
Methods: Retrospective case series. Signalment, initial neurological function as assessed by a modified Frankel score (MFS), and ambulatory outcome at hospital discharge and >3 months (long-term) follow-up were recorded from medical records and telephone interview of owners. Associations were estimated between these parameters and MRI signal and morphometric data.
Results: Dogs with intramedullary T2W hyperintensity had more severe pre-MRI MFS (median 2, range 0–4) and lower ambulatory proportion at long-term follow-up (0.76) than those dogs lacking hyperintensity (median MFS 3, range 0–5; ambulatory proportion, 0.93) ( P =.001 and .013, respectively). Each unit of T2W length ratio was associated with a 1.9 times lower odds of long-term ambulation when adjusted for pre-MRI MFS (95% confidence interval 1.0–3.52, P =.05). Dogs with a compressive length ratio >1.31 (which was the median ratio within this population) had more severe pre-MRI MFS (median 3, range 0–5) compared with those with ratios ≤1.31 (median MFS 3, range 0–4; P =.006).
Conclusions and Clinical Importance: MRI features were associated with initial injury severity in dogs with thoracolumbar disk herniation. Based on results of this study, the T2W length ratio and presence of T2W intramedullary hyperintensity appear to be predictive of long-term ambulatory status.     

Lumbar cerebrospinal fluid in dogs with type I intervertebral disc herniation

BACKGROUND: Cerebrospinal fluid (CSF) in dogs with Hansen type I intervertebral disc herniation (IVDH) is classically described as normal or mildly inflammatory with a predominance of large mononuclear cells or neutrophils in severe acute herniations. However, we have observed a moderate to marked pleocytosis with a predominance of lymphocytes in some dogs with IVDH. HYPOTHESIS: Moderate to marked CSF pleocytosis occurs more commonly in dogs with type I IVDH than is reported in the literature. Lymphocytic predominance is more common than nonlymphocytic pleocytosis in dogs with chronic IVDH. ANIMALS: Four hundred twenty-three client-owned dogs with type I IVDH. METHODS: Retrospective study. Lumbar CSF of dogs with surgically confirmed type I IVDH was evaluated cytologically. Information obtained from medical records included signalment, prior clinical history, time from onset of signs to presentation, neurologic status, and intraoperative findings. Dogs with prior history and/or intraoperative evidence consistent with chronic IVDH before an acute herniation were termed acute-on-chronic (AOC). RESULTS: Pleocytosis (> 5 cells/uL) was present in 51% of dogs, including 23% with cervical IVDH and 61% with thoracolumbar IVDH. Moderate or marked inflammation (> or = 20 cells/uL) was identified in the CSF of 51% of dogs with thoracolumbar IVDH and pleocytosis. A predominance of lymphocytes was significantly more common in dogs examined > 7 days from onset of signs (P= .032) and in dogs with AOC IVDH (P= .0013). CONCLUSIONS AND CLINICAL IMPORTANCE: Moderate to marked CSF pleocytosis in dogs with type I IVDH is more common than previously reported. Lymphocytic pleocytosis is most common in dogs with chronic progression or AOC IVDH. Lymphocytic inflammation in the CSF of some dogs might suggest an immune-mediated response to chronically herniated disc material.     

Matrix metalloprotease-9 activity in the cerebrospinal fluid and spinal injury severity in dogs with intervertebral disc herniation

We investigated whether matrix metalloproteinase (MMP)-9 expression in the cerebrospinal fluid (CSF) of dogs with intervertebral disc herniation (IVDH) is associated with the severity of neurological signs and prognosis. CSF from the cisterna magna (C-CSF) and the lumbar spine (L-CSF) of 34 dogs with IVDH was analyzed using zymography. Activity of MMP-9 in L-CSF was detected in 6 of 34 dogs with IVDH, often for more than 7 days after injury. MMP-9 activity was not detected from any of the C-CSF samples. Of the six cases that were MMP-9 positive, all four cases with grade V that had loss of deep pain were non-ambulatory 6 months after treatment. The remaining two cases with grade III and IV could recover mobility. In dogs with grade V thoracolumbar IVDH, MMP-9 expression in the CSF may indicate severe spinal cord injury with poor prognosis.     

Measurement of myelin basic protein in the cerebrospinal fluid of dogs with degenerative myelopathy

BACKGROUND: Analysis of cerebrospinal fluid (CSF) is part of a routine clinical workup in veterinary patients when neurologic disease is suspected. However, knowledge of particular protein markers of disease in CSF is limited. The concentration of myelin basic protein (MBP) in CSF is used as a biochemical marker in humans to evaluate demyelinating lesions in the central nervous system (CNS). OBJECTIVE: The purpose of this study was to evaluate an ELISA for determination of MBP concentration in the CSF of German shepherd dogs with degenerative myelopathy (GSDM). METHODS: Cross-reactivity of the anti-human polyclonal antibody used in a commercial ELISA (Active MBP ELISA, Diagnostic Systems Laboratories Inc, Webster, TX, USA) was tested with canine MBP by immunoblotting. CSF samples were collected from both the cisterna magna and the lumbar cistern of 8 clinically healthy control dogs and 8 German shepherd dogs clinically diagnosed with GSDM. MBP concentrations were measured in all CSF samples using the ELISA. RESULTS: The mean MBP concentration in CSF from the lumbar cistern of dogs with GSDM (3.13 -/+ 0.46 ng/mL) was significantly higher than that in the cisterna magna (0.70 -/+ 0.06 ng/mL) and from both cisternal (0.47 -/+ 0.07 ng/mL) and lumbar (0.94 -/+ 0.37 ng/mL) samples from control dogs. CONCLUSION: The MBP ELISA has potential as a supplemental test of CSF to diagnose demyelinating disorders in dogs.     

Matrix metalloprotease-9 activity in the cerebrospinal fluid and spinal injury severity in dogs with intervertebral disc herniation

We investigated whether matrix metalloproteinase (MMP)-9 expression in the cerebrospinal fluid (CSF) of dogs with intervertebral disc herniation (IVDH) is associated with the severity of neurological signs and prognosis. CSF from the cisterna magna (C-CSF) and the lumbar spine (L-CSF) of 34 dogs with IVDH was analyzed using zymography. Activity of MMP-9 in L-CSF was detected in 6 of 34 dogs with IVDH, often for more than 7 days after injury. MMP-9 activity was not detected from any of the C-CSF samples. Of the six cases that were MMP-9 positive, all four cases with grade V that had loss of deep pain were non-ambulatory 6 months after treatment. The remaining two cases with grade III and IV could recover mobility. In dogs with grade V thoracolumbar IVDH, MMP-9 expression in the CSF may indicate severe spinal cord injury with poor prognosis.     

Combination of serum phosphorylated neurofilament heavy subunit and hyperintensity of intramedullary T2W on magnetic resonance imaging provides better prognostic value of canine thoracolumbar intervertebral disc herniation

The aim of this study was to evaluate the prognostic value of concurrent measurement of serum phosphorylated neurofilament heavy subunit (pNF-H) concentration and intramedullary T2W hyperintensity in paraplegic to paraplegic dogs. Our hypothesis was that concurrent measurement of these would provide a more accurate prediction of functional outcome in dogs with thoracolumbar intervertebral disc herniation (IVDH). A prospective case-control clinical study was designed using 94 dogs with acute onset of thoracolumbar IVDH. The association of serum pNF-H concentration, T2W hyperintensity on sagittal MRI (T2H/L2), deep pain perception and surgical outcome were evaluated with logistic regression analysis after three months for all 94 surgically treated dogs. Sensitivity to predict non-ambulatory outcome was compared among pNF-H and T2H/L2 and combination of both. Logistic regression analysis indicated that serum pNF-H concentration and T2H/L2 were significantly correlated with surgical outcome (P<0.05); however, deep pain perception was not (P=0.41). The results of logistic regression analysis indicated that the odds ratios of unsuccessful long-term outcome were 2.6 for serum pNF-H concentration, 1.9 for T2H/L2 and 2.3 for deep pain sensation. The sensitivity and specificity to predict non-ambulatory outcome for using serum parameter pNF-H>2.6 ng/ml, using T2H/L2 value of>0.84 and using both serum pNF-H and T2H/L2, were 95% and 75.7%, 65% and 86.5%, and 90.0% and 97.5%, respectively. Therefore, combined measurements of serum pNF-H and T2H/L2 might be useful for predicting long-term outcome in dogs with thoracolumbar IVDH.     

Association of cerebrospinal fluid analysis findings with clinical signs and outcome in acute nonambulatory thoracolumbar disc disease in dogs

Background: Cerebrospinal fluid (CSF) pleocytosis recently was associated with the severity of neurologic signs in dogs with intervertebral disc disease (IVDD). Hypothesis/Objectives: To look for an association among CSF cell counts, total protein concentration, and severity of neurologic signs at presentation with outcome in dogs with acute thoracolumbar IVDD. Our hypothesis was that CSF total nucleated cell count (TNCC) and percentage cell types would be associated with the severity of spinal cord damage and therefore with both the presenting clinical signs and the prognosis of affected dogs. Animals: Fifty‐four dogs with acute nonambulatory thoracolumbar IVDD were evaluated. Methods: Retrospective study. Signalment, neurologic grade, CSF TNCC, protein concentration, red blood cells count and differential cell percentages, and short‐ and long‐term outcomes were evaluated. Results: CSF pleocytosis (>5 cells/μL) was present in 54% of dogs and was positively associated with neurologic grade at presentation and with postoperative time to regaining ambulation. Neutrophils were observed most frequently. The percentage of CSF macrophages and macrophage to monocyte ratio were higher (P= .001, for both) in dogs presented without deep pain sensation (DPS) that did not regain ambulation. Receiver operator characteristics curve analysis yielded a cut‐off point of 13% macrophages with a sensitivity and specificity of 100 and 83%, respectively, for prediction of a negative outcome. Conclusions and Clinical Importance: CSF pleocytosis is positively associated with the severity of spinal cord damage in dogs with thoracolumbar IVDD. The percentage of CSF macrophages can be used as a prognostic indicator for regaining ambulation in dogs that have lost DPS.     

COMPARISON BETWEEN NONCONTRAST COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING FOR DETECTION AND CHARACTERIZATION OF THORACOLUMBAR MYELOPATHY CAUSED BY INTERVERTEBRAL DISK HERNIATION IN DOGS

Magnetic resonance imaging (MRI) and computed tomography (CT) are commonly used to evaluate dogs with thoracolumbar myelopathy; however, relative diagnostic sensitivities for these two modalities have not been previously reported. The purpose of this prospective study was to compare diagnostic sensitivity and observer agreement for MRI and CT in a group of dogs with thoracolumbar myelopathy due to surgically confirmed intervertebral disk herniation (IVDH). All included dogs had magnetic resonance (MR) imaging followed by noncontrast CT using standardized protocols. Three experienced observers interpreted each imaging study independently without knowledge of clinical or surgical findings. The operating surgeon was aware of MR findings but not CT findings at the time surgical findings were recorded. Forty‐four dogs met the inclusion criteria. The sensitivity of CT was 88.6% (79.5%–94.2%) and of MR was 98.5% (95% confidence interval, 94.1%–99.7%) for diagnosis of intervertebral disk herniation. Specificity was not calculated, as all dogs had IVDH at surgery. Magnetic resonance imaging was more accurate than CT for identifying the site of intervertebral disk herniation‐associated spinal cord compression and differentiating disk extrusion vs. protrusion. Computed tomography was less accurate for lesion localization in per acute cases, as well as for chondrodystrophic, female, older and smaller (<7 kg) dogs. Inter‐rater agreement was good for lesion lateralization for both MR and CT (κ = 0.687, 95% CI = 0.552, 0.822, P = 0.002, and κ = 0.692, 95% CI = 0.542, 0.842, P = 0.003). Findings from the current study indicated that MR imaging was more sensitive and accurate than noncontrast CT for diagnosis and characterization of thoracolumbar myelopathy due to IVDH in dogs.     

Evaluation of the success of medical management for presumptive cervical intervertebral disk herniation in dogs

Objective— To determine the success of medical management of presumptive cervical disk herniation in dogs and variables associated with treatment outcome. Design— Retrospective case series. Animals— Dogs (n=88) with presumptive cervical disk herniation. Methods— Dogs with presumptive cervical and thoracolumbar disk herniation were identified from medical records at 2 clinics and clients were mailed a questionnaire related to the success of therapy, clinical recurrence of signs, and quality of life (QOL) as interpreted by the owner. Signalment, duration and degree of neurologic dysfunction, and medication administration were determined from medical records. Results— Ninety‐seven percent of dogs (84/87) with complete information were described as ambulatory at initial evaluation. Successful treatment was reported for 48.9% of dogs with 33% having recurrence of clinical signs and 18.1% having therapeutic failure. Bivariable logistic regression showed that non‐steroidal anti‐inflammatory drug (NSAID) administration was associated with success (P=.035; odds ratio [OR]=2.52). Duration of cage rest and glucocorticoid administration were not significantly associated with success or QOL. Dogs with less‐severe neurologic dysfunction were more likely to have a successful outcome (OR=2.56), but this association was not significant (P=.051). Conclusions— Medical management can lead to an acceptable outcome in many dogs with presumptive cervical disk herniation. Based on these data, NSAIDs should be considered as part of the therapeutic regimen. Cage rest duration and glucocorticoid administration do not appear to benefit these dogs, but this should be interpreted cautiously because of the retrospective data collection and use of client self‐administered questionnaire follow‐up. Clinical Relevance— These results provide insight into the success of medical management for presumptive cervical disk herniation in dogs and may allow for refinement of treatment protocols.     

Hemilaminectomy and vertebral stabilisation for the treatment of thoracolumbar disc protrusion in 28 dogs

Objectives : To evaluate the results of hemilaminectomy and vertebral stabilisation (+/? annulectomy) for the treatment of thoracolumbar disc protrusion. Methods : The medical records of dogs with thoracolumbar annular protrusions treated by hemilaminectomy and vertebral stabilisation were reviewed. Neurological function was assessed 24 hours following surgery. Long‐term follow‐up was by clinical examination or telephone questionnaire. Results : Twenty‐eight dogs fulfilled the criteria. Age ranged from 4 to 12·5 years (median 8 years, mean 7·7 years), bodyweight from 5·1 to 51·5 kg (median 28 kg, mean 27·1 kg), and duration of neurological signs before presentation from 48 hours to 104 weeks (median 5 weeks, mean 9·3 weeks). At presentation 22 dogs were ambulatory and six were non‐ambulatory. Myelography and/or magnetic resonance imaging (MRI) identified 31 thoracolumbar protrusions causing spinal cord compression. Unilateral hemilaminectomy was performed in 27 dogs and bilateral hemilaminectomy in one dog. Partial annulectomy was performed in 24 of 31 protrusions. Stabilisation was performed using vertebral body bone plates in 26 dogs and vertebral body screws and bone cement in two dogs. Internal vertebral venous plexus haemorrhage was recorded in nine dogs. A screw was inadvertently placed into an intervertebral disc in two dogs. Neurological examination 24 hours postoperatively revealed deterioration in pelvic limb motor function in 17 dogs. One dog was euthanatised at the owner’s request 6 days after surgery. Long‐term evaluation of 24 cases was performed 3 to 52 months following surgery (median 21 months, mean 23·9 months). Six dogs had improved from their preoperative status and one had deteriorated as assessed by the authors. Fifteen dogs had improved from their preoperative status and two were unchanged as assessed by owners. Clinical Significance : Hemilaminectomy and vertebral stabilisation are an effective treatment for chronic spinal cord compression due to thoracolumbar annular protrusion in dogs. A temporary deterioration in neurological function is not uncommon following surgery. Internal vertebral plexus haemorrhage and inappropriate vertebral body screw placement are potential complications.     

Prevalence and significance of extracellular myelin‐like material in canine cerebrospinal fluid

Background: Myelin‐like material in canine cerebrospinal fluid (CSF) specimens has been attributed to demyelinating or myelomalacic conditions. In our experience, myelin‐like material is observed frequently, especially in lumbar samples, and in a variety of disease conditions. Objectives: The objective of this study was to determine if there are associations between the presence of myelin‐like material and CSF collection site, body weight, underlying disease, and patient outcome. Methods: Wright–Giemsa‐stained cytocentrifuged specimens of CSF from the cerebellomedullary cistern (n=51) and lumbar cistern (n=47) of 98 dogs with neurologic disease were evaluated retrospectively for the presence and amount of extracellular myelin‐like material. Results were compared based on collection site, body weight, type of neurologic disease, and outcome. Results: Myelin‐like material was observed in 20/98 (20%) samples and was more frequently observed in lumbar (17/47, 36%) than cerebellomedullary samples (3/51, 6%) (P=.0028). Samples from dogs <10 kg were more likely to contain myelin (14/36, 39%) compared with dogs ≥10 kg (5/60, 8%) (P=.0052). Larger amounts of myelin‐like material were observed in CSF from dogs with intervertebral disk disease compared with other diseases (P=.045). No association was found between myelin‐like material and outcome. Conclusion: The association of extracellular myelin‐like material in canine CSF samples with sampling site and body weight suggests it is more often an artifact of collection technique and anatomy rather than the result of neurologic disease. Myelin‐like material in CSF is not associated with a poorer prognosis.     

Use of serum concentrations of interleukin-18 and monocyte chemoattractant protein-1 as prognostic indicators in primary immune-mediated hemolytic anemia in dogs

Background: The cytokine response in immune‐mediated hemolytic anemia (IMHA) is poorly characterized and correlation with outcome is unknown. Hypothesis/Objectives: To determine if cytokine activity is correlated with outcome in dogs with IMHA. Animals: Twenty dogs with primary IMHA and 6 control dogs. Methods: Prospective study on dogs with IMHA with blood sampling at admission. Serum activity of interleukin‐2 (IL‐2), IL‐4, IL‐6, IL‐7, IL‐8, IL‐10, IL‐15, IL‐18, monocyte chemoattractant protein‐1 (MCP‐1), granulocyte‐macrophage colony stimulating factor (GM‐CSF), interferon‐inducible protein‐10, interferon‐gamma, and keratinocyte chemoattractant (KC) was assessed. Results: Thirty‐day case fatality rate was 25% (5/20 dogs). Increased concentrations (median [range]) of IL‐2 (45.5 ng/L [0;830] versus 0 ng/L [0;46.8]), IL‐10 (8.2 ng/L [0;60.6] versus 0 ng/L [0;88.2]), KC (1.7 μg/L [0.3;4.7] versus 0.5 μg/L [0.2;1.1]), and MCP‐1 (162 ng/L [97.6;438] versus 124 ng/L [90.2;168]) were observed in dogs with IMHA compared with controls. The cytokine profile was indicative of a mixture of pro‐ and anti‐inflammatory cytokines of various cellular origins. Cytokines/chemokines strongly associated with macrophage/monocyte activation and recruitment were significantly increased in nonsurvivors compared with survivors; IL‐15 (179 ng/L [48.0;570] versus 21.3 ng/L [0;193]), IL‐18 (199 ng/L [58.7;915] versus 37.4 ng/L [0;128]), GM‐CSF (134 ng/L [70.0;863] versus 57.6 ng/L [0;164]), and MCP‐1 (219 ng/L [135;438] versus 159 ng/L [97.6;274]), respectively. Logistic regression suggested increased IL‐18 and MCP‐1 concentrations were independently associated with mortality in this population (P<.05, Wald's type 3). Conclusions and Clinical Importance: A mixed cytokine response is present in dogs with IMHA and mediators of macrophage activation and recruitment might serve as prognostic indicators.     

Myoglobin as a prognostic indicator for outcome in dogs with gastric dilatation-volvulus

Objective – To determine whether myoglobin (Mb) is a useful prognostic indicator for outcome and to investigate any relationship between Mb and mortality in dogs with gastric dilatation‐volvulus (GDV). Design – Prospective study. Setting – Veterinary teaching hospital. Animals – Seventy‐two dogs with GDV. Interventions – Blood sampling. Measurements and Main Results – Mb levels were measured at the time of diagnosis (Mbt₀), 24 hours (Mbt₁), and 48 hours (Mbt₂) after signs of GDV were recognized. Fifty‐seven dogs survived (group I) and 15 dogs did not survive (group II). Mb t₀ differed significantly between groups (P=0.04). Mbt₀ in group I ranged from <30 to >700 ng/mL (n=57, median 74 ng/mL), and in group II from 34 to >700 ng/mL (n=15, median 238 ng/mL). Analysis of a receiver operating characteristic curve of Mbt₀ suggested that the best single cutpoint would be 168 ng/mL (sensitivity 60.0%, specificity 84.2%). Fifty percent of dogs with Mbt₀>168 ng/mL were euthanized, while 88.9% with Mbt₀<168 ng/mL survived. Mbt₁ and Mbt₂ differed significantly between groups I and II. Mbt₁ in group I ranged from 32 to >700 ng/mL (n=55, median 123 ng/mL), and Mbt₁ in group II ranged from 131 to 643 ng/mL (n=7, median 343 ng/mL) (P=0.006). Mbt₂ in group I ranged from 30 to 597 ng/mL (n=54, median 101 ng/mL), and in group II from 141 to >700 ng/mL (n=8, median 203 ng/mL) (P=0.02). Conclusions – In this study, Mbt₀ is a moderately sensitive and specific prognostic indicator. Almost 90% of the dogs below the cutpoint survived to discharge, whereas 50% with Mbt₀ above the cutpoint did not survive.     

The Influence of High‐Intensity Moderate Duration Exercise on Cardiac Troponin I and C‐Reactive Protein in Sled Dogs

Background: C‐reactive protein (CRP) and cardiac troponin I (cTnI) are biomarkers of systemic inflammation and cardiac damage, respectively. Objective: To investigate the effects of short‐duration high‐intensity exercise on plasma cTnI and serum CRP concentrations in sprint racing sled dogs. Animals: Twenty‐two Alaskan sled dogs of 2 different teams participating in a 2‐day racing event. Methods: In this prospective field study, cephalic venipuncture was performed on all dogs before racing and immediately after racing on 2 consecutive days. Plasma cTnI and serum CRP concentrations were evaluated at each time point. Results: There was a mild, significant rise (P < .01) in median cTnI concentrations from resting (0.02 ng/mL; 0.0–0.12 ng/mL) on both days after racing (day 1 = 0.06, 0.02–0.2 ng/mL; day 2 = 0.07, 0.02–0.21 ng/mL). Serum CRP concentrations showed a mild significant increase (P < .01) on day 2 after racing mean (9.2 ± 4.6 μg/mL) as compared with resting (6.5 + 4.3 μg/mL) and day 1 after racing (5.0 + 2.9 μg/mL). Neither cTnI or CRP concentrations exceeded the upper reference range for healthy dogs. Conclusions and Clinical Relevance: Strenuous exercise of short duration did not result in cTnI concentrations above the reference range for healthy dogs. Although increased after 2 days of short‐duration strenuous exercise, CRP did not reach concentrations suggestive of inflammation, as reported previously in the endurance sled dogs. Therefore, we surmise that moderate exercise does not present a confounding variable in the interpretation of cTnI and CRP concentrations in normal dogs.     

Hemilaminectomy for the treatment of thoracolumbar disc disease in the dog: a follow-uo studv of 40 cases

A study was made of dogs with Hansen type I thoracolumbar disc extrusions that had been treated by hemilaminectomy and fenestration of the affected disc. Follow-up information was available for 40 dogs undergoing treatment over a five-year period. The follow-up period ranged from 12 to 72 months (mean 34 months). The case details and the results of treatment of these 40 dogs are presented. All dogs were graded according to the degree of neurological dysfunction at the time of initial presentation and at the conclusion of the study period. Twenty-seven dogs (68 per cent) had no detectable signs of neurological dysfunction or thoracolumbar pain at the final assessment and a further eight dogs (20 per cent) had mild ambulatory paraparesis but were regarded by their owners as functional pets. Recurrence of neurological signs consistent with thoracolumbar disc disease was seen in five dogs (13 per cent) and was successfully resolved completely in one of three dogs that were treated.     

A retrospective study of intervertebral disc herniation in dogs in Japan: 297 cases

We investigated the epidemiological characteristics of intervertebral disc herniation (IVDH) in Japan in a large population using a retrospective study. The sample population was dogs (n=297) with IVDH in Japan. Medical records were reviewed for breed, sex, age, affected interspace and neurological severity. The dogs were comprised of 132 cases of cervical IVDH (C-IVDH) and 165 cases of thoracolumbar IVDH (TL-IVDH). In Japan, the Dachshund, Beagle and Shih Tzu tended to suffer from both C-IVDH and TL-IVDH. The Shiba Inu, a characteristic Japanese dog breed, suffered from both C-IVDH and TL-IVDH, although there was little data relating to the whole breed. Male dogs tended to suffer from C-IVDH and TL-IVDH at a rate almost twice that of females in Japan. Among the three predominant dog breeds, the Dachshund, Beagle and Shih Tzu, the Dachshund tended to suffer from both C-IVDH and TL-IVDH at an earlier age than the Beagle, and the Beagle tended to suffer from both C-IVDH and TL-IVDH earlier than the Shih Tzu. Among the three predominant breeds, the Shih Tzu, in particular, tended to suffer from both C-IVDH and TL-IVDH at multiple sites. Our data from Japan were in partial agreement with previous data from the U.S.A., and epidemiological characteristics of IVDH peculiar to Japan were also identified.     

Characterization of matrix metalloproteinase-2 and -9 in cerebrospinal fluid of clinically normal dogs

OBJECTIVE: To characterize matrix metalloproteinase (MMP)-2 and -9 in CSF of clinically normal dogs. SAMPLE POPULATION: Samples of CSF collected from 23 dogs. PROCEDURE: Dogs were anesthetized, CSF samples were collected, and dogs were then euthanatized. Each CSF sample was evaluated immediately for RBC count, WBC count, and protein and glucose concentrations, and cytologic examination also was performed. Samples were considered normal when protein concentration was < 25 mg/dL and CSF contained < 6WBCs/microL and < 25 RBCs/microL. Samples were stored at -70 degrees C. Sections of brain tissue were collected and processed for histologic examination. The MMPs were evaluated by use of gelatin zymography and a polyclonal antibody-based sandwich ELISA. RESULTS: Mean WBC count for CSF samples was < 1 WBC/microL (range, 0 to 3 WBCs/mL). Mean protein concentration was 12 mg/dL (range, 8 to 17 mg/dL). Mean RBC count was 3.65 RBCs/microL (range, 0 to 21 RBCs/microL). All CSF samples generated a clear band on zymography gels that corresponded to the human commercial standard of proenzyme MMP-2. Other major clear bands were not detected on zymography gels. Bands correlating to MMP-9 were not detected in any samples. The ELISA results revealed a mean +/- SD proenzyme MMP-2 concentration of 5.61 +/- 1.92 ng/mL (range, 3.36 to 10.83 ng/mL). CONCLUSIONS AND CLINICAL RELEVANCE: The proenzyme form of MMP-2 is detectable in CSF of clinically normal dogs, whereas MMP-9 is not detectable. Additional investigation of MMPs in CSF from dogs with various diseases of the nervous system is indicated.     

Pharmacokinetics of a low dose and FDA‐labeled dose of diclazuril administered orally as a pelleted topdressing in adult horses

The purpose of this study was to determine the pharmacokinetics of the FDA‐approved labeled dose of diclazuril and compare it to a low dose in plasma and CSF in adult horses. During each research period, six healthy adult horses received 0.5 mg/kg of 1.56% diclazuril pellets (Protazil^TM, Merck Animal Health) compared to the approved labeled dose of 1 mg/kg orally once in two separate phases. A dose of 0.5 mg/kg was calculated to each horse's weight. Blood was then collected immediately before diclazuril administration and then at regular intervals up to a 168 h. After the last blood collection following the single dose at hour 168, a once daily oral dose was administered for the next 10 days to ensure the drug's concentration reached steady‐state. To determine the CSF concentration at steady‐state, CSF samples were collected after the 9th oral dose. Blood was then collected after the 10th dose and then at regular intervals up to 168 h. A washout period of 4 weeks was allowed before repeating this protocol for the FDA‐labeled dose at 1 mg/kg. Plasma and CSF samples were analyzed by high‐pressure liquid chromatography. A one‐compartment pharmacokinetic model with first‐order oral absorption was fitted to the single administration data. Steady‐state pharmacokinetics was performed using noncompartmental analysis for steady‐state analysis. The mean (standard deviation) concentration of diclazuril in CSF following the low dose was 26 ng/mL (5 ng/mL), while CSF in the FDA‐labeled dose was 25 ng/mL (4 ng/mL), P = 0.3750. Substantial accumulation in plasma occurred at steady‐state after the 10th dose for both doses. The results of this study show that diclazuril pellets given at the approved label dose and a lower dose both produce similar plasma drug concentrations at steady‐state and attain plasma and CSF concentrations known to inhibit Sarcocystis neurona in cell culture.     

Effect of parvoviral enteritis on plasma citrulline concentration in dogs

Background: Plasma citrulline concentration is a reliable marker of global enterocyte mass in humans and is markedly decreased in diffuse small intestinal diseases. However, the relationship between acute intestinal damage and plasma citrulline concentration in dogs has never been documented. Hypothesis: That dogs with parvoviral enteritis have a lower plasma citrulline concentration than healthy dogs and that plasma citrulline concentration is a predictor of death in puppies with parvoviral enteritis. Animals: Sixty‐one dogs with spontaneous parvoviral enteritis and 14 healthy age‐matched control dogs. Methods: Observational cohort study. Plasma citrulline concentration was measured by liquid chromatography and tandem mass spectrometry in blood samples collected at admission and each day until death or discharge from the hospital. Parvovirus enteritis was confirmed by electron microscopy on a fecal sample. Results: Median (interquartile range) plasma citrulline concentrations at admission were 2.8 μmol/L (range: 0.3, 49.0; P < .001 versus controls) in survivors (n = 49), 2.1 μmol/L (range: 0.5, 6.4, P < .001 versus controls) in nonsurvivors (n = 12) and 38.6 μmol/L (range: 11.4, 96.1) in controls (n = 14), respectively. There was no significant difference in plasma citrulline concentration between survivors and nonsurvivors within the parvovirus‐infected puppies, and plasma citrulline concentration was not significantly associated with outcome in parvoviral enteritis. There were no significant changes in plasma citrulline concentration over the 8‐day follow‐up period. Conclusion and Clinical Importance: Parvovirus enteritis is associated with a severe decrease in plasma citrulline concentration that does not appear to have any significant prognostic value.     

Association of admission plasma D-dimer concentration with diagnosis and outcome in horses with colic

Background: Coagulopathies detected in horses with gastrointestinal problems seem to be associated with poor outcome. Plasma D‐Dimer concentration is a sensitive test for assessing coagulopathies. Hypothesis: Plasma D‐Dimer concentration tested on admission is related to diagnosis and outcome in horses with colic. Animals: Four hundred and ninety three horses referred for evaluation of abdominal pain. Methods: Prospective observational clinical study. Horses were grouped according to diagnosis (medical and surgical intestinal obstructions, ischemic disorders with and without intestinal resection, enteritis, peritonitis), outcome (survivors, nonsurvivors), and number of coagulopathies (normal profile, 1 or 2 coagulopathies, subclinical disseminated intravascular coagulation [DIC]). Blood samples were collected on admission and plasma D‐Dimer concentration, clotting times (PT and aPTT), and antithrombin activity were determined. Positive likelihood ratios (LR+) were calculated for evaluation of D‐Dimer cut‐off values, which were later tested in a logistic regression model. Results: Horses with enteritis or peritonitis had significantly (P < .001) higher plasma D‐Dimer concentrations and more severe coagulopathies on admission than horses with other diagnoses. Nonsurvivors also had significantly (P < .001) higher plasma D‐Dimer concentrations at presentation than did survivors, and those horses with subclinical DIC on presentation had an odds ratio (OR) 8.6 (95% confidence interval [CI], 3.3–22.5, P < .001) for nonsurvival. Finally, D‐Dimer concentrations >4,000 ng/mL had a LR+ of 5.9 and an OR 8.8 (95% CI, 4.5–17.1, P < .001) for nonsurvival. Conclusion and Clinical Importance: Plasma D‐Dimer concentration measured on admission can be used to facilitate diagnosis and outcome prediction in horses with colic. A potential cut‐off value for nonsurvival was found at approximately 4,000 ng/mL.