Cerebrospinal Fluid Eosinophilia in Dogs

Background: Marked eosinophilic meningitis or meningoencephalomyelitis (EME) is rarely reported in dogs and the cause is usually undetermined. Long-term prognosis for dogs with cerebrospinal fluid (CSF) eosinophilia is variable.
Animals: Twenty-three client-owned dogs.
Methods: Retrospective case series. Dogs with eosinophilic CSF, defined as total nucleated cell count (TNCC) >3 cells/μL with >20% eosinophils, were identified by a computerized search of all dogs having cisternal and/or lumbar CSF analyzed as part of the diagnostic workup between 1992 and 2007.
Results: TNCC in CSF ranged from 4 to 4,740 cells/μL (median 84 cells/μL, reference range ≤3 cells/μL), with 22 to 95% (median 78%) eosinophils in the differential count. An infectious agent was identified on necropsy in 4 of 23 (17%) dogs ( Cryptococcus neoformans [n = 2], Neospora caninum [n = 1], and Baylisascaris procyonis [n = 1]). Each of these dogs had progressive neurologic deterioration. Sixteen dogs had idiopathic EME. Magnetic resonance imaging (MRI) findings were abnormal in 7 of 13 dogs with EME; 2 dogs had focal lesions and 5 dogs had multifocal lesions. Clinical signs in 12 of 16 (75%) dogs with idiopathic EME resolved with prednisone treatment. Three dogs with acute intervertebral disc herniations recovered after decompressive surgery alone.
Conclusions: Idiopathic EME is a common cause of eosinophilic pleocytosis in dogs. MRI findings are variable. Infectious causes of EME were less common and had a poor prognosis.     

Metagenomic Investigation of Idiopathic Meningoencephalomyelitis in Dogs

Background

Meningoencephalomyelitis of unknown origin (MUO) is a common and life‐threatening neuroinflammatory disease in dogs. Features of the disease are suggestive of an underlying immune‐mediated process, but the association of this disease with a pathogen is still unknown.

Hypothesis/Objectives

To search for candidate etiologic agent associated with cases if MUO using next generation metagenomic sequencing.

Animals

Twenty‐two dogs diagnosed with either MUO (11/22; 10 CSF and 3 brain), or noninflammatory CNS diseases inconsistent with MUO (11/22; 11 CSF and 2 brain) that served as negative controls.

Methods

A case control study was performed by identifying MUO and non‐MUO cases. Samples were blindly processed and then unblinded for comparative analyses. Inclusion criteria for MUO cases included consistent MRI lesions and inflammatory CSF with a negative PCR panel for infectious agents or histopathologic diagnosis. Dogs with glucocorticoid therapy within 2 weeks of sample collection were excluded. Fresh‐frozen cerebrospinal fluid (CSF; 21) and brain (5) samples were collected and RNA and DNA were extracted separately for shotgun metagenomic sequencing. Known positive samples were used as controls to validate our sequencing and analysis pipelines and to establish limits of detection. Sequencing results were analyzed at a nucleotide and protein level for broad comparison to known infectious organisms.

Results

No candidate etiologic agents were identified in dogs with MUO.

Conclusions and Clinical Importance

These results support but do not prove the hypothesis that MUO is not associated with infectious agents and might be an autoimmune disease.     

Comparison of Cerebrospinal Fluid Pressure in Propofol-and Thiopental-anesthetized Eucapnic Dogs

Cerebrospinal fluid pressure (CSF_P) was measured as part of the neurologic assessment of dogs with suspected intracranial disease. Because propofol has not been shown to cause an increase in intracranial pressure in humans, the authors examined its effect on (CSF_P) in dogs to determine if it would be an appropriate substitute for thiopental as an anesthetic agent for the measurement of CSF_P. The CSF pressure in eucapnic propofol-anesthetized dogs (105 ± 5.6 mm H_PO) was not significantly different (p < .05) from CSF_P in eucapnic thiopental-anesthetized dogs (103.8 ± 6.6 mm H_PO).     

Clinical Features and Outcome of Dogs with Epiglottic Retroversion With or Without Surgical Treatment: 24 Cases

Background

Published information describing the clinical features and outcome for dogs with epiglottic retroversion (ER) is limited.

Hypothesis/Objectives

To describe clinical features, comorbidities, outcome of surgical versus medical treatment and long‐term follow‐up for dogs with ER. We hypothesized that dogs with ER would have upper airway comorbidities and that surgical management (epiglottopexy or subtotal epiglottectomy) would improve long‐term outcome compared to medical management alone.

Animals

Twenty‐four client‐owned dogs.

Methods

Retrospective review of medical records to identify dogs with ER that underwent surgical or medical management of ER.

Results

Dogs with ER commonly were middle‐aged to older, small breed, spayed females with body condition score (BCS) ≥6/9. Stridor and dyspnea were the most common presenting signs. Concurrent or historical upper airway disorders were documented in 79.1% of cases. At last evaluation, 52.6% of dogs that underwent surgical management, and 60% of dogs that received medical management alone, had decreased severity of presenting clinical signs. In dogs that underwent surgical management for ER, the incidence of respiratory crisis decreased from 62.5% before surgery to 25% after surgical treatment. The overall calculated Kaplan–Meier median survival time was 875 days.

Conclusion and clinical importance

Our study indicated that a long‐term survival of at least 2 years can be expected in dogs diagnosed with epiglottic retroversion. The necessity of surgical management cannot be determined based on this data, but dogs with no concurrent upper airway disorders may benefit from a permanent epiglottopexy to alleviate negative inspiratory pressures.     

Clinical Features and Outcome of Heterobilharzia americana Infection in Dogs

Background: Heterobilharzia americana (HA), the causative agent of canine schistosomiasis, is a flatworm with a freshwater snail as an intermediate host. Only case reports or small case series evaluating naturally infected dogs have been published.
Objective: Describe clinical signs in dogs naturally infected with HA.
Animals: Twenty-two dogs naturally infected with HA from 1985 to 2009.
Methods: Retrospective study. All medical records were searched for HA and schistosomiasis. Only dogs with a diagnosis based on identification of ova on histopathology or fecal saline sedimentation were included.
Results: The median age was 3.1 years (1–12). The median duration of clinical signs before diagnosis was 0.63 months (0.03–12). The most common clinical signs were lethargy (91%), weight loss (77%), hyporexia (68%), vomiting (59%), and diarrhea (55%). Eleven of the 22 dogs were hypercalcemic. Hypercalcemia did not resolve without definitive treatment with praziquantel. HA infection was an incidental diagnosis in 7/22 dogs. Diagnosis was obtained via necropsy (4), histopathology (9), and fecal examination (9). Definitive treatment included praziquantel and fenbendazole. Eighteen dogs were diagnosed antemortem and 17 were treated. Twelve dogs were alive for 6 months to 3 years after diagnosis.
Conclusions and Clinical Importance: HA infection occurs in younger, larger breed, indoor dogs. Hypercalcemia does not resolve without praziquantel treatment. Prognosis is good and neither hypercalcemic-induced renal failure nor ascites appears to worsen prognosis. Dogs in affected areas or that have traveled to affected areas that present for weight loss, gastrointestinal or liver disease, and hypercalcemia, should be tested.     

Oxytocin Content of the Cerebrospinal Fluid of Dogs and Its Relationship to Pain Induced by Spinal Cord Compression

Objectives —To determine whether oxytocin exists in the cerebrospinal fluid (CSF) of dogs and whether the amount of oxytocin in the CSF of dogs with neck or back pain caused by spinal cord compression is significantly different than that in the CSF of clinically normal dogs.
Study Design —Prospective controlled study.
Animal Population —A total of 15 purpose-bred beagles and 17 client-owned dogs.
Methods —CSF was collected by needle puncture of the cerebellar medullary cistern after induction of general anesthesia. Oxytocin levels within the samples were determined through radioimmunoassay.
Results —Dogs with spinal cord compression had significantly more oxytocin in their CSF than the clinically normal dogs (13.76 ± 2.0 pg/mL and 3.61 ± 0.63 pg/mL, respectively; P < .0001). Dogs with chronic signs (>7 days) had significantly more oxytocin in their CSF than dogs with acute signs (<7 days) (21.60 ± 0.86 pg/mL and 6.80 ± 0.81 pg/mL, respectively; P < .0001). Both acutely and chronically affected dogs had significantly more oxytocin in their CSF than the controls ( P < .005 and P < .0001 respectively).
Conclusions —Dogs with neck and back pain caused by spinal cord compression have significantly more oxytocin in their CSF than clinically normal dogs. Dogs with chronic clinical signs have significantly more oxytocin in their CSF than dogs with acute clinical signs.
Clinical Relevance —In humans, intrathecal injection of oxytocin is effective in treating low back pain for up to 5 hours. Intrathecal oxytocin may be a logical choice for perioperative analgesia in dogs undergoing myelography because the intrathecal space is accessed for injection of contrast agent.     

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: Five hundred and seventy‐four 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 ≥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 ≥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.     

Antimicrobial Resistance Impacts Clinical Outcome of Granulomatous Colitis in Boxer Dogs

Background: Escherichia coli have recently been identified within the colonic mucosa of Boxer dogs with granulomatous colitis (GC). Eradication of invasive E. coli is associated with clinical and histological remission. Objectives: To determine antimicrobial susceptibility profiles of E. coli strains from GC and healthy dogs, and the association of antimicrobial resistance with clinical outcome. Animals: Fourteen Boxer dogs with GC and 17 healthy pet dogs. Methods: Prospective study: E. coli was cultured from GC biopsies and rectal mucosal swabs of healthy dogs. Individual strains were selected by phylogroup and overall genotype, determined by triplex‐ and random amplified polymorphic DNA‐polymerase chain reaction respectively. Antimicrobial susceptibility was determined by broth microdilution minimal inhibitory concentration. Results: Culture yielded 23 E. coli strains from GC (1–3/dog, median 2) and 34 strains from healthy (1–3/dog, median 2). E. coli phylogroups were similar (P= .18) in GC (5A, 7B1, 5B2, 6D) and healthy (2A, 10B1, 15B2, 7D). Resistance to ampicillin, amoxicillin‐clavulanate, cefoxitin, tetracycline, trimethoprim‐sulfa (TMS), ciprofloxacin, and chloramphenicol was greater (P < .05) in GC (21–64%) than healthy (0–24%). Enrofloxacin resistant E. coli were isolated from 6/14 GC versus 0/17 healthy (P= .004). Of the enrofloxacin resistant cases, 4/6 were also resistant to macrophage‐penetrating antimicrobials such as chloramphenicol, rifampicin, and TMS. Enrofloxacin treatment before definitive diagnosis was associated with antimicrobial resistance (P < .01) and poor clinical outcome (P < .01). Conclusions and Clinical Importance: Antimicrobial resistance is common among GC‐associated E. coli and impacts clinical response. Antimicrobial therapy should be guided by mucosal culture and antimicrobial susceptibility testing rather than empirical wisdom.     

Cerebrospinal Fluid PCR and Antibody Concentrations against Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in Dogs with Neurological Signs

Background: The tick-borne bacteria Borrelia burgdorferi sensu lato (sl) and Anaplasma phagocytophilum have been suspected to cause neurological signs in dogs. Diagnosis often has been made based on positive antibody titers in serum of dogs with neurological signs, but a high seroprevalence in dogs in at-risk populations makes diagnosis difficult.
Objective: To determine if the neurological signs in dogs examined were caused by any of these bacteria.
Animals: Fifty-four dogs presented to a board-certified neurologist.
Methods: Prospective study. We divided dogs into 2 groups: those with inflammatory diseases of the central nervous system (CNS) and those with neurological signs from other diseases. Blood and cerebrospinal fluid (CSF) from all dogs were analyzed.
Results: Dogs with inflammatory CNS diseases showed no serum antibodies against any of the agents. Among dogs with neurological signs from other diseases, 10.3% had serum antibodies for B. burgdorferi sl and 20.5% for A. phagocytophilum . All blood samples analyzed for bacterial deoxyribonucleic acid (DNA) and all CSF analyzed for antibodies and bacterial DNA for the 2 agents were negative.
Conclusions and Clinical Importance: Based on this study, these bacteria are unlikely causes of neurologic disease in dogs and the presence of serum antibodies alone does not document or establish a definitive diagnosis of CNS disease caused by these organisms. Dogs that have neurologic disease and corresponding serum antibodies against these agents should have additional tests performed to assess for other potential etiologies of the signs.     

Unilateral and Bilateral Stifle Arthrodesis in Eight Dogs

Nine stifle arthrodeses in eight dogs were reviewed retrospectively to evaluate use of the limb, each dog's comfort, complications, and factors that may have influenced the final outcome. Ability to use the limb after unilateral fusion was good (limb used at all times) in three dogs, fair (limb used at all gaits except a gallop) in three dogs, and poor (limb used only when running) in one dog. Factors that appeared to affect the outcome included angle at which the stifle was fused and lesions in the ipsilateral coxofemoral joint. One dog with bilateral arthrodesis had a good outcome with minor limitations. The only potentially devastating complications occurred in one dog in which infection and premature implant loosening jeopardized the fusion. None of the dogs exhibited signs of pain and all owners were satisfied with the results.     

Idiopathic Eosinophilic Masses of the Gastrointestinal Tract in Dogs

Background: Eosinophilic inflammation of the gastrointestinal tract of dogs occurs in numerous disorders, typically resulting in diffuse intestinal thickening. Rarely, eosinophilic masses have been reported.
Objective: Describe a series of dogs with 1 or more idiopathic eosinophilic gastrointestinal masses (IEGM) to better characterize the clinical features, treatment, and prognosis.
Animals: Seven dogs with 1 or more gastrointestinal masses composed primarily of eosinophilic infiltrates for which no underlying cause was found.
Methods: Retrospective case series.
Results: Rottweilers and purebred, large breed dogs predominated. Dogs were middle-aged and typically had chronic signs of upper or lower gastrointestinal disease. Decreased appetite, vomiting, and evidence of gastrointestinal hemorrhage were present in the majority of cases. An abdominal or rectal mass was frequently noted on physical examination. Common laboratory abnormalities included peripheral eosinophilia, mature neutrophilia, hypoproteinemia, and hypocholesterolemia. The masses were histologically composed of moderate to severe eosinophilic infiltrates, which were often transmural and accompanied by fibrosis. All dogs treated with surgery alone died of complications of their disease. Treatment with corticosteroids and ivermectin improved clinical signs, caused resolution of eosinophilic infiltrates, and prolonged survival in most dogs treated medically.
Conclusions and Clinical Importance: These findings suggest that the prognosis for dogs with IEGM may be good when recognized and managed appropriately. When surgery is performed, medical treatment should also be added.     

Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy

Background

Dogs with a chronic enteropathy (CE) have a lower vitamin D status, than do healthy dogs. Vitamin D status has been associated with a negative clinical outcome in humans with inflammatory bowel disease.

Objectives

To examine the relationship between serum 25 hydroxyvitamin D (25(OH)D) concentrations at diagnosis and clinical outcome in dogs with a CE.

Animals

Forty‐one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary Studies, Hospital for Small Animals between 2007 and 2013.

Methods

Retrospective review. Serum 25(OH)D concentrations were compared between dogs which were alive at follow up or had died because of non‐CE‐related reasons (survivors) and dogs which died or were euthanized due to their CE (non‐survivors). A binary logistic regression analysis was performed to determine significant predictors of death in dogs with CE.

Results

Serum concentrations of 25(OH)D at the time a CE was diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors 4.36 ng/mL, interquartile range 1.6–17.0 ng/mL), median survivors (n = 26) (24.9 ng/mL interquartile range 15.63–39.45 ng/mL, P < .001). Serum 25(OH)D concentration was a significant predictor of death in dogs with CE (odds ratio 1.08 [95% CI 1.02–1.18)]).

Conclusions

Serum 25(OH)D concentrations at diagnosis are predictive of outcome in dogs with CE. The role of vitamin D in the initiation and outcome of chronic enteropathies in dogs is deserving of further study.     

Proteomic Characterization of Equine Cerebrospinal Fluid

Cerebrospinal fluid (CSF) is a biofluid that is reflective of overall health. Although proteomic profiling of human CSF has been performed in the context of a variety of disease states, this report represents the first comprehensive proteomic analysis of equine CSF. A total of 320 proteins were confidently identified across six healthy horses, and these proteins were further characterized by gene ontology terms mapped in UniProt, and normalized spectral abundance factors were calculated as a measure of relative abundance. Theses results provide an optimized protocol for analysis of equine CSF and lay the groundwork for future studies involving the study of equine CSF in the context of pathogenic disease states.     

The Clinical Significance of Cerebrospinal Fluid Lipid Peroxides in Central Nervous System Disease

Forty-four dogs were referred to our hospital presenting with neurological symptoms such as seizure or paraparesis. Magnetic resonance imaging (MRI) revealed abnormal results in 21 (abnormal MRI group) and normal results in 23 dogs (normal MRI group). Cerebrospinal fluid (CSF) (normal MRI group, n = 22; abnormal MRI group, n = 21) and serum lipid peroxide (LP) concentrations (normal MRI group, n = 11; abnormal MRI group, n = 15) were measured in a number of these dogs, and revealed a significant difference in the CSF/serum LP values (normal MRI group, n = 10; abnormal MRI group, n = 14) between the abnormal and the normal MRI groups (t-test and Mann–Whitney U-test p < 0.05). No other significant differences were observed. CSF/serum LP values exceeding 1.0 were exhibited in 10 of 14 dogs (71%) in the abnormal MRI group, and in 1 of 10 dogs (10%) in the normal MRI group. In the remaining animals, 4 dogs of the abnormal MRI group showed CSF/serum values lower than 1.0, 3 dogs had morphological abnormalities but no abnormal MRI signals in the central nervous system, and 1 dog had an abnormal MRI signal but no pathological abnormality. In the CSF analysis, 3 of 16 dogs (19%) of the abnormal MRI groupshowed abnormal cell counts and/or protein content. We conclude that the CSF/serum LP value can be used for the detection of neurological lesions such as oedema, inflammation and tumour.     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.