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Abstract
OBJECTIVE
To investigate the time course of circulating neutrophil priming and activity in dogs with spinal cord injury secondary to intervertebral disk herniation that undergo decompressive surgery.
ANIMALS
9 dogs with spinal cord injury and 9 healthy dogs (controls).
PROCEDURES
For dogs with spinal cord injury, blood samples were collected on the day of hospital admission and 3, 7, 30, and 90 days after injury and decompressive surgery. A single blood sample was collected from the control dogs. Flow cytometry analysis was performed on isolated neutrophils incubated with antibody against CD11b and nonfluorescent dihydrorhodamine 123, which was converted to fluorescent rhodamine 123 to measure oxidative burst activity.
RESULTS
Expression of CD11b was increased in dogs with spinal cord injury 3 days after injury and decompressive surgery, relative to day 7 expression. Neutrophils expressed high oxidative burst activity both 3 and 7 days after injury and decompressive surgery, compared with activity in healthy dogs.
CLINICAL RELEVANCE
For dogs with spinal cord injury, high CD11b expression 3 days after injury and decompressive surgery was consistent with findings for rodents with experimentally induced spinal cord injury. However, the high oxidative burst activity 3 and 7 days after injury and decompressive surgery was not consistent with data from other species, and additional studies on inflammatory events in dogs with naturally occurring spinal cord injury are needed.
Abstract
OBJECTIVE
To investigate the association between changes in cerebral blood flow and electrographic epileptic seizure in dogs using transcranial Doppler ultrasonography (TCD).
ANIMALS
6 healthy Beagle dogs.
PROCEDURES
Each dog was administered pentetrazol (1.5 mg/kg/min) or saline (0.9% NaCl) solution under general anesthesia with continuous infusion of propofol. Both pentetrazol and saline solution were administered to all 6 dogs, with at least 28 days interval between the experiments. Blood flow waveforms in the middle cerebral artery and the basilar artery were obtained using TCD at baseline, after pentetrazol administration, and after diazepam administration. TCD velocities, including peak systolic velocity, end-diastolic velocity, and mean velocity and resistance variables, were determined from the Doppler waveforms.
RESULTS
During ictal-phase of pentetrazol-induced seizures, the TCD velocities significantly increased in the basilar and middle cerebral arteries while TCD vascular resistance variables did not change in either artery. The TCD velocities significantly decreased after diazepam administration. Systemic parameters, such as the heart rate, mean arterial pressure, systemic vascular resistance, cardiac index, end-tidal carbon dioxide, oxygen saturation, and body temperature, did not change significantly during seizures.
CLINICAL RELEVANCE
This study showed that cerebral blood flow, as obtained from TCD velocities, increased by 130% during ictal-phase of pentetrazol-induced seizures in dogs. The elevated velocities returned to baseline after seizure suppression. Thus, TCD may be used to detect electrographic seizures during the treatment of status epilepticus in dogs, and further clinical studies clarifying the association between changes in cerebral blood flow and non-convulsive seizure cases are needed.
Abstract
OBJECTIVE
To evaluate the utility of enzyme immunoassays (EIAs) for the detection of Coccidioides antigen and antibody in CSF in the diagnosis of CNS coccidioidomycosis in dogs.
ANIMALS
51 dogs evaluated for CNS disease in a single specialty center in Tucson in 2016.
PROCEDURES
Excess CSF after routine analysis was banked after collection from dogs presented to the neurology service. Samples were tested by EIA for presence of Coccidioides antigen and antibody. Clinical data were collected from medical records retrospectively.
RESULTS
22 dogs were diagnosed with CNS coccidioidomycosis (CCM) or another neurologic disease (non-CCM). These groups of dogs overlapped in the presenting complaints, MRI results, and routine CSF analysis results. Four dogs, all with CCM, had positive antigen EIA results. With clinical diagnosis used as the reference standard, CSF antigen testing had low sensitivity (20%) but high specificity (100%) for diagnosis of CCM. Ten dogs with CCM and 4 dogs with other diagnoses had antibody detected in CSF by EIA. Sensitivity of CSF antibody testing was 46%, specificity was 86%, and positive and negative predictive values for the study population were 71% and 68%, respectively.
Clinical Relevance
Diagnosis of CNS coccidioidomycosis in dogs in an endemic region was hampered by overlap of clinical signs with other neurologic disorders and the low sensitivity of confirmatory diagnostics. The evaluated Coccidioides-specific EIAs performed on CSF can aid in the diagnosis. A prospective study is warranted to corroborate and refine these preliminary findings
Abstract
OBJECTIVE
To evaluate intradiskal pressure (IDP) in the C6-7 intervertebral disk (IVD) after destabilization and distraction-fusion of the C5-C6 vertebrae.
SAMPLE
7 cadaveric C4-T1 vertebral specimens with no evidence of IVD disease from large-breed dogs.
PROCEDURES
Specimens were mounted in a custom-made 6 degrees of freedom spinal loading simulator so the C5-C6 and C6-C7 segments remained mobile. One specimen remained untreated and was used to assess the repeatability of the IDP measurement protocol. Six specimens underwent 3 sequential configurations (untreated, partial diskectomy of the C5-6 IVD, and distraction-fusion of the C5-C6 vertebrae). Each construct was biomechanically tested under neutral, flexion, extension, and right-lateral bending loads. The IDP was measured with a pressure transducer inserted into the C6-7 IVD and compared between the nucleus pulposus and annulus fibrosus and across all 3 constructs and 4 loads.
RESULTS
Compared with untreated constructs, partial diskectomy and distraction-fusion of C5-C6 decreased the mean ± SD IDP in the C6-7 IVD by 1.3 ± 1.3% and 0.8 ± 1.3%, respectively. During motion, the IDP remained fairly constant in the annulus fibrosus and increased by 3.8 ± 3.0% in the nucleus pulposus. The increase in IDP within the nucleus pulposus was numerically greatest during flexion but did not differ significantly among loading conditions.
CONCLUSIONS AND CLINICAL RELEVANCE
Distraction-fusion of C5-C6 did not significantly alter the IDP of healthy C6-7 IVDs. Effects of vertebral distraction-fusion on the IDP of adjacent IVDs with degenerative changes, such as those in dogs with caudal cervical spondylomyelopathy, warrant investigation.
Abstract
OBJECTIVE
To investigate the change in the lumbosacral angle (ΔLSA) and conus medullaris (CM) displacement in healthy dogs undergoing dynamic MRI with changes in the posture of their pelvic limbs from neutral posture to flexion or extension posture and to evaluate for potential correlation between ΔLSA and CM displacement.
ANIMALS
9 healthy adult Beagles.
PROCEDURES
Dogs underwent dynamic MRI with their pelvic limbs positioned in neutral, flexion, and extension postures. From T2-weighted sagittal midline plane MRI images, 2 observers measured the lumbosacral angle and CM location in duplicate for each posture for each dog. Intra- and interobserver agreement was assessed, and the Spearman rank correlation coefficient (ρ) was used to assess for potential correlation between ΔLSA and CM displacement for changes in pelvic limb posture from neutral to flexion or extension.
RESULTS
Overall, the mean ΔLSA and CM displacement for changes in posture were 23° and 9.09 mm (caudal displacement) for the change from neutral to flexion posture, 8.4° and −2.5 mm (cranial displacement) for the change from neutral to extension posture, and 32.2° and 11.64 mm (caudal displacement) for the change from extension to flexion posture. The ΔLSA strongly correlated (ρ = 0.705; 95% CI, 0.434 to 0.859) with displacement of the CM.
CONCLUSIONS AND CLINICAL RELEVANCE
The use of dynamic MRI, compared with conventional MRI, will better help to characterize clinically normal and abnormal features of the lumbosacral region of the vertebral column and associated spinal cord during postural changes. Further, when limited translocation of the CM is evident on dynamic MRI, veterinarians should suspect underlying lumbosacral pathophysiologic processes or anatomic abnormalities.
Abstract
OBJECTIVE
To examine whether glucocorticoid (GC) administration alters hippocampal cerebral blood flow (CBF) or volume in dogs.
ANIMALS
6 clinically normal adult Beagles.
PROCEDURES
Each dog underwent CT and MRI to measure the CBF in the hippocampus, basal ganglia, thalamus, and cerebral cortex and the volume of the hippocampus in each hemisphere of the brain before (day 0) and during (days 7 and 21) a 21-day treatment with prednisolone (1.0 mg/kg, PO, q 24 h) and famotidine (0.5 mg/kg, PO, q 12 h). Results for hippocampal volume, anesthesia-related variables, and semiquantitative measurements of CBF (hemisphere-specific ratios of the CBF in the hippocampus, basal ganglia, and thalamus relative to the CBF in the ipsilateral cerebral cortex and the left cerebral cortex CBF-to-right cerebral cortex CBF ratio) were compared across assessment time points (days 0, 7, and 21).
RESULTS
The ratios of CBF in the right hippocampus and right thalamus to that in the right cerebral cortex on day 21 were significantly lower than those on day 0. No meaningful differences were detected in results for the hippocampal volume in either hemisphere or for the anesthesia-related variables across the 3 time points.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that GC administration reduced CBF in the hippocampus and thalamus in dogs of the present study, similar to that which occurs in humans. Research on GC-related brain alteration in dogs could potentially contribute to advancements in understanding Alzheimer disease in humans and neurodegenerative conditions in dogs.
Abstract
OBJECTIVE
To evaluate whether cell-based and tissue-based immunofluorescent assays (IFAs) run in parallel could be used to detect glial fibrillary acidic protein (GFAP) autoantibodies in the CSF of dogs with meningoencephalitis of unknown origin (MUO) and other CNS disorders
ANIMALS
15 CSF samples obtained from dogs with presumed MUO (n = 5), CNS disease other than MUO (5), and idiopathic epilepsy (5).
PROCEDURES
All CSF samples underwent parallel analysis with a cell-based IFA that targeted the α isoform of human GFAP and a tissue-based IFA that involved mouse brain cryosections. Descriptive data were generated.
RESULTS
Only 1 CSF sample yielded mildly positive results on the cell-based IFA; that sample was from 1 of the dogs with presumed MUO. The remaining 14 CSF samples tested negative on the cell-based IFA. All 15 CSF samples yielded negative results on the tissue-based IFA.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that concurrent use of a cell-based IFA designed to target the human GFAP-α isoform and a tissue-based IFA that involved mouse tissue cryosections was inadequate for detection of GFAP autoantibodies in canine CSF samples. Given that GFAP autoantibodies were likely present in the CSF samples analyzed, these findings suggested that epitopes differ substantially between canine and human GFAP and that canine GFAP autoanti-body does not bind to mouse GFAP. Without a positive control, absence of GFAP autoantibody in this cohort cannot be ruled out. Further research is necessary to develop a noninvasive and sensitive method for diagnosis of MUO in dogs.
Abstract
OBJECTIVE
To determine whether cell-free DNA (cfDNA) was detectable in CSF samples from dogs, whether CSF sample volume impacted CSF cfDNA concentration measurement, and whether CSF cfDNA concentration was associated with CNS disease category or CSF RBC count (RBCC), nucleated cell count (NCC), or protein concentration, which could aid in the diagnosis of neurologic diseases in dogs.
SAMPLE
80 CSF samples collected from dogs with (n = 60) and without (20) clinical neurologic disease between February 2017 and May 2018.
PROCEDURES
Results for CSF RBCC, NCC, protein concentration, and cfDNA concentration were compared across CSF groups established on the basis of whether they were obtained from dogs with (case groups) or without (control group) clinical signs of neurologic disease In addition, 5 paired CSF samples representing large (3.0-mL) and small (0.5-mL) volumes, were used to evaluate whether sample volume impacted measurement of CSF cfDNA concentration.
RESULTS
cfDNA was detected in 76 of the 80 (95%) CSF samples used to evaluate parameters across disease categories and in all 5 of the paired samples used to evaluate whether sample volume impacted cfDNA quantification. There were no substantial differences in cfDNA concentrations identified between groups (on the basis of disease category or sample volume), and the CSF cfDNA concentration did not meaningfully correlate with CSF RBCC, NCC, or protein concentration.
CONCLUSIONS AND CLINICAL RELEVANCE
Although results indicated that the CSF cfDNA concentration could not be used to differentiate between categories of neurologic disease in dogs of the the present study, further investigation is warranted regarding the use of CSF analysis, including sequencing specific cfDNA mutations, for diagnosing and monitoring neurologic disease in dogs.
Abstract
OBJECTIVE
To determine values of F-wave parameters for the tibial nerve in clinically normal Miniature Dachshunds and those with thoracolumbar intervertebral disk herniation (IVDH).
ANIMALS
53 Miniature Dachshunds (10 clinically normal and 43 with various clinical grades of thoracolumbar IVDH).
PROCEDURES
F-waves were elicited in the interosseous muscles of 1 hind limb in each dog by stimulation of the tibial nerve. F-wave parameters were measured for 32 stimuli/dog, and mean values were calculated. Linear regression was performed to assess correlations between F-wave parameters and clinical severity of IVDH.
RESULTS
For clinically normal dogs, mean ± SD values of shortest F-wave latency, mean F-wave conduction velocity, mean F-wave duration, and ratio of the mean F-wave amplitude to M response amplitude were 8.6 ± 0.6 milliseconds, 83.7 ± 6.1 m/s, 6.6 ± 1.5 milliseconds, and 9.8 ± 8.5%, respectively. F-wave persistence was 100%. Mean F-wave duration was positively correlated with clinical grade of IVDH. Linear regression yielded the following regression equation: F-wave duration (milliseconds) = 6.0 + 2.7 × IVDH grade. One dog with grade 2 IVDH had a mean F-wave duration shorter than that of all 5 dogs with grade 1 IVDH; 1 dog with grade 3 IVDH had a longer duration than that of all 10 dogs with grade 4 IVDH.
CONCLUSIONS AND CLINICAL RELEVANCE
Mean F-wave duration was correlated with the severity of inhibitory motor tract dysfunction in the spinal cord of dogs. F-wave examination may be useful for objective functional evaluation of upper motor neurons in the spinal cord.
Abstract
OBJECTIVE
To measure expression of microRNAs (miRNAs) in plasma and in extracellular vesicles (EVs) derived from plasma for dogs with glioma and dogs with other brain diseases.
SAMPLE
Plasma samples from 11 dogs with glioma and 19 control dogs with various other brain diseases.
PROCEDURES
EVs were isolated from plasma samples by means of ultracentrifugation. Expression of 4 candidate reference miRNAs (let-7a, miR-16, miR-26a, and miR-103) and 4 candidate target miRNAs (miR-15b, miR-21, miR-155, and miR-342-3p) was quantified with reverse transcription PCR assays. Three software programs were used to select the most suitable reference miRNAs from among the 4 candidate reference miRNAs. Expression of the 4 target miRNAs was then calculated relative to expression of the reference genes in plasma and EVs, and relative expression was compared between dogs with glioma and control dogs with other brain diseases.
RESULTS
The most suitable reference miRNAs were miR-16 for plasma and let-7a for EVs. Relative expression of miR-15b in plasma and in EVs was significantly higher in dogs with glioma than in control dogs. Relative expression of miR-342-3p in EVs was significantly higher in dogs with glioma than in control dogs.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that miR-15b and miR-342-3p have potential as noninvasive biomarkers for differentiating glioma from other intracranial diseases in dogs. However, more extensive analysis of expression in specific glioma subtypes and grades, compared with expression in more defined control populations, will be necessary to assess their clinical relevance.
