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Abstract

OBJECTIVE To develop a spasticity scale for dogs with chronic deficits following severe spinal cord injury (SCI) for use in clinical assessment and outcome measurement in clinical trials.

ANIMALS 20 chronically paralyzed dogs with a persistent lack of hind limb pain perception caused by an acute SCI at least 3 months previously.

PROCEDURES Spasticity was assessed in both hind limbs via tests of muscle tone, clonus, and flexor and extensor spasms adapted from human scales. Measurement of patellar clonus duration and flexor spasm duration and degree was feasible. These components were used to create a canine spasticity scale (CSS; overall score range, 0 to 18). Temporal variation for individual dogs and interrater reliability were evaluated. Gait was quantified with published gait scales, and CSS scores were compared with gait scores and clinical variables. Owners were questioned regarding spasticity observed at home.

RESULTS 20 dogs were enrolled: 18 with no apparent hind limb pain perception and 2 with blunted responses; 5 were ambulatory. Testing was well tolerated, and scores were repeatable between raters. Median overall CSS score was 7 (range, 3 to 11), and flexor spasms were the most prominent finding. Overall CSS score was not associated with age, SCI duration, lesion location, or owner-reported spasticity. Overall CSS score and flexor spasm duration were associated with gait scores.

CONCLUSIONS AND CLINICAL RELEVANCE The CSS could be used to quantify hind limb spasticity in dogs with chronic thoracolumbar SCI and might be a useful outcome measure. Flexor spasms may represent an integral part of stepping in dogs with severe SCI.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate the effects of postoperative photobiomodulation therapy and physical rehabilitation on early recovery variables for dogs after hemilaminectomy for treatment of intervertebral disk disease.

ANIMALS 32 nonambulatory client-owned dogs.

PROCEDURES Dogs received standard postoperative care with photobiomodulation therapy (n = 11), physical rehabilitation with sham photobiomodulation treatment (11), or sham photobiomodulation treatment only (10) after surgery. Neurologic status at admission, diagnostic and surgical variables, duration of postoperative IV analgesic administration, and recovery grades (over 10 days after surgery) were assessed. Time to reach recovery grades B (able to support weight with some help), C (initial limb movements present), and D (ambulatory [≥ 3 steps unassisted]) was compared among groups. Factors associated with ability to ambulate on day 10 or at last follow-up were assessed.

RESULTS Time to reach recovery grades B, C, and D and duration of postoperative IV opioid administration did not differ among groups. Neurologic score at admission and surgeon experience were negatively associated with the dogs' ability to ambulate on day 10. The number of disk herniations identified by diagnostic imaging before surgery was negatively associated with ambulatory status at last follow-up. No other significant associations and no adverse treatment-related events were identified.

CONCLUSIONS AND CLINICAL RELEVANCE This study found no difference in recovery-related variables among dogs that received photobiomodulation therapy, physical rehabilitation with sham photobiomodulation treatment, or sham photobiomodulation treatment only. Larger studies are needed to better evaluate effects of these postoperative treatments on dogs treated surgically for intervertebral disk disease.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate the pharmacokinetics of zonisamide following rectal administration of 20 or 30 mg/kg suspended in sterile water or polyethylene glycol (PEG) to healthy dogs and determine whether either dose resulted in plasma zonisamide concentrations within the recommended therapeutic target range (10 to 40 μg/mL).

ANIMALS 8 healthy mixed-breed dogs.

PROCEDURES Each dog received each of 2 doses (20 or 30 mg/kg) of zonisamide suspended in each of 2 delivery substrates (sterile water or PEG) in a randomized crossover study with a 7-day washout period between phases. A blood sample was collected from each dog immediately before and at predetermined times for 48 hours after zonisamide administration. Plasma zonisamide concentrations were determined by high-performance liquid chromatography, and data were analyzed with a noncompartmental model.

RESULTS Mean maximum plasma concentration, time to maximum plasma concentration, mean residence time, and elimination half-life did not differ significantly among the 4 treatments. The mean maximum plasma concentration for all 4 treatments was less than the therapeutic target range. The mean ± SD area under the concentration-time curve for the 30 mg/kg-in-water treatment (391.94 ± 237.00 h•μg/mL) was significantly greater than that for the 20 mg/kg-in-water (146.19 ± 66.27 h•μg/mL) and 20 mg/kg-in-PEG (87.09 ± 96.87 h•μg/mL) treatments.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that rectal administration of zonisamide at doses of 20 and 30 mg/kg failed to achieve plasma zonisamide concentrations within the recommended therapeutic target range. Therefore, rectal administration of zonisamide cannot be recommended as a suitable alternative to oral administration.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To develop and assess the feasibility, repeatability, and safety of an ultrasound-guided technique to stimulate the first cervical nerve (FCN) at the level of the alar foramen of the atlas of horses.

ANIMALS 4 equine cadavers and 6 clinically normal Standardbreds.

PROCEDURES In each cadaver, the FCN pathway was determined by dissection, and any anastomosis between the first and second cervical nerves was identified. Subsequently, each of 6 live horses underwent a bilateral ultrasound-guided stimulation of the FCN at the alar foramen 3 times at 3-week intervals. After each procedure, horses were examined daily for 5 days.

RESULTS In each cadaver, the FCN passed through the alar foramen; a communicating branch between the FCN and the accessory nerve and anastomoses between the ventral branches of the FCN and second cervical nerve were identified. The anastomoses were located in the upper third of the FCN pathway between the wing of the atlas and the nerve's entry in the omohyoideus muscle. Successful ultrasound-guided electrical stimulation was confirmed by twitching of the ipsilateral omohyoideus muscle in all 6 live horses; this finding was observed bilaterally during each of the 3 experimental sessions. No complications developed at the site of stimulation.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that ultrasound-guided stimulation of the FCN at the alar foramen appears to be a safe and straightforward procedure in horses. The procedure may have potential for use in horses with naturally occurring recurrent laryngeal neuropathy to assess reinnervation after FCN transplantation or nerve-muscle pedicle implantation in the cricoarytenoideus dorsalis muscle.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate the potential usefulness of epiduroscopy for clinical diagnosis and treatment of vertebral canal and spinal cord lesions in dogs.

SAMPLE Cadavers of 6 mixed-breed dogs.

PROCEDURES Dogs were positioned in sternal recumbency, and an endoscope was introduced into the lumbosacral epidural space. A fiberscope (diameter, 0.9 mm; length, 30 cm) was used for 3 dogs, and a videoscope (diameter, 2.8 mm; length, 70 cm) was used for the other 3 dogs. Visibility and identities of anatomic structures were recorded, and maneuverability of the endoscopes was assessed. Extent of macroscopic tissue damage was evaluated by manual dissection of the vertebral canal at the end of the procedure.

RESULTS Intermittent saline (0.9% NaCl) solution infusion, CO2 insufflation, and endoscope navigation improved visualization by separating the epidural fat from the anatomic structures of interest. Images obtained with the fiberscope were small and of poor quality, making identification of specific structures difficult. Maneuverability of the fiberscope was difficult, and target structures could not be reliably reached or identified. Maneuverability and image quality of the videoscope were superior, and spinal nerve roots, spinal dura mater, epidural fat, and blood vessels could be identified. Subsequent manual dissection of the vertebral canal revealed no gross damage in the spinal cord, nerve roots, or blood vessels.

CONCLUSIONS AND CLINICAL RELEVANCE A 2.8-mm videoscope was successfully used to perform epiduroscopy through the lumbosacral space in canine cadavers. Additional refinement and evaluation of the technique in live dogs is necessary before its use can be recommended for clinical situations.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To develop representative MRI atlases of the canine brain and to evaluate 3 methods of atlas-based segmentation (ABS).

ANIMALS 62 dogs without clinical signs of epilepsy and without MRI evidence of structural brain disease.

PROCEDURES The MRI scans from 44 dogs were used to develop 4 templates on the basis of brain shape (brachycephalic, mesaticephalic, dolichocephalic, and combined mesaticephalic and dolichocephalic). Atlas labels were generated by segmenting the brain, ventricular system, hippocampal formation, and caudate nuclei. The MRI scans from the remaining 18 dogs were used to evaluate 3 methods of ABS (manual brain extraction and application of a brain shape–specific template [A], automatic brain extraction and application of a brain shape–specific template [B], and manual brain extraction and application of a combined template [C]). The performance of each ABS method was compared by calculation of the Dice and Jaccard coefficients, with manual segmentation used as the gold standard.

RESULTS Method A had the highest mean Jaccard coefficient and was the most accurate ABS method assessed. Measures of overlap for ABS methods that used manual brain extraction (A and C) ranged from 0.75 to 0.95 and compared favorably with repeated measures of overlap for manual extraction, which ranged from 0.88 to 0.97.

CONCLUSIONS AND CLINICAL RELEVANCE Atlas-based segmentation was an accurate and repeatable method for segmentation of canine brain structures. It could be performed more rapidly than manual segmentation, which should allow the application of computer-assisted volumetry to large data sets and clinical cases and facilitate neuroimaging research and disease diagnosis.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To compare the pharmacokinetics of various formulations of levetiracetam after oral administration of a single dose to healthy dogs.

ANIMALS 6 neurologically normal mixed-breed dogs.

PROCEDURES A crossover study design was used. Blood samples for serum harvest were collected from each dog before and at various points after oral administration of one 500-mg tablet of each of 2 generic extended-release (ER) formulations, 1 brand-name ER formulation, or 1 brand-name immediate-release (IR) formulation of levetiracetam. Serum samples were analyzed to determine pharmacokinetic properties of each formulation by means of ultra–high-performance liquid chromatography with tandem mass spectrometry.

RESULTS No dogs had clinically important adverse effects for any formulation of levetiracetam. All ER formulations had a significantly lower maximum serum drug concentration and longer time to achieve that concentration than did the IR formulation. Half-lives and elimination rate constants did not differ significantly among formulations. Values for area under the drug concentration-versus-time curve did not differ significantly between ER formulations and the IR formulation; however, 1 generic ER formulation had a significantly lower area under the curve than did other ER formulations.

CONCLUSIONS AND CLINICAL RELEVANCE All ER formulations of levetiracetam had similar pharmacokinetic properties in healthy dogs, with some exceptions. Studies will be needed to evaluate the clinical efficacy of the various formulations; however, findings suggested that twice-daily administration of ER formulations may be efficacious in the treatment of seizures in dogs.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate the association between ultrasonographically measured optic nerve sheath diameter (ONSD) and acute increases in intracranial pressure (ICP) as measured by an epidural intracranial pressure monitoring system (EICPMS) in healthy dogs.

ANIMALS 6 young healthy dogs.

PROCEDURES An EICPMS connected to a pressure monitor was used to generate a continuous pressure waveform in each anesthetized dog. A 22-gauge IV catheter was inserted into the brain parenchyma through the contralateral parietal bone, and 0.5 to 2.0 mL of anticoagulated autologous blood was injected at predetermined intervals. At baseline (immediately after EICPMS placement) and following each injection, the ICP as indicated by EICPMS was recorded, and 3 ultrasonographic images of the optic nerve sheath of each eye were obtained. The ONSD was measured at maximum diameter and at 5 mm caudal to the optic disk.

RESULTS In linear models, the maximum ONSD was positively associated with increasing ICP. Specifically, the rate of maximum ONSD increase was greater for pressures ≤ 20 mm Hg above baseline (0.0534 mm/1 mm Hg ICP increase) than for pressures > 40 mm Hg above baseline (0.0087 mm/1 mm Hg ICP increase). The relationship of ICP to maximum ONSD was slightly nonlinear and best explained by comparison of fractional polynomial regression models.

CONCLUSIONS AND CLINICAL RELEVANCE ICP was positively and nonlinearly associated with increasing maximum ONSD, especially when ICP was ≤ 20 mm Hg above baseline, supporting the conclusion that ultrasonographic measurement of maximum ONSD may provide a noninvasive monitoring tool for evaluation of ICP in dogs. Further research is needed to assess the utility of these measurements in clinical patients.

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in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine in vivo effects of nitric oxide (NO) on blood-brain barrier (BBB) permeability in common carp (Cyprinus carpio L.).

ANIMALS 148 carp.

PROCEDURES Carp received glyceryl trinitrate (1 mg/kg) as an NO donor or received no treatment (control group). Nitrite and nitrate concentrations in carp sera were determined 0.25, 1, 3, 6, 8, 12, and 24 hours after treatment. In control and treatment groups, BBB permeability was analyzed by assessment of leakage of Evans blue dye into various brain areas at 6, 12, and 24 hours after glyceryl trinitrate treatment. Brain edema was determined by means of the wet-dry weight method and assessed with light microscopy on H&E-stained preparations of tissues obtained 6 and 24 hours after glyceryl trinitrate treatment.

RESULTS Treatment with glyceryl trinitrate induced endogenous synthesis of NO, which was upregulated 6 and 8 hours after treatment. Increased NO synthesis was associated with increased permeability of the BBB, which developed 6 hours after treatment with the NO donor. Although the BBB became impermeable again by 12 hours after glycerol trinitrate treatment, brain edema still persisted 24 hours after treatment.

CONCLUSIONS AND CLINICAL RELEVANCE In this study, treatment with an NO donor caused reversible opening of the BBB and brain edema in common carp. An intact BBB is important to prevent influx of potentially harmful substances into the brain. This investigation highlighted the possibility of BBB disarrangement caused by NO, a substance found in the CNS of all vertebrates evaluated.

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in American Journal of Veterinary Research

Abstract

Objective—To assess kinetic 2-([18F]fluoro)-2-deoxy-d-glucose (18FDG) uptake in the brain of anesthetized healthy adult dogs by use of positron emission tomography (PET) and to determine whether 18FDG uptake differs among anatomic regions of the brain.

Animals—5 healthy Beagles.

Procedures—Each isoflurane-anesthetized dog was administered 18FDG IV (dose range, 3.0 to 5.2 mCi), and PET data were acquired for 2 hours. A CT scan (without contrast agent administration) was performed to allow more precise neuroanatomic localization. Defined regions of interest within the brain were drawn on reconstructed image data. Standard uptake values (SUVs) for 18FDG were calculated to generate time-activity curves and determine time to peak uptake.

Results—Time-activity curve analysis identified 4 regional uptake patterns: olfactory, gray matter, white matter, and other (brainstem, cerebellum, and occipital and frontal regions). The highest maximum SUVs were identified in the olfactory bulbs and cerebral gray matter, and the lowest maximum SUV was identified in cerebral white matter. Mean time to peak uptake ranged from 37.8 minutes in white matter to 82.7 minutes in the olfactory bulbs.

Conclusions and Clinical Relevance—Kinetic analysis of 18FDG uptake revealed differences in uptake values among anatomic areas of the brain in dogs. These data provide a baseline for further investigation of 18FDG uptake in dogs with immune-mediated inflammatory brain disease and suggest that 18FDG-PET scanning has potential use for antemortem diagnosis without histologic analysis and for monitoring response to treatment. In clinical cases, a 1-hour period of PET scanning should provide sufficient pertinent data.

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in American Journal of Veterinary Research