A Multielectrode Nerve Cuff for Chronic Velocity Selective Recording in a sheep model.

Supra-sacral spinal cord injury (SCI) causes loss of bladder fullness sensation and bladder over-activity, leading to retention and incontinence respectively. Velocity selective recording (VSR) of nerve roots innervating the bladder might enable identification of bladder activity. A 10-electrode nerve cuff for sacral nerve root VSR was developed and tested in a sheep model during acute surgeries and chronic implantation for 6 months. The cuff performed well, with 5.90±1.90 kΩ electrode, and <~800 Ω tissue impedance after 189 days implantation with a stable device and tissues. This is important information for assessing the feasibility of chronic VSR.Clinical Relevance-This demonstrates the manufacturing and performance of a neural interface for chronic monitoring of bladder nerve afferents with applications in urinary incontinence and retention management following SCI.

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis.

OBJECTIVES: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). CLINICAL SIGNIFICANCE: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.

Influence of peri-incisional epaxial muscle infiltration with bupivacaine pre- or post-surgery on opioid administration in dogs undergoing thoraco-lumbar hemilaminectomy.

This study investigated the influence of bupivacaine infiltration before or after hemilaminectomy on peri-operative opioid requirement in dogs. Thirty dogs undergoing T3-L3 hemilaminectomy were randomly assigned to receive peri-incisional infiltration of bupivacaine 2 mg/kg into the epaxial muscles before surgery (Group A), at wound closure (Group B), or no infiltration (Group C). Anaesthesia comprised dexmedetomidine 4 mcg/kg and methadone 0.3 mg/kg IV (premedication), alfaxalone IV (induction), and isoflurane in oxygen (maintenance). All dogs received meloxicam SC/PO prior to induction of general anaesthesia. Response to surgery, defined as a change in autonomic physiological variables >20% above baseline, was treated with fentanyl 2.5 mcg/kg boluses, followed by a continuous rate infusion of fentanyl at 5 mcg/kg/h. The Glasgow Composite Pain Score-Short Form (GCPS-SF) was performed before premedication and at regular intervals until 24 h postoperatively. Methadone 0.2 mg/kg analgesia was given IV if GCPS-SF was ≥5/20. Number of intraoperative, postoperative and total analgesic interventions were recorded. Analgesic interventions were analysed using a chi-squared test using a Pocock approach and statistical significance was set at P < 0.029. The number of intra-operative analgesic interventions in Group A (median, 0; range, 0-2), was significantly lower than in Group B (median, 3; range, 0-5) and Group C (median, 3; range, 0-5; P = 0.019). Regarding postoperative interventions, there were significantly fewer in Group A (median, 0; range, 0-1) and Group B (median, 0; range, 0-1) than in Group C (median, 1; range, 0-2; P = 0.047). Group A (median, 0; range, 0-3), had significantly fewer total analgesic interventions than Group B (median, 3; range, 0-6) and Group C (median, 4; range, 1-7; P = 0.014). Bupivacaine reduced peri-operative opioid administration and pre-surgical peri-incisional infiltration yielded the greatest benefit.

The Effects of the Presence of Multiple Conduction Velocities in the Analysis of Electrically-Evoked Compound Action Potentials (eCAPs).

New methods for the analysis of electrically-evoked compound action potentials (eCAPs) are described. Mammalian nerves tend to have broad multi-modal distributions of fibre diameters, which translates into a spread of conduction velocities. The method of velocity selective recording (VSR) is unable to distinguish between this spectral spread and the transfer function of the system. The concept of the velocity impulse function (VIF) is introduced as a tool to differentiate between these signal and system attributes. The new methods enable separate estimates of velocity spectral broadening and signal-to-noise ratio (SNR) to be obtained.

Selective Recording of Urinary Bladder Fullness from the Extradural Sacral Roots.

Managing the urinary bladder is of primary importance to clinicians and patients after trauma to the spinal cord. Sacral Anterior Root Stimulators that control the bladder have been available as clinical technology for many years, however these devices cannot measure the fullness of the urinary bladder or detect the onset of reflex voiding. In order to address this fundamental limitation, it is necessary to develop a method for recording the neural signals that encode bladder fullness. This paper presents a proof of concept technique for recording bladder afferents from the extradural sacral roots using a multiple electrode cuff. Results are provided from acute in-vivo experiments performed in sheep.

Canine urethral sphincter pressure profile under incremental inflation of an artificial cuff: a cadaver study.

OBJECTIVES: To determine whether artificial urethral sphincter filling volume is proportional to peak pressure exerted on the urethra. MATERIALS AND METHODS: Urethral pressure profilometry was performed in five female, medium-sized, mixed-breed canine cadavers following artificial urethral sphincter placement. Maximum urethral pressure was recorded following sequential incremental inflation of 0.15 mL and compared to baseline pressure and between dogs using two-way analysis of variance. RESULTS: Artificial urethral sphincter placement in cadavers was associated with an increase in urethral pressure, which was significantly correlated with inflation volume. The correlation was non-linear and demonstrated considerable individual variation. Maximum urethral pressures after artificial urethral sphincter placement exceeded those reported in conscious continent dogs within a narrow volume range, in which a 0.15 mL infusion more than doubled maximal urethral pressures. CLINICAL SIGNIFICANCE: Rapid increases in urethral pressure from the artificial urethral sphincter over a small range of filling volumes (0.15 mL increments) might explain why some clinical cases can become suddenly dysuric following incremental inflations. We suggest that smaller increments of filling (0.05 to 0.1 mL) may achieve finer pressure control.

Somatosensory and motor evoked potentials in dogs with chronic severe thoracolumbar spinal cord injury.

Some dogs that become paraplegic after severe spinal cord injury regain ambulation on the pelvic limbs despite permanent loss of pelvic limb sensation, a phenomenon termed 'spinal walking'. Plastic changes in spinal cord circuitry are thought to mediate this form of recovery but the precise circumstances that favor its development are not known. More information on this phenomenon would be helpful because it might be possible to coax more function in chronically paraplegic animals so improving their, and their owners', quality of life. We analysed the correlation of 'spinal walking' and pelvic limb pain sensation with recordings of scalp and spinal somatosensory and transcranial magnetic motor evoked potentials. We prospectively examined 94 paraplegic dogs (including 53 Dachshunds) that had sustained T10 to L3 spinal cord injury (including 78 dogs with acute intervertebral disc herniation) at a median time of 12.0 months from injury. Nine dogs exhibited 'spinal walking' and nine other individuals had intact pelvic limb pain sensation. Of 34 tested, 12 dogs had recordable scalp somatosensory evoked potentials. Fifty-three of 59 tested dogs had recordable spinal somatosensory evoked potentials, but only six had recordable potentials cranial to the lesion. Twenty-two of 94 tested dogs had recordable transcranial magnetic motor evoked potentials in the pelvic limb(s). There was no apparent association between intact evoked potential recording and either spinal walking or intact pain sensation. We conclude that factors other than influence, or lack of influence, of input carried by spinal cord long tracts mediate recovery of spinal walking.

25-Hydroxy vitamin D3 serum concentration in dogs with acute polyradiculoneuritis compared to matched controls.

OBJECTIVES: To determine if dogs with acute polyradiculoneuritis have lower serum 25-hydroxy vitamin D3 concentration compared to a control group of dogs with idiopathic epilepsy. MATERIALS AND METHODS: Retrospective case-control study of 21 dogs with acute canine polyradiculoneuritis and 21 control dogs with idiopathic epilepsy matched for year and season of presentation from a referral hospital population in the UK. Serum concentration of 25-hydroxy vitamin D3 was compared between groups using Student's t-test. RESULTS: Dogs with acute canine polyradiculoneuritis had significantly lower (P=0·033) serum 25-hydroxy vitamin D3 concentration (87·1 nmol/L ±55·4 nmol/L) compared to a control group with idiopathic epilepsy (113 nmol/L ±66·3 nmol/L). CLINICAL SIGNIFICANCE: The cause and clinical significance of the altered vitamin D status in dogs with acute polyradiculoneuritis are not clear and require further investigation. Our findings pave the way for improved understanding of acute canine polyradiculoneuritis and, potentially, improved clinical management, if a causal role for 25-hydroxy vitamin D3 is defined.

An exploratory study into factors influencing development of acute canine polyradiculoneuritis in the UK.

OBJECTIVES: To investigate whether the development of acute canine polyradiculoneuritis is associated with various putative risk factors. MATERIALS AND METHODS: Retrospective case-control study with conditional logistic regression analysis from a referral hospital population in the UK where controls were matched for year of presentation. RESULTS: Forty-three cases were identified with acute canine polyradiculoneuritis and 86 controls were selected. Jack Russell terriers and West Highland white terriers were found to have a significantly greater odds of developing acute canine polyradiculoneuritis compared to a mixed baseline group of dogs. The odds of developing acute canine polyradiculoneuritis were greater in the autumn and winter compared to spring. Vaccination, rural/urban habitation, sex, neuter status and age were not associated with development of acute canine polyradiculoneuritis in our population of dogs. CLINICAL SIGNIFICANCE: Breed and season were associated with development of acute canine polyradiculoneuritis. However, this is a small sample and so this observation needs confirmation in further studies and other factors may also be involved. Nevertheless, these findings may be important in further understanding the aetiopathogenesis of this condition.

Prognostic Factors Associated with Recovery of Ambulation and Urinary Continence in Dogs with Acute Lumbosacral Spinal Cord Injury.

BACKGROUND: Limited information is available about prognostic factors for recovery after spinal cord injury (SCI) to the L4-S3 segments. Previous research suggests that L4-S3 SCI does not have a worse prognosis than T3-L3 SCI. HYPOTHESIS/OBJECTIVES: To elucidate prognostic factors for regaining urinary continence and ambulation in dogs with L4-S3 SCI and compare prognosis to T3-L3 SCI. ANIMALS/METHODS: A retrospective study on 61 nonambulatory dogs with L4-S3 SCI, matched to dogs with T3-L3 SCI, compared 3 weeks after onset. Prognostic factors explored using logistic regression and used for matching: nonchondrodystrophic dogs >15 kg versus dogs that were chondrodystrophic or <15 kg; compressive versus noncompressive lesions; presence versus absence of conscious pain perception (CPP); and lower vs upper motor neuron (LMN/UMN) incontinence. RESULTS: Fewer L4-S3 dogs regained continence compared to T3-L3 dogs (64 vs 85%, P = .0033), but no difference existed for regaining ambulation (66 vs 75%, P = .1306). In L4-S3 SCI dogs, fewer dogs regained continence with loss of CPP (P < .001), LMN incontinence (P = .004), and noncompressive lesions (P = .006). Negative prognostic factors for regaining ambulation included absent CPP (P < .001) and large nonchondrodystrophic breed (P = .022). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with L4-S3 SCI have a poorer short-term prognosis than do dogs with T3-L3 SCI. Dogs with L4-S3 SCI had a poor prognosis with loss of CPP, or noncompressive lesions combined with LMN incontinence. Small-breed or chondrodystrophic dogs with retained CPP, compressive lesions, and UMN incontinence had an excellent prognosis. These findings may help guide decision-making in L4-S3 SCI.

Suspected air embolism through the thoracic ventral internal vertebral venous plexus during hemilaminectomy in dogs.

Venous air embolism entering via the ventral internal vertebral venous plexus was suspected during thoracic spinal surgery in two dogs. In both cases, air was seen bubbling from a pool of blood on the floor of the vertebral canal accompanied by sudden cardiopulmonary disturbances: low end-tidal carbon dioxide pressure, tachycardia and reduction in oxygen in the blood. One dog became dyspnoeic and one died.

Degenerative Encephalopathy in Nova Scotia Duck Tolling Retrievers Presenting with a Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Neurodegenerative diseases are a heterogeneous group of disorders characterized by loss of neurons and are commonly associated with a genetic mutation. HYPOTHESIS/OBJECTIVES: To characterize the clinical and histopathological features of a novel degenerative neurological disease affecting the brain of young adult Nova Scotia Duck Tolling Retrievers (NSDTRs). ANIMALS: Nine, young adult, related NSDTRs were evaluated for neurological dysfunction and rapid eye movement sleep behavior disorder. METHODS: Case series review. RESULTS: Clinical signs of neurological dysfunction began between 2 months and 5 years of age and were progressive in nature. They were characterized by episodes of marked movements during sleep, increased anxiety, noise phobia, and gait abnormalities. Magnetic resonance imaging documented symmetrical, progressively increasing, T2-weighted image intensity, predominantly within the caudate nuclei, consistent with necrosis secondary to gray matter degeneration. Abnormalities were not detected on clinicopathological analysis of blood and cerebrospinal fluid, infectious disease screening or urine metabolite screening in most cases. Postmortem examination of brain tissue identified symmetrical malacia of the caudate nuclei and axonal dystrophy within the brainstem and spinal cord. Genealogical analysis supports an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: A degenerative encephalopathy was identified in young adult NSDTRs consistent with a hereditary disease. The prognosis is guarded due to the progressive nature of the disease, which is minimally responsive to empirical treatment.

Pathophysiology, Clinical Importance, and Management of Neurogenic Lower Urinary Tract Dysfunction Caused by Suprasacral Spinal Cord Injury.

Management of persistent lower urinary tract dysfunction resulting from severe thoracolumbar spinal cord injury can be challenging. Severe suprasacral spinal cord injury releases the spinal cord segmental micturition reflex from supraspinal modulation and increases nerve growth factor concentration in the bladder wall, lumbosacral spinal cord, and dorsal root ganglion, which subsequently activates hypermechanosensitive C-fiber bladder wall afferents. Hyperexcitability of bladder afferents and detrusor overactivity can cause urine leaking during the storage phase. During urine voiding, the loss of supraspinal control that normally coordinates detrusor contraction with sphincter relaxation can lead to spinal cord segmental reflex-mediated simultaneous detrusor and sphincter contractions or detrusor-sphincter dyssynergia, resulting in inefficient urine voiding and high residual volume. These disease-associated changes can impact on the quality of life and life expectancy of spinal-injured animals. Here, we discuss the pathophysiology and management considerations of lower urinary tract dysfunction as the result of severe, acute, suprasacral spinal cord injury. In addition, drawing from experimental, preclinical, and clinical medicine, we introduce some treatment options for neurogenic lower urinary tract dysfunction that are designed to: (1) prevent urine leakage arising because of detrusor overactivity during bladder filling, (2) preserve upper urinary tract integrity and function by reducing intravesical pressure and subsequent vesicoureteral reflux, and (3) prevent urinary tract and systemic complications by treating and preventing urinary tract infections.

Prevalence of Chiari-like malformations in clinically unaffected dogs.

BACKGROUND: The importance of Chiari-like malformation (CM) in the generation of clinical signs or the formation of syringomyelia in dogs is incompletely understood, partly because the prevalence of various CM definitions in unaffected dogs is unknown. HYPOTHESIS/OBJECTIVES: The aims were: to estimate the prevalence of CM in dogs asymptomatic for CM or syringomyelia, according to 3 currently used definitions; and, to investigate the effect of brachycephaly and head position during magnetic resonance (MR) imaging on estimates of the prevalence of CM. ANIMALS: One ninety-nine client-owned dogs without apparent signs of CM or syringomyelia. METHODS: Blinded, retrospective analysis. Archived MR images were analyzed for evidence of cerebellar indentation and impaction into or herniation through the foramen magnum. Logistic regression analysis was used to investigate the relationship of CM diagnosis with head position and the cranial index (a measure of brachycephaly). RESULTS: In 185 non-Cavalier King Charles Spaniel (CKCS) dogs, indentation was identified in 44% (95% CI, 47-51%) and impaction in 22% (95% CI, 16-28%). No asymptomatic, non-CKCS dogs showed herniation. Regression analysis showed a significant increase in the odds of indentation and impaction in an extended head position and as the cranial index increased (became more brachycephalic). CONCLUSIONS AND CLINICAL IMPORTANCE: The high prevalence of cerebellar indentation and impaction suggests that they may be normal anatomical variations and therefore unsuitable as definitions of CM. We suggest that future research into CM in dogs should define cases and controls more strictly so that overlap between normal and abnormal animals is minimized.

Hypothalamic-anterior pituitary hormone deficiencies following traumatic brain injury in dogs.

Traumatic brain injury is an important cause of hypopituitarism in human beings, but limited information exists in the veterinary literature regarding this condition. The primary study objective was to investigate whether hypothalamic-anterior pituitary axis dysfunction exists following traumatic brain injury in 17 client owned dogs. In this retrospective, observational, open, cohort study, information about dogs presented to four separate referral centres between April 2008 and October 2013 was reviewed. Cases were included if they had suffered from non-fatal traumatic brain injury, resulting in neurological dysfunction, and follow-up evaluation included measurement of the serum concentration of insulin-like growth factor 1 (IGF-1), endogenous adrenocorticotrophic hormone (ACTH), basal cortisol, thyroid-stimulating hormone, total thyroxine (TT4) and, if appropriate, free thyroxine. Decreased IGF-1 concentration was the most common abnormality detected (7/17, 41 per cent; median 132 ng/ml, range <15-536), followed by a decreased TT4 concentration (4/17, 23 per cent; median 19, range 4-49). Basal cortisol concentration was less than 20 nmol/l in two cases (2/17, 12 per cent; median 65, range <20-1735), with concurrently undetectable ACTH (<5 pg/ml). This study demonstrates that dogs with a history of traumatic brain injury can develop endocrine abnormalities indicative of hypothalamic-anterior pituitary dysfunction.

The impact of demographic, social, and environmental factors on the development of steroid-responsive meningitis-arteritis (SRMA) in the United Kingdom.

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is an inflammatory disease of dogs that is suspected to be immune-mediated. The development of other immune-mediated diseases has been linked to vaccinations, time of the year, geographic location, sex, neuter status, and breed. HYPOTHESIS/OBJECTIVES: To identify if the development of SRMA is associated with time of year, vaccination, geographic location, sex, neuter status, and breed. ANIMALS: Sixty SRMA cases and 180 controls, all ≤24 months of age and matched for year of presentation, from a referral hospital population in the United Kingdom. METHODS: Retrospective case-control study with unconditional logistic regression analysis. RESULTS: Beagles (P = .001), Border Collies (P = .001), Boxers (P = .032), Jack Russell Terriers (P = .001), Weimaraners (P = .048), and Whippets (P < .001) had significantly greater odds of developing SRMA in this population of dogs. Vaccination, time of year, geographic category, sex, and neuter status did not increase the odds of developing SRMA. CONCLUSIONS AND CLINICAL IMPORTANCE: Only breed increased the odds of developing SRMA. It would be prudent to investigate the genetics of the identified breeds to help elucidate the etiopathogenesis of SRMA.

Use of an implanted sacral nerve stimulator to restore urine voiding in chronically paraplegic dogs.

BACKGROUND: Loss of urinary control after spinal cord injury increases risk of urinary tract disease and is problematical for owners of affected dogs. OBJECTIVES: To design, implant, and test a sacral nerve stimulating device for controlling urine voiding in paraplegic dogs. ANIMALS: Nine pet dogs with severe thoracolumbar spinal cord injury causing paraplegia, loss of hindquarter sensation, and incontinence for more than 3 months. The procedure was offered prospectively to owners of suitable candidates after the irreversibility of the incontinence had been ascertained. METHODS: Open label clinical study. Surgically implantable electrode "books" were designed for insertion and retention of mixed sacral nerves. Sacral nerves were accessed via laminectomy and stimulated to test their ability to elicit detrusor contraction and then inserted into the electrode book, which was attached to a subcutaneously implanted, externally activated receiver. RESULTS: In 8/9 dogs, S2 nerves elicited the largest increases in intravesicular pressure with minimum stimulation and were placed in electrode books. Voiding efficiency was >90% in 8 of the 9 implanted dogs. No important detrimental effects of the procedure were observed. CONCLUSIONS AND CLINICAL IMPORTANCE: This sacral nerve stimulating implant is a simple and apparently effective neuroprosthetic device that restores urine voiding in paraplegic dogs.

A novel movement disorder in related male Labrador Retrievers characterized by extreme generalized muscular stiffness.

OBJECTIVES: To describe the clinical phenotype of a new motor disorder in Labrador Retrievers. ANIMALS AND METHODS: Case series study. Seven young male Labrador Retrievers presented for evaluation of stiff gait. RESULTS: All affected dogs had generalized muscular stiffness, persistent at rest and resulting in restricted joint movements. They showed a forward flexed posture, festinating gait, and bradykinesia. Signs developed between 2 and 16 months of age and tended to stabilize in adulthood. Needle electromyogram in the conscious state showed continuous motor unit activity in resting epaxial and proximal limb muscles. This activity was abolished by general anesthesia. Muscle and nerve histopathology was normal. In 2 dogs necropsied, astrocytosis was evident throughout the spinal cord gray matter, reticular formation and caudate nuclei. Decreased neuronal counts were selectively found in the spinal cord Rexed's lamina VII, but not in VIII and IX. Pedigree analysis showed that the affected dogs were from 5 related litters. CONCLUSIONS AND CLINICAL IMPORTANCE: This new hypertonicity syndrome in Labrador Retrievers is unique because of the selective distribution of the histological lesions, the lack of progression in adulthood, and its exclusive occurrence in male dogs. Pedigree analysis suggests an X-linked hereditary disease, although other modes of inheritance cannot be ruled out with certainty. We hypothesize that altered output from basal nuclei and reticular formation together with motor neuron disinhibition caused by a decreased number of spinal cord interneurons leads to the muscular stiffness.

Designing clinical trials in canine spinal cord injury as a model to translate successful laboratory interventions into clinical practice.

Many interventions have been shown to improve outcome after experimental spinal cord injury in laboratory animals. The challenge now is to determine whether any of these can be translated to become an efficacious therapy for clinical lesions - a process that is often difficult and frequently fails. Here, we discuss the steps that are required to make this transition and the need for rigorous clinical trials. A key component is an outcome measure that is amenable to statistical analysis; we describe methods that we have developed to accurately measure function after spinal cord injury in dogs. The general methodology may have parallels in the development of veterinary models to test putative therapies for other diseases of humans and animals.

Comparison of two regimens for the treatment of meningoencephalomyelitis of unknown etiology.

BACKGROUND: The optimal treatment for meningoencephalomyelitis of unknown etiology (MUE) remains unknown, despite the widespread use of a variety of immunosuppressive drugs. OBJECTIVE/HYPOTHESIS: To compare the efficacy of prednisolone combined with either vincristine and cyclophosphamide (COP group; n= 10) or with cytosine arabinoside (AraC group; n= 9). ANIMALS: Nineteen dogs with neurological deficits, neuroimaging, and cerebrospinal fluid abnormalities consistent with a diagnosis of MUE. METHODS: Prospective, blinded, and randomized clinical trial. Dogs fulfilling the inclusion criteria were randomly allocated to receive 1 drug regimen. RESULTS: Four of 10 dogs in the COP group and 5/9 in the AraC group survived > 12 months but neither the survival time nor the time-to-treatment failure differed between the 2 groups. Treatment with COP resulted in an unacceptable incidence of adverse effects. CONCLUSIONS: The adverse effects of COP make it an unsuitable treatment for MUE. Although survival of animals treated with AraC was broadly similar to that reported in recently published studies describing this treatment, it remains unclear whether it confers any benefit over using prednisolone alone.