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.

Innervation of canine skin: an immunohistochemical study.

The general appearance of the innervation of samples of skin from 10 young beagles was studied by using the pan-neuronal immunolabel PGP9.5, and quantitative data on the density of the nerve fibres was obtained. The data provide a baseline for the development of a diagnostic test for small fibre neuropathy in domestic dogs.

Clinical diagnosis and treatment of suspected neuropathic pain in three dogs.

Three dogs were referred to The Queen's Veterinary School Hospital at University of Cambridge for chronic behavioural or locomotor disorders associated with pain. All three had been unsuccessfully treated with conventional analgesics, including non-steroidal anti-inflammatory drugs, glucocorticoids and opiate agonists, prior to referral, with minimal or no response. They were investigated by neurological examination plus conventional ancillary diagnostic tests and therapeutic drug trials. Ruling out other causes of pain and applying previously well-described criteria, each case was diagnosed as consistent with neuropathic pain, a poorly recognised condition in domestic dogs. Treatment with the tricyclic antidepressant drug, amitriptyline, or the antiepileptic drug, gabapentin, resulted in either a dramatic improvement or full resolution of clinical signs in all cases.

Use of a lateral surgical approach to the femoral nerve in the management of two primary femoral nerve sheath tumours.

This case report describes the diagnosis and management of primary femoral nerve sheath tumours in two dogs. Both of the tumours were localised by electromyography (EMG) and magnetic resonance imaging (MRI), and were then surgically resected using a novel approach to the iliopsoas muscle via osteotomy of the ventral ilial wing. This approach should be considered when attempting surgical treatment of conditions affecting the iliopsoas muscle or the femoral nerve because it provides excellent exposure of these structures.

Thoracic stenosis causing lateral compression of the spinal cord in two immature Dogues de Bordeaux.

This case report describes a novel developmental vertebral malformation in two young Dogues de Bordeaux, which was diagnosed by magnetic resonance imaging. Both dogs were treated surgically with reasonable success.

Findings on low-field cranial MR images in epileptic dogs that lack interictal neurological deficits.

Recurrent seizuring is a common neurological problem in dogs and can present diagnostic difficulties for the attending clinician. Associated interictal neurological deficits strongly suggest brain disease but the frequency of structural abnormalities in patients without such deficits is unknown. In this study the prevalence of clinically significant magnetic resonance imaging (MRI) abnormalities was determined in two groups of interictally normal dogs, those younger than 6 years and those older than 6 years of age. In the former group, only 1/46 dogs (2.2%) had significant MRI abnormalities, whereas in the latter group, 8/30 (26.7%) were abnormal. None of the dogs had an identifiable metabolic cause for the seizures. These findings suggest that the diagnostic yield of advanced neuroimaging techniques in young seizuring dogs without interictal neurological deficits is low, but reaffirms their value in similar older individuals.

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.

Two-Year Follow-Up Magnetic Resonance Imaging and Spectroscopy Findings and Cerebrospinal Fluid Analysis of a Dog with Sandhoff's Disease.

A 13-month-old female Toy Poodle was presented for progressive ataxia and intention tremors of head movement. The diagnosis of Sandhoff's disease (GM2 gangliosidosis) was confirmed by deficient ß-N-acetylhexosaminidase A and B activity in circulating leukocytes and identification of the homozygous mutation (HEXB: c.283delG). White matter in the cerebrum and cerebellum was hyperintense on T2-weighted and fluid-attenuated inversion recovery magnetic resonance images. Over the next 2 years, the white matter lesions expanded, and bilateral lesions appeared in the cerebellum and thalamus, associated with clinical deterioration. Magnetic resonance spectroscopy showed progressive decrease in brain N-acetylaspartate, and glycine-myo-inositol and lactate-alanine were increased in the terminal clinical stage. The concentrations of myelin basic protein and neuron specific enolase in cerebrospinal fluid were persistently increased. Imaging and spectroscopic appearance correlated with histopathological findings of severe myelin loss in cerebral and cerebellar white matter and destruction of the majority of cerebral and cerebellar neurons.

Brain abscess in a dog immunosuppressed using cyclosporin.

This report describes a dog that developed brain abscesses following prolonged immunosuppression with cyclosporin. Bacteria within the abscess were most likely Nocardia, an organism well recognised in immunosuppressed humans, and probably reached the brain through haematogenous spread from a more long-standing abscess in the mediastinum. Bacterial brain abscesses developing in this manner are very rare in dogs and this case highlights the wider range of possible diagnoses that need to be considered in immunosuppressed patients and the care with which potent drugs such as cyclosporin should be used.

Syringomyelia in cavalier King Charles spaniels: the relationship between syrinx dimensions and pain.

OBJECTIVES: This study was designed to test the hypothesis that pain associated with syringomyelia in dogs is dependent upon size and involvement of the dorsal part of the spinal cord. METHODS: Masked observers determined syrinx dimensions and precise location within the spinal cord on magnetic resonance images of 55 cavalier King Charles spaniels with syringomyelia. After removal of masking, syrinx size and location were compared between the cohorts of dogs that exhibited pain with those that did not. RESULTS: Maximum syrinx width was the strongest predictor of pain, scratching behaviour and scoliosis in dogs with syringomyelia. Both pain and syrinx size were positively correlated with syrinxes located in the dorsal half of the spinal cord. CLINICAL SIGNIFICANCE: Large syrinxes associated with damage to the dorsal part of the spinal cord are associated with persistent pain suggesting that the pain behaviour expressed by this group of patients is likely to be "neuropathic pain," resulting from disordered neural processing in the damaged dorsal horn. As such it is likely that conventional analgesic medication may be ineffective.

Re-opening the window on fenestration as a treatment for acute thoracolumbar intervertebral disc herniation in dogs.

Acute thoracolumbar intervertebral disc herniation in dogs is a common cause of "back" pain, pelvic limb paresis or paralysis and incontinence. Treatment of this condition has long been a source of controversy, especially since the introduction of surgical interventions in the 1950s. Unfortunately, formal clinical trials to compare efficacy of conservative and surgical interventions have never been carried out and the current lack of clinical equipoise on this subject now precludes such a trial on ethical grounds. In this article we re-examine and discuss earlier published data on recovery associated with the various therapies, focusing on evidence suggesting that decompressive surgery and fenestration may be equally efficacious.

Intranasal Midazolam versus Rectal Diazepam for the Management of Canine Status Epilepticus: A Multicenter Randomized Parallel-Group Clinical Trial.

BACKGROUND: Intranasal administration of benzodiazepines has shown superiority over rectal administration for terminating emergency epileptic seizures in human trials. No such clinical trials have been performed in dogs. OBJECTIVE: To evaluate the clinical efficacy of intranasal midazolam (IN-MDZ), via a mucosal atomization device, as a first-line management option for canine status epilepticus and compare it to rectal administration of diazepam (R-DZP) for controlling status epilepticus before intravenous access is available. ANIMALS: Client-owned dogs with idiopathic or structural epilepsy manifesting status epilepticus within a hospital environment were used. Dogs were randomly allocated to treatment with IN-MDZ (n = 20) or R-DZP (n = 15). METHODS: Randomized parallel-group clinical trial. Seizure cessation time and adverse effects were recorded. For each dog, treatment was considered successful if the seizure ceased within 5 minutes and did not recur within 10 minutes after administration. The 95% confidence interval was used to detect the true population of dogs that were successfully treated. The Fisher's 2-tailed exact test was used to compare the 2 groups, and the results were considered statistically significant if P < .05. RESULTS: IN-MDZ and R-DZP terminated status epilepticus in 70% (14/20) and 20% (3/15) of cases, respectively (P = .0059). All dogs showed sedation and ataxia. CONCLUSIONS AND CLINICAL IMPORTANCE: IN-MDZ is a quick, safe and effective first-line medication for controlling status epilepticus in dogs and appears superior to R-DZP. IN-MDZ might be a valuable treatment option when intravenous access is not available and for treatment of status epilepticus in dogs at home.

The relationship between clinical signs and brain herniation associated with rostrotentorial mass lesions in the dog.

Retrospective analysis of magnetic resonance imaging and clinical findings in a referral population of dogs was used to determine the relationship between rostrotentorial space-occupying lesions and the development of secondary neurological signs. Brain herniation was detected in 54/153 cases of uni-focal rostrotentorial space-occupying lesions; of these 30 had caudal transtentorial herniation (CTH) and 24 had both transtentorial and foramen magnum herniation (CTH/FMH). Masses associated with herniation were larger and situated more dorsally and caudally within the cranial vault. Clinical signs classically associated with CTH, e.g., oculomotor nerve palsy, were seen in only one case of isolated CTH and seven (14%) of all herniation cases. Deficits in caudal cranial nerve function were detectable in 39% of cases with FMH. We conclude that severe shifts in brain parenchyma can exist in the absence of detectable localising signs.

Acquired idiopathic laryngeal paralysis as a prominent feature of generalised neuromuscular disease in 39 dogs.

A retrospective evaluation of 17 dogs treated surgically for idiopathic acquired laryngeal paralysis demonstrated a marked variability in outcome, with many dogs continuing to exhibit weakness and exercise tolerance. In a subsequent prospective study, 22 consecutive affected dogs were tested for neurological deficits by neurological examination, electrodiagnostic evaluation, and blood analysis to measure thyroxine and thyroid-stimulating hormone and to detect any evidence of myasthenia gravis. Clinical neurological deficits and/or electrodiagnostic abnormalities were found in each case. There was limited evidence that specific neurological deficits were associated with a poor prognosis for full recovery of exercise tolerance. None of the dogs was positive for anti-acetylcholine receptor antibodies, and only three showed evidence of thyroid dysfunction.

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.

Treadmill measures of ambulation rates in ovine models of spinal cord injury and neuropathic pain.

Our laboratories are developing treadmill-based gait analysis employing sheep to investigate potential efficacy of intra-dural spinal cord stimulation in the treatment of spinal cord injury and neuropathic pain. As part of efforts to establish the performance characteristics of the experimental arrangement, this study measured the treadmill speed via a tachometer, video belt-marker timing and ambulation-rate observations of the sheep. The data reveal a 0.1-0.3% residual drift in the baseline (unloaded) treadmill speed which increases with loading, but all three approaches agree on final speed to within 1.7%, at belt speeds of ≈ 4 km/h. Using the tachometer as the standard, the estimated upper limit on uncertainty in the video belt-marker approach is ± 0.18 km h(-1) and the measured uncertainty is ± 0.15 km h(-1). Employment of the latter method in determining timing differences between contralateral hoof strikes by the sheep suggests its utility in assessing severity of SCI and responses to therapeutic interventions.

Nasal and frontal sinus mucosa of the adult dog contain numerous olfactory sensory neurons and ensheathing glia.

Olfactory glial cells have been the focus of much recent research interest because of their possible future use as cellular transplants in repair of spinal cord injury. Although olfactory glial cells can be collected from the olfactory bulb for in vitro culture, alternative sites would be preferable for safer surgical access. This study was designed to investigate the distribution of olfactory sensory neurons and olfactory glial cells within the canine peripheral olfactory system. Using immunohistochemistry and electron microscopy on perfused tissue we demonstrate that olfactory sensory neurons are found in both the caudal nasal and the frontal sinus epithelia. Olfactory ensheathing glia were found in the mucosa at both these sites implying that surgical access for harvesting cells for transplantation would be straightforward.