International veterinary canine dyskinesia task force ECVN consensus statement: Terminology and classification.

Movement disorders are a heterogeneous group of clinical syndromes in humans and animals characterized by involuntary movements without changes in consciousness. Canine movement disorders broadly include tremors, peripheral nerve hyperexcitability disorders, paroxysmal dyskinesia, and dystonia. Of these, canine paroxysmal dyskinesias remain one of the more difficult to identify and characterize in dogs. Canine paroxysmal dyskinesias include an array of movement disorders in which there is a recurrent episode of abnormal, involuntary, movement. In this consensus statement, we recommend standard terminology for describing the various movement disorders with an emphasis on paroxysmal dyskinesia, as well as a preliminary classification and clinical approach to reporting cases. In the clinical approach to movement disorders, we recommend categorizing movements into hyperkinetic vs hypokinetic, paroxysmal vs persistent, exercise-induced vs not related to exercise, using a detailed description of movements using the recommended terminology presented here, differentiating movement disorders vs other differential diagnoses, and then finally, determining whether the paroxysmal dyskinesia is due to either inherited or acquired etiologies. This consensus statement represents a starting point for consistent reporting of clinical descriptions and terminology associated with canine movement disorders, with additional focus on paroxysmal dyskinesia. With consistent reporting and identification of additional genetic mutations responsible for these disorders, our understanding of the phenotype, genotype, and pathophysiology will continue to develop and inform further modification of these recommendations.

Sleep Disorders in dogs: A Pathophysiological and Clinical Review.

Sleep is a fundamental process in mammals, including domestic dogs. Disturbances in sleep affect physiological functions like cognitive and physical performance, immune response, pain sensation and increase the risk of diseases. In dogs, sleep can be affected by several conditions, with narcolepsy, REM sleep behavior disorder and sleep breathing disorders being the most frequent causes. Furthermore, sleep disturbances can be a symptom of other primary diseases where they can contribute to the worsening of clinical signs. This review describes reciprocally interacting sleep and wakefulness promoting systems and how their dysfunction can explain the pathophysiological mechanisms of sleep disorders. Additionally, this work discusses the clinical characteristics, diagnostic tools and available treatments for these disorders while highlighting areas in where further studies are needed so as to improve their treatment and prevention.

Stereotaxic Diffusion Tensor Imaging White Matter Atlas for the in vivo Domestic Feline Brain.

The cat brain is a useful model for neuroscientific research and with the increasing use of advanced neuroimaging techniques there is a need for an open-source stereotaxic white matter brain atlas to accompany the cortical gray matter atlas, currently available. A stereotaxic white matter atlas would facilitate anatomic registration and segmentation of the white matter to aid in lesion localization or standardized regional analysis of specific regions of the white matter. In this article, we document the creation of a stereotaxic feline white matter atlas from diffusion tensor imaging (DTI) data obtained from a population of eight mesaticephalic felines. Deterministic tractography reconstructions were performed to create tract priors for the major white matter projections of Corpus callosum (CC), fornix, cingulum, uncinate, Corona Radiata (CR), Corticospinal tract (CST), inferior longitudinal fasciculus (ILF), Superior Longitudinal Fasciculus (SLF), and the cerebellar tracts. T1-weighted, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) population maps were generated. The volume, mean tract length and mean FA, MD, AD and RD values for each tract prior were documented. A structural connectome was then created using previously published cortical priors and the connectivity metrics for all cortical regions documented. The provided white matter atlas, diffusivity maps, tract priors and connectome will be a valuable resource for anatomical, pathological and translational neuroimaging research in the feline model. Multi-atlas population maps and segmentation priors are available at Cornell's digital repository: https://ecommons.cornell.edu/handle/1813/58775.2.

Normal diffusivity of the domestic feline brain.

Diffusion magnetic resonance imaging (MRI) provides useful information about neuroanatomy and improves detection of neuropathology. As yet, a comprehensive evaluation of the diffusivity parameters within the feline brain has not been documented. In this study, we anesthetized and performed in vivo MRI on the brain of eight neurologically normal felines. A T1-weighted structural sequence with a resolution of 0.5 mm3 and a parallel diffusion weighted sequence with 61 directions and a resolution of 1.5 mm3 was obtained. After correction and processing the diffusion brain data were parcellated into 151 regions of interest using previously published priors. These regions were grouped according to their lobar location within the brain (frontal, occipital, temporal, parietal, thalamus, midbrain, cerebellum, and white matter). The mean and standard deviation of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) for these 151 individual regions and lobar groups were calculated and averaged across participants, creating a comprehensive distribution range of diffusion tensor values. When regions were statistically evaluated, white matter had significantly higher FA and RD and lower AD and MD diffusivity parameters when compared to other regions. Additionally, thalamic regions had significantly higher FA values than parietal and occipital regions. This information will not only help inform feline neuroanatomy but also will serve as a reference standard for future feline neuroimaging studies.

Investigation of sensory thresholds in Cavalier King Charles Spaniels with and without Chiari-like malformations and syringomyelia.

BACKGROUND: Cavalier King Charles Spaniels (CKCS) suffer pain associated with Chiari-like malformation and syringomyelia (CMSM). People suffer from a similar condition and describe numerous sensory abnormalities. Sensory changes have not been quantified in affected CKCS. OBJECTIVES: To use quantitative sensory testing (QST) to quantify thermal and mechanical thresholds in CKCS and to compare QST in dogs with and without syringomyelia (SM). ANIMALS: Forty-four CKCS. METHODS: Prospective study. Dogs underwent neurological examinations and craniocervical magnetic resonance imaging (MRI). Thermal testing was performed over the humerus and thorax (n = 32); mechanical testing was performed on the paw and neck (n = 44). Latencies, thresholds, and response rates were compared with presence and severity of SM on MRI, presence of pain reported by the owner and pain identified on examination. RESULTS: Thirty dogs had SM, 30 were painful on examination, 29 were owner-reported symptomatic. Thermal and mechanical variables were not significantly different based on presence or severity of SM. Dogs with pain on examination had decreased mechanical thresholds on the paw (0.38 kg, SD = 0.18) and neck (2.05 kg, SD = 0.74) compared to thresholds of dogs without pain on examination on the paw (0.60 kg, SD = 0.30) and neck (2.72 kg, SD = 0.57; P = .021). CONCLUSIONS AND CLINICAL IMPORTANCE: Mechanical and thermal sensitivity does not appear to be related to the presence of SM, but mechanical sensitivity appears to be related to the presence of pain and clinical signs. Mechanical testing may be useful for assessing sensory abnormalities during clinical trials.

A cross-species approach to disorders affecting brain and behaviour.

Structural and functional elements of biological systems are highly conserved across vertebrates. Many neurological and psychiatric conditions affect both humans and animals. A cross-species approach to the study of brain and behaviour can advance our understanding of human disorders via the identification of unrecognized natural models of spontaneous disorders, thus revealing novel factors that increase vulnerability or resilience, and via the assessment of potential therapies. Moreover, diagnostic and therapeutic advances in human neurology and psychiatry can often be adapted for veterinary patients. However, clinical and research collaborations between physicians and veterinarians remain limited, leaving this wealth of comparative information largely untapped. Here, we review pain, cognitive decline syndromes, epilepsy, anxiety and compulsions, autoimmune and infectious encephalitides and mismatch disorders across a range of animal species, looking for novel insights with translational potential. This comparative perspective can help generate novel hypotheses, expand and improve clinical trials and identify natural animal models of disease resistance and vulnerability.

Cholesteatoma and meningoencephalitis in a dog with chronic otitis externa.

A 10-year-old female spayed German Shepherd dog, with a year-long history of recurrent left ear infections, was presented for progressive ataxia, head tilt, and pain on opening of the mouth. On physical examination, a large amount of ceruminous debris was present in the left ear and multiple neurologic defects localizing to the cerebellum and vestibular system were identified. Magnetic resonance imaging (MRI) demonstrated a minimally contrast-enhancing mass within the left bulla, an intracranial space-occupying, heterogeneously contrast-enhancing lesion at the level of the left cerebello-medullary junction, and contrast enhancement of the ipsilateral meninges. Cerebrospinal fluid analysis revealed a marked mixed cell pleocytosis (nucleated cell count 655 cells/µL). The mass was visualized within the horizontal ear canal by otoscopic examination and a biopsy was taken. Impression smears of the biopsy contained many anucleate keratinized squamous epithelial cells, mild mixed inflammation, and few presumptive fibroblasts. With the provided clinical history and MRI findings, a cytologic diagnosis of cholesteatoma was made. A ventral bulla osteotomy was performed, and histopathologic examination of resected tissue confirmed the cytologic diagnosis of cholesteatoma. The dog's clinical symptoms improved postoperatively, but the dog died of unrelated causes, 3.5 months later. To our knowledge, this is the first description of the cytologic features of a cholesteatoma, which is a nonneoplastic, but locally invasive epidermoid cyst, in the middle ear of dogs.

Necrotizing meningoencephalitis in a large mixed-breed dog.

CASE DESCRIPTION: A 4-year-old 26-kg (57.2-lb) spayed female Staffordshire Bull Terrier mix was evaluated because of a 24-hour history of cluster seizures. CLINICAL FINDINGS: Neurologic examination revealed altered mentation and multifocal intracranial signs; MRI was performed. The MRI findings included multifocal, asymmetric forebrain lesions affecting both the gray and white matter, an area suggestive of focal necrosis, and loss of corticomedullary distinction. A midline shift and caudal transtentorial herniation were noted, suggestive of greater than normal intracranial pressure. TREATMENT AND OUTCOME: Because the dog's clinical signs worsened despite medical treatment and additional evidence of increased intracranial pressure, bilateral craniectomy and durectomy were performed. Histologic evaluation of a brain biopsy specimen revealed bilateral and asymmetric areas of necrosis in the subcortical white matter and adjacent gray matter. At the periphery of the necrotic areas, there was increased expression of glial fibrillary acidic protein and Virchow-Robin spaces were expanded by CD3+ lymphocytes. Results of immunohistochemical analysis of brain tissue were negative for canine distemper virus, Neospora canis, and Toxoplasma gondii. These clinical, imaging, and histopathologic findings were compatible with necrotizing meningoencephalitis. The dog's neurologic status continued to worsen following surgery. Repeated MRI revealed ongoing signs of increased intracranial pressure, despite the bilateral craniectomy. The owners elected euthanasia. CLINICAL RELEVANCE: To the author's knowledge, this is the first report of necrotizing meningoencephalitis in a large mixed-breed dog. Necrotizing meningoencephalitis should be considered as a differential diagnosis in dogs other than small or toy breeds that have signs suggestive of inflammatory disease.

Spinal cord nephroblastoma in dogs: 11 cases (1985-2007).

OBJECTIVE: To evaluate clinical features and outcome of dogs with a confirmed spinal cord nephroblastoma and to describe the use of Wilms tumor-1 (WT-1) immunohistochemical staining to confirm a diagnosis of nephroblastoma in dogs. DESIGN: Retrospective case series. Animals-11 dogs with a spinal cord nephroblastoma. PROCEDURES: Medical records of dogs with a spinal cord nephroblastoma were reviewed. Information extracted included signalment, history, clinical signs, results of diagnostic testing, tumor location, treatment, and outcome. The diagnosis was confirmed through histologic review and WT-1 immunohistochemical staining of a tumor sample. In dogs with negative results for staining with WT-1, staining for cytokeratin, vimentin, and glial fibrillar acidic protein was performed. RESULTS: 11 dogs had a spinal cord tumor with a histologic appearance and immunohistochemical staining consistent with a nephroblastoma. Positive results for staining with WT-1 were detected in 9 of 11 dogs. Age at admission ranged from 5 to 48 months (median, 14 months). Nine dogs were female. All had progressive paraparesis, paraplegia, or ataxia. Duration of clinical signs ranged from 2 to 60 days (median, 14 days). Median survival time was 30 days from the time of diagnosis. Median survival time in dogs treated via surgical resection was 70.5 days. CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis for dogs with a spinal cord nephroblastoma appeared to be poor, although combined surgical resection and radiation therapy may provide a good functional outcome. Results for staining with WT-1 can be used to support a diagnosis of nephroblastoma.

Mycophenolate mofetil treatment in dogs with serologically diagnosed acquired myasthenia gravis: 27 cases (1999-2008).

OBJECTIVE-To compare clinical outcome in dogs with serologically diagnosed acquired myasthenia gravis (MG) treated with pyridostigmine bromide (PYR) with that of dogs treated with mycophenolate mofetil (MMF) and PYR (MMF + PYR). DESIGN-Retrospective case series. ANIMALS-27 dogs. PROCEDURES-Medical records from August 1999 through February 2008 were reviewed to identify dogs with serologically diagnosed acquired MG treated with PYR or MMF + PYR. Data collected for each dog included signalment, whether the dog had megaesophagus or pneumonia (or both), thyroid hormone concentration, remission, time to remission, and survival time. Rates for detection of clinical signs and survival time were compared. Survival time was estimated via the Kaplan-Meier method. Influence of drug treatment protocol on likelihood of remission, time to remission, and survival time was examined. Effects of MMF treatment, megaesophagus, pneumonia, and low serum thyroid hormone concentration on time to remission and survival time were also analyzed. RESULTS-12 dogs were treated with PYR, and 15 were treated with MMF + PYR. Mortality rates were 33% (PYR) and 40% (MMF + PYR). There was pharmacological remission in 5 and 6 dogs in the PYR and MMF + PYR groups, respectively. No significant differences were detected between treatment groups for remission rate, time to remission, or survival time. Megaesophagus, pneumonia, and low serum thyroid hormone concentration had no significant effect on time to remission or survival time for either treatment group. CONCLUSIONS AND CLINICAL RELEVANCE-The results did not support routine use of MMF for the treatment of dogs with acquired MG.

Congenital diseases of the craniocervical junction in the dog.

Craniocervical junction disorders are most frequently seen in toy and small-breed dogs. They can present a diagnostic challenge, as multiple anomalies can be present concurrently and share similar clinical manifestations. Some, such as Chiari-like malformations, may be present in asymptomatic dogs. A thorough evaluation of the entire craniocervical junction, frequently using more than 1 imaging modality, is necessary before making treatment decisions.

Pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with suspected idiopathic epilepsy.

OBJECTIVE: To assess tolerability and short-term efficacy of oral administration of pregabalin as an adjunct to phenobarbital, potassium bromide, or a combination of phenobarbital and potassium bromide for treatment of dogs with poorly controlled suspected idiopathic epilepsy. DESIGN: Open-label, noncomparative clinical trial. ANIMALS: 11 client-owned dogs suspected of having idiopathic epilepsy that was inadequately controlled with phenobarbital, potassium bromide, or a combination of these 2 drugs. PROCEDURES: Dogs were treated with pregabalin (3 to 4 mg/kg [1.4 to 1.8 mg/lb], PO, q 8 h) for 3 months. Number of generalized seizures in the 3 months before and after initiation of pregabalin treatment was recorded. Number of responders (>or= 50% reduction in seizure frequency) was recorded, and seizure frequency before and after initiation of pregabalin treatment was compared by use of a nonparametric Wilcoxon signed rank test. RESULTS: Seizures were significantly reduced (mean, 57%; median, 50%) after pregabalin administration in the 9 dogs that completed the study; 7 were considered responders with mean and median seizure reductions of 64% and 58%, respectively. Adverse effects for pregabalin were reported in 10 dogs. Mean and median plasma pregabalin concentrations for all dogs were 6.4 and 7.3 microg/mL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Pregabalin may hold promise as a safe and effective adjunct anticonvulsant drug for epileptic dogs poorly controlled with the standard drugs phenobarbital or potassium bromide. Adverse effects of pregabalin appeared to be mild. Additional studies with larger numbers of dogs and longer follow-up intervals are warranted.

Effects of hypocalcemia on electrical restitution and ventricular fibrillation.

We have shown previously that verapamil reduces the slope of the action potential duration (APD) restitution relation, suppresses APD alternans and converts ventricular fibrillation (VF) into a periodic rhythm. To determine whether these effects result primarily from reduction of the APD restitution slope, as opposed to alteration of calcium dynamics unrelated to restitution, we tested the effects of hypocalcemia ([CaCl2]=31-125 microM) in canine ventricle. At normal [CaCl2] (2.0 mM), the slope of the APD restitution relation was >1, APD alternans occurred during rapid pacing and VF was inducible. During hypocalcemia the slope of the restitution relation remained >1 and the magnitude of APD alternans was unchanged. VF still was inducible and the mean cycle length and the variance of the FFT spectra during VF were not altered significantly. These results suggest that reduction of APD restitution slope, rather than blockade of ICa per se, is responsible for the antifibrillatory effects of verapamil in this model of pacing-induced VF, lending further support to the idea that APD restitution kinetics is a key determinant of VF.

Characteristics of cerebrospinal fluid flow in Cavalier King Charles Spaniels analyzed using phase velocity cine magnetic resonance imaging.

Syringomyelia is an important morbidity source in Cavalier King Charles Spaniels. Although abnormal cerebrospinal fluid (CSF) flow secondary to Chiari malformations is thought to cause syringomyelia in humans, this relationship is unknown in dogs. We used phase-contrast magnetic resonance (MR) imaging to evaluate CSF flow in dogs. Fifty-nine Cavalier King Charles Spaniels were assigned a neurologic grade reflecting their neurologic status. Five normal control dogs of other breeding were imaged for comparison. The presence of syringomyelia was noted from sagittal MR images. The pattern and velocity of CSF flow were assessed using phase-contrast cine MRI at the foramen magnum, C2-C3 disc space, and within syrinxes. Flow was measured most easily with the neck flexed to mimic standing. CSF flow velocity in the dorsal aspect of the subarachnoid space at the foramen magnum was significantly higher in control dogs than Cavalier King Charles Spaniels (P = 0.035). Flow was obstructed at the foramen magnum in 41 of 59 Cavalier King Charles Spaniels. Turbulent flow and jets were associated with syringomyelia presence and severity, and CSF flow velocity at C2/3 dorsally was inversely related to the presence of syringomyelia (P = 0.0197). Peak dorsal subarachnoid space CSF flow velocity at the foramen magnum and C2-C3 were together highly predictive of syringomyelia. CSF flow can be assessed in dogs using phase-contrast cine MRI. Obstruction to flow at the foramen magnum is common in Cavalier King Charles Spaniels and CSF flow pattern and velocity are related to the presence of syringomyelia.

Imaging features of atlanto-occipital overlapping in dogs.

The imaging features of four dogs with atlanto-occipital overlapping are described. This malformation appeared to play a role in the development of neck pain, ataxia, variable cerebellar involvement, medullary kinking, and possibly syringomyelia. Using cervical radiographs, three of the four dogs were initially diagnosed with an atlanto-axial malformation. Because this disorder could not account for all clinical signs, magnetic resonance and computed tomography images were also acquired. These provided a more complete evaluation of the craniocervical junction, allowing detection of atlanto-occipital overlapping, medullary kinking, occipital dysplasia, abnormalities of the dens, and syringomyelia in these dogs. Head position during imaging affected the degree of atlanto-occipital overlap. These findings emphasize the need to modify the currently accepted imaging recommendations for dogs with head and neck pain and/or cranial cervical myelopathy. We suggest that the entire craniocervical junction be evaluated, even if atlanto-axial subluxation has already been detected. Moreover, we propose that atlanto-occipital overlapping is a perhaps underrecognized disorder that can influence the clinical signs and therapeutic outcome of dogs with anomalies of the craniocervical junction.

Cerebrospinal fluid signal-void sign in dogs.

The cerebrospinal fluid signal-void sign is an observable signal loss from cerebrospinal fluid (CSF), especially on T2-weighted magnetic resonance (MR) images. In people, this sign is attributed to rapid CSF flow or turbulence from arterial pulsations and occurs more frequently with reduced intracranial compliance. The purposes of this study were to describe the CSF signal-void sign, document whether a similar sign occurs in dogs and investigate associations between it and other conditions. The sample population consisted of 327 dogs admitted for neurocranium evaluation using a 0.2 T system. Review of the medical records and MR images was performed to characterize the presence and location of a CSF signal-void sign, ventricular size, syringomyelia, and other lesions. A CSF signal-void sign was detected in at least the mesencephalic aqueduct in 59/327 (18.0%) dogs, including some with no morphologic brain abnormality. The majority of these dogs (45/59% or 76%) weighed < 15 kg. In two other dogs, a CSF signal-void sign was detected only in a cervical syrinx. In dogs weighing > 15 kg, a CSF signal-void sign was seen with various conditions. In 137/327 (41.9%) dogs weighing < 15 kg, the presence of a CSF signal-void sign in the aqueduct (45 dogs) was associated with syringomyelia (P = 0.0468) and increased ventricular size (P = 0.0054): syringomyelia also was associated with increased ventricular size (P = 0.0009). In conclusion, a CSF signal-void sign was seen in dogs with various conditions. In small-breed dogs, a CSF signal-void sign in the aqueduct was associated with ventricular enlargement and syringomyelia.

Intracranial arachnoid cysts in dogs.

Intracranial arachnoid cyst (IAC) is an infrequently reported developmental disorder seen primarily in small-breed dogs. It usually occurs in the caudal fossa, in the region of the quadrigeminal cistern. Although still considered uncommon, IAC is being recognized more frequently in veterinary medicine, coinciding with the increased availability of magnetic resonance imaging. In this article, clinical information from previously reported cases of canine IAC is combined with additional case information from our hospitals. Similar to IAC in people, it is thought that canine IAC is often an incidental finding. When IAC is responsible for neurologic disease in dogs, generalized seizures and cerebellovestibular dysfunction are the most common clinical presentations. Medical therapy of IAC focuses on management of increased intracranial pressure and seizures, if the latter are part of the clinical complaints. Surgical therapy of IAC involves either cyst fenestration or shunting the excess fluid to the peritoneal cavity

Morphology of the caudal fossa in Cavalier King Charles Spaniels.

Chiari malformations and syringohydromyelia are an important disease complex in Cavalier King Charles Spaniels. Although abnormalities in caudal fossa morphology are considered major contributors to the development of this disease, limited information exists on the range of morphologies in Cavalier King Charles Spaniels and on the relationship of these to clinically evident disease. Sixty-four Cavalier King Charles Spaniels were studied. Each underwent a neurologic examination and magnetic resonance imaging of the cervical spine and brain. T2-weighted sagittal images were used to determine both the morphologic characteristics and volume of the caudal fossa in each dog. This volume was also analyzed as a percentage of total cranial cavity volume. Each attribute was correlated with neurological grade and presence of syringohydromyelia. Fifteen dogs had neurologic signs, and 59 had morphologic abnormalities of the craniocervical junction. While 27 dogs had syringohydromyelia, 13 of these were clinically normal. Cerebellar herniation and occipital dysplasia were common findings but were not associated with syringohydromyelia. Dorsal compressive lesions were noted at the first and second cervical vertebral junction. Factors associated with the presence of neurologic signs included syringohydromyelia and the ratio of caudal fossa/total cranial cavity volume; dogs with signs had significantly larger syringohydromyelia than asymptomatic dogs. Caudal fossa size was not associated with syringohydromyelia. A positive association was identified between foramen magnum size and length of cerebellar herniation. The prevalence of craniocervical junction abnormalities is high in Cavalier King Charles Spaniels. While several factors are associated with neurologic signs, occipital hypoplasia appears to be the most important factor.

Case report --surgical stabilization of a craniocervical junction abnormality with atlanto-occipital overlapping in a dog.

A 3-year-old male neutered Pomeranian presented with severe, poorly localizable pain that was unresponsive to a combination of oral medications (gabapentin, tramadol, prednisone, and methocarbamol) and a fentanyl patch. A Chiari-like malformation with associated syringomyelia was evident on magnetic resonance imaging (MRI). In addition, overlapping of the dorsal arch of C1 and the dorsal aspect of the foramen magnum was suspected from the MRI scans and verified via computed tomography, suggesting a condition similar to basilar invagination/impression in people. At surgery, a combination of foramen magnum decompression with cranioplasty and stabilization of the atlanto-occipital junction was performed. The atlanto-occipital junction was stabilized using an adaptation of a procedure used in people for basilar invagination/impression. Over the next several months, the dog's clinical signs improved dramatically, allowing substantial reduction of oral pain medications. This is the first report of surgical stabilization for atlanto-occipital overlapping in a dog.