Use of video-electroencephalography as a first-line examination in veterinary neurology: development and standardization of electroencephalography in unsedated dogs and cats.

Objective: To assess the feasibility and validate the use of video-electroencephalography (EEG) in conscious dogs and cats and to propose guidelines of routine EEG in veterinary clinical practice. Design: Prospective clinical study. Data: One hundred and fifty EEG recordings were carried out to validate the clinical adding-value, reproducibility, and guidelines on 140 owned animals. One hundred and one EEGs were performed on dogs and 49 on cats. Procedures: We compared recordings performed with 8 EEG unwired stud Ag/AgCl electrodes held by elastic straps and 8 EEG wired cup Ag electrodes held by a tailor-made manufactured headset combined with a wired video-EEG device. Electrodes placement was determined according to previously published animal EEG protocols. Physiological sensors, such as electrocardiography, electromyography, and respiratory sensors were added. Stimulation protocols were tested. Quality and interpretability were evaluated. Results: Headsets and recording procedures appeared suitable for all skull shapes and sizes. Video-EEG recordings were successfully performed without tranquilization or anesthesia except for 9 animals. Median EEG recordings time was 40 min. Impedance remained below 20 kΩ in 99% of dog EEGs and 98% of cat EEGs. Isosynchrony was reported in 6% of the channels. Seventy-five percent of dog EEGs and 83% of cat EEGs were readable for more than 50% (to 100%) of their duration. Successful discrimination of vigilance states from rhythm analysis (wakefulness, drowsiness, and sleepiness) was possible in 99% of dog EEGs and 91% of cat EEGs. Photic driving responses during photic stimulations were observed in 11% of dog EEGs and 85% of cat EEGs. Electroencephalography recordings were directly informative in 32% of the examinations: in 25% EEG abnormalities were associated with clinical signs and 7% concerned EEG abnormalities without clinical symptoms during recording. Thirteen percent of dogs subjected to photic stimulation exhibited epileptic anomalies. Among 9 EEGs with other history-based stimulations, three displayed epileptic graphoelements. Conclusions: We have developed a standardized unanesthetized video-EEG procedure easily performed and reproducible in dogs and cats. Qualitative and quantitative technical and medical criteria were evaluated and were in accordance with human EEG recommendations. Moreover, we have demonstrated its relevance and accuracy for diagnostic purposes, providing further arguments for the use of EEG as a first-line neurological functional exploration test.

A PNPLA8 frameshift variant in Australian shepherd dogs with hereditary ataxia.

Hereditary ataxias are common among canine breeds with various molecular etiology. We identified a hereditary ataxia in young-adult Australian Shepherd dogs characterized by uncoordinated movements and spasticity, worsening progressively and leading to inability to walk. Pedigree analysis suggested an autosomal recessive transmission. By whole genome sequencing and variant filtering of an affected dog we identified a PNPLA8:c.1169_1170dupTT variant. This variant, located in PNPLA8 (Patatin Like Phospholipase Domain Containing 8), was predicted to induce a PNPLA8:p.(His391PhefsTer394) frameshift, leading to a premature stop codon in the protein. The truncated protein was predicted to lack the functional patatin catalytic domain of PNPLA8, a calcium-independent phospholipase. PNPLA8 is known to be essential for maintaining mitochondrial energy production through tailoring mitochondrial membrane lipid metabolism and composition. The Australian Shepherd ataxia shares molecular and clinical features with Weaver syndrome in cattle and the mitochondrial-related neurodegeneration associated with PNPLA8 loss-of-function variants in humans. By genotyping a cohort of 85 control Australian Shepherd dogs sampled in France, we found a 4.7% carrier frequency. The PNPLA8:c.[1169_1170dupTT] allele is easily detectable with a genetic test to avoid at-risk matings.

X-linked muscular dystrophy in a Labrador Retriever strain: phenotypic and molecular characterisation.

BACKGROUND: Canine models of Duchenne muscular dystrophy (DMD) are a valuable tool to evaluate potential therapies because they faithfully reproduce the human disease. Several cases of dystrophinopathies have been described in canines, but the Golden Retriever muscular dystrophy (GRMD) model remains the most used in preclinical studies. Here, we report a new spontaneous dystrophinopathy in a Labrador Retriever strain, named Labrador Retriever muscular dystrophy (LRMD). METHODS: A colony of LRMD dogs was established from spontaneous cases. Fourteen LRMD dogs were followed-up and compared to the GRMD standard using several functional tests. The disease causing mutation was studied by several molecular techniques and identified using RNA-sequencing. RESULTS: The main clinical features of the GRMD disease were found in LRMD dogs; the functional tests provided data roughly overlapping with those measured in GRMD dogs, with similar inter-individual heterogeneity. The LRMD causal mutation was shown to be a 2.2-Mb inversion disrupting the DMD gene within intron 20 and involving the TMEM47 gene. In skeletal muscle, the Dp71 isoform was ectopically expressed, probably as a consequence of the mutation. We found no evidence of polymorphism in either of the two described modifier genes LTBP4 and Jagged1. No differences were found in Pitpna mRNA expression levels that would explain the inter-individual variability. CONCLUSIONS: This study provides a full comparative description of a new spontaneous canine model of dystrophinopathy, found to be phenotypically equivalent to the GRMD model. We report a novel large DNA mutation within the DMD gene and provide evidence that LRMD is a relevant model to pinpoint additional DMD modifier genes.

Juvenile-onset polyneuropathy in American Staffordshire Terriers.

BACKGROUND: The only hereditary neurologic disorder described so far in American Staffordshire Terriers is adult-onset cerebellar degeneration secondary to ceroid lipofuscinosis. We have seen several dogs with a newly recognized neurological disease characterized by locomotor weakness with or without respiratory signs and juvenile onset consistent with degenerative polyneuropathy of genetic origin. OBJECTIVES: To characterize a novel polyneuropathy in juvenile American Staffordshire Terriers. ANIMALS: Fourteen American Staffordshire Terriers presented with clinical signs consistent with juvenile-onset polyneuropathy at 5 veterinary hospitals between May 2005 and July 2017. METHODS: Case series. Dogs were included retrospectively after a diagnosis of degenerative polyneuropathy had been confirmed by nerve biopsy. Clinical, pathological, electrophysiological, histological data, and outcome were reviewed and a pedigree analysis performed. RESULTS: All dogs displayed clinical signs of neuromuscular disease with generalized motor and sensory involvement, associated with focal signs of laryngeal paralysis (10/14 dogs) and megaesophagus (1/14 dogs). Histopathological findings were consistent with degenerative polyneuropathy. Follow-up was available for 11 dogs, and 3 dogs were euthanized shortly after diagnosis. In these 11 dogs, the disease was slowly progressive and the animals maintained good quality of life with ability to walk. Pedigree analysis was mostly consistent with an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: Juvenile polyneuropathy, associated with laryngeal paralysis, is a newly described entity in American Staffordshire Terriers, and results from degenerative neuropathy. When surgery for laryngeal paralysis is performed, lifespan may be similar to that of normal dogs even though affected dogs have locomotor disturbance.

Evaluation of coexisting polymyositis in feline myasthenia gravis: A case series.

Acquired myasthenia gravis (MG) is relatively uncommon in cats. In humans, MG may be associated with other immune-mediated disorders, in particular polymyositis (PM). In this study, we described in-depth electrodiagnostic findings and pathological changes in muscles of cats diagnosed with MG, and assessed the presence of concurrent PM. Six cats with confirmed acetylcholine receptor antibody seropositive MG, and two suspected cases with clinical signs and electrophysiological changes consistent with MG, were reviewed. All animals presented with severe typical signs of generalized weakness and/or fatigability, resembling late-onset MG in humans, in addition to regurgitation. Five cats presented a cranial mediastinal mass, with 3 confirmed as thymoma. Repetitive nerve stimulation revealed a decrement of the compound muscle action potential in all tested cases, starting from low frequencies of stimulation. Serum creatine kinase activity was increased in 6/8 cats. Muscle biopsies performed in 5 cats revealed varying degrees of mixed mononuclear cell infiltrates, positive for the leukocyte markers CD3/CD4/CD8 and CD11b. Further MHC-1/C5b-9 positive sarcolemmal deposits were identified in all tested cases, with or without thymoma. This study documents an association of MG and PM in cats, and provides further support for feline MG as a relevant animal model of human MG.

C8 cross transfer for the treatment of caudal brachial plexus avulsion in three dogs.

OBJECTIVE: To evaluate the cervical nerve 8 cross-transfer technique (C8CT) as a part of surgical treatment of caudal brachial plexus avulsion (BPA) in the dog. STUDY DESIGN: Case series. ANIMALS: Client-owned dogs suspected to have caudal BPA based on neurological examination and electrophysiological testing (n = 3). METHODS: The distal stump of the surgically transected contralateral C8 ventral branch (donor) was bridged to the proximal stump of the avulsed C8 ventral branch (recipient) and secured with 9-0 polypropylene suture under an operating microscope. A carpal panarthrodesis was performed on the injured limb after C8CT. RESULTS: Surgical exploration confirmed avulsion of nerve roots C7, C8, and T1 in all cases. There was no evidence of an iatrogenic effect on the donor forelimb. Gradual improvement in function of the affected forelimb occurred in all dogs, with eventual recovery of voluntary elbow extension. Reinnervation was evident in EMG recordings 6 months postoperatively in all three dogs. Stimulation of the donor C8 ventral branch led to motor evoked potentials in the avulsed side triceps brachialis and radial carpus extensor muscles. Variable functional outcome was observed in the 3 dogs during clinical evaluation 3-4 years after surgery. Digital abrasion wounds, distal interphalangeal infectious arthritis, and self-mutilation necessitated distal phalanx amputation of digits 3 and 4 in 2 dogs. CONCLUSION: C8CT provided partial reconnection of the donor C8 ventral branch to the avulsed brachial plexus in the 3 dogs of this series. Reinnervation resulted in active elbow extension and promoted functional recovery in the affected limb.

Spinal neurenteric cyst in a dog.

A 2-year-old female crossbreed dog was presented with progressive ataxia and paraparesis. A T3-L3 spinal lesion was determined by neurological examination. Magnetic resonance imaging (MRI) revealed an ovoid-shaped, well-circumscribed mass affecting the spinal cord at the level of the T9 vertebra. A left hemilaminectomy and a durotomy at the level of T9 allowed discovery of an ovoid deformation of the meninges with a cystic appearance. En bloc removal was performed and appeared to be complete. Pathological analysis showed a voluminous cystic lesion lined by a heterogeneous epithelium. Three types of epithelium were present: a pseudostratified columnar epithelium, a stratified squamous epithelium and a transitional epithelium. Mucus production, the morphology of some cells with microvilli at the apical pole and immunohistochemical assays were highly in favor of an endodermal origin of the cyst. The age of the dog, anamnesis, MRI study and histological findings were consistent with an intradural neurenteric cyst as described in humans. Total surgical removal led to a progressive clinical improvement with no recurrence at 18 months. We report an unusual intradural extramedullary cyst, called a neurenteric cyst, in a 2-year-old female crossbreed dog. This type of cyst is well-known in humans but has never been described in dogs. We propose that neurenteric cysts should be included in the differential diagnoses for tumor-like or cystic intradural lesions in the young dog. Prognosis for this type of cyst seems to be good, as total surgical removal led to a progressive clinical improvement with no recurrence at 18 months.

Supratentorial arachnoid cyst management by cystoperitoneal shunt in a 1-year-old European cat.

Arachnoid cysts are defined as an accumulation of fluid within the arachnoid membrane. Feline intracranial arachnoid cysts are seldom reported, with only three cases in the veterinary literature. A 1-year-old male neutered European cat with a 24 h history of seizures was presented to the small animal neurology department at Vetagro Sup, Lyon. Magnetic resonance imaging (MRI) revealed a large intracranial arachnoid cyst ventral to the brain in the left temporal area. Cystoperitoneal shunt placement resulted in complete resolution of the cyst without recurrence (follow-up MRIs 3 weeks and 21 months after surgery). Anticonvulsant treatment (phenobarbital 2.5 mg/kg q12h) was initiated at presentation and gradually stopped after 17 months. Seizures recurred 4 months after ending treatment, and seizure therapy was therefore restarted at the initial dose. We report a case of an intracranial arachnoid cyst in an unusual location not previously described. A cystoperitoneal shunt resolved the cyst without complications. Maintenance anticonvulsant treatment was required to control symptomatic epilepsy.

Original surgical treatment of thoracolumbar subarachnoid cysts in six chondrodystrophic dogs.

BACKGROUND: Subarachnoid cysts are rare conditions in veterinary medicine, associated with spinal cord dysfunction. Most of the 100 cases of subarachnoid cysts described since the first report in 1968 were apparently not true cysts. Reported cysts are usually situated in the cervical area and occur in predisposed breeds such as the Rottweiler. The purpose of this retrospective study, from May 2003 to April 2012, was to describe the distinctive features of thoracolumbar spinal subarachnoid cysts, together with their surgical treatment and outcome in 6 chondrodystrophic dogs. RESULTS: Five Pugs and 1 French Bulldog were examined. Images suggestive of a subarachnoid cyst were obtained by myelography (2/6) and computed tomography myelography (4/6), and associated disc herniation was observed in 3/6 dogs. A hemilaminectomy was performed. The protruding disc eventually found in 5/6 dogs was treated by lateral corpectomy. The ventral leptomeningeal adhesions observed in all dogs after durotomy were dissected. No or only mild post-operative neurological degradation was observed. Follow-up studies (7 months to 4 years) indicated good outcome and no recurrence. CONCLUSIONS: All the thoracolumbar subarachnoid cysts described in these 6 chondrodystrophic dogs were associated with leptomeningeal adhesions. Good results seemed to be obtained by dissecting and removing these adhesions. A protruding disc, found here in 5/6 dogs, needs to be ruled out and can be treated by lateral corpectomy.

Environmental effects on compulsive tail chasing in dogs.

Obsessive Compulsive Disorder (OCD) is a neuropsychiatric disorder observed both in humans and animals. Examples of Canine Compulsive Disorder (CD) include excessive tail chasing (TC), light/shadow chasing and flank sucking. We performed a questionnaire survey to investigate the characteristics of compulsive (TC) and its possible associations with environmental correlates and personality in a pet population of 368 dogs from four dog breeds. We observed an early onset of TC at 3-6 months of age and a large variation in TC frequency in all breeds, with an overrepresentation of milder cases. Almost half of the TC dogs showed lowered responsiveness during bouts and displayed also other types of compulsions more often than the controls. Interestingly, dogs that received dietary supplements, especially vitamins and minerals, expressed less TC compared to dogs that did not receive any supplements. Neutered females had less TC, suggesting an influence of ovarian hormones on TC. Tail chasers were shyer and had separated earlier from their mothers than the controls. Finally, our genetic study did not find an association between TC and CDH2, a locus previously associated with the canine flank sucking compulsion. In conclusion, the early-onset and the variable nature of the repetitive behaviour, which is affected by environmental factors such as micronutrients, neutering and maternal care, share several similar components between canine and human compulsions and supports canine TC as a model for human OCD.

Restoration of elbow flexion by performing contralateral lateral thoracic and thoracodorsal nerve transfers after experimental musculocutaneous nerve transection.

OBJECT: The immediate transfer of the right lateral thoracic nerve (LTN) and the thoracodorsal nerve (TDN) to the transected left musculocutaneous nerve (MCN), leading to nerve cross-neurotization, was performed in cats to evaluate reinnervation of the biceps brachii muscle (BBM). METHODS: Surgery to produce cross-neurotization of the MCN was performed in 12 cats (treatment group). Transection of the MCN was performed without attempts at neurotization in three cats (control group). Reinnervation of the BBM was assessed by performing electromyography (EMG) 6 months (14 cats) and 26 months (one cat) postsurgery. True Blue retrograde axonal tracing studies, tensile force measurements (muscle extensometry), and histopathological analyses were performed. All cats in the treatment group recovered voluntary contraction of the BBM and regained elbow flexion. Electromyography revealed no abnormal spontaneous activity in the BBM. Muscle evoked potentials were recorded in that muscle after right C-8 ventral branch stimulation. The muscle contraction strength in the left BBM varied from 108 to 557 g. The BBMs regained their normal appearances. The region of the MCN distal to the anastomosis displayed a normal histological appearance. Fluorescence was detected in the ventral horn of the spinal cord in the right C-8 and T-1 segments. In contrast, in all cats in the control group there was atrophy of the BBM, no EMG signal, and no clinical sign of recovery. There was no contraction of the BBM, no labeled neuron in the spinal cord, and the MCN displayed major degenerative changes. CONCLUSIONS: These findings demonstrate that the LTN and TDN can be used to neurotize injured contralateral brachial plexus nerves and obtain successful reinnervation in cats.

Tissue Doppler assessment of diastolic and systolic alterations of radial and longitudinal left ventricular motions in Golden Retrievers during the preclinical phase of cardiomyopathy associated with muscular dystrophy.

OBJECTIVE: To quantify radial and longitudinal left ventricular free wall (LVFW) velocities in dogs during the preclinical phase of Golden Retriever muscular dystrophy (GRMD)-associated cardiomyopathy by use of tissue Doppler imaging (TDI). ANIMALS: 9 dogs with GRMD and 6 healthy control dogs. PROCEDURE: All dogs (< 3 years old) were examined via conventional echocardiography and 2-dimensional color TDI. Myocardial velocities in the LVFW were recorded from right parasternal ventricular short-axis (radial motion) and left apical 4-chamber (longitudinal motion) views. Cardiac assessments via TDI included maximal systolic and early and late diastolic LVFW velocities in the endocardial and epicardial layers (for radial motion) and in the basal and apical segments (for longitudinal motion) (for longitudinal motion), RESULTS: -No notable ventricular dilatation or alteration of inotropism was detected in dogs with GRMD via conventional echocardiography. Compared with healthy dogs, endocardial velocities were significantly decreased in dogs with GRMD, resulting in marked decreases in radial myocardial velocity gradients during systole and early and late diastole. Similarly, basal and apical velocities were significantly decreased in systole and the former also in early diastole, resulting in significant decreases in the 2 corresponding longitudinal myocardial velocity gradients. The radial epicardial and longitudinal late diastolic velocities were comparable in the 2 groups. CONCLUSION AND CLINICAL RELEVANCE: Results indicated that GRMD-associated cardiomyopathy in dogs is associated with early marked dysfunction of both radial and longitudinal LVFW motions. These combined regional myocardial abnormalities might be useful criteria for detection of dilated cardiomyopathy at the preclinical stage of the disease in dogs.

Tissue Doppler imaging detects early asymptomatic myocardial abnormalities in a dog model of Duchenne's cardiomyopathy.

AIMS: Early diagnosis of Duchenne's dilated cardiomyopathy remains a challenge for conventional echocardiography. We sought to determine whether tissue Doppler imaging (TDI) could detect early alteration in myocardial function in a dog model of Duchenne muscular dystrophy, i.e. the Golden Retriever Muscular Dystrophy (GRMD). METHODS AND RESULTS: Myocardial function was assessed by TDI in 20 dogs with normal conventional parameters of systolic function (eight controls and 12 GRMD, 25+/-11 weeks) without knowledge of the genotype. M-mode TDI was recorded from a short-axis view for measurement of endocardial and epicardial velocities and myocardial velocity gradient (MVG) within the posterior wall. Controls and GRMD dogs were comparable regarding left ventricular fractional shortening (37+/-2 vs 42+/-3%, p=ns). Conversely, TDI showed, in all GRMD dogs, a dramatic decrease in systolic MVG (0.8+/-0.1 vs 2.9+/-0.3 s(-1), p<0.0001) and early diastolic MVG (2.3+/-2.2 vs 10.8+/-1.1 s(-1), p<0.0001). This MVG alteration was related to a significant decrease in endocardial velocities in GRMD whereas epicardial velocities were comparable in the two groups. CONCLUSION: These results show that TDI is more sensitive than conventional echocardiography in detecting pre-clinical myocardial abnormalities before occurrence of left ventricular dilation and dysfunction. TDI should be part of the screening techniques for the early diagnosis of cardiomyopathy.

Diagnostic potential of natriuretic peptides in the occult phase of golden retriever muscular dystrophy cardiomyopathy.

The objective of the study was to determine whether the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP, respectively) could be reliable markers of cardiac alterations during occult cardiomyopathy in Golden Retriever Muscular Dystrophy (GRMD). Fifty Golden Retrievers without any clinical or radiographic sign of heart disease were included in this study (21 GRMD dogs and 29 controls). Controls and GRMD dogs were divided into 2 subgroups according to age (< and > or =12 months old, respectively). All dogs underwent echocardiography and determination of BNP and ANP plasma concentrations by radioimmunoassay. No ventricular dilatation or dysfunction was observed in either control or GRMD dogs. ANP plasma concentration did not differ significantly between controls and GRMD dogs (mean +/- SD = 72 +/- 49 versus 58 +/- 23 pg/mL, respectively, P = .21). This finding was confirmed in both subgroups of dogs (ie, those < and > or =12 months old). In contrast, BNP plasma concentrations were significantly higher in GRMD dogs than in controls (mean +/- SD = 117 +/- 92 versus 46 +/- 22 pg/mL, respectively, P < .05). In dogs > or =12 months old, sensitivity and specificity of BNP for identifying GRMD with a cutoff of 65 pg/mL were 78 and 86%, respectively. For the same cutoff value, sensitivity dropped to 42%, whereas specificity reached 100% in dogs <12 months old. In conclusion, BNP may be a useful biochemical marker of asymptomatic cardiomyopathy. However, this peptide does not allow very early detection because its optimal discriminatory power was observed in adult dogs (ie, > or =12 months of age).