Corpus Callosotomy in 3 Cavalier King Charles Spaniel Dogs with Drug-Resistant Epilepsy.
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ABSTRACT:
SUBMITTER: Asada R
PROVIDER: S-EPMC8615928 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAlmost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the cavalier King Charles spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in mitral valves showing myxomatous degeneration from CKCS dogs compared to valves from non-CKCS dogs.ResultsGene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, diseased valves from CKCS and diseased valves from other breeds; the latter were more similar to the normal valves than were the valves from CKCS. Gene expression patterns in diseased valves from CKCS dogs were quite different from those in the valves from other dogs, both affected and normal. Patterns in all diseased valves (from CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in the diseased valves from CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS diseased valves compared to normal) and MEF2C pathway activation (CKCS diseased valves compared to non-CKCS diseased valves) had the strongest association with the gene changes. A large number of genes that were differentially expressed in the CKCS diseased valves compared with normal valves and diseased valves from other breeds were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2.ConclusionTranscriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.
| S-EPMC7509937 | biostudies-literature
Project description:BackgroundMyoclonus is observed in older Cavalier King Charles Spaniels (CKCS) but a full description is lacking.ObjectivesThe presence, age of onset, characteristics and treatment of myoclonic episodes were retrospectively evaluated in a cohort of CKCS which presented to 1 board-certified neurologist. Clinical data, imaging studies, presence of seizures and their management, as well as other comorbidities were noted.AnimalsThirty-nine CKCS that were presented to 2 institutions between 2001 and 2018 with signs consistent with myoclonus. Clinical examination, blood sampling, advanced diagnostic imaging, cerebrospinal fluid analysis, and record keeping of other comorbidities was performed.MethodsThis is a retrospective case series, describing the presence of myoclonus in CKCS.ResultsClinical signs reported were spontaneous in onset, lasted a few seconds and consisted of rapid blinking with head nodding and variable extension down the thoracic limbs. Myoclonus occasionally led to stumbling of the thoracic limbs or collapse. Mean age of onset was 8.38 years (SD ±1.96). Thirteen of 39 dogs with myoclonus had paroxysmal events, such as generalized seizures (9/13).Conclusions and clinical importanceMyoclonus occurs in middle-aged to older CKCS and seems to be another epiphenomena of this breed. A link to epilepsy might be present.
| S-EPMC9151451 | biostudies-literature
Project description:ObjectivesTo characterize and compare the phenotypic variables of the hindbrain and craniocervical junction associated with syringomyelia (SM) in the Chihuahua, Affenpinscher and Cavalier King Charles Spaniel (CKCS).MethodAnalysis of 273 T1-weighted mid-sagittal DICOM sequences of the hindbrain and craniocervical junction from 99 Chihuahuas, 42 Affenpinschers and 132 CKCSs. The study compared 22 morphometric features (11 lines, eight angles and three ratios) of dogs with and without SM using refined techniques based on previous studies of the Griffon Bruxellois (GB) using Discriminant Function Analysis and ANOVA with post-hoc corrections.ResultsThe analysis identified 14/22 significant traits for SM in the three dog breeds, five of which were identical to those reported for the GB and suggest inclusion of a common aetiology. One ratio, caudal fossa height to the length of the skull base extended to an imaginary point of alignment between the atlas and supraoccipital bones, was common to all three breeds (p values 0.029 to <0.001). Associated with SM were a reduced occipital crest and two acute changes in angulation i) 'sphenoid flexure' at the spheno-occipital synchondrosis ii) 'cervical flexure' at the foramen magnum allied with medulla oblongata elevation. Comparing dogs with and without SM, each breed had a unique trait: Chihuahua had a smaller angle between the dens, atlas and basioccipital bone (p value < 0.001); Affenpinschers had a smaller distance from atlas to dens (p value 0.009); CKCS had a shorter distance between the spheno-occipital synchondrosis and atlas (p value 0.007).ConclusionThe selected morphometries successfully characterised conformational changes in the brain and craniocervical junction that might form the basis of a diagnostic tool for all breeds. The severity of SM involved a spectrum of abnormalities, incurred by changes in both angulation and size that could alter neural parenchyma compliance and/or impede cerebrospinal fluid channels.
| S-EPMC5266279 | biostudies-literature
Project description:ObjectivesTo characterise the symptomatic phenotype of Chiari-like malformation (CM), secondary syringomyelia (SM) and brachycephaly in the Cavalier King Charles Spaniel using morphometric measurements on mid-sagittal Magnetic Resonance images (MRI) of the brain and craniocervical junction.MethodsThis retrospective study, based on a previous quantitative analysis in the Griffon Bruxellois (GB), used 24 measurements taken on 130 T1-weighted MRI of hindbrain and cervical region. Associated brachycephaly was estimated using 26 measurements, including rostral forebrain flattening and olfactory lobe rotation, on 72 T2-weighted MRI of the whole brain. Both study cohorts were divided into three groups; Control, CM pain and SM and their morphometries compared with each other.ResultsFourteen significant traits were identified in the hindbrain study and nine traits in the whole brain study, six of which were similar to the GB and suggest a common aetiology. The Control cohort had the most elliptical brain (p = 0.010), least olfactory bulb rotation (p = 0.003) and a protective angle (p = 0.004) compared to the other groups. The CM pain cohort had the greatest rostral forebrain flattening (p = 0.007), shortest basioccipital (p = 0.019), but a greater distance between the atlas and basioccipital (p = 0.002) which was protective for SM. The SM cohort had two conformation anomalies depending on the severity of craniocervical junction incongruities; i) the proximity of the dens (p <0.001) ii) increased airorhynchy with a smaller, more ventrally rotated olfactory bulb (p <0.001). Both generated 'concertina' flexures of the brain and craniocervical junction.ConclusionMorphometric mapping provides a diagnostic tool for quantifying symptomatic CM, secondary SM and their relationship with brachycephaly. It is hypothesized that CM pain is associated with increased brachycephaly and SM can result from different combinations of abnormalities of the forebrain, caudal fossa and craniocervical junction which compromise the neural parenchyma and impede cerebrospinal fluid flow.
| S-EPMC5266281 | biostudies-literature
Project description:A 2-month-old, intact male domestic shorthair cat with dullness, bilateral central blindness, and recurrent epileptic seizures was presented to a local clinic. Seizures were the generalized myoclonic and tonic-clonic type. Phenobarbital was initiated and maintained; however, seizures were not controlled. Other anti-seizure drugs, including levetiracetam, zonisamide, and diazepam, also provided insufficient seizure control with seizures occurring hourly to daily. By 8 months of age, the cat displayed non-ambulatory tetraparesis and deep somnolence. Magnetic resonance imaging (MRI), cerebrospinal fluid analysis, and pre- and post-prandial total bile acid analyses were unremarkable. Scalp electroencephalography (EEG) revealed central dominant but generally synchronized spikes and multiple spikes. The cat was diagnosed with drug-resistant epilepsy of unknown cause and was included in a clinical trial of epilepsy surgery. Given the unremarkable MRI and bilateral synchronized EEG abnormalities, a corpus callosotomy was performed at 12 months of age, and partial desynchronization of spikes was confirmed on EEG. Incomplete transection was found in the genu of the corpus callosum on postoperative MRI. After surgery, the mental status and ambulation clearly improved, and seizure frequency and duration were remarkably reduced. Recheck with follow-up EEG and MRI were performed at 3, 6, and 12 months after surgery. Scores of activities of daily living and visual analog scales including cat's and owner's quality of life had also improved considerably. This case report is the first documentation of the one-year clinical outcome of corpus callosotomy in a clinical feline case with drug-resistant epilepsy.
| S-EPMC8511771 | biostudies-literature
Project description:OBJECTIVECorpus callosotomy is a palliative surgery for drug-resistant epilepsy that reduces the severity and frequency of generalized seizures by disconnecting the two cerebral hemispheres. Unlike with resection, seizure outcomes remain poorly understood. The authors systematically reviewed the literature and performed a meta-analysis to investigate rates and predictors of complete seizure freedom and freedom from drop attacks after corpus callosotomy.METHODSPubMed, Web of Science, and Scopus were queried for primary studies examining seizure outcomes after corpus callosotomy published over 30 years. Rates of complete seizure freedom or drop attack freedom were recorded. Variables showing a potential relationship to seizure outcome on preliminary analysis were subjected to formal meta-analysis.RESULTSThe authors identified 1742 eligible patients from 58 included studies. Overall, the rates of complete seizure freedom and drop attack freedom after corpus callosotomy were 18.8% and 55.3%, respectively. Complete seizure freedom was significantly predicted by the presence of infantile spasms (OR 3.86, 95% CI 1.13-13.23), normal MRI findings (OR 4.63, 95% CI 1.75-12.25), and shorter epilepsy duration (OR 2.57, 95% CI 1.23-5.38). Freedom from drop attacks was predicted by complete over partial callosotomy (OR 2.90, 95% CI 1.07-7.83) and idiopathic over known epilepsy etiology (OR 2.84, 95% CI 1.35-5.99).CONCLUSIONSThe authors report the first systematic review and meta-analysis of seizure outcomes in both adults and children after corpus callosotomy for epilepsy. Approximately one-half of patients become free from drop attacks, and one-fifth achieve complete seizure freedom after surgery. Some predictors of favorable outcome differ from those in resective epilepsy surgery.
| S-EPMC6274594 | biostudies-literature
Project description:Masticatory muscle myositis (MMM) is the second most common inflammatory myopathy diagnosed in dogs, but it is rarely described in puppies. The disease is characterized by the production of autoantibodies against 2M myofibers contained in masticatory muscle, although the cause of this production is still unclear. The aim of the present case report was to describe the clinical presentation, diagnostic findings, treatment, and follow-up of an atypical case of chronic masticatory muscle myositis in a very young dog. A 5-month old Cavalier king Charles Spaniel (CKCS) was presented to the AniCura Istituto Veterinario Novara with a two weeks, progressive history of lethargy and difficulty in food prehension. Neurological examination revealed bilateral masticatory muscle atrophy, mandibular ptosis with the jaw kept open, inability to close the mouth without manual assistance, jaw pain, and bilateral reduction of palpebral reflex and menace reaction; vision was maintained. A myopathy was suspected. Computed tomography (CT), magnetic resonance imaging (MRI), enzyme-linked immunosorbent assay test for 2M antibodies, and histopathological examination of masticatory muscle biopsy confirmed the diagnosis of MMM. Glucocorticoids treatment was started and clinical signs promptly improved. To the authors' knowledge, this is the first case describing mandibular ptosis in a dog affected by chronic MMM, successfully managed with medical treatment and the first report describing the CT and MRI findings in a young CKCS affected by MMM.
| S-EPMC9516294 | biostudies-literature
Project description:BACKGROUND:Syringomyelia (SM) is a debilitating condition in the cavalier King Charles spaniel (CKCS) that results in neuropathic pain and diminished quality of life. Von Frey aesthesiometry (VFA) is a method of mechanical quantitative sensory testing that provides an objective sensory threshold (ST) value and can be used to quantify neuropathic pain (NP) and monitor response to therapy. The utility of VFA has been previously established in client-owned dogs with acute spinal cord injury but the technique has not been evaluated in dogs with SM. The goal of this study was to evaluate ST, as determined by VFA, in dogs with and without SM, to assess the utility of VFA in quantifying NP in SM-affected dogs. We hypothesized the SM-affected CKCS would have lower ST values, consistent with hyperesthesia, when compared to control CKCS. Additionally, we hypothesized that ST values in SM-affected dogs would be inversely correlated with syrinx size on MRI and with owner-derived clinical sign scores. RESULTS:ST values for the thoracic and pelvic limbs differed significantly between the SM-affected and control CKCS (p?=?0.027; p?=?0.0396 respectively). Median ST value (range) for the thoracic limbs was 184.1?g (120.9-552) for control dogs, and 139.9?g (52.6-250.9) for SM-affected dogs. The median ST value (range) for the pelvic limbs was 164.9?g (100.8-260.3) in control dogs and 129.8?g (57.95-168.4) in SM-affected dogs. The ST values in SM-affected dogs did not correlate with syrinx height on MRI (r?=?0.314; p?=?0.137). Owner-reported clinical sign scores showed an inverse correlation with pelvic limb ST values, where dogs with lower ST values (hyperesthesia) were reported by their owners to display more frequent and severe clinical signs (r?=?-?0.657; p?=?0.022). CONCLUSION:ST values were lower in SM-affected CKCS compared to control dogs, suggesting the presence of neuropathic pain. Dogs with lower ST pelvic limb values were perceived by their owners to have more severe clinical signs classically associated with SM. Our results suggest that VFA might offer quantitative assessment of neuropathic pain in SM-affected dogs and could be useful for monitoring response to therapy in future clinical studies.
| S-EPMC7085174 | biostudies-literature
Project description:Cavalier King Charles spaniels (CKCSs) show the earliest onset and the highest incidence of myxomatous mitral valve disease (MMVD). Previous studies have suggested a polygenic inheritance of the disease in this breed and revealed an association with regions on canine chromosomes 13 and 14. Following clinical and echocardiographic examinations, 33 not-directly-related CKCSs were selected and classified as cases (n = 16) if MMVD was present before 5 years of age or as controls (n = 17) if no or very mild MMVD was present after 5 years of age. DNA was extracted from whole blood and genotyped with a Canine 230K SNP BeadChip instrument. Cases and controls were compared with three complementary genomic analyses (Wright's fixation index-FST, cross-population extended haplotype homozygosity-XP-EHH, and runs of homozygosity-ROH) to identify differences in terms of heterozygosity and regions of homozygosity. The top 1% single-nucleotide polymorphisms (SNPs) were selected and mapped, and the genes were thoroughly investigated. Ten consensus genes were found localized on chromosomes 3-11-14-19, partially confirming previous studies. The HEPACAM2, CDK6, and FAH genes, related to the transforming growth factor β (TGF-β) pathway and heart development, also emerged in the ROH analysis. In conclusion, this work expands the knowledge of the genetic basis of MMVD by identifying genes involved in the early onset of MMVD in CKCSs.
| S-EPMC7602727 | biostudies-literature
Project description:BackgroundDevelopment and progression of myxomatous mitral valve disease (MMVD) in dogs are difficult to predict. Identification at a young age of dogs at high risk of adverse outcome in the future is desirable.Hypothesis/objectivesTo study the predictive value of selected clinical and echocardiographic characteristics associated with MMVD obtained at a young age for prediction of long-term cardiac and all-cause mortality in Cavalier King Charles Spaniels (CKCS).Animals1125 privately owned CKCS.MethodsA retrospective study including CKCS examined at the age of 1-3 years. Long-term outcome was assessed by telephone interview with owners. The value of variables for predicting mortality was investigated by Cox proportional hazard and Kaplan-Meier analyses.ResultsPresence of moderate to severe mitral regurgitation (MR) (hazard ratio (HR) = 3.03, 95% confidence interval (95% CI) = 1.48-6.23, P = 0.0025) even intermittent moderate to severe MR (HR = 2.23, 95% CI = 1.48-6.23, P = 0.039) on color flow Doppler echocardiography was significantly associated with increased hazard of cardiac death. An interaction between MR and sex was significant for all-cause mortality (P = 0.035), showing that males with moderate to severe MR had a higher all-cause mortality compared to males with no MR (HR = 2.38, 95% CI = 1.27-4.49, P = 0.0071), whereas no difference was found between female MR groups. The risk of cardiac (HR = 1.37, 95% CI = 1.14-1.63, P < 0.001) and all-cause (HR = 1.13, 95% CI = 1.02-1.24, P = 0.016) mortality increased with increasing left ventricular end-systolic internal dimension normalized for body weight (LVIDSN ).Conclusions and clinical importanceModerate to severe MR, even if intermittent, and increased LVIDSN in dogs <3 years of age were associated with cardiac death later in life in CKCS.
| S-EPMC5508320 | biostudies-literature