RESUMEN
X-linked recessive dystrophinopathies are the most common muscular dystrophies (MDs) in humans and dogs. To date, 20 breed-specific MD-associated variants are described in the canine dystrophin gene (DMD), including one associated with dystrophin-deficient MD in the Border Collie mixed breed. Here, we report the diagnosis and follow-up of mild dystrophin-deficient MD in a 5-month-old male Border Collie, associated with a novel DMD variant. Diagnosis was based on neurological examination and laboratory evaluations including creatine kinase activity, electromyography and muscle biopsies with immunofluorescent staining. Inspection of the Sashimi plots of the RNA-seq data from the affected muscle biopsy led to the discovery of a 162-bp L1 pseudoexon in DMD intron 63, introducing a frameshift and a premature stop codon (NM_001003343.1: c.9271_9272insN[162] p.(Ala3091fs*21)). Reduced DMD mRNA levels were detected for both the non-pseudoexon (50× less) and pseudoexon (3× less) containing transcripts in the affected muscle, compared with the level of the non-pseudoexon containing transcript in a control muscle, resulting in very low dystrophin protein levels and the upregulation of utrophin. Because the variant was only found in the affected dog, not in the healthy mother and grandmother, or in 108 unrelated Border Collies from the Belgian population (46 males and 62 females), it was considered a de novo variant. Although the prognosis for dystrophinopathy is generally regarded as poor, the dog stabilised at the age of 6 months and is still clinically stable at the age of 2 years.
RESUMEN
Cerebrospinal fluid metabolomics is a promising research technology in the elucidation of nervous system disorders. Therefore, in this work, a cerebrospinal fluid (CSF) metabolomics method using liquid chromatography coupled to mass spectrometry was optimized and validated to cover a wide range of metabolites. An acceptable coefficient of variance regarding instrumental, within-lab and intra-assay precision was found for 95, 70 and 96 of 102 targeted metabolites, together with 1256, 676 and 976 untargeted compounds, respectively. Moreover, approximately 75% of targeted metabolites and 50% of untargeted compounds displayed good linearity across different dilution ranges. Consequently, metabolic alterations in CSF of dogs with idiopathic epilepsy (IE) were studied by comparing CSF of dogs diagnosed with IE (Tier II) to dogs with non-brain related disease. Targeted metabolome analysis revealed higher levels of cortisol, creatinine, glucose, hippuric acid, mannose, pantothenol, and 2-phenylethylamine (P values < 0.05) in CSF of dogs with IE, whereas CSF of dogs with IE showed lower levels of spermidine (P value = 0.02). Untargeted CSF metabolic fingerprints discriminated dogs with IE from dogs with non-brain related disease using Orthogonal Partial Least Squares Discriminant Analysis (R2(Y) = 0.997, Q2(Y) = 0.828), from which norepinephrine was putatively identified as an important discriminative metabolite.
Asunto(s)
Enfermedades de los Perros , Epilepsia , Metabolómica , Animales , Perros , Epilepsia/líquido cefalorraquídeo , Metabolómica/métodos , Enfermedades de los Perros/líquido cefalorraquídeo , Metaboloma , Cromatografía Liquida , Masculino , Biomarcadores/líquido cefalorraquídeo , FemeninoRESUMEN
OBJECTIVE: Episodic mandibular tremor (EMT), manifested as teeth chattering, is not well described in dogs. The aim of this study was to describe clinical signs, MRI findings, and outcome of dogs with EMT. ANIMALS: 11 dogs retrospectively and 31 dogs in an online survey. METHODS: A retrospective multicenter study of dogs with EMT between 2018 and 2023 and prospective online questionnaire open to owners of pets with teeth chattering. RESULTS: All dogs had rapid and short-lasting (< 1 minute) episodes of EMT in the absence of other neurological signs. Lip smacking occasionally accompanied the tremor in 5 of 11 (45.5%) hospital dog cases. Excitement was a common trigger in 14 of 31 (45.2%) dogs from the survey. Cavalier King Charles Spaniel was the most common breed in both clinical and survey populations. Median age at presentation was 3 years for both hospital cases and the survey dogs. A concurrent medical condition was present in 8 of 11 (72.7%) hospital cases and 20 of 31 (64.5%) survey dogs. In 3 hospital dogs that underwent further investigations, no brain disease was present. CLINICAL RELEVANCE: EMT and its clinical features are presented for the first time, shedding light on a clinical sign that might resemble an idiopathic movement disorder or a manifestation of pain in dogs.
Asunto(s)
Enfermedades de los Gatos , Enfermedades de los Perros , Epilepsia , Animales , Gatos , Perros , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Perros/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Epilepsia/veterinaria , Convulsiones/tratamiento farmacológico , Convulsiones/veterinariaRESUMEN
Background: Emergency seizure disorders such as status epilepticus and cluster seizures are unlikely to cease spontaneously while prolonged seizure activity become progressively more resistant to treatment. Early administration of rescue medication in canine epileptic patients, in particular benzodiazepines, at seizure onset by the owners can be life-saving and brain protecting. Clinical studies in dogs evaluating the use of rescue medication in hospital environment exist, however, the owner perspective has not been assessed to date. Hypothesis or objectives: To evaluate the use of rescue medication in dogs with seizure emergencies by the owner at home. Method: Observational study based on online surveys of owners of dogs with emergency seizure disorders. Results: The questionnaire was answered by 1,563 dog owners, of which 761 provided complete and accurate answers suitable for analysis. Of these, 71% administered diazepam, 19% midazolam, 6% levetiracetam, 3% lorazepam, and 4% more than one rescue or other medication. Overall, the success rates based on owners' perspective for intranasal midazolam and rectal diazepam were 97 and 63%, respectively. Owners reported a compliance level of 95 and 66% for intranasal midazolam and rectal diazepam administration, respectively. Conclusions and clinical importance: Even though rectal diazepam was the most used rescue medication in this survey population, intranasal midazolam was perceived by the owners as a better option regarding effectiveness, time to seizure cessation and owner compliance.
RESUMEN
BACKGROUND: Although idiopathic episodic head tremor (IEHT) in dogs is well-known, little is known about structural brain lesions causing structural episodic head tremor (SEHT). HYPOTHESIS/OBJECTIVES: Describe semiology, magnetic resonance imaging (MRI) findings and outcome of dogs with IEHT or SEHT. We hypothesized that structural lesions affecting the middle cranial fossa or mesencephalic aqueduct could lead to SEHT. ANIMALS: One hundred dogs with IEHT (n = 71) or SEHT (n = 29). METHODS: Retrospective, multicenter, study of dogs with episodic (nonintentional) head tremor and brain MRI between 2004 and 2022. RESULTS: Lesions on MRI in SEHT dogs were localized to the middle cranial fossa (15/29), cerebrocortex (3/29), brainstem (2/29), fourth ventricle (1/29) or multifocal (8/29) with thalamus involvement (6/8). Secondary compression of the mesencephalic aqueduct (19/29), third ventricle or interthalamic adhesion or both (14/29) was common. The most common underlying condition in dogs with SEHT was a pituitary mass. Dogs with SEHT were older, had additional neurological signs and were more likely to be euthanized after diagnosis (P < .001 for all) compared to IEHT dogs. Two SEHT dogs had only tremor. In IEHT dogs, 8/10 owners reported that the tremor decreased or abated over time (range, 106-2315 days) without treatment. Tremor remission occurred in SEHT dogs treated for underlying meningoencephalitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Presence of additional neurological signs and older age may indicate an underlying structural cause for episodic (nonintentional) head tremor involving the mesencephalic aqueduct, third ventricle, interthalamic adhesion or some combination of these. An intracranial structural abnormality cannot be excluded in dogs with normal neurological examination.
Asunto(s)
Enfermedades de los Perros , Tercer Ventrículo , Perros , Animales , Temblor/veterinaria , Estudios Retrospectivos , Encéfalo , Cabeza , Imagen por Resonancia Magnética/veterinaria , Enfermedades de los Perros/diagnósticoRESUMEN
BACKGROUND: KCNJ10 and CAPN1 variants cause "spinocerebellar" ataxia in dogs, but their association with generalized myokymia and neuromyotonia remains unclear. OBJECTIVE: To investigate the association between KCNJ10 and CAPN1 and myokymia or neuromyotonia, with or without concurrent spinocerebellar ataxia. ANIMALS: Thirty-three client-owned dogs with spinocerebellar ataxia, myokymia neuromytonia, or a combination of these signs. METHODS: Genetic analysis of a cohort of dogs clinically diagnosed with spinocerebellar ataxia, myokymia or neuromyotonia. KCNJ10 c.627C>G and CAPN1 c.344G>A variants and the coding sequence of KCNA1, KCNA2, KCNA6, KCNJ10 and HINT1 were sequenced using DNA extracted from blood samples. RESULTS: Twenty-four Jack Russell terriers, 1 Jack Russell terrier cross, 1 Dachshund and 1 mixed breed with spinocerebellar ataxia were biallelic (homozygous) for the KCNJ10 c.627C>G variant. Twenty-one of those dogs had myokymia, neuromyotonia, or both. One Parson Russell terrier with spinocerebellar ataxia alone was biallelic for the CAPN1 c.344G>A variant. Neither variant was found in 1 Jack Russell terrier with ataxia alone, nor in 3 Jack Russell terriers and 1 Yorkshire terrier with myokymia and neuromyotonia alone. No other causal variants were found in the coding sequence of the investigated candidate genes in these latter 5 dogs. CONCLUSION: The KCNJ10 c.627C>G variant, or rarely the CAPN1 c.344G>A variant, was confirmed to be the causal variant of spinocerebellar ataxia. We also report the presence of the KCNJ10 c.627C>G variant in the Dachshund breed. In dogs with myokymia and neuromyotonia alone the reported gene variants were not found. Other genetic or immune-mediated causes should be investigated to explain the clinical signs of these cases.
Asunto(s)
Enfermedades de los Perros , Síndrome de Isaacs , Miocimia , Ataxias Espinocerebelosas , Humanos , Perros , Animales , Miocimia/genética , Miocimia/veterinaria , Síndrome de Isaacs/genética , Síndrome de Isaacs/veterinaria , Ataxias Espinocerebelosas/veterinaria , Ataxia/veterinaria , Cruzamiento , Proteínas del Tejido Nervioso , Canal de Potasio Kv1.6 , Enfermedades de los Perros/genéticaRESUMEN
BACKGROUND: Since the introduction of next-generation sequencing (NGS) techniques, whole-exome sequencing (WES) and whole-genome sequencing (WGS) have not only revolutionized research, but also diagnostics. The gradual switch from single gene testing to WES and WGS required a different set of skills, given the amount and type of data generated, while the demand for standardization remained. However, most of the tools currently available are solely applicable for human analysis because they require access to specific databases and/or simply do not support other species. Additionally, a complicating factor in clinical genetics in animals is that genetic diversity is often dangerously low due to the breeding history. Combined, there is a clear need for an easy-to-use, flexible tool that allows standardized data processing and preferably, monitoring of genetic diversity as well. To fill these gaps, we developed the R-package variantscanR that allows an easy and straightforward identification and prioritization of known phenotype-associated variants identified in dogs and other domestic animals. RESULTS: The R-package variantscanR enables the filtering of variant call format (VCF) files for the presence of known phenotype-associated variants and allows for the estimation of genetic diversity using multi-sample VCF files. Next to this, additional functions are available for the quality control and processing of user-defined input files to make the workflow as easy and straightforward as possible. This user-friendly approach enables the standardisation of complex data analysis in clinical settings. CONCLUSION: We developed an R-package for the identification of known phenotype-associated variants and calculation of genetic diversity.
Asunto(s)
Animales Domésticos , Programas Informáticos , Humanos , Animales , Perros , Animales Domésticos/genética , Secuenciación Completa del Genoma/métodos , Fenotipo , Bases de Datos Genéticas , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Hereditary ataxias are a large group of neurodegenerative diseases that have cerebellar or spinocerebellar dysfunction as core feature, occurring as an isolated sign or as part of a syndrome. Based on neuropathology, this group of diseases has so far been classified into cerebellar cortical degenerations, spinocerebellar degenerations, cerebellar ataxias without substantial neurodegeneration, canine multiple system degeneration, and episodic ataxia. Several new hereditary ataxia syndromes are described, but most of these diseases have similar clinical signs and unspecific diagnostic findings, wherefore achieving a definitive diagnosis in these dogs is challenging. Eighteen new genetic variants associated with these diseases have been discovered in the last decade, allowing clinicians to reach a definitive diagnosis for most of these conditions, and allowing breeding schemes to adapt to prevent breeding of affected puppies. This review summarizes the current knowledge about hereditary ataxias in dogs, and proposes to add a "multifocal degenerations with predominant (spino)cerebellar component" category regrouping canine multiple system degeneration, new hereditary ataxia syndromes that do not fit in 1 of the previous categories, as well as specific neuroaxonal dystrophies and lysosomal storage diseases that cause major (spino)cerebellar dysfunction.
Asunto(s)
Ataxia Cerebelosa , Enfermedades de los Perros , Degeneraciones Espinocerebelosas , Perros , Animales , Degeneraciones Espinocerebelosas/genética , Degeneraciones Espinocerebelosas/veterinaria , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/veterinaria , Ataxia Cerebelosa/diagnóstico , Enfermedades de los Perros/genéticaRESUMEN
(1) Idiopathic epilepsy (IE) is thought to have a genetic cause in several dog breeds. However, only two causal variants have been identified to date, and few risk loci are known. No genetic studies have been conducted on IE in the Dutch partridge dog (DPD), and little has been reported on the epileptic phenotype in this breed. (2) Owner-filled questionnaires and diagnostic investigations were used to characterize IE in the DPD. A genome-wide association study (GWAS) involving 16 cases and 43 controls was performed, followed by sequencing of the coding sequence and splice site regions of a candidate gene within the associated region. Subsequent whole-exome sequencing (WES) of one family (including one IE-affected dog, both parents, and an IE-free sibling) was performed. (3) IE in the DPD has a broad range in terms of age at onset, frequency, and duration of epileptic seizures. Most dogs showed focal epileptic seizures evolving into generalized seizures. A new risk locus on chromosome 12 (BICF2G630119560; praw = 4.4 × 10-7; padj = 0.043) was identified through GWAS. Sequencing of the GRIK2 candidate gene revealed no variants of interest. No WES variants were located within the associated GWAS region. However, a variant in CCDC85A (chromosome 10; XM_038680630.1: c.689C > T) was discovered, and dogs homozygous for the variant (T/T) had an increased risk of developing IE (OR: 6.0; 95% CI: 1.6-22.6). This variant was identified as likely pathogenic according to ACMG guidelines. (4) Further research is necessary before the risk locus or CCDC85A variant can be used for breeding decisions.
RESUMEN
Background: To our knowledge, this is the first description of long-term nutritional management in a dog with paroxysmal dyskinesia. Case summary: An obese 9-year-old, male entire, German Spitz was presented for dietary management after being diagnosed with calcium oxalate urolithiasis and suspected pancreatitis. Since he was seven years old, the dog has had a history of neurological signs, which were thought to be epileptic seizures. He was treated with phenobarbital and potassium bromide and was clinically controlled. For his nutritional advice, aiming to minimize one of the most important risk factors for the diseases, a weight loss program was started and successfully executed. However, 10 months later, the dog restarted presenting neurological episodes at a high frequency (3x/week). Based on videos and the characteristics of the neurological signs, the dog was diagnosed with paroxysmal dyskinesia. To investigate the role of gluten intake on this patient's neurological signs, a dietary trial with a commercial hypoallergenic diet (gluten-free; hydrolyzed protein) was followed. During the 3 months of the dietary trial, four neurologic episodes related to food indiscretion occurred. Upon the decrease in neurological episodes, the anti-seizure drugs were slowly discontinued. During this period, the dog presented only two neurologic episodes that were related to the days that the anti-seizure drugs were decreased. For 4 months the dog remained episode-free. However, a change in the dog's diet to another gluten-free diet (higher fat) led the dog to vomit and experience another neurologic episode. Once the dog was back to the previous gluten-free diet, it clinically improved, and no other clinical signs were reported by the client during the next 5 months. Conclusion: Although a relationship between gluten and paroxysmal dyskinesia cannot be confirmed, the dog's improvement after the nutritional management and the removal of the anti-seizure therapy is supportive of dietary association.
RESUMEN
Epilepsy is a challenging multifactorial disorder with a complex genetic background. Our current understanding of the pathophysiology and treatment of epilepsy has substantially increased due to animal model studies, including canine studies, but additional basic and clinical research is required. Drug-resistant epilepsy is an important problem in both dogs and humans, since seizure freedom is not achieved with the available antiseizure medications. The evaluation and exploration of pharmacological and particularly non-pharmacological therapeutic options need to remain a priority in epilepsy research. Combined efforts and sharing knowledge and expertise between human medical and veterinary neurologists are important for improving the treatment outcomes or even curing epilepsy in dogs. Such interactions could offer an exciting approach to translate the knowledge gained from people and rodents to dogs and vice versa. In this article, a panel of experts discusses the similarities and knowledge gaps in human and animal epileptology, with the aim of establishing a common framework and the basis for future translational epilepsy research.
Asunto(s)
Enfermedades de los Perros , Epilepsia Refractaria , Epilepsia , Neurología , Humanos , Animales , Perros , Enfermedades de los Perros/tratamiento farmacológico , Epilepsia/veterinaria , Epilepsia Refractaria/veterinaria , Resultado del Tratamiento , Anticonvulsivantes/uso terapéuticoRESUMEN
Recent work identified anti-GM2 and anti-GalNAc-GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain-Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune-mediated polyneuropathies. The sera from 41 cats clinically diagnosed with immune-mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc-GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide. A total of 29/41 IPN-cats had either anti-GM2 or anti-GalNAc-GD1a IgG antibodies, with 24/29 cats having both. Direct comparison of anti-GM2 (sensitivity: 70.7%; specificity: 78.2%) and anti-GalNAc-GD1a (sensitivity: 70.7%; specificity: 70.9%) antibodies narrowly showed anti-GM2 IgG antibodies to be the better marker for identifying IPN-cats when compared to the combined ONM and CTRL groups (P = .049). Anti-GA1 and/or anti-sulphatide IgG antibodies were ubiquitously present across all sample groups, whereas antibodies against GM1, GD1a, GD1b, SGPG, LM1 and galactocerebroside were overall only rarely observed. Anti-GM2 and anti-GalNAc-GD1a IgG antibodies may serve as serum biomarkers for immune-mediated polyneuropathies in cats, as previously observed in dogs and humans.
Asunto(s)
Síndrome de Guillain-Barré , Polineuropatías , Humanos , Gatos , Animales , Perros , Galactosilceramidas , Gangliósido G(M1) , Gangliósidos , Inmunoglobulina G , Polineuropatías/diagnóstico , Polineuropatías/veterinaria , Biomarcadores , Autoanticuerpos , Gangliósido G(M2)RESUMEN
BACKGROUND: In Belgian Malinois, a KCNJ10 variant causes progressive spinocerebellar degeneration. HYPOTHESIS/OBJECTIVES: Describe the clinical, diagnostic, pathological and genetic features of spinocerebellar degeneration in the Bouvier des Ardennes breed. ANIMALS: Five affected Bouvier des Ardennes puppies with spinocerebellar ataxia (SCA), 8 healthy related dogs, and 63 healthy unrelated Bouvier des Ardennes. METHODS: Sequential case study. RESULTS: Clinical signs started at 6 weeks of age in 1 puppy with severe signs of cerebellar disease, and at 7 to 10 weeks of age in the 4 remaining puppies with milder signs of spinocerebellar disease. The first puppy displayed severe intention tremors and rapidly progressive generalized hypermetric ataxia, whereas the 4 others developed a milder progressive SCA. Euthanasia after progression to nonambulatory status was performed by 8 weeks of age in the first puppy, and before 11 months of age in the 4 remaining puppies. Histopathology revealed cerebellar spongy degeneration and a focal symmetrical demyelinating myelopathy. All cases were homozygous for KCNJ10 XM_545752.6:c.986T>C(p.(Leu329Pro)), which is pathogenic for SCA with (or without) myokymia, seizures or both (SAMS) and spongy degeneration and cerebellar ataxia (SDCA) 1 in Belgian Malinois dogs. All sampled parents were heterozygous and none of the healthy dogs were homozygous for this recessive variant. This variant has an allele frequency of 15% in the 63 healthy dogs studied. CONCLUSIONS AND CLINICAL IMPORTANCE: Inherited spinocerebellar degeneration also affects the Bouvier des Ardennes breed and is caused by a KCNJ10 variant. It can present with a spectrum of severity grades, ranging from severe cerebellar to milder spinocerebellar signs.
Asunto(s)
Ataxia Cerebelosa , Enfermedades de los Perros , Ataxias Espinocerebelosas , Degeneraciones Espinocerebelosas , Perros , Animales , Ataxias Espinocerebelosas/genética , Ataxias Espinocerebelosas/veterinaria , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/patología , Ataxia Cerebelosa/veterinaria , Degeneraciones Espinocerebelosas/genética , Degeneraciones Espinocerebelosas/veterinaria , Mutación Missense , Homocigoto , Enfermedades de los Perros/genéticaRESUMEN
A 9-month-old male entire Doberman Pinscher presented with acute onset of severe cervical hyperesthesia after a fall. Neurological examination revealed a normal gait with low head carriage and severe cervical hyperesthesia. A CT scan of the cervical vertebral column revealed the presence of a comminuted fracture at the dorsomedial aspect of the right occipital condyle and sclerosis of the underlying bone. Medical management was initiated consisting of an external bandage, strict rest, and pain medication. Due to the lack of clinical improvement, the dog was euthanized 2 months after diagnosis. Histopathology of the lesion was compatible with a healing fracture.
Asunto(s)
Enfermedades de los Perros , Fracturas Craneales , Masculino , Perros , Animales , Hiperestesia/veterinaria , Fracturas Craneales/veterinaria , Hueso Occipital/diagnóstico por imagen , Tomografía Computarizada por Rayos X/veterinaria , Vértebras Cervicales/diagnóstico por imagen , Enfermedades de los Perros/diagnóstico por imagenRESUMEN
In the last decade, nutrition has gained interest in the management of canine idiopathic epilepsy (IE) based on growing scientific evidence. Diets can serve their functions through many pathways. One potential pathway includes the microbiota-gut-brain axis, which highlights the relationship between the brain and the intestines. Changing the brain's energy source and a number of dietary sourced anti-inflammatory and neuroprotective factors appears to be the basis for improved outcomes in IE. Selecting a diet with anti-seizure effects and avoiding risks of proconvulsant mediators as well as interference with anti-seizure drugs should all be considered in canine IE. This literature review provides information about preclinical and clinical evidence, including a systematic evaluation of the level of evidence, suggested mechanism of action and interaction with anti-seizure drugs as well as pros and cons of each potential dietary adaptation in canine IE.
Asunto(s)
Enfermedades de los Perros , Epilepsia , Perros , Animales , Epilepsia/veterinaria , Dieta/veterinariaRESUMEN
(1) Feline dystrophin-deficient muscular dystrophy (ddMD) is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles and is caused by variants in the DMD gene. To date, only two feline causal variants have been identified. This study reports two cases of male Maine coon siblings that presented with muscular hypertrophy, growth retardation, weight loss, and vomiting. (2) Both cats were clinically examined and histopathology and immunofluorescent staining of the affected muscle was performed. DMD mRNA was sequenced to identify putative causal variants. (3) Both cats showed a significant increase in serum creatine kinase activity. Electromyography and histopathological examination of the muscle samples revealed abnormalities consistent with a dystrophic phenotype. Immunohistochemical testing revealed the absence of dystrophin, confirming the diagnosis of dystrophin-deficient muscular dystrophy. mRNA sequencing revealed a nonsense variant in exon 11 of the feline DMD gene, NC_058386.1 (XM_045050794.1): c.1180C > T (p.(Arg394*)), which results in the loss of the majority of the dystrophin protein. Perfect X-linked segregation of the variant was established in the pedigree. (4) ddMD was described for the first time in the Maine coon and the c.1180C>T variant was confirmed as the causal variant.
RESUMEN
The anticonvulsant effect of cannabidiol (CBD), which has been confirmed by findings from animal models and human trials, has attracted the interest of veterinary practitioners and dog owners. Moreover, social media and public pressure has sparked a renewed awareness of cannabinoids, which have been used for epilepsy since ancient times. Unfortunately, at this moment veterinarians and veterinary neurologists have difficulty prescribing cannabinoids because of the paucity of sound scientific studies. Pharmacokinetic studies in dogs have demonstrated a low oral bioavailability of CBD and a high first-pass effect through the liver. Administering CBD in oil-based formulations and/or with food has been shown to enhance the bioavailability in dogs, rats and humans. Tolerability studies in healthy dogs and dogs with epilepsy have demonstrated that CBD was safe and well tolerated with only mild to moderate adverse effects. In this context, it should be noted that the quality of available CBD varies widely, underscoring the importance of pharmaceutical quality and its control. One clinical trial in dogs with drug-resistant idiopathic epilepsy failed to confirm a difference in response rates between the CBD group and the placebo group, while in another cross-over trial a ≥ 50 % reduction in epileptic seizure frequency was found in six of 14 dogs in the treatment phase, a reduction that was not observed during the placebo phase. Based on the current state of knowledge it is not possible to provide clear-cut recommendations for the use of CBD in canine epilepsy. Randomized controlled canine trials with large sample sizes are needed to determine the range of therapeutic plasma concentrations, develop evidence-based dosing regimens, determine the efficacy of cannabidiol in drug-refractory epilepsy, and explore potential associations between treatment effects and different etiologies, epilepsy types, and drug combinations.
Asunto(s)
Cannabidiol , Cannabinoides , Enfermedades de los Perros , Epilepsia Refractaria , Epilepsia , Enfermedades de los Roedores , Humanos , Perros , Animales , Ratas , Cannabidiol/uso terapéutico , Cannabidiol/efectos adversos , Epilepsia/tratamiento farmacológico , Epilepsia/veterinaria , Anticonvulsivantes , Convulsiones/tratamiento farmacológico , Convulsiones/veterinaria , Epilepsia Refractaria/veterinaria , Cannabinoides/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/inducido químicamenteRESUMEN
We investigated two litters of distantly related Nova Scotia Duck Tolling Retrievers (NSDTR), of which four puppies were affected by cerebellar signs with or without neuromuscular weakness. The phenotype was termed cerebellar degenerationmyositis complex (CDMC). We suspected a heritable condition and initiated a genetic analysis. The genome of one affected dog was sequenced and compared to 565 control genomes. This search yielded a private protein-changing SLC25A12 variant in the affected dog, XM_038584842.1:c.1337C>T, predicted to result in the amino acid change XP_038440770.1:(p.Pro446Leu). The genotypes at the variant co-segregated with the phenotype as expected for a monogenic autosomal recessive mode of inheritance in both litters. Genotyping of 533 additional NSDTR revealed variant allele frequencies of 3.6% and 1.3% in a European and a North American cohort, respectively. The available clinical and biochemical data, together with current knowledge about SLC25A12 variants and their functional impact in humans, mice, and dogs, suggest the p.Pro446Leu variant is a candidate causative defect for the observed phenotype in the affected dogs.
Asunto(s)
Enfermedades de los Perros , Miositis , Animales , Enfermedades de los Perros/diagnóstico , Perros , Pruebas Genéticas , Genotipo , Humanos , Ratones , Proteínas de Transporte de Membrana Mitocondrial/genética , Miositis/genética , Nueva EscociaRESUMEN
Modulation of neuronal activity for seizure control using various methods of neurostimulation is a rapidly developing field in epileptology, especially in treatment of refractory epilepsy. Promising results in human clinical practice, such as diminished seizure burden, reduced incidence of sudden unexplained death in epilepsy, and improved quality of life has brought neurostimulation into the focus of veterinary medicine as a therapeutic option. This article provides a comprehensive review of available neurostimulation methods for seizure management in drug-resistant epilepsy in canine patients. Recent progress in non-invasive modalities, such as repetitive transcranial magnetic stimulation and transcutaneous vagus nerve stimulation is highlighted. We further discuss potential future advances and their plausible application as means for preventing epileptogenesis in dogs.