A TNR Frameshift Variant in Weimaraner Dogs with an Exercise-Induced Paroxysmal Movement Disorder.

BACKGROUND: Some paroxysmal movement disorders remain without an identified genetic cause. OBJECTIVES: The aim was to identify the causal genetic variant for a paroxysmal dystonia-ataxia syndrome in Weimaraner dogs. METHODS: Clinical and diagnostic investigations were performed. Whole genome sequencing of one affected dog was used to identify private homozygous variants against 921 control genomes. RESULTS: Four Weimaraners were presented for episodes of abnormal gait. Results of examinations and diagnostic investigations were unremarkable. Whole genome sequencing revealed a private frameshift variant in the TNR (tenascin-R) gene in an affected dog, XM_038542431.1:c.831dupC, which is predicted to truncate more than 75% of the open read frame. Genotypes in a cohort of 4 affected and 70 unaffected Weimaraners showed perfect association with the disease phenotype. CONCLUSIONS: We report the association of a TNR variant with a paroxysmal dystonia-ataxia syndrome in Weimaraners. It might be relevant to include sequencing of this gene in diagnosing humans with unexplained paroxysmal movement disorders. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Severe propofol-associated dystonia in a dog.

A 2-year-old castrated dog was presented for chronic coughing that was evaluated with bronchoscopy following intravenous boluses of propofol. During recovery the dog developed severe rigidity of muscles of the neck and thoracic limbs, which was unresponsive to treatment but subsided over 25 minutes. A presumptive diagnosis of propofol-associated dystonia was made. The clinical characteristics and theorized pathophysiology of propofol-associated dystonia are discussed.

Dystonie grave associée au propofol chez un chien. Un chien castré âgé de 2 ans a été présenté pour une toux chronique qui a été évaluée par bronchoscopie après des bolus intraveineux de propofol. Durant le réveil, le chien a développé une grave rigidité des muscles du cou et des membres thoraciques, qui n'a pas répondu au traitement mais qui s'est apaisée sur une période de 25 minutes. Un diagnostic présumé de dystonie associée au propofol a été posé. Les caractéristiques cliniques et la théorie de la pathophysiologie de la dystonie associée au propofol sont discutées.(Traduit par Isabelle Vallières).

Dystonic head tremor in paroxysmal dyskinesia in 17 dogs (2021-2023).

BACKGROUND: Dystonia is a common component of the movement disorder paroxysmal dyskinesia (PD) in dogs. However, the incidence of dystonic head tremor (DHT) in these dogs has not previously been evaluated. METHODS: The medical records of dogs presenting with PD between 2021 and 2023 were retrospectively reviewed, and those with available video footage and the presence of a head tremor were selected for further analysis. RESULTS: Seventeen of the 39 (43.6%) dogs diagnosed with PD that had video footage available manifested DHT. Poodle or Poodle-cross was the most commonly affected breed (7/17). DHTs were described as fine irregular head tremors accompanied by cervical dystonia (17/17), truncal (11/17) or head (10/17) sway, shifting limb (10/17) or single limb (6/17) dystonia, freezing (8/17), ataxia (6/17), ptyalism (5/17), falling (5/17), kyphosis (4/17) and prayer posture (4/17). Neurological examination and advanced imaging, when available, were within normal limits. LIMITATIONS: The limitations of the study include its retrospective nature, the lack of video recordings for all PD patients and the lack of electrophysiological evaluation of tremors and electroencephalography. CONCLUSIONS: DHT exists in dogs with PD; it has characteristic features, and it should be considered in differential diagnoses for dogs with head tremors.

Identification of congenital muscular dystonia 2 associated with an inherited GlyT2 defect in Belgian Blue cattle from the United Kingdom.

Two newborn Belgian Blue calves from a farm in the United Kingdom exhibited lateral recumbency, low head carriage and transient muscle spasms following tactile or auditory stimulation. DNA sequence analysis indicated that both calves were homozygous for the recessive congenital muscular dystonia type 2 (CMD2) mutation (c.809T>C, p.Leu270Pro) in SLC6A5, encoding the neuronal glycine transporter GlyT2. Further testing of animals from the index farm and a sample of Belgian Blue sires revealed an unexpectedly high frequency of CMD2 carriers. This implies that linked quantitative trait loci may be influencing the prevalence of CMD2 in the estimated 55,000 Belgian Blue cattle in the United Kingdom. We have therefore developed new inexpensive tests for the CMD2 allele that can be used to confirm diagnosis, identify carriers and guide future breeding strategy, thus avoiding animal distress/premature death and minimizing the future economic impact of this disorder.

Phenotypic characterisation of paroxysmal dyskinesia in Sphynx cats.

OBJECTIVES: The aim of this study was to identify the phenotypic features of a paroxysmal dyskinesia observed in Sphynx cats. METHODS: The owners of affected Sphynx cats were invited to provide video footage of abnormal episodes for review. Those that demonstrated episodes consistent with paroxysmal dyskinesia were then invited to complete an online questionnaire designed to allow further characterisation. RESULTS: Ten Sphynx cats were included in the study. All affected cats were <4 years of age at the onset of the episodes (range 0.5-4.0). The episodes had a duration of <5 mins in 9/10 cats (range 0.5-10), while episode frequency was variable between and within individual cats. The episodes were characterised by impaired ambulation due to muscle hypertonicity, most commonly affecting the hips and pelvic limbs (9/10) and shoulders and thoracic limbs (8/10). The head and neck (6/10), tail (5/10), and back and abdomen (3/10) were also involved in some cats. Sudden movement, excitement and stress were identified as possible triggers for the episodes in three cats. Therapeutic intervention was not attempted in 7/10 cases, although two cats were reported to become free of the episodes while receiving acetazolamide. The two cats that were followed beyond 2 years from onset entered spontaneous remission. None of the owners believed that the abnormal episodes had affected the quality of life of their cat. CONCLUSIONS AND RELEVANCE: The phenotype of paroxysmal dyskinesia in Sphynx cats presented in this study appears to share similarities with paroxysmal kinesigenic dyskinesia described in human classification systems. Some cats appear to achieve episode freedom spontaneously. Subsequent research should focus on evaluating response to treatment and determining an underlying genetic cause.

Dystonia in veterinary neurology.

Dystonia is a clinical sign and main feature of many movement disorders in humans as well as veterinary species. It is characterized by sustained or intermittent involuntary muscle contractions causing abnormal (often repetitive) movements, postures, or both. This review discusses the terminology and definition of dystonia, its phenomenology, and its pathophysiology, and provides considerations regarding the diagnosis and treatment of dystonia in dogs and cats. In addition, currently recognized or reported disorders in dogs and cats in which dystonia is a particular or main feature are discussed and comparisons are made between disorders featuring dystonia in humans and animals. We suggest that when describing the phenomenology of dogs and cats with dystonia, if possible the following should be included: activity being performed at onset (e.g., resting or running or exercise-induced), body distribution, duration, responsiveness (subjective), severity, temporal pattern (i.e., paroxysmal or persistent, severity at onset and at later stages), presence or absence of autonomic signs (e.g., salivation), presence or absence of preceding signs (e.g., restlessness), presence or absence of signs after dystonia subsides (e.g., sleepiness), coexistence of other movement disorders, any other neurological manifestations, and possible links to administered medications, intoxications or other associated factors. We also suggest that dystonia be classified based on its etiology as either structural genetic, suspected genetic, reactive, or unknown.

Causes of mortality and non-fatal conditions among grey seals (Halichoerus grypus) found dead on the coasts of England, Wales and the Isle of Man.

A survey of the diseases detectable in 141 grey seals stranded on the coasts of England and Wales away from breeding colonies was carried out between mid-1989 and early 1997. The most common fatal conditions in pups less than three weeks of age were trauma (24 per cent of deaths) and dystocia (12 per cent); in pups more than three weeks of age thy were starvation (22 per cent) and pneumonia (22 per cent); in juveniles they were drowning in fishing gear (30 per cent) and starvation (19 per cent), and in adults a variety of respiratory diseases were the most common causes of death (45 per cent). Many other diseases, both fatal and non-fatal, were recorded.

Phenotypic characterisation of canine epileptoid cramping syndrome in the Border terrier.

OBJECTIVES: To characterise the phenotype of Border terriers suspected to be affected by canine epileptoid cramping syndrome and to identify possible contributing factors. METHODS: Owners of Border terriers with suspected canine epileptoid cramping syndrome were invited to complete an online questionnaire. The results of these responses were collated and analysed. RESULTS: Twenty-nine Border terriers were included. Most affected dogs had their first episode before 3 years of age (range: 0·2 to 7·0 years). The majority of episodes lasted between 2 and 30 minutes (range: 0·5 to 150 minutes). The most frequent observations during the episodes were difficulty in walking (27 of 29), mild tremor (21 of 29) and dystonia (22 of 29). Episodes most frequently affected all four limbs (25 of 29) and the head and neck (21 of 29). Borborygmi were reported during episodes in 11 of 29 dogs. Episodes of vomiting and diarrhoea occurred in 14 of 29, with 50% of these being immediately before or after episodes of canine epileptoid cramping syndrome (7 of 14). Most owners (26 of 29) had changed their dog's diet, with approximately 50% (14 of 26) reporting a subsequent reduction in the frequency of episodes. CLINICAL SIGNIFICANCE: This study demonstrates similarities in the phenotype of canine epileptoid cramping syndrome to paroxysmal dystonic choreoathetosis, a paroxysmal dyskinesia reported in humans. This disorder appears to be associated with gastrointestinal signs in some dogs and appears at least partially responsive to dietary adjustments.

Highly effective SNP-based association mapping and management of recessive defects in livestock.

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.

Different forms of rumen dystonia in dairy cows.

Four naturally occurring main forms of rumen dystonia of alimentary origin were observed in cattle: acidotic conditions; microflora inactivity; acidosis, and alkalosis. The following disturbances in the metabolism of carbohydrates, protein and energy were observed: 1. Acidotic conditions in rumen--ruminal pH, total and protein nitrogen decreased, whereas the total amount of VFA and the reduction activity of bacteria increased. 2. Inactivity of rumen microflora--significant changes of pH of rumen fluid were not observed, but the total number and activity of infusoria decreased. Fermentation of glucose, digestibility of cellulose, and reduction activity of bacteria decreased, whereas the amount of non-protein nitrogen increased. 3. Acidosis--ruminal pH, reduction activity of bacteria, and total number of VFA decreased. The percentage ratio between VFA changed--acetic acid concentration decreased, the concentration of valeric and caproic acids increased. The amount of total and non-protein nitrogen increased. 4. Alkalosis--ruminal pH increased, reduction activity of bacteria, fermentation of glucose, and concentration of VFA decreased. The amount of total and non-protein nitrogen increased. This investigation of different forms of rumen dystonia of alimentary origin is believed to be useful for the development of more effective treating methods and measures.

Electroencephalographic studies of chlorpromazine methiodide and somatostatin-induced barrel rotation in rats.

It has been reported that intraventricular injection of chlorpromazine methiodide (CPZMI), a quaternary ammonium derivative of chlorpromazine, in rats induces abnormal, twisting postures which may serve as an experimental model of the human movement disorder dystonia. We have shown elsewhere that the behavior induced by intraventricular CPMZI is identical to what has been called "barrel rotation," first observed to follow intraventricular injection of somatostatin (SRIF), which consists of twisting about the long axis, with repetitive lateral rolling. The suitability of barrel rotation, induced by CPZMI or SRIF, as an experimental model for dystonia depends on its physiologic basis. Human dystonia is clinically not a convulsive phenomenon. SRIF-induced barrel rotation has been reported to be associated with epileptiform activity recorded by the electroencephalogram (EEG). The purpose of this study was to investigate EEG activity during CPZMI- and SRIF-induced rotation. We found that CPZMI barrel rotation was not associated with epileptiform activity in cortex, amygdala, or hippocampus, and contrary to prior reports, neither was SRIF rotation. Both CPZMI and SRIF injected in high doses could induce epileptiform activity, but this was associated with clonic motor phenomena and not barrel rotation. We conclude that electroencephalographic criteria do not exclude either CPZMI- or SRIF-induced rotation as models for movement disorders, but their validity as such requires further study.