Myoclonus in older Cavalier King Charles Spaniels.

BACKGROUND: Myoclonus is observed in older Cavalier King Charles Spaniels (CKCS) but a full description is lacking. OBJECTIVES: The 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. ANIMALS: Thirty-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. METHODS: This is a retrospective case series, describing the presence of myoclonus in CKCS. RESULTS: Clinical 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 IMPORTANCE: Myoclonus occurs in middle-aged to older CKCS and seems to be another epiphenomena of this breed. A link to epilepsy might be present.

Myoclonus and hypersensitivity of the hind limbs and tail with urinary retention following neuraxial administration of morphine in a cat.

An adult female domestic shorthair cat developed myoclonus, muscle rigidity, and hypersensitivity of the hind limbs and tail with urinary retention following neuraxial administration of morphine. Myoclonic contractions resolved following treatment with midazolam and a urinary catheter was placed until normal micturition returned. The cat was clinically normal 36 hours after neuraxial morphine injection. The cat underwent a second surgery without neuraxial morphine and control of postoperative pain required more intervention. Key clinical message: Neuraxial morphine may cause myoclonus and urinary retention. The response to pharmacological treatment of myoclonus is varied, but a benzodiazepine drug may be effective.

Myoclonie et hypersensibilité des membres postérieurs et de la queue avec rétention urinaire après administration neuraxiale de morphine chez un chat. Une chatte domestique à poils courts adulte a développé une myoclonie, une rigidité musculaire et une hypersensibilité des membres postérieurs et de la queue avec rétention urinaire après l'administration neuraxiale de morphine. Les contractions myocloniques se sont résolues après un traitement avec du midazolam et un cathéter urinaire a été placé jusqu'à ce que les mictions normales reviennent. Le chat était cliniquement normal 36 heures après l'injection neuraxiale de morphine. Le chat a subi une deuxième intervention chirurgicale sans morphine neuraxiale et le contrôle de la douleur postopératoire a nécessité plus d'intervention.Message clinique clé:La morphine neuraxiale peut provoquer une myoclonie et une rétention urinaire. La réponse au traitement pharmacologique de la myoclonie est variée, mais un médicament à base de benzodiazépine peut être efficace.(Traduit par Dr Serge Messier).

Descriptive assessment of adverse events associated with midazolam-etomidate versus saline-etomidate in healthy hydromorphone premedicated dogs.

OBJECTIVES: To determine the frequency, severity and duration of adverse events including myoclonus, pain on injection, hypersalivation, regurgitation and apnoea after administration of midazolam or saline followed by etomidate in hydromorphone premedicated dogs. MATERIALS AND METHODS: Dogs undergoing elective dental prophylaxis or soft tissue surgeries were enrolled in this randomised trial. Dogs were premedicated with hydromorphone 0.1 mg/kg IV. Sixty seconds later, midazolam 0.3 mg/kg or saline at an equivalent volume was administered IV. Sixty seconds after that, etomidate 1.5 mg/kg IV was administered over 60 seconds. Additional doses of 0.5 mg/kg etomidate were administered until endotracheal intubation was successful. Observers were blinded to the treatment. Frequency, duration and a severity score of 0 to 3 were recorded for myoclonus, pain on injection, hypersalivation and regurgitation. Duration of apnoea and frequency of any additional complications was recorded. RESULTS: Forty variable breed healthy dogs were enrolled in the study. Myoclonus, pain on injection, regurgitation, hypersalivation, gagging, tachypnoea and pigmenturia occurred, respectively, in 10%, 40%, 0%, 15%, 35%, 25% and 5% of dogs in the saline group and 0%, 65%, 0%, 10%, 45%, 15% and 5% of dogs in the midazolam group. Apnoea occurred for 115 seconds (range 0 to 660 seconds) and 160 seconds (range 0 to 600 seconds) in the saline and midazolam groups, respectively. Two dogs developed pigmenturia. The trial was stopped early due to the occurrence of pigmenturia. CLINICAL SIGNIFICANCE: Due to early stopping of the trial, the predefined sample size was not reached. Further investigation is needed to determine if midazolam reduced the incidence of adverse events or improved the induction quality when combined with hydromorphone and etomidate.

Características epizootiológicas da infecção natural pelo vírus da cinomose canina em Belo Horizonte / Natural canine distemper virus infection epizootiology characteristics in Belo Horizonte

O perfil epizootiológico da cinomose canina em Belo Horizonte é desatualizado e não alberga algumas características relevantes. Uma análise recente da distribuição do vírus em relação às características do hospedeiro e do meio ambiente associada aos principais sinais clínicos e achados laboratoriais são importantes para se adotarem medidas estratégicas para o controle da enfermidade. Objetivou-se, assim, determinar as características epizootiológicas da infecção pelo vírus da cinomose canina associada à variedade de sinais clínico-neurológicos e laboratoriais em Belo Horizonte, auxiliando no diagnóstico precoce da infecção e na diminuição das taxas de morbidade e mortalidade da doença. A avaliação do perfil epizootiológico de 90 cães revelou que a doença é mais frequente em animais adultos (um a seis anos de idade) e que não receberam vacinas conforme recomendado pelos protocolos. Os sinais clínicos extraneurais e neurais foram variados, com predomínio para manifestações gastrentérica e respiratória, mioclonia e déficit motor, respectivamente. O exame do fluido cérebro-espinhal demonstrou predomínio de proteinorraquia associada à pleocitose linfocítica. O teste de imunocromatografia para pesquisa de antígeno com amostras do fluido cerebroespinhal foi eficaz para identificar a doença em pacientes com sinais neurológicos, diferentemente das amostras do swab conjuntival, que não devem ser utilizadas.(AU)

The epizootiology profile of canine distemper in Belo Horizonte is outdated and does not harbor some important characteristics. A recent analysis of the virus distribution in relation to host and environmental characteristics associated with the main clinical signs and laboratory findings are important for adopting strategic measures to control the disease. The aim of this study was to determine the epizootiology characteristics of canine distemper virus infection associated with a variety of clinical and neurologic signs and laboratory findings in Belo Horizonte, helping to detect early infection and reduce morbidity and mortality rates. The evaluation of the epizootiology profile of 90 dogs revealed that the disease is more frequent in adult animals (1-6 years of age) and did not receive vaccines as recommended by the protocols. Extra neural and neural clinical signs were varied, with predominance for gastrointestinal and respiratory manifestations and myoclonus and motor deficit, respectively. Examination of the cerebrospinal fluid of 16 dogs showed a predominance of increase protein associated with lymphocytic pleocytosis. The immunochromatography test for antigen screening with samples of cerebrospinal fluid in 76 animals with neurological signs was effective in identifying the disease, unlike conjunctival swab samples, which should not be used.(AU)

Myoclonus and hypercalcemia in a dog with poorly differentiated lymphoproliferative neoplasia.

A 1-year, 8-month-old Rhodesian Ridgeback was presented with obtundation, ambulatory tetraparesis, and myoclonus. Initial clinical findings included ionized hypercalcemia with an apparent marked increase in parathyroid hormone, thrombocytopenia, and nonregenerative anemia. Low numbers of circulating atypical cells were noted on blood film evaluation. Brain magnetic resonance imaging identified an extra-axial contrast enhancing subtentorial lesion, and cerebrospinal fluid (CSF) analysis documented a marked atypical lymphocytic pleocytosis. Flow cytometry performed on the CSF demonstrated expression of only CD45, CD90, and MHC class II, with Pax5 positivity on subsequent immunohistochemistry. The final diagnosis was of B-cell lymphoblastic lymphoma or acute leukemia, given the distribution of disease and the presence of significant bone marrow infiltration alongside an aggressive clinical course. The unusual immunophenotype of the neoplastic cells and hypercalcemia presented antemortem diagnostic challenges, highlighting the need for a multidisciplinary approach and caution in the interpretation of clinical abnormalities in cases with multiple comorbidities.

Abnormal locomotor muscle recruitment activity is present in horses with shivering and Purkinje cell distal axonopathy.

BACKGROUND: Cerebellar Purkinje cell axonal degeneration has been identified in horses with shivering but its relationship with abnormal hindlimb movement has not been elucidated. OBJECTIVES: To characterise surface electromyographic (sEMG) hindlimb muscle activity in horses with shivering, correlate with clinical scores and examine horses for Purkinje axonal degeneration. STUDY DESIGN: Descriptive controlled clinical study. METHODS: The hindlimb of seven shivering and six control draught horses were clinically scored. Biceps femoris (BF), vastus lateralis (VL), tensor fasciae latae and extensor digitorum longus were recorded via sEMG during forward/backward walking and trotting. Integrated (iEMG) and peak EMG activity were compared between groups and correlated with clinical locomotor exam scores. Sections of the deep cerebellar nuclei (DCN) of six of the seven shivering horses were examined with calbindin immunohistochemistry. RESULTS: In control horses, backward walking resembled forward walking (right hindlimb peak EMG: backward: 47.5 ± 21.9%, forward: 36.9 ± 15.7%) but displayed significantly higher amplitudes during trotting (76.1 ± 3.4%). However, in shivering horses, backward walking was significantly different from forward (backward: 88.5 ± 21.5%, forward: 49.2 ± 8.9%), and resembled activity during trotting (81.4 ± 4.8%). Specific to backward walking, mean sEMG amplitude fell outside two standard deviations of mean control sEMG for ≥25% of the stride in the BF for all seven and the VL for six of the seven shivering horses. Locomotor exam scores were correlated with peak EMG (r = 0.87) and iEMG (r = 0.87). Calbindin-positive spheroids were present in Purkinje axons in DCN of all shivering horses examined. MAIN LIMITATIONS: The neuropathological examination focused specifically on the DCN and, therefore, we cannot fully exclude additional lesions that may have influenced abnormal sEMG findings in shivering horses. CONCLUSION: Shivering is characterised by abnormally elevated muscle recruitment particularly in BF and VL muscles during backward walking and associated with selective Purkinje cell distal axonal degeneration.

Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia.

Myoclonus is a sudden brief, involuntary muscle jerk. Of all the movement disorders, myoclonus is the most difficult to encapsulate into any simple framework. On the one hand, a classification system is required that is clinically useful to aid in guiding diagnosis and treatment. On the other hand, there is need for a system that organizes current knowledge regarding biological mechanisms to guide scientific research. These 2 needs are distinct, making it challenging to develop a robust classification system suitable for all purposes. We attempt to classify myoclonus as "epileptic" and "nonepileptic" based on its association with epileptic seizures. Myotonia in people may be divided into 2 clinically and molecularly defined forms: (1) nondystrophic myotonias and (2) myotonic dystrophies. The former are a group of skeletal muscle channelopathies characterized by delayed skeletal muscle relaxation. Many distinct clinical phenotypes are recognized in people, the majority relating to mutations in skeletal muscle voltage-gated chloride (CLCN1) and sodium channel (SCN4A) genes. In dogs, myotonia is associated with mutations in CLCN1. The myotonic dystrophies are considered a multisystem clinical syndrome in people encompassing 2 clinically and molecularly defined forms designated myotonic dystrophy types 1 and 2. No mutation has been linked to veterinary muscular dystrophies. We detail veterinary examples of myotonia and attempt classification according to guidelines used in humans. This more precise categorization of myoclonus and myotonia aims to promote the search for molecular markers contributing to the phenotypic spectrum of disease. Our work aimed to assist recognition for these 2 enigmatic conditions.

The Equine Movement Disorder "Shivers" Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration.

"Shivers" is a progressive equine movement disorder of unknown etiology. Clinically, horses with shivers show difficulty walking backward, assume hyperflexed limb postures, and have hind limb tremors during backward movement that resembles shivering. At least initially, forward movements are normal. Given that neither the neurophysiologic nor the pathologic mechanisms of the disease is known, nor has a neuroanatomic locus been identified, we undertook a detailed neuroanatomic and neuropathologic analysis of the complete sensorimotor system in horses with shivers and clinically normal control horses. No abnormalities were identified in the examined hind limb and forelimb skeletal muscles nor the associated peripheral nerves. Eosinophilic segmented axonal spheroids were a common lesion. Calretinin-positive axonal spheroids were present in many regions of the central nervous system, particularly the nucleus cuneatus lateralis; however, their numbers did not differ significantly from those of control horses. When compared to controls, calretinin-negative, calbindin-positive, and glutamic acid decarboxylase-positive spheroids were increased 80-fold in Purkinje cell axons within the deep cerebellar nuclei of horses with shivers. Unusual lamellar or membranous structures resembling marked myelin decompaction were present between myelin sheaths of presumed Purkinje cell axons in the deep cerebellar nuclei of shivers but not control horses. The immunohistochemical and ultrastructural characteristics of the lesions combined with their functional neuroanatomic distribution indicate, for the first time, that shivers is characterized by end-terminal neuroaxonal degeneration in the deep cerebellar nuclei, which results in context-specific hypermetria and myoclonus.

The incidence of spontaneous movements (myoclonus) in dogs undergoing total intravenous anaesthesia with propofol.

OBJECTIVE: To evaluate the incidence of myoclonus (involuntary movements during anaesthesia, unrelated to inadequate hypnosis or analgesia, and of sufficient severity to require treatment) in dogs anaesthetized with a TIVA of propofol with or without the use of fentanyl. STUDY DESIGN: Retrospective clinical study. ANIMALS: Dogs, undergoing general anaesthesia for clinical procedures between January 2012 and January 2013 and subject to TIVA with propofol. METHODS: A retrospective analysis reviewed the medical and anaesthetic records. Animals with existing or potential neurological or neuromuscular pathology in the anamnesis or upon clinical examination and cases with incomplete clinical records were excluded. Myoclonus was considered as involuntary muscle contractions which did not cease following a bolus administration of propofol or fentanyl and, due to their intensity and duration, made continuation of the procedure impracticable without other drug administration. Tremors, paddling or muscle spasms, explicable as insufficient hypnosis or analgesia, and transient excitatory phenomena only present during the awakening phase, were not considered as myoclonus. RESULTS: Out of a total of 492 dogs undergoing anaesthesia, six mixed breed dogs (1.2%), one male and five females, American Society of Anaesthesiologists (ASA) physical status I, median (range) weight 20.5 (7-37) kg and age 1.5 (1-5) years had myoclonus according to the aforementioned definition. In all subjects, myoclonus appeared within 20 minutes after induction of anaesthesia, and mainly involved the limb muscles. All subjects appeared to be in an adequate plane of anaesthesia before and during myoclonus. CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that 1.2% of dogs, undergoing TIVA with propofol with or without fentanyl administration, developed myoclonus, which required to be, and were treated successfully pharmacologically. The cause of this phenomenon is yet to be determined.

The use of botulinum toxin for the treatment of generalized myoclonus in a dog.

A 13 mo old spayed female mixed-breed dog presented in a nonambulatory state that was attributed to severe myoclonus secondary to distemper. The authors hypothesized that mitigating the myoclonus would help the dog become ambulatory and expedite convalescence. They injected the severely affected muscles with botulinum toxin on two separate occasions over a period of 18 days. Those injections reduced the myoclonus, helping the dog become ambulatory and attaining a comfortable, functional state.

Brain regions and genes affecting myoclonus in animals.

Myoclonus is defined as large-amplitude rhythmic movements. Brain regions underlying myoclonic jerks include brainstem, cerebellum, and cortex. Gamma-aminobutyric acid (GABA) appears to be the main neurotransmitter involved in myoclonus, possibly interacting with biogenic amines, opiates, acetylcholine, and glycine. Myoclonic jumping is a specific subtype seen in rodents, comprising rearing and hopping continuously against a wall. Myoclonic jumping can be seen in normal mouse strains, possibly as a result of simply being put inside a cage. Like other types, it is also triggered by changes in GABA, 5HT, and dopamine neurotransmission. Implicated brain regions include hippocampus and dorsal striatum, possibly with respect to D(1) dopamine, NMDA, and δ opioid receptors. There is reason to suspect that myoclonic jumping is underreported due to insufficient observations into mouse cages.

Severe pruritus and myoclonus following intrathecal morphine administration in a dog.

During epidural needle placement in a 32-kg dog the subarachnoid space was punctured and half the intended dose of lidocaine, bupivacaine, and morphine was injected. After recovery from anesthesia the dog showed signs of severe pruritus of the tail base and limbs and myoclonus of the tail and hind limbs. Methadone, acepromazine, ketamine, buprenorphine, and butorphanol were administered to control myoclonus and pruritus, but were unsuccessful. Diazepam was used to control myoclonus until the effects of morphine abated.During epidural needle placement in a 32-kg dog the subarachnoid space was punctured and half the intended dose of lidocaine, bupivacaine, and morphine was injected. After recovery from anesthesia the dog showed signs of severe pruritus of the tail base and limbs and myoclonus of the tail and hind limbs. Methadone, acepromazine, ketamine, buprenorphine, and butorphanol were administered to control myoclonus and pruritus, but were unsuccessful. Diazepam was used to control myoclonus until the effects of morphine abated.

RésuméPrurit aigu et myoclonie après l'administration intrathécale de morphine chez un chien. Durant le placement d'une aiguille épidurale chez un chien de 32 kg, l'espace sous-arachnoïdien a été ponctionné et la moitié de la dose prévue de lidocaïne, de bupivacaïne et de morphine a été injectée. Après le réveil de l'anesthésie, le chien a manifesté des signes de prurit grave à la base de la queue et sur les membres et une myoclonie de la queue et des membres postérieurs. La méthadone, l'acépromazine, la kétamine, la buprénorphine et le butorphanol ont été administrés pour contrôler la myoclonie et le prurit, mais sans succès. Le diazépam a été utilisé pour contrôler la myoclonie jusqu'à ce que les effets de la morphine se résorbent.(Traduit par Isabelle Vallières).

Neurological diseases of ruminant livestock in Australia. V: congenital neurogenetic disorders of cattle.

As part of a series on neurological disorders in ruminant livestock in Australia, this review focuses on the congenital neurogenic disorders of cattle. The genetic pressures that contribute to the emergence of congenital neurogenic disorders, as well as the methods of diagnosis, are discussed. Disorders reviewed are ordered by breed and include arthrogryposis multiplex, fawn calf syndrome, inherited congenital myoclonus and maple syrup urine disease.

[Case report: congenital myoclonus in a German Holstein calf]. / Fallbericht. Kongenitale Myoklonie bei einem Kalb der Rasse Deutsche Holsteins.

A female German Holstein calf was not able to stand up after birth. Resting the animal was lying in normal position and could lift its head. Sensory stimuli like auditory or tactile impulses induced myoclonic jerking of the whole body. Afterwards it calmed down quickly. The signs observed correspond to the clinical findings of congenital myoclonus in poll Hereford calves. The pathological examination revealed no indications for changes in organs. The inbreeding coefficient of the calf was 1.56 %. The present type of congenital myoclonus in the calf examined is likely to be genetically determined, even if the point mutation in exon 2 of the glycin receptor alpha 1 gene was not confirmed.

Myoclonus and urinary retention following subarachnoid morphine injection in a dog.

A 5-year-old German Shepherd dog which presented for total hip replacement developed myoclonus and urinary retention after the subarachnoid injection of preservative-free morphine. Myoclonus was resistant to treatment, except pentobarbital anesthesia. Urinary retention was treated with bethanechol and subsided within a few days. Involuntary muscular activity can result from the epidural, subarachnoid or systemic injection of various opioid drugs, or as a result of the toxic or irritant effect of preservatives or autologous blood. The latter were not causative factors in this case. Opioid agonist inhibition of central inhibitory neurotransmitter action may have explained the myoclonus. Postoperative urinary retention was attributed to the spinal action of morphine inhibiting efferent parasympathetic nervous activity.

Genotyping cattle for inherited congenital myoclonus and maple syrup urine disease.

OBJECTIVE: To develop a routine procedure for establishing the inherited congenital myoclonus (ICM) genotype of cattle and to obtain an estimate of the prevalence of heterozygotes for ICM and maple syrup urine disease (MSUD) in Australian Poll Herefords. DESIGN: A mismatch amplification procedure was developed to genotype for ICM. The ICM and MSUD genotypes of subjects from a 'neuraxial oedema' experimental breeding herd were investigated. Tail hair roots were used as a source of target DNA to determine the ICM and MSUD genotypes of 455 Poll Hereford bulls. RESULTS: An Acc I mismatch procedure was found to be suitable to genotype cattle for the ICM alleles using tail hair roots as the source of DNA. Based on the prevalence of heterozygotes among saleyard and sale bulls in the early 1990s, and contemporary slaughter bulls, the frequencies of the alleles responsible for ICM and MSUD were estimated to be between 0.01 and 0.02. CONCLUSION: This survey demonstrates that the mutations responsible for ICM and MSUD are present in the Australian Poll Hereford population. PCR tests could be used to advantage in differential diagnosis of neurological disease in newly born calves and in selection of Poll Hereford seed stock.