Use of levetiracetam for the successful treatment of suspected myoclonic seizures: five dogs (2016-2022).

OBJECTIVES: Myoclonic seizures are considered a type of generalised seizure characterised by brief, jerking movements of the body. The aim of this study is to describe cases of suspected canine myoclonic seizure of idiopathic aetiology and to discuss the successful use of the anticonvulsant levetiracetam as treatment in each of these cases. MATERIALS AND METHODS: Dogs with epileptic myoclonus suspected to be idiopathic in aetiology were considered for inclusion. Medical records were reviewed for physical and neurologic examination findings, clinicopathologic results, and diagnostic imaging results. All included dogs were treated with levetiracetam, and their response was reported. RESULTS: Five dogs were included, all of which had suspected myoclonic seizures either observed in-person or on video recording by a board-certified veterinary neurologist. The duration of myoclonic seizures preceding treatment ranged from one day to one year. One dog also experienced a generalised tonic-clonic seizure. All dogs were treated with levetiracetam. Two dogs experienced long-term myoclonic seizure freedom (duration seizure-free of at least 1 year), and two dogs experienced marked decreased myoclonic seizure frequency. One dog experienced immediate abatement of myoclonic seizures, although levetiracetam was only utilised for 1 month following onset of myoclonic seizures in this patient. CLINICAL SIGNIFICANCE: Myoclonic seizures can be idiopathic in aetiology. Levetiracetam can be used effectively to rapidly stop myoclonic seizures and to decrease the frequency of myoclonic seizures.

Absence Seizures as a Feature of Juvenile Myoclonic Epilepsy in Rhodesian Ridgeback Dogs.

Myoclonic epilepsy in Rhodesian Ridgeback (RR) dogs is characterized by myoclonic seizures occurring mainly during relaxation periods, a juvenile age of onset and generalized tonic-clonic seizures in one-third of patients. An 8-month-old female intact RR was presented for myoclonic seizures and staring episodes that both started at 10 weeks of age. Testing for the DIRAS1 variant indicated a homozygous mutant genotype. Unsedated wireless video-electroencephalography (EEG) identified frequent, bilaterally synchronous, generalized 4 Hz spike-and-wave complexes (SWC) during the staring episodes in addition to the characteristic myoclonic seizures with generalized 4-5 Hz SWC or 4-5 Hz slowing. Photic stimulation did not evoke a photoparoxysmal response. Repeat video-EEG 2 months after initiation of levetiracetam treatment disclosed a >95% decrease in frequency of myoclonic seizures, and absence seizures were no longer evident. Absence seizures represent another seizure type in juvenile myoclonic epilepsy (JME) in RR dogs, which reinforces its parallels to JME in humans.

Canine epilepsy as a translational model?

Dogs with spontaneous diseases can exhibit a striking similarity in etiology, clinical manifestation, and disease course when compared to human patients. Therefore, dogs are intensely discussed as a translational model of human disease. In particular, genetic studies in selected dog breeds serve as an excellent tool to identify epilepsy disease genes. In addition, canine epilepsy is discussed as a translational platform for drug testing. On one hand, epileptic dogs might serve as an interesting model by allowing the evaluation of drug efficacy and potency under clinical conditions with a focus on chronic seizures resistant to standard medication, preventive strategies, or status epilepticus. On the other hand, several limitations need to be considered including owner-based seizure monitoring, species differences in pharmacokinetics and drug interactions, as well as cost-intensiveness. The review gives an overview on the current state of knowledge regarding the etiology, clinical manifestation, pathology, and drug response of canine epilepsy, also pointing out the urgent need for further research on specific aspects. Moreover, the putative advantages, the disadvantages, and limitations of antiepileptic drug testing in canine epilepsy are critically discussed.

Canine idiopathic epilepsy: prevalence, risk factors and outcome associated with cluster seizures and status epilepticus.

OBJECTIVES: To evaluate the prevalence of cluster seizures and status epilepticus in dogs with idiopathic epilepsy and determine risk factors for cluster seizure frequency, severity and patient outcome. METHODS: Retrospective review of medical records of 407 dogs with idiopathic epilepsy was made. Follow-up questionnaires were evaluated in cases with cluster seizures. RESULTS: Mean age at diagnosis of idiopathic epilepsy was 4 years. Cluster seizures were documented in 169 (41%) dogs. German shepherds and boxers were significantly (P=0·04 and 0·01, respectively) more likely to suffer from cluster seizures compared to Labrador retrievers. There was no association between the occurrence of status epilepticus and cluster seizures and frequency and severity of cluster seizures and status epilepticus episodes with age or breed. Intact males were twice as likely (P=0·003) than neutered dogs to suffer from cluster seizures. Intact females had significantly (P=0·007) more frequent cluster seizures than neutered dogs. The median survival time for all dogs with cluster seizures was 95 months. Significantly (P=0·03) more dogs with frequent cluster seizures were euthanased because of the cluster seizures. CLINICAL SIGNIFICANCE: There was a high prevalence of cluster seizures in dogs with idiopathic epilepsy. Neutering status appears to influence cluster seizure occurrence with intact females more likely to experience more frequent episodes. Euthanasia is associated with frequency of cluster seizure episodes.

Epilepsia em cães: 66 casos (2005-2010) / Epilepsy in dogs: 66 cases (2005-2010)

O objetivo deste estudo foi identificar cães com epilepsia e obter informações a respeito da raça, do sexo, da idade, da classificação da epilepsia e da crise convulsiva, dos estágios e do período de ocorrência das crises convulsivas. Em 66,7% (44/66) dos cães a epilepsia foi primária, em 21,2% (14/66) sintomática e em 12,1% (8/66) provavelmente sintomática. Os cães sem raça definida (27%) foram os mais acometidos e a faixa etária predominou entre um e cinco anos de idade. A crise convulsiva generalizada tônico-clônica (66,7%) foi a mais observada, a procura pelo dono (72,7%) no período pré-ictal e o andar compulsivo (60,5%) no período pós-ictal foram os sinais mais encontrados e a ocorrência das crises convulsivas foi maior no período noturno (79,2%).

The objective of this study was to identify dogs with epilepsy and to obtain information about breed, sex, age, classification of the epilepsy and the seizures, as well as the stage and time of occurrence of the seizures. Epilepsy was primary in 66.7% (44/66) of dogs, symptomatic in 21.2% (14/66), and probably symptomatic in 12.1% (8/66). Crossbred dogs (27%) were the most affected and the predominant age group ranged from one to five years; the generalized tonic-clonic seizures (66.7%) was the most frequent presentation. The search for the owner (72.7%) during the preictal period and the compulsive walking (60.5%) in post-ictal period were the more frequent signs observed in the affected dogs, and the occurrence of seizures was higher at night (79.2%).

Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic Border Collies.

BACKGROUND: Variation in the ABCB1 gene is believed to play a role in drug resistance in epilepsy. HYPOTHESIS/OBJECTIVES: Variation in the ABCB1 gene encoding the permeability-glycoprotein could have an influence on phenobarbital (PB) resistance, which occurs with high frequency in idiopathic epileptic Border Collies (BCs). ANIMALS: Two hundred and thirty-six client-owned BCs from Switzerland and Germany including 25 with idiopathic epilepsy, of which 13 were resistant to PB treatment. METHODS: Prospective and retrospective case-control study. Data were collected retrospectively regarding disease status, antiepileptic drug (AED) therapy, and drug responsiveness. The frequency of a known mutation in the ABCB1 gene (4 base-pair deletion in the ABCB1 gene [c.296_299del]) was determined in all BCs. Additionally, the ABCB1 coding exons and flanking sequences were completely sequenced to search for additional variation in 41 BCs. Association analyses were performed in 2 case-control studies: idiopathic epileptic and control BCs and PB-responsive and resistant idiopathic epileptic BCs. RESULTS: One of 236 BCs (0.4%) was heterozygous for the mutation in the ABCB1 gene (c.296_299del). A total of 23 variations were identified in the ABCB1 gene: 4 in exons and 19 in introns. The G-allele of the c.-6-180T > G variation in intron 1 was significantly more frequent in epileptic BCs resistant to PB treatment than in epileptic BCs responsive to PB treatment (P(raw) = .0025). CONCLUSIONS AND CLINICAL IMPORTANCE: A variation in intron 1 of the ABCB1 gene is associated with drug responsiveness in BCs. This might indicate that regulatory mutations affecting the expression level of ABCB1 could exist, which may influence the reaction of a dog to AEDs.

Absence seizures with myoclonic features in a juvenile Chihuahua dog.

Long-term video-EEG was recorded for an eight-month-old Chihuahua dog with recurrent episodes of altered behaviour associated with head and nose twitching. Each episode lasted one to two seconds, multiple times per day before treatment. Ictal EEG showed generalised bilaterally synchronous 4 Hz spike-and-wave complexes during the "absence-like" event, along with rhythmically correlated head and nose twitching. We present video documentation of such attacks and discuss their similarities to human epilepsy with myoclonic absences.

Electroencephalographic evaluation of gold wire implants inserted in acupuncture points in dogs with epileptic seizures.

The purpose of this study was to evaluate both, clinically and with electroencephalographic (EEG) recordings, the effect of gold wire implants in acupuncture points in dogs with uncontrolled idiopathic epileptic seizures. Fifteen dogs with such diagnosis were enrolled in the study. A first EEG recording was performed in all dogs under anaesthesia with xylazine (1mg/kg) and propofol (6 mg/kg) before the treatment protocol, and a second EEG was performed 15 weeks later. Relative frequency power, intrahemispheric coherence available through EEG, number of seizures and seizure severity were compared before and after treatment using a Wilcoxon signed-rank test. There were no significant statistical differences before and after treatment in relative power or in intrahemispheric coherence in the EEG recording. However, there was a significant mean difference in seizure frequency and seizure severity between control and treatment periods. After treatment, nine of the 15 dogs (60%) had at least a 50% reduction in seizures frequency during the 15 weeks established as follow-up of this treatment.

Intrathecal morphine overdose in a dog.

CASE DESCRIPTION: A healthy 6-year-old 28.5-kg (62.7-lb) spayed female Boxer undergoing surgical repair of a ruptured cranial cruciate ligament was inadvertently administered an overdose of morphine (1.3 mg/kg [0.59 mg/lb]) via subarachnoid injection. CLINICAL FINDINGS: 50 minutes after administration of the overdose, mild multifocal myoclonic contractions became apparent at the level of the tail; the contractions migrated cranially and progressively increased in intensity and frequency during completion of the surgery. TREATMENT AND OUTCOME: The myoclonic contractions were refractory to treatment with midazolam, naloxone, phenobarbital, and pentobarbital; only atracurium (0.1 mg/kg [0.045 mg/lb], IV) was effective in controlling the movements. The dog developed hypertension, dysphoria, hyperthermia, and hypercapnia. The dog remained anesthetized and ventilated mechanically; treatments included continuous rate IV infusions of propofol (1 mg/kg/h [0.45 mg/lb/h]), diazepam (0.25 mg/kg/h [0.11 mg/lb/h]), atracurium (0.1 to 0.3 mg/kg/h [0.045 to 0.14 mg/lb/h]), and naloxone (0.02 mg/kg/h [0.009 mg/lb/h]). Twenty-two hours after the overdose, the myoclonus was no longer present, and the dog was able to ventilate without mechanical assistance. The dog remained sedated until 60 hours after the overdose, at which time its mentation improved, including recognition of caregivers and response to voice commands. No neurologic abnormalities were detectable at discharge (approx 68 hours after the overdose) or at a recheck evaluation 1 week later. CLINICAL RELEVANCE: Although intrathecal administration of an overdose of morphine can be associated with major and potentially fatal complications, it is possible that affected dogs can completely recover with immediate treatment and extensive supportive care.

Inheritance of occipital bone hypoplasia (Chiari type I malformation) in Cavalier King Charles Spaniels.

Occipital bone hypoplasia with foramen magnum obstruction and secondary syringomyelia (SM) is a common condition in the Cavalier King Charles Spaniel (CKCS) that is similar to human Chiari type I malformation. A worldwide family tree of more than 5,500 CKCSs spanning a maximum of 24 generations was established by obtaining pedigree information from 120 dogs diagnosed with SM secondary to occipital bone hypoplasia. The ongoing study showed 6 of 8 great grandparents of all affected dogs could be traced back to 2 female ancestors so that all 8 were descended from one or the other or both. The disease appears to be more severe and have an earlier onset with increased inbreeding, especially when breeding from affected dogs. The family tree of idiopathic epilepsy (IE) appears to be a different subset of the CKCS population, although some overlap was observed. Idiopathic epilepsy is more frequent in lines originating from whole-color dogs. Selection for coat color is believed to have influenced the development of both occipital hypoplasia with secondary SM and IE. In addition, breeding guidelines to reduce the incidence of mitral valve disease have placed further pressures on the gene pool.

Animal models of myoclonus: an overview.

Attempts to characterize the mechanism(s) associated with myoclonus have led to the development of several naturally occurring and pharmacologically based animal models of myoclonus. Congenital disorders in animals that result in myoclonic seizures have been found in subpopulations of baboons that exhibit photoresponsive myoclonus and in herds of Hereford cattle that possess a fatal, autosomal-inherited imbalance in spinal glycine neurotransmission. Pharmacologically based models of myoclonus use a variety of approaches to product myoclonic seizures in test animals.

Lafora disease in the cow?

Lafora disease in man is an autosomal recessive defect which affects carbohydrate metabolism and results in a progressive, ultimately fatal neurological condition. It is characterized histologically by intraneuronal cytoplasmic polyglucosan inclusions (Lafora bodies). Similar inclusions have been seen in association with neurological signs in other species, including the dog, the cockatiel and the cow. Polyglucosan bodies, however, are not always considered to be disease specific, and have also been reported as an age-related change in cats, dogs and man. The only recorded case in cattle to date has been a single animal in the USA. The present report records a case study of two animals with Lafora inclusion bodies, together with a survey of the occurrence of non-specific polyglucosan bodies in aged cattle. It is concluded that the inclusions in the two putative cases of Lafora disease were not non-specific age-related changes, and that these cases represent the first report of the disease in cattle in the UK.

[Lafora disease (progressive myoclonic epilepsy) in the Bassett hound--possibility of early diagnosis using muscle biopsy?]. / Lafora-Erkrankung (progressive Myoklonusepilepsie) beim Bassethund--Möglichkeit der Früherkennung mittels Muskelbiopsie? Vergleich der Einschlusskörperchen in Hirn und Muskel, dargestellt an zwei ausgewerteten Fällen.

A progressive, hereditary disease has been observed in Basset Hounds, which appears clinically and neuromorphologically as myoclonus epilepsy (ME) and is similar to Lafora-Glueck disease in humans. The characteristic intracellular accumulations are typical myoclonus inclusion bodies. Four forms of inclusion bodies (IB) can be distinguished: a) very small, homogeneous, PAS-positive IBs, b) IBs consisting of an accumulation of PAS-positive particles, c) IBs with a concentric internal structure and a smooth or radial outer zone, and d) IBs with a homogeneous center, concentric layering, light intermediate zone, and a smooth outer zone. The occurrence of IBs is restricted largely to nerve cells. Here they are located mainly in pericarya, to a lesser extent in dendrites, and rarely in the neurites of the peripheral nervous system. IBs are also found in samples of skeletal muscle where they lie between myofibrils or beneath the sarcolemma. They are slightly basophilic in HE-staining and markedly PAS-positive. In transmission electron micrographs IBs prove to consist of chain-like filamentous material of varying density with focal concentrations. They are similar to IBs of the brain. Both muscular and neuronal IBs lack surrounding membranes. Diagnosis of Lafora disease in dogs by examination of muscle biopsies is discussed.

Systemic glycoproteinosis resembling Lafora's disease in a cow.

A 6-year-old, Hereford/Angus crossbred cow which died acutely was submitted for necropsy and diagnostic evaluation. A toxicity was suspected by the owner who had noticed incoordination of one week's duration. The animal was last observed 24 hours prior to death. Toxicology screens for alkaloids, heavy metals, pesticides and nitrates were negative. The significant histologic abnormalities were confined to the thalamic nuclei, periventricular neurons and the liver. Neurons and hepatocytes contained 1 to 2 intracytoplasmic inclusions which stained faintly eosinophilic to slightly basophilic with H&E. The inclusions frequently had dense central cores and a fibrillar to homogeneous periphery. Based on a battery of histochemical stains for carbohydrates, and other mucosubstances and the morphology and location of the inclusions, a diagnosis of systemic glycoproteinosis consistent with Lafora's disease was made. This case represents the first report of lesions consistent with Lafora's disease in the bovine species.

Lafora-like bodies in a cat. Case report suggestive of glycogen metabolism disturbances.

Lafora-like bodies in an 8-year-old cat were studied light and electron microscopically and histochemically. In addition ot Lafora-like bodies composed of branching filaments, glycogen granules and electron-dense materaisl, abnormal accumulations of glycogen granules attracted attention. The most remarkable features were the developmental processes of the branching filaments originating directly from glycogen granules. Lafora-like bodies in the present study showed ultrastructural, histochemical, and enzymatic similarities to those described in the previous reports in Lafora's disease, glycogenosm is considered to be probably related to the productive mechanism of Lafora-like bodies.