Characteristics and clinical course of myoclonus in Cavalier King Charles Spaniels

Abstract

Background

Myoclonus has been described in aging Cavalier King Charles Spaniels (CKCS), but the natural course of the disease and response to treatment have not been described.

Objectives

Report the clinical features and course of myoclonus in CKCS.

Animals

Twenty‐seven caregivers provided questionnaire responses at a median of 24 months after the onset of myoclonus in their CKCS. Fifteen caregivers completed a second follow‐up questionnaire at a median of 17 months after submission of the first questionnaire.

Methods

The caregivers of affected CKCS were invited to provide video footage for review. Owners of CKCS with videos demonstrating myoclonus then completed the online questionnaire for further evaluation. A second shortened questionnaire was sent to participants at least 6 months after completion of the first.

Results

Most CKCS displayed spontaneous myoclonus affecting predominantly the head (25/27). Overall, the majority had episodes that increased in frequency (20/27) and severity (17/27). Eighteen dogs had developed changes in behavior since the onset of myoclonus. These dogs were typically older and had experienced myoclonic episodes for longer than dogs without behavioral changes. Generalized epileptic seizures were reported in 4/27 dogs. Ten dogs received medical treatment. Eight were prescribed levetiracetam; all had an initial decrease in episode frequency, but a subsequent increase in both frequency and severity of episodes was common.

Conclusions and Clinical Importance

Myoclonus in CKCS tends to progress in frequency and severity regardless of treatment. Progressive behavioral changes suggestive of cognitive decline are common. These findings support the possibility of an underlying neurodegenerative process.

Abbreviations

CKCS

Cavalier King Charles Spaniels

FARS

feline audiogenic reflex seizures

GTCS

generalized tonic‐clonic seizures

LD

Lafora disease

LEV

levetiracetam

1. INTRODUCTION

Myoclonus is an involuntary, shock‐like movement of a muscle or group of muscles, occurring as a result of sudden increased contraction (positive myoclonus) or cessation of contraction (negative myoclonus). ¹ The sudden and brief nature of myoclonic movements, typically resulting in movement of the affected body part, helps to distinguish it from other involuntary movements such as tremor or dyskinesia. Numerous methods have been used to classify myoclonus in humans according to body distribution (focal, multifocal, segmental or generalized), etiology (physiologic, essential, epileptic or symptomatic), or presumed neural generator based on electrophysiological testing (cortical, subcortical, segmental or peripheral). ² Myoclonus also may be described as spontaneous, action‐related or reflex depending on the presence and nature of provoking factors.

Myoclonus associated with epileptic seizures, or progressive myoclonic epilepsies (PMEs), occur in veterinary medicine and include neuronal glycoproteinosis (Lafora disease [LD]), ³ , ⁴ neuronal ceroid lipofuscinosis, ⁴ juvenile myoclonic epilepsy of Rhodesian Ridgeback dogs, ⁴ , ⁵ and audiogenic reflex seizures in cats. ⁶ In addition, myoclonus may be observed in aging dogs alongside epileptic seizures of unknown origin. ⁷ Non‐epileptic forms of myoclonus occur in dogs with distemper, ⁸ often a constant repetitive myoclonus affecting the limb and facial muscles, and in hereditary hyperekplexia reported in Irish Wolfhounds, ⁹ Spanish Greyhounds, ¹⁰ and Miniature Australian Shepherds. ¹¹ Myoclonus also may be toxin or drug‐induced, ² as has been reported secondary to gabapentin toxicity. ¹²

A recent retrospective study described myoclonus in aged CKCS, in which the abnormal episodes consisted predominantly of rapid eye blinking and head nodding with variable extension to the thoracic limbs. ¹³ An association with epilepsy was speculated, because 9/39 dogs also suffered ≥1 generalized tonic‐clonic seizures (GTCS).

The aim of our questionnaire‐based study was to collect information regarding myoclonus in CKCS, to further assess the phenotypic features and natural clinical course, as well as explore a potential link to generalized epileptic seizures.

2. MATERIALS AND METHODS

2.1. Case recruitment

Cases were recruited via veterinary media (Veterinary Record, The Veterinary Times) and the internet (CKCS forums) requesting veterinary practitioners, caregivers and breeders to contact us regarding suspected cases of myoclonus in CKCS. Caregivers of affected dogs were asked to provide video footage of the abnormal episodes, which subsequently was reviewed by the authors. If video footage confirmed the presence of myoclonus, the caregivers were invited to complete an online questionnaire. Cases were excluded if video footage was not available. Examples of submitted video footage are found in Video S1.

2.2. Questionnaire design

The questionnaire was divided into 6 sections including: (1) general information regarding signalment of the affected dog; (2) general health and underlying conditions; (3) overview of the myoclonus; (4) management strategies directed at the myoclonus; (5) overview of the generalized epileptic seizures; and, (6) management strategies directed at the generalized epileptic seizures. Each section contained open‐ended and closed questions. Sections 5 and 6 only were completed by owners that answered “Yes” to the question of whether their dog suffered generalized epileptic seizures (“Does your dog also have seizures—involving loss of consciousness, paddling movements of the limbs, excessive drooling, urination or defecation?”). Questions were aimed at acquiring detailed phenotypic information regarding the episodes including age of onset, duration, frequency, nature of the abnormal movements, regions of the body affected and any alterations in the episodes over time. Cases were excluded if major discrepancies were found between the video footage and the caregiver's description in the questionnaire. The complete questionnaire is given in the Supporting Information.

2.3. Second follow‐up

An additional follow‐up e‐mail was sent to all participants at the end of the study period, a minimum of 6 months after completion of the first questionnaire (range, 6‐19 months). This message included 5 questions regarding: (1) any change to the frequency of myoclonus; (2) any change to the severity of myoclonus; (3) whether any medical treatment had been attempted; (4) the presence of GTCS; and, (5) any changes to the dog's character or behavior.

3. RESULTS

3.1. Cases

Twenty‐eight caregivers responded, but 1 was unable to provide video footage of the episodes and was excluded from the study. All 27 remaining dogs were considered to display myoclonus based on review of video footage and subsequent questionnaire responses. There were 19 female dogs (2 intact, 17 neutered) and 8 male dogs (1 intact, 7 neutered). The median age of onset was 9 years (range, 5.5‐12.1 years; mean, 8.7 years). The median initial follow‐up period (time from age of onset to first questionnaire submission) was 24 months (range, 2‐73 months; mean, 27 months).

3.2. Questionnaire responses

All dogs experienced multiple episodes of myoclonus per day. A word cloud summarizing the freehand description of the episodes by the caregivers is depicted in Figure 1. In most dogs, the frequency of the episodes was reported to increase (18/27) or remain unchanged (6/10) since onset, although in 3 dogs the frequency decreased. The severity of the episodes often was reported to increase (15/27) or remain unchanged (11/26), although in 1 dog the severity decreased.

FIGURE 1.

A word cloud summarizing the terms most commonly used by caregivers to describe the myoclonic episodes demonstrated by their Cavalier King Charles Spaniels.

Myoclonic episodes usually involved the head (25/27), whereas forelimbs (13/27), facial features (12/27), hindlimbs (8/27), back and abdomen (7/27) and neck (7/27) also were variably affected.

The episodes most often occurred spontaneously or at rest (25/27). Only 3 respondents identified possible triggers of the episodes including stress (2/3), touch (2/3), excitement (1/3) and sudden movement (1/3). Eight respondents believed the episodes had negatively affected the quality of life of the dog.

Diagnostic investigations consisted of blood tests (8), magnetic resonance imaging (MRI) of the brain (7), and cerebrospinal fluid analysis (3). Reported findings and comorbidities included mitral valve disease (12), Chiari‐like malformation (7), syringomyelia (6), keratoconjunctivitis sicca (5), and otitis media with effusion (2). Thirteen dogs were receiving medication for comorbidities, most commonly gabapentin or pregabalin for Chiari‐like malformation and syringomyelia in 6 dogs, pimobendan for mitral valve disease in 3 dogs, and cyclosporine for keratoconjunctivitis sicca in 3 dogs.

Medical management of the myoclonic episodes was attempted in 8 dogs. Levetiracetam (LEV) was prescribed for 6 dogs. In 4 of these dogs, the episodes completely stopped after initiation of treatment, whereas in 2 dogs there was partial improvement. Regardless, 5/6 dogs were reported to have a later progressive increase in the frequency and severity of myoclonic episodes. The perceived duration of effect of LEV generally was not stated. Two dogs received prednisolone, 1 in addition to gabapentin; in both dogs the episode frequency and severity decreased.

Generalized epileptic seizures were reported in 4 dogs. In 2 dogs, the onset of myoclonus preceded the onset of seizures by 20 and 22 months (seizure onset of 10 years, and 11 years 10 months, respectively). One dog began having seizures at 1 year of age and was diagnosed with idiopathic epilepsy; myoclonus first occurred 8 years later. In 1 dog, the seizures and myoclonic episodes were reported to have the same age of onset (8 years). In the latter 2 cases, the caregivers reported effective control of generalized seizures using zonisamide and phenobarbitone, respectively.

Fifteen dogs had displayed changes in behavior since experiencing the myoclonic episodes, in their caregiver's opinion. These changes included a perceived desire to stay close to the caregiver (7), being less playful (6), being more restless (4), sleeping more (3), a perceived desire to be on their own (2) and aggression towards people (1). No such changes were reported for 12 dogs.

3.3. Second follow‐up

A response to follow‐up e‐mail was received for 15 dogs. The median time between first and second questionnaire submission was 17 months (range, 6.5‐20 months; mean, 14.5 months).

The median second follow‐up period (time from age of onset to second questionnaire submission) was 40 months (range, 13‐82 months; mean, 44 months). Seven dogs had a further increase in frequency of the episodes, including 2 in which the frequency previously had remained unchanged. Five dogs had a further increase in severity of the episodes, including 2 in which the severity previously had remained unchanged. Two dogs had since been prescribed LEV and shown a positive response. No dogs were reported to have developed GTCS. Six dogs displayed further changes in behavior, including 3 in which none had been reported previously. These changes comprised loss of house training (2), a perceived desire to stay close to the caregiver (1), restlessness (1), a perceived desire to be on their own (1), aggression towards other dogs (1), perceived memory loss (1) and obsessive licking of objects and self (1).

4. DISCUSSION

Most CKCS experienced daily episodes of spontaneous myoclonus affecting predominantly the head, with variable involvement of the thoracic limbs, facial features, pelvic limbs, back, abdomen, and neck. There was a tendency for increasingly frequent and severe myoclonic episodes over time, both in dogs that received medical treatment and those that did not. Provoking factors only rarely were identified, such as touch, stress, excitement, and sudden movement. The most frequent descriptive terms used by caregivers are depicted in Figure 1. This clinical phenotype is broadly consistent with that described previously. ¹³ However, in the current cohort, GTCS were reported slightly less commonly (4/27 rather than 9/39). The rarity of provoking factors contrasts with some progressive myoclonic epilepsies described in veterinary medicine such as LD and feline audiogenic reflex seizures (FARS), in which reflex myoclonus in response to light and sound is a prominent feature.

Most dogs were reported to have displayed changes in behavior since the onset of myoclonic episodes (18/27). These changes most often involved being more attached to and dependent on the caregiver and less playful, although 3 dogs had a preference to be on their own and 2 tended to display aggression to other dogs. Restless or obsessive behavior, excessive sleepiness and perceived loss of memory also were identified. A similar spectrum of behavioral changes is commonly reported as a manifestation of progressive cognitive decline in dogs with LD. In Miniature Wirehaired Dachshunds with LD, late clinical signs (>3 years after onset) included dementia defined as disorientation and memory loss with or without altered sleep/wake cycle and anxiety, loss of house training, and aggression towards people or dogs. ³ Similarly, Beagles with LD exhibited staring into space, decreased stress resistance, increased noise sensitivity, separation anxiety, decreased playfulness, reclusiveness, loss of house training, attachment to the caregiver, and aggression towards people or dogs. ¹⁴

In a previous study, ¹³ only 2/39 CKCS showed signs of cognitive dysfunction consisting of staring into space, being less interactive with the caregiver, aimlessly wandering, and anxiety. It was speculated that these signs may not have been directly related to the myoclonus, and could correlate with a historical diagnosis of idiopathic epilepsy in both dogs. Similarly, 2 dogs in our study had idiopathic epilepsy, of which 1 was reported to have behavioral changes. In contrast, however, most CKCS (18/27) developed signs consistent with cognitive dysfunction. ¹⁵ Overall, dogs with behavioral changes were generally older (median age, 145 months) and had experienced the myoclonic episodes for longer (median, 25 months) than those without behavioral changes (median age, 129.5 months; median duration, 18.5 months). Although it cannot be excluded that some behavioral changes may have been related to concurrent age‐related health problems such as undiagnosed orthopedic conditions, this finding lends support to the possibility of an underlying neurodegenerative disorder involving cognitive decline alongside progressive myoclonus.

Ten dogs were prescribed medication for myoclonus. Eight dogs with behavioral changes were prescribed medication, as opposed to only 2 dogs without behavioral changes. This difference could suggest that medication was more likely to be offered, or accepted, for dogs that displayed behavioral abnormalities alongside the myoclonus. However, in most cases it was not possible to determine the exact nature of the clinical signs at the time of the first prescription, which is one limitation of our study. Although an adverse influence of medication on behavior cannot be ruled out, most dogs reported to have behavioral changes did not receive any medication (10/18).

Levetiracetam was the most commonly prescribed medication. It has a unique mechanism of action among the more frequently used anti‐seizure drugs (ASD). By binding to synaptic vesicle glycoprotein 2A (SV2A) LEV is believed to inhibit presynaptic calcium channels and decrease neurotransmitter release. ¹⁶ Levetiracetam is considered a useful ASD in the treatment of myoclonic seizures in both humans and animals, with high response rates reported in several veterinary epileptic syndromes in which myoclonus is a prominent feature, including LD. ¹⁷ , ¹⁸ For example, in Rhodesian Ridgebacks with juvenile myoclonic epilepsy, treatment with LEV resulted in significant reduction in frequency and intensity of myoclonic and absence seizures on video‐electroencephalogram. ⁵ In another study of FARS, in which myoclonus is a hallmark feature, all 28 cats that were treated with LEV showed a >50% decrease in seizure frequency. ¹⁹ Half of the cats achieved complete seizure freedom.

All dogs that received LEV showed a positive response initially, including complete cessation of myoclonic episodes in half of the dogs (4/8). However, later recurrence of myoclonus was common, progressing in frequency in severity and necessitating dose increases of LEV in some dogs. The specific period of time for which the effect of LEV lasted generally was not stated, other than the owners usually described any subsequent worsening as slow or gradual. This trend has been reported in dogs with LD ¹⁸ and idiopathic epilepsy. ²⁰ , ²¹ , ²² One explanation is a possible preliminary effect observed as the development of functional tolerance to LEV with chronic use. This phenomenon has been demonstrated in rat models of epilepsy, in which the anticonvulsant effect of LEV decreased with repeated administration despite no change in plasma concentrations. ²³ , ²⁴ Similar effects have been observed in both dogs ²⁰ and people ²⁵ , ²⁶ with refractory epilepsy. Alternative, or perhaps concurrent, reasons for decreasing seizure control may include an initial placebo effect or recall bias by the owners, natural progression or fluctuation of the epilepsy, pharmacokinetic alterations such as would occur with poor caregiver compliance, or other mechanisms of acquired drug resistance. ²⁷ Given the tendency for natural progression of the myoclonic syndrome described in both treated and untreated CKCS in our cohort, it is possible that the loss of effect of LEV over time is at least partly reflective of an underlying neurodegenerative process. It also suggests that use of LEV is unlikely to prevent progression of the disease but can provide effective relief of clinical signs in the early stages. Caregivers of affected dogs should be made aware of this possibility at the outset.

The main limitations of our study are its retrospective nature and relatively small sample size. In particular, the number of dogs that underwent diagnostic investigation and medical treatment was low and the approach not standardized, and additional prospective case series ideally would be required to establish firm conclusions regarding outcomes. As with most questionnaire‐based studies, recall by the participants may have included inaccuracies and been subject to bias.

5. CONCLUSION

Myoclonus in CKCS tends to increase in frequency and severity with increasing age. The proportion of dogs that had concurrent GTCS was low. Later‐onset behavioral changes suggestive of cognitive decline are commonly reported. Although the number of dogs prescribed medication was relatively low, there often was an initial positive response to LEV followed by later deterioration. These findings support the possibility of an underlying neurodegenerative process.

CONFLICT OF INTEREST DECLARATION

Authors declare no conflict of interest.

OFF‐LABEL ANTIMICROBIAL DECLARATION

Authors declare no off‐label use of antimicrobials.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) OR OTHER APPROVAL DECLARATION

Authors declare no IACUC or other approval was needed.

HUMAN ETHICS APPROVAL DECLARATION

Authors declare human ethics approval was not needed for this study.

Supporting information

Data S1: Supporting Information.

Video S1: Example of myoclonus in Cavalier King Charles Spaniel.

James M, Lowrie M, Rusbridge C. Characteristics and clinical course of myoclonus in Cavalier King Charles Spaniels . J Vet Intern Med. 2025;39(1):e17227. doi: 10.1111/jvim.17227