Phenotypic characterisation of paroxysmal dyskinesia in Sphynx cats

Abstract

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.

Introduction

Paroxysmal dyskinesia (PxD) is a heterogeneous group of movement disorders characterised by episodic, involuntary and sustained muscle contraction resulting in abnormal movements and postures.^1–4 The abnormal episodes are not associated with altered consciousness or autonomic signs, thus allowing, in most cases, differentiation of PxD from epileptic seizures based on visualisation. Primary PxD is familial or idiopathic, whereas secondary PxD can be associated with a variety of underlying central nervous system or systemic disorders. ¹ The presence of neurological abnormalities in the inter-ictal period may therefore be a key distinguishing feature of secondary PxD. PxD was first characterised in humans in 1940, at which time Mount and Reback described, in a male individual, a paroxysmal choreoathetosis that was incited by alcohol and caffeine. ⁵ The most widely used classification system in humans is based on precipitating factors, event duration and response to treatment. This allows categorisation of PxD as paroxysmal kinesogenic dyskinesia (PKD; incited by sudden movement), paroxysmal non-kinesogenic dyskinesia (PNKD; occurring spontaneously) and paroxysmal exertion-induced dyskinesia (PED; incited by strenuous exercise and fatigue). ⁶ A paroxysmal hypnogenic dyskinesia associated with rapid-eye-movement sleep was also described; however, this may represent a form of nocturnal frontal lobe epilepsy. ⁷

PxD in veterinary patients is becoming increasingly recognised, although some are limited to sporadic reports and remain poorly characterised. Primary PxD is presumed in the majority of cases; however, specific genetic mutations have been identified in Cavalier King Charles Spaniels with episodic falling syndrome, Soft-Coated Wheaten Terriers with a PNKD, Shetland Sheepdogs with a PED and Markiesje dogs with a juvenile PxD.^8–11 Proven secondary PxD in dogs is restricted to a gluten-sensitive movement disorder of Border Terriers, as well as individual reports of drug-induced PxD associated with phenobarbitone and propofol administration.^12–14 The natural course of the disorder in dogs appears to be variable both in frequency and severity, although in Labradors and Jack Russell Terriers there is an overall propensity for the episodes to eventually stabilise and improve. ¹⁵

To date, there are no official reports of PxD in cats and information is scarce. There are, however, occasional anecdotal accounts from owners and veterinarians regarding an episodic movement disorder in Sphynx cats. The aim of this study was to corroborate such reports in order to describe the phenotypic features and clinical course of this disorder in the Sphynx breed.

Materials and methods

Case recruitment

Cases were recruited via the veterinary media (Veterinary Record, The Veterinary Times), the internet (Sphynx cat forums, International Cat Care website) and magazines (Your Cat) requesting veterinary practitioners, owners and breeders to contact us regarding suspected cases of PxD in Sphynx cats. Owners of affected cats were asked to provide video footage of the abnormal episodes, which was subsequently reviewed by the authors (MG and ML). If video footage supported a diagnosis of PxD, the owners were invited to complete an online questionnaire. Cases were excluded if video footage was not available. Examples of submitted video footage are provided in the supplementary material.

Questionnaire design

The questionnaire was divided into five sections: (1) signalment of the affected cat; (2) general health and underlying conditions; (3) overview of the abnormal episodes; (4) detailed characterisation of the abnormal episodes; and (5) management of the abnormal episodes. Each section contained open-ended and closed questions. 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. Also embedded within the questionnaire were questions or multiple-choice questions to act as a screen in order to further exclude cases that were not consistent with PxD. Owners had the opportunity to highlight any change in consciousness, presence of autonomic signs such as urination, defaecation and salivation, as well as the presence of abnormalities in the immediate post-ictal and inter-ictal period. Cases were excluded if there were major discrepancies between the video footage and the owner’s description within the questionnaire. Spontaneous remission was defined as no episodes for ⩾1 year while not receiving medical or dietary intervention. The full questionnaire design may be viewed in the supplementary material.

Results

There were a total of 11 respondents; however, one was unable to provide video footage of the abnormal episodes and was excluded from the study. All 10 remaining cats were considered to display episodes consistent with PxD based on review of video footage and subsequent questionnaire responses. Owner description of the episodes was considered to be consistent with video footage in all 10 cats. There were five male and five female cats, of which most were neutered (9/10). The median age of onset was 2.0 years (range 0.5-4.0, mean 2.2). The median follow-up period was 14.5 months (range 3–141, mean 32.2).

Overall episode frequency was variable, ranging from once daily to no more than once every 6 months. The majority of cats (6/10) had suffered no more than one episode in a single day, while four cats had, at some point, suffered a cluster of up to six episodes. The frequency of the episodes was reported to increase (4/9), decrease (2/9) or remain unchanged (3/9). However, two cats that had an initial increase in frequency were later reported as being free of episodes for 12 and 14 months, respectively, at the time of writing. Two cats met the criteria for spontaneous remission. The duration of the episodes ranged from 30 s to 10 mins, with most lasting between 30 s and 2 mins (7/10). Most owners reported no change in episode duration over time, although in three cats the episodes were reported to have become longer.

When prompted, all owners described the episodes to involve slow involuntary movements of the limb(s), rather than violent shaking, sudden jerking or lack of movement. The most frequent observations were clumsiness when walking (10/10), abnormal posture (10/10) and stiffness (8/10). Two respondents additionally reported shaking and twitching of the face and ears. Rolling of the head was noted in one case. In the majority of cats the episode was reported to involve just part of the body at the onset, then progress to involve other regions (6/10). The body regions most frequently involved were 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 affected in some cases. Nine cats were reported to be normal immediately following the end of an episode, while one cat was described as wobbly and sleepy afterwards but recovered fully within minutes.

None of the owners believed they were able to predict the occurrence of an episode, nor stop or change the course of an episode at all after it had commenced. Three respondents identified possible triggers of the episodes including sudden movement (2/3), excitement (2/3) and stress (2/3). Most owners responded during an episode by comforting their cat or simply observing to try and ensure their cat did not harm itself. The episodes were not believed to have negatively affected the quality of life of any cat. None of the owners was aware of any affected cats related to their own.

Diagnostic testing was performed in most cases, including haematology and biochemistry (8/10), bile acid stimulation test (2/9), evaluation of thyroid function (1/9), urinalysis (2/9) and blood pressure measurement (2/9). Five cats also underwent MRI of the brain with cerebrospinal fluid analysis. All investigations were reported to have unremarkable findings.

Medical management was attempted in three cats. Acetazolamide was prescribed for two cats, for which the episodes were occurring once daily or once weekly. Both were reported to be free of abnormal episodes while receiving acetazolamide; however, the dosage was not available. One cat received acetazolamide for 7 months, while in the other cat it was discontinued after only 1 week owing to sedation. Phenobarbitone was prescribed at a dose of 3 mg/kg q12h for one cat with an episode frequency of once per month, but was later withdrawn after 2 months owing to no effect.

Dietary modification was implemented in one cat with the introduction of a food without grains and wheat, after which the cat achieved freedom from episodes. This was the same cat that had received acetazolamide for 1 week.

Concurrent proven medical conditions were reported for two cats with hypertrophic cardiomyopathy and one cat with unilateral patella luxation. Vomiting or diarrhoea was reported for 8/10 cats and in most of these was occasional or infrequent (7/8). No cats were reported to have known underlying food or environmental related allergic disease.

The individual case details are summarised in Table 1.

Table 1.

Case details of 10 Sphynx cats with paroxysmal dyskinesia

Case	Age of onset	Length of follow-up (mo)	Episode frequency	Episode duration (mins)	Reported triggers	Medication	Dietary modification	Spontaneous remission
1	0 y 7 mo	11	Once monthly	1–2	None	None	None	NA
2	2 y 0 mo	16	Once a fortnight	1–2	Stress, excitement	None	None	No
3	3 y 9 mo	12	Once every >6 mo	1–2	None	None	None	No
4	4 y 0 mo	5	Once weekly	2–5	None	Acetazolamide	None	NA
5	0 y 6 mo	141	Once monthly	0.5–1	Stress, sudden movement	Phenobarbitone (discontinued after 2 mo)	None	Yes (after 4 y)
6	0 y 8 mo	82	Once every 2 mo	1–2	Excitement, sudden movement	None	None	Yes (after 5 y, 10 mo)
7	2 y 0 mo	22	Once weekly	0.5–1	None	None	None	No
8	1 y 10 mo	3	Once every 3–6 mo	5–10	None	None	None	NA
9	2 y 7 mo	17	Once daily	2–5	None	Acetazolamide (discontinued after 1 week)	Yes	No
10	3 y 11 mo	13	Once a fortnight	1–2	None	None	None	No

y = years; mo = months; NA = not available

Discussion

This study is the first report of PxD in cats and provides valuable information regarding the phenotypic features of the condition in the Sphynx breed. Affected Sphynx cats typically display difficulty walking, abnormal posture and muscle hypertonicity, frequently involving the thoracic and pelvic limbs, with occasional inclusion of the head and neck and tail. All cats returned to normal immediately or within minutes of the end of an episode and there were no abnormalities reported in the inter-ictal period. The duration of the episodes was always <10 mins and in the majority of cases was between 30 s and 2 mins. The frequency of the episodes appeared to be variable within and between individuals, with clustering of episodes (up to six in a 24 h period) reported in some cats. Owners did not feel that they could predict the occurrence of an episode or alter the course of an episode once it had commenced. In most cases the episodes would occur without an obvious trigger, although sudden movement, excitement and stress were identified as possible precipitating factors in three cats. Where performed, diagnostic investigations reportedly yielded no significant abnormal findings, albeit this work-up was inconsistent and not performed in every case.

The phenotypic characteristics described in this survey suggest that PxD in Sphynx cats may be most analogous to a PKD described in human classification systems.^6,16 PKD is characterised by short dystonic attacks typically <5 mins in duration, although occasionally can last for hours. Precipitating factors, often considered to be the most important defining characteristic, include sudden movement or acceleration, orofacial movements, startle or hyperventilation. ⁶ All Sphynx cats had episodes that were <10 mins in duration, and in 9/10 cats were <5 mins. Sudden movement and excitement were reported as precipitating factors in two cats. PNKD and PED typically involve episodes that are >5 mins in duration and trigger factors in humans more often include caffeine, alcohol, sleep deprivation, stress or prolonged exercise. ⁶ Stress was also identified as a possible trigger in two cats. Reports of suspected PKD in veterinary patients are limited to the German Short-Haired Pointer, which displays episodic kyphosis and ataxia, triggered by excitement. ¹⁷ Instead, the majority of PxD in other dog breeds share characteristics resembling PNKD.^9,18–23 In spite of this designation, a recent consensus statement has suggested that designation according to the human classification may be clinically irrelevant and could be misleading. ²⁴

A distinguishing feature of PKD in humans is a generally favourable response to antiepileptic drugs (AEDs), although treatment failure has been reported. Carbamazepine is considered the medication of choice in humans; however, other AEDs, including oxcarbazepine, phenobarbitone, levetiracetam and gabapentin can also provide benefit. ²⁵ The aforementioned PKD in a German Short-Haired Pointer dramatically improved in response to phenobarbitone therapy, with a marked reduction in episode frequency. ¹⁷ If PxD in Sphynx cats did, indeed, represent PKD, a good response to AEDs may be expected. One cat that had an episode frequency of once per week was started on acetazolamide and reportedly suffered no further episodes in the subsequent 7 months until it died as a result of underlying hypertrophic cardiomyopathy. A second cat that had an episode frequency of once daily also received acetazolamide and, similarly, the episodes ceased to occur; however, the medication was only given for 1 week before being stopped as a result of unwanted sedative effects. Interestingly, this cat later underwent dietary manipulation to a hypoallergenic food lacking in cereals and grains, and the episodes stopped again. The third cat received phenobarbitone at a dosage of 3 mg/kg q12h and apparently did not display any alteration in the episodes until the cessation of therapy after 2 months. It is not possible, however, to draw meaningful conclusions regarding treatment efficacy in in this study. This is primarily owing to the small number of cases, of which only a minority received any medical intervention. Subsequent studies involving a larger cohort of cases would be required to investigate these findings further, with scientifically controlled drugs trials including appropriate monitoring of dosages and therapeutic concentrations. In a clinical setting the decision as to whether to trial AEDs in affected Sphynx cats is likely to vary depending on the individual patient, particularly given the variability in episode frequency and natural course of the condition reported here. Importantly, the episodes of PxD were not deemed to affect the quality of life of any of the affected cats, suggesting that therapeutic intervention may not always be necessary.

Lowrie and Garosi reported that the natural progression of PxD in Labrador Retrievers and Jack Russell Terriers is variable but with a propensity to improve after the first few years following onset. ¹⁵ All of the dogs in their study had a follow-up period of at least 3 years and the majority of those that displayed spontaneous remission did so after 2 years of the onset of PxD. Only two cats in this study had a follow-up period of at least 2 years (6 years 10 months and 11 years 9 months, respectively). Both were reported to have been free of episodes without therapeutic intervention for 1 year and 7 years and 6 months, respectively. This followed an initial episode frequency of once every 2 months and once every month, respectively. The first cat experienced the episodes for 5 years 10 months, while the second cat experienced episodes for 4 years before achieving this remission. These findings suggest that PxD in Sphynx cats may also have an overall tendency to spontaneously improve over time in a similar manner to dogs but that this may occur later after the onset of disease. The follow-up period in 3/10 cats was not sufficiently long to assess for spontaneous remission. It is possible that more cats in this study would have achieved episode freedom if followed for a longer period of time, thus future studies with a longer follow-up period are required to investigate this further.

As with many similar studies into PxD, a limitation of this study is the inability to completely exclude seizure activity as a cause of the abnormal episodes owing to the fact that focal epileptic seizures are not always associated with a change in mentation. ²⁶ Ideally, electroencephalogram (EEG) monitoring during or following attacks can be used to provide additional support to a diagnosis of PxD over epilepsy.^27,28 However, EEG is rarely performed in veterinary patients, and, indeed, was not performed in any cat in this study. As such, diagnosis more often relies on the overall phenotypic characteristics of the episodes. The absence of altered consciousness, autonomic signs and post-ictal abnormalities provides much of the distinction between PxD and focal epileptic seizures. Wahle et al reported focal seizures to be relatively common in cats, occurring in 9/18 cats with epilepsy of unknown cause. ²⁹ In 8/9 cats there was hypersalivation, and in 6/9 cats there was secondary generalisation of the seizures with loss of consciousness. ²⁹ Neither autonomic signs such as hypersalivation, urination and defaecation nor altered consciousness were described for any Sphynx cat in the present study. Nine of 10 cats fully recovered immediately following the episode, while one appeared to recover within minutes. In addition, the availability of video footage was a requirement for inclusion in the study, meaning all cases were reviewed to ensure that the episodes were consistent with the associated questionnaire responses and with a diagnosis of PxD.

Conclusions

PxD in Sphynx cats appears to have features that resemble PKD based on human classification systems. Episode frequency is variable, both between individuals and within the same individual over time. Some cats appear to achieve episode freedom spontaneously although more cases with longer follow-up periods are needed to evaluate this further. Additional research is required to assess therapeutic outcomes and to identify a possible genetic component of the condition.