Seizure etiologic classification and long-term outcome for cats with juvenile-onset seizures

Muna Qahwash Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Heidi L. Barnes Heller Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706.

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Abstract

OBJECTIVE To identify seizure etiologic classification for cats that developed seizures at < 12 months of age and describe the long-term outcome of affected cats.

DESIGN Retrospective cohort study.

ANIMALS 15 client-owned cats with seizures that began at < 12 months of age.

PROCEDURES Information on each cat was obtained from the medical records, veterinarians, and owners. Inclusion required an onset of seizures before 12 months of age and a complete medical record, including a final diagnosis.

RESULTS 7 of the 15 cats had structural epilepsy, 4 had idiopathic epilepsy, and 4 had reactive seizures. Median age at seizure onset was 27 weeks (range, 0.4 to 41 weeks). Cluster seizures were reported in 6 cats, and status epilepticus was reported in 2. Age at the onset of seizures, presence of cluster seizures, and seizure semiology (ie, generalized vs focal seizures) were not significantly associated with seizure etiologic classification.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that cats that developed seizures at < 12 months of age were more likely to have structural epilepsy than idiopathic epilepsy or reactive seizures. Therefore, advanced diagnostic imaging is recommended in cats with juvenile-onset seizures if metabolic and toxic causes are excluded.

Abstract

OBJECTIVE To identify seizure etiologic classification for cats that developed seizures at < 12 months of age and describe the long-term outcome of affected cats.

DESIGN Retrospective cohort study.

ANIMALS 15 client-owned cats with seizures that began at < 12 months of age.

PROCEDURES Information on each cat was obtained from the medical records, veterinarians, and owners. Inclusion required an onset of seizures before 12 months of age and a complete medical record, including a final diagnosis.

RESULTS 7 of the 15 cats had structural epilepsy, 4 had idiopathic epilepsy, and 4 had reactive seizures. Median age at seizure onset was 27 weeks (range, 0.4 to 41 weeks). Cluster seizures were reported in 6 cats, and status epilepticus was reported in 2. Age at the onset of seizures, presence of cluster seizures, and seizure semiology (ie, generalized vs focal seizures) were not significantly associated with seizure etiologic classification.

CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that cats that developed seizures at < 12 months of age were more likely to have structural epilepsy than idiopathic epilepsy or reactive seizures. Therefore, advanced diagnostic imaging is recommended in cats with juvenile-onset seizures if metabolic and toxic causes are excluded.

Seizures are a common reason for referral to a veterinary specialist,1,2 and underlying causes, including idiopathic epilepsy, hippocampal necrosis, infectious meningoencephalitis, noninfectious meningoencephalitis, cerebrovascular disease, and neoplasia, are well documented for adult cats and dogs.3–9 However, the developing brain is suspected to be more sensitive to seizure onset and propagation, and therefore, causes and long-term outcomes may be different in animals with juvenile-onset versus adultonset seizure disorders.10 Recently, a study by Arrol et al11 found that most young dogs with seizures starting at < 12 months of age had idiopathic epilepsy. However, because idiopathic epilepsy is commonly reported2 in dogs < 6 years of age, this finding was somewhat unsurprising.

Several case reports11–17 have outlined specific causes of seizures in young cats; however, the relative distribution of seizure etiologies in young cats is currently unknown. The objectives of the study reported here were to identify seizure etiologies in cats with seizures that developed at < 12 months of age and describe long-term outcomes of affected cats.

Materials and Methods

Case selection

The medical database of the University of Wisconsin Veterinary Care Hospital was searched to identify cats evaluated between 2000 and 2014 because of a seizure onset at < 12 months old. The search terms were seizure, seizure-like, epilepsy, encephalopathy, episodes, event, and shunt. Inclusion criteria were a confirmed or suspected seizure before 12 months of age and a complete medical record, including a final diagnosis. Cats were excluded if the seizure description was inadequate to support a diagnosis of a seizure or a final diagnosis was not adequately supported.

The IVETF has recommended classifying patients with seizures on the basis of semiology (ie, clinical signs of the seizures) or underlying cause, in accordance with ILAE consensus reports from 2010.18–21 The IVETF etiologic classification system22 includes idiopathic epilepsy, when no identifiable cause could be found on diagnostic investigation, and structural epilepsy, when an inciting cause could be found on diagnostic investigation. Seizures secondary to toxic or metabolic diseases were not considered epilepsy and were classified as reactive seizures. Seizure classification for the present study followed the 2015 IVETF recommendations for dogs,23 with the exception that cats were classified as having idiopathic epilepsy if they had had ≥ 2 seizures prior to diagnosis; results of serum biochemical analyses, a CBC, CSF analysis, and MRI of the brain were within reference limits or unremarkable; and any serum bile acids concentration was below 28.0 μmol/L for tier I confidence–level recommendations for diagnosing idiopathic epilepsy in dogs.21,23

Data collection

Information collected from the medical records included age at seizure onset, sex, breed, body weight on initial evaluation, neurologic examination results, diagnosis, type of seizure (ie, focal or generalized), presence of cluster seizures or status epilepticus, initial treatment, outcome (dead or alive), and cause of death and necropsy results (if applicable). Veterinarians, clients, or a combination of both were contacted to obtain information on outcome, perceived seizure control and quality of life, and current seizure management (if applicable). Focal seizures were defined as focal twitching of the ears, face, or 1 limb with or without loss of consciousness. Generalized seizures were defined as tonic, clonic, and tonic-clonic bilateral movements.

Statistical analysis

Descriptive statistics, including median and ranges, were calculated for continuous variables. Cats were grouped on the basis of seizure etiologic classification (structural epilepsy vs idiopathic epilepsy vs reactive seizures), and age at the onset of seizures was compared across groups with an ANOVA. The Fisher exact test was used to test whether seizure etiologic classification was associated with the presence of cluster seizures (yes vs no) or with seizure semiology (generalized vs focal seizures). Survival analyses were not performed because there were too few deaths for meaningful interpretation. All analyses were performed with standard softwarea; values of P < 0.05 were considered significant.

Results

Fifteen cats met the inclusion criteria for the study, consisting of 9 (60%) domestic shorthair cats, 2 (13%) domestic longhair cats, 1 (7%) domestic medium-hair cat, 1 (7%) Tonkinese, 1 (7%) Ragdoll, and 1 (7%) Abyssinian. Eight (53%) were neutered males, 3 (20%) were spayed females, 2 (13%) were sexually intact females, and 2 (13%) were sexually intact males. Median age at the time of initial evaluation was 30 weeks (range, 0.4 to 41 weeks), and median body weight was 3.0 kg (6.6 lb; range, 1.2 to 5.2 kg [2.6 to 11.4 lb]). Weight data were missing for 2 cats, 1 of which was the youngest kitten. Median age at seizure onset was 27 weeks (range, 0.4 to 41 weeks). Generalized seizures alone were documented in the medical records of 9 (60%) cats, whereas focal seizures alone were noted in 3 (20%), and a combination of generalized and focal seizures was noted in 3. Cluster seizures were noted in the records of 6 (40%) cats, and status epilepticus was noted in 2 (13%). Etiologic seizure classification was structural epilepsy in 7 (47%)cats, idiopathic epilepsy in 4 (26%), and reactive seizures in 4 (26%).

Structural epilepsy

On initial examination, all 7 cats in the structural epilepsy group had neurologic abnormalities (generalized ataxia, n = 5 cats; menace reflex deficits, 4; postural reflex deficits, 6; anisocoria, 2; and opisthotonus, 2), and 3 cats had histories of cluster seizures. Six cats had generalized seizures, and 1 had both focal and generalized seizures. Median age at the time of seizure onset was 24 weeks (range, 4 to 41 weeks). Underlying causes that were identified were FIP (n = 2 [including 1 with concurrent hydrocephalus]), head trauma (2), porencephaly (1), bilateral occipital arachnoid diverticula (1), and noninfectious meningoencephalitis (1).

Four of the 7 cats were still alive at the time of last follow-up. The 2 cats with FIP and the cat with noninfectious meningoencephalitis had been euthanized because of the perceived poor prognoses. The 1-year survival rate was 57% (4/7).

One cat was euthanized prior to hospital discharge, surviving 0.9 weeks after diagnosis. For the remaining cats, pharmaceutical treatments prescribed at discharge included phenobarbital alone (n = 4) and phenobarbital combined with potassium bromide (2). In 1 cat, potassium bromide administration was discontinued 2 days after initiation, and levetiracetam was prescribed instead. Of the 4 cats alive at the time of last follow-up, 3 were being treated with phenobarbital alone, and 1 was being treated with a combination of phenobarbital, potassium bromide, and zonisamide. The owners of all 4 cats perceived improved seizure control and quality of life relative to the time of diagnosis.

Idiopathic epilepsy

Neurologic abnormalities detected on initial examination of the 4 cats in the idiopathic epilepsy group were limited to mild obtundation in 1 cat. Two cats in this group had a history of cluster seizures. One cat had focal seizures, 1 had generalized seizures, and 2 had both focal and generalized seizures. Median age at seizure onset was 29 weeks (range, 17 to 37 weeks).

Pharmaceutical treatments prescribed at discharge for the 4 cats included phenobarbital alone (n = 2) and phenobarbital combined with levetiracetam (1). The remaining cat was not prescribed any anticonvulsant medication at discharge.

Two of the 4 cats were still alive at last follow-up and 2 cats had died of unrelated causes. Both surviving cats were receiving phenobarbital, and 1 was also receiving levetiracetam. The 1-year survival rate was 100% (4/4). For all 4 cats, the owners perceived improved seizure control and quality of life, compared with that at initial evaluation.

Reactive seizures

In all 4 cats with reactive seizures, the seizures were secondary to portosystemic shunts diagnosed on the basis of high pre- and postprandial serum bile acids concentrations and results of abdominal ultrasonography or CT-guided angiography. Results of neurologic examinations for 2 of these cats were unremarkable; however, results of neurologic examinations for the remaining 2 cats were not available in the medical records. Status epilepticus was diagnosed in 2 of 4 cats, and cluster seizures were diagnosed in another. Two cats had focal seizures, and the other 2 had generalized seizures. Mean age at seizure onset was 20 weeks (range, 0.4 to 28 weeks).

Surgical placement of an ameroid constrictor was performed in 2 cats and recommended but not performed in another. Surgical treatment was not recommended for the remaining cat because it had multiple extrahepatic shunts. None of the cats in this group were prescribed anticonvulsant drugs at the time of discharge.

Of the 4 cats with reactive seizures, 1 was alive at last follow-up, 2 were dead, and 1 had been lost to follow-up. The 1-year survival rate was 25% (1/4). Information on survival time was not available for 1 cat that died or for the cat that was lost to follow-up. The remaining 2 cats survived 224 and 613 weeks.

Statistical analysis

Age at the onset of seizures did not differ significantly (P = 0.35) among the 3 seizure etiologic classification groups (structural epilepsy vs idiopathic epilepsy vs reactive seizures). In addition, neither the presence of cluster seizures (yes vs no) nor the seizure semiology (ie, generalized vs focal seizures) was significantly (P = 1.0 and P = 0.07, respectively) associated with seizure etiologic classification group.

Discussion

Findings in the present study suggested that cats < 12 months of age at the onset of seizures commonly had structural epilepsy. This was in agreement with findings of a recent study,3 in which 4 of 6 cats < 12 months of age had structural epilepsy; however, it differed from findings for dogs with juvenile-onset seizures.11 The most common abnormalities for cats with structural epilepsy in the present study were congenital malformations, FIP, and head trauma. Clinical signs associated with congenital malformations and FIP could be expected to start at a young age, as reported previously for cats with lissencephaly, arachnoid cysts, congenital polioencephalomyelopathy, and external hydrocephalus.10,13,15,17,24 The incidence of structural epilepsy in cats of all ages is 47% to 62%. However, although neoplasia is the most common underlying cause reported in older cats with structural epilepsy,3,7,25 neoplasia was not diagnosed in any cats in the present study, which was likely attributable to the low incidence of neoplasia in cats < 12 months of age.7 Findings of the present study suggested that structural epilepsy is common in young cats with juvenile-onset seizures; therefore, diagnostic investigation, including advanced imaging, should be pursued when results of metabolic testing are within reference ranges and no evidence of toxin exposure is found.

According to the IVETF classification system, idiopathic epilepsy includes animals with a known or suspected genetic predisposition to seizures as well as animals in which no structural change is identified.21 In the present study, idiopathic epilepsy was diagnosed in 4 of the 15 (27%) young cats, which was comparable to reports that 22% to 59% of adult cats with seizures have idiopathic epilepsy.8,25,26 In contrast, idiopathic epilepsy has been reported as the most common cause of seizures in young dogs.11 In addition, in dogs, idiopathic epilepsy has a typical onset age of 6 months to 6 years and is known, or suspected, to have a genetic predisposition. Therefore, it is not surprising that idiopathic epilepsy will be commonly diagnosed in dogs with seizures that begin at < 12 months of age. Further, a genetic predisposition has been reported for many dog breeds,27 but rarely in cats,28 and it is therefore realistic that a lower percentage of cats, compared with dogs, would have idiopathic epilepsy.

One cat with idiopathic epilepsy in the present study was noted to be mildly obtunded on initial examination. The obtundation may have been secondary to recent seizure activity in this cat. On the other hand, interobserver agreement among veterinarians for assessment of mentation and level of consciousness of animals is low.29 Therefore, the clinical importance of the mild obtundation noted in the cat's record was difficult to ascertain.

No association between seizure semiology and etiologic classification was identified in the present study. However, Wahle et al24 reported that focal or focal-onset seizures were common in cats with idiopathic epilepsy, and 6 of 9 cats in that report with focal seizures had secondary generalization. The differences between findings of that study and those of the present study may have been attributable to differences in client reporting of focal onset, lack of medical record description of focal seizures, lack of observer identification of focal onset, or the small number of cats included in the present study. Similarly, in a recent study,29 identification of a focal seizure was shown to have low interobserver agreement, which further complicates the reporting of these events in veterinary patients. Performing electroencephalography during the ictal or interictal stage may improve the identification of focal seizures in cats, but may be impractical or too expensive.

The presence of cluster seizures was also not significantly associated with seizure etiologic classification in the present study. However, this should be evaluated further in a larger study to determine whether this lack of association represented a type II error.

In the present study, 1-year survival rates differed for the 3 groups. However, survival analyses were not performed because ≥ 50% of the cats in each group were still alive at the time of final follow-up. Therefore, we cannot state whether survival time differed among classification groups. In addition, although the 1-year survival rate for cats with idiopathic epilepsy in the present study was higher than rates reported in previous studies25,26 of cats with idiopathic epilepsy (73% to 82%), cats of all ages were included in those previous studies, and survival rate could have been affected by concurrent diseases or owner-perceived quality of life in older cat with seizures. A larger study evaluating a greater number of cats with juvenile-onset seizures is required to better understand 1-year survival rates.

Limitations of the present study included the small sample size, reliance on medical records for reporting of seizures and seizure type, and selection bias related to the fact that the study population was compiled from patients evaluated at a referral hospital. We recommend a larger-scale, multi-institutional study covering a larger geographic region to determine more comprehensively whether seizure semiology in cats with seizure onset at < 12 months of age is related to etiologic classification.

In conclusion, findings of the present study suggested that cats with an onset of seizures at < 12 months of age were more likely to have structural epilepsy than to have idiopathic epilepsy or reactive seizures. Therefore, advanced diagnostic imaging is recommended for cats with juvenile-onset seizures if metabolic and toxic causes are excluded. Although idiopathic epilepsy was diagnosed less commonly in cats of the present study, most cats with idiopathic epilepsy had a favorable long-term outcome. Therefore, appropriate anticonvulsant treatment is recommended for cats with juvenile-onset idiopathic epilepsy.

Acknowledgments

No funding was obtained for the present study, and the authors did not have any conflicts of interest.

Presented as an abstract at the American College of Veterinary Internal Medicine Forum, Denver, June 2016.

ABBREVIATIONS

FIP

Feline infectious peritonitis

ILAE

International League Against Epilepsy

IVETF

International Veterinary Epilepsy Task Force

Footnotes

a.

R: a language and environment for statistical computing, version 3.3.2, R Foundation for Statistical Computing, Vienna, Austria.

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