Clinical Signs of Epileptic Seizures
It is important to be aware of 4 characteristic stages of epileptic seizure as it is helpful to differentiate them from nonepileptic seizures. The 4 stages are the prodrome, aura, ictus, and postictal stages. The prodrome is the least consistent. It precedes seizure onset, lasts hours to days, and usually includes restless activity and attention-seeking or anxious behavior. Aura is a subjective initial feeling of the ictal event and without EEG, it is impossible to differentiate it from the prodrome in animals. It should be emphasized that aura is an ictal phenomenon and can precede an observable seizure. It might contain information about the initial localization of the ED. The ictus is the seizure event itself and is followed by the postictal stage. Postictal changes are more consistent in their presentation than prodrome or auras and can frequently give indications of whether the seizure event was epileptic. Different features have been frequently reported in cats such as aggression, polyphagia, polydipsia, blindness/deafness, and ataxia.[4, 7] Clinical signs in the aura, ictus, and postictal stages can have diagnostic value in localizing the origin of the seizure in the brain, although this point needs to be further analyzed in cats.
Seizures in cats are frequently complex focal seizures with or without secondary generalization.[10, 11, 14, 15] The ictal signs frequently include drooling, facial twitching, tremor, rapid running, mydriasis, hypersalivation, urination, and defecation. During focal seizure, a cat can remain in sternal recumbency or can show running or climbing activity. Seizures might be particularly violent. Generalized seizures might involve the whole body. Both focal and generalized seizure types can occur in an individual patient. However, focal epileptic seizures can become generalized so rapidly that their true nature is missed and the seizure might then be classified as primary generalized. The ictus usually lasts for not longer than 3 minutes.[6-8, 10]
Paroxysmal Clinical Signs Can Be Caused by Epileptic or Nonepileptic Disorders
Cats might exhibit a large number of paroxysms that can resemble epileptic seizures. The differential diagnosis includes a wide range of clinical conditions: behavioral changes, obsessive-compulsive disorder, movement disorders, narcolepsy/cataplexy, sleep disorders, increased intracranial pressure, pain-associated behavior, tremor syndromes, syncope, feline orofacial pain syndrome, vestibular or neuromuscular disorder, and other encephalopathies (Table 3).[4, 5, 16, 17]
Table 3. Epileptic and nonepileptic paroxysms in cats.
|Paroxysmal Events||Important Features for Differentiation|
|Generalized epileptic seizure||Most often tonic-clonic seizure with impaired consciousness|
|Focal epileptic seizure||Very variable, may include drooling, facial movement, vocalization, abnormal head and limb movement (secondary generalization possible)|
|Temporal lobe seizure (special type of focal seizure)||Orofacial automatism: salivation, facial twitching, lip smacking, chewing, licking, swallowing (secondary generalization possible)|
|Cardiac syncope||Arrhythmia, evidence of heart disease|
|Neck pain||Pain on neck manipulation|
|Compulsive disorders||No loss of consciousness|
|Feline estrus behavior||Howling, rolling, lordosis|
|Vestibular disease||Nystagmus, head tilt, falling|
|Increased intracranial pressure||No sudden start and termination|
|Feline orofacial pain syndrome||Acute oral discomfort and automutilation|
|Feline hyperesthesia syndrome||Rolling skin on the lumbar region (unclear etiology, may be epileptic)|
Clinical Differentiation between Epilepsies
Idiopathic (primary) epilepsy in dogs is believed to be usually genetic in origin, but there is little information to support such an assumption in cats. One study indicates that some cat breeds might have a predisposition to IE. The European shorthair breed was slightly overrepresented in cats with IE, but this finding cannot be considered as proof of a genetic origin for IE. Recently, a possible spontaneous model of human genetic epilepsy was detected in laboratory cats.
The age of onset is important in epileptic dogs for differentiating between IE and SE. On average, cats with IE are younger than cats with SE, with the mean age of onset in the IE/SE groups of 4.6/8.4 and 3.5/8.2 years in the 2 studies.[7, 11] The information is of limited diagnostic value as there is an overlap between the groups. Nevertheless, a young adult cat is more likely to have IE and an older cat more likely to have SE.
Historically, focal seizures have been associated with structural brain disease, but there is increasing evidence that focal and generalized seizures occur with nearly equal frequency in IE and SE.[6, 7, 11] In practice, this means that focal seizure does not rule out IE, nor does generalized seizure suggest IE. The situation is actually even less clear, as 40–50% of cats in the IE and SE groups showed both focal and generalized seizures. This observation is easier to understand when we are aware of the modern concept of epileptic networks. In modern epileptology, focal and generalized epilepsies are not thought of as different pathophysiologic phenomena but as representing a continuum. Generalized epilepsy also originates from a specific brain region, although it does so bilaterally. In addition, some individuals fall in a gray zone in the transition from focal to generalized epilepsy (Table 1).
Seizures in cats with IE have been reported to be more frequent during resting conditions. Non-REM sleep in particular can activate ED and certain seizure events. There is an increase in cortical neuronal synchronization during sleep, decreasing the seizure threshold.[20, 21] Seizures frequently occur in cats with experimentally provoked epilepsy during drowsiness and slow-wave sleep, which is the feline equivalent of non-REM sleep in humans. Seizure activity is much less prominent during alert wakefulness and REM sleep.[22, 23] This effect is probably less important in the presence of an underlying disorder (SE), which presumably has a stronger effect on seizure threshold than do daytime changes and the sleep/wake cycle.
Despite the problem confirming IE, there are examples of IE where the diagnosis has a high degree of certainty. A classic case might be a cat with very similar convulsive seizure events for 1–2 minutes during resting, postictal disorientation for 5–20 minutes, and no interictal impairment. The age of onset is between 1 and 4 years, the episodes recur monthly, the complete work-up is negative, remission occurs after antiepileptic treatment, and there is recurrence after cessation of treatment. More problematic are cases where the episodes are nonconvulsive and the patient only shows unusual behavior, the work-up is not complete, the changes are only borderline (eg, inconsistent neurologic findings, very slightly enlarged lateral ventricles, mild azotemia), or antiepileptic treatment is unsuccessful.
There is less literature dealing with confirmation of SE than of IE, although it is generally difficult to confirm that a certain brain disorder is responsible for the clinical signs. SE can be a particularly problematic issue when more potentially epileptogenic conditions are present in an individual person. In such a case, it is difficult or even impossible to tell what is the cause and it is likely that different causes can lead to epileptic seizures together. The diagnosis of SE can be made with a high degree of certainty, for example, in a 14-year-old cat with acute onset of cluster seizures and permanent neurologic deficits where MRI shows evidence of a meningioma. Cases without permanent neurologic deficits and negative work-up are more problematic.
Careful history taking is the first step. Video recording of the episodic event could be helpful for differentiation. The important points to note are those described above: age of onset, focal or generalized, when the event occurred, recognition of 4 (usually only 2) possible stages of epileptic seizure, and the presence of autonomic signs such as urination and hypersalivation. Clinical and neurologic examination should be undertaken. Interictal clinical signs other than postictal signs are more likely to be indicative of structural brain disease. However, a normal neurologic examination does not eliminate the possibility of a brain lesion. Evaluation of behavior and movement can best be carried out by permitting the cat to walk freely in the examination room, although some cats might refuse to walk in such a stressful situation.
Further diagnostic work-up ideally includes blood pressure monitoring, urinalysis, hematology, biochemistry, CSF analysis, and MRI of the brain. Routine laboratory tests are usually of little diagnostic value, but should be performed to rule out metabolic encephalopathy and could also be helpful for guiding anesthesia (for diagnostic procedure) and for the later evaluation of treatment-induced changes, for example, by phenobarbital.[8, 25] Bile acid testing can be diagnostic, as hepatic encephalopathy is known to occur in cats.[7, 8, 11] Serology testing for feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline infectious peritonitis (FIP), and toxoplasmosis is frequently requested, but there is little evidence for its usefulness. In North America, FeLV, FIV, FIP, and toxoplasmosis testing was nondiagnostic in all cats tested with seizure and concluded that those disorders are unlikely to be the primary cause of brain disorder, especially in the absence of any other systemic involvement. In a European study, infectious disease was rarely diagnosed in seizing cats (2 of 125 cases) in an urban environment, although the study suggested that there can be geographic differences. For older cats, thyroid hormone concentration should be tested to rule out hyperthyroidism, which is a possible etiology for epileptic seizures. Similarly, hypertensive encephalopathy is regularly suspected in older cats with seizures.[7, 11] Computed tomography and particularly MRI can be used to rule out the presence of structural brain disorders.
As previously noted, EEG diagnostic in small animals is of limited value. Consistently, most articles about seizure in cats do not recommend EEG for the routine work-up.[8, 10, 14, 15, 26, 27]
Epileptic discharge can be detected by EEG, which is a standard diagnostic procedure in the epilepsy work-up for a human patient. A problem in veterinary epilepsy is that EEG data are not consistent and there is no agreement about the appropriate technique and sedation protocol, or about the graphoelements that are associated with epileptic seizures. There are only limited data relating to clinical EEG in healthy cats and cats with recurrent seizures.[9, 12, 28] Recently encouraging EEG results were reported in cats. Under propofol restrain, 6 of 13 epileptic cats showed paroxysmal discharges (focal or generalized spikes), while such activity was not detected in any of 6 healthy control cats. In this study, interictal EEG records with ED were also presented. There have been no previous clinical studies to suggest convincingly that epileptic activity in cats can be recorded under clinical conditions. The practical consequence of this limitation is that it is usually not possible to confirm the “abnormal excessive or synchronous neuronal activity in the brain,” so whether a seizure event is epileptic can only be suspected based on clinical, laboratory, and neuroimaging findings. In accordance with the uncertainty that the episode is really epileptic, a diagnosis of “probable/possible epileptic seizure” would be more appropriate in small animals as the diagnosis of definite epileptic seizure requires confirmation by EEG. Such a diagnosis would be consistent with human terminology, not with regard to the likelihood of recurrence, but to the likelihood of an epileptic origin.
In contrast to the limited clinical EEG data, there has been a large amount of experimental research on EEG recording in cats. Either electrically or chemically induced epileptic seizures have been recorded. The most frequently used technique has been intracranial ictal recording with implanted electrodes for freely moving cats. However, ictal surface EEG patterns after electrically induced seizures were also reported. Very characteristic hippocampal 14–39 Hz discharges were detected and found to be constant in an individual cat in different seizure episodes. In contrast, ED of the isocortex were usually at 8–16 Hz. The ictal termination was always abrupt and preceded by spike-wave activity. Others found that 4–6 Hz is a typical ictal pattern for amygdala. The authors also indicated that during the spread of seizures, the pattern in the newly affected areas can be identical or slightly or completely different from that in the primary focus. Discharges after amygdala kindling were analyzed and interictal spikes were observed in amygdala, substancia nigra, putamen, globus pallidus, and midbrain reticular formation; the frequency was about 6 per minute during the experience, but thereafter diminished to 0.04 per minute.
There are significant problems in translating experimental results to the clinic. Ictal recording could be very time-consuming, the influence of anesthetic drugs reduces the recordable epileptiform activity, and surface electrodes only deliver limited information about what is happening in deeper structures. Healthy control cats have been included in some studies, although intracranial recording was usually performed and this is impossible in daily practice and provides very limited conclusions. For these reasons, EEG is currently not widely used clinically, although strictly speaking, it is necessary for the objective differentiation of the paroxysmal event and for confirming epilepsy. Based on the experimental studies, it is clear that EDs are detectable ictally and interictally in epileptic cats, but appropriate technique is needed. Systematic studies by multiple centers on various aspects of EEG might result in a protocol that can be recommended for practical use in the small animal clinic. Advances in EEG diagnostic procedures are urgently necessary for veterinary medicine.