Since antiquity, the attempt to classify symptoms has been intended to identify a specific disease or syndrome. The first known mention of epilepsy is from about 500–700 BC. Stone tablets found in Babylon contain detailed observations of epileptic seizure types, provoking factors, and postictal symptoms. The ancient Greek Hippocrates (460–377 B.C.) recognized that the symptoms of epilepsy originated from the brain. Still, classification of epileptic seizures is a crucial tool in the diagnosis of epilepsy. It is of special importance in distinguishing between partial (focal) and generalized seizures as well as predicting the outcome of seizure control.
Epilepsy is defined as “a chronic brain disorder of various etiologies characterized by recurrent seizures due to excessive discharge of cerebral neurons (epileptic seizures), associated with a variety of clinical and laboratory manifestations.” (Gastaut 1973)
Epileptic seizures are clinically expressed by signs reflecting abnormal function of the entire brain or of specific cerebral areas involved in the epileptic activity. Since the individual animal has particular lesions/neurotransmitter imbalances leading to epilepsy, the symptomatology/phenomenology reflecting the disease will be repeated every time the animal experiences a seizure. The characteristic symptoms will be recognized by the owner, if questioned closely by the veterinarian.
The diagnosis of epilepsy is in essence clinical, based upon the medical history, physical and neurological examination, and the history of the epileptic seizures (Parent 1988, le Couteur and Child 1989, Shell 1993a, 1993b, Schwartz-Porsche 1994, Podell et al., 1996, Heynold et al., 1997, Jaggy and Bernardini 1998, Berendt and Gram 1999).
Detailed description of seizure symptomatology and video taped registration of suspected seizure episodes are of the greatest importance in the work-up of the epileptic patient. Electroencelphalogram (EEG) registration has never been established as a routine laboratory test in the diagnosis of canine epilepsy.
Classification of epileptic seizures
Classification of epileptic seizures in man has been established by The Commission on Classification and Terminology of the International League Against Epilepsy, ILAE (1981). This classification system is based upon localisation of the seizure focus (the area in the brain from where seizures are generated) and the degree of alteration of consciousness expressed by the seizure symptomatology experienced and reported by the patient and/or her/his relatives. The diagnosis may be supported by abnormalities recorded in the EEG. A model for classification of epileptic seizures in dogs based upon the guidelines of the ILAE, but with an emphasis on seizure symptomatology/phenomenology has been described by Berendt and Gram (1999).
Epileptic seizures are divided into two main categories: primary generalized seizures and partial seizures. In primary generalized seizures, the first clinical changes indicate initial involvement of both hemispheres (ILAE 1981). This is reflected in the ictal EEG by a sudden and simultaneous loss of the normal electroencephalographic background activity in both hemispheres, being replaced by epileptiform discharges representing hypersyncronous neuronal activity. Motor symptoms are bilateral.
The symptomatology of primary generalized seizure activity so far scientifically documented in dogs and cats is consistently convulsions. The classical generalized tonic-clonic seizure is easily recognized based on the history and clinical features. There is a sudden loss of consciousness, without any premonitory symptoms, followed by convulsions.
In partial seizures, in general, the first clinical and electroencephalographic changes indicate initial activation of a system of neurons limited to part of one cerebral hemisphere (the epileptic focus). The clinical signs reflect the functions of the area involved (ILAE 1981).
In the majority of cases the epileptic focus represents structural brain pathology e.g., post traumatic lesions, space occupying lesions, or cortical developmental disorders. Partial seizures with no detectable underlying lesion (idiopathic partial seizures) have been documented in humans, but so far, not in dogs or cats.
Partial seizures are subdivided into simple and complex partial seizures. Partial seizures can become secondary generalized seizures. Partial seizures are classified as simple, if consciousness is unimpaired, and complex, if consciousness is impaired; impaired consciousness being defined as an inability to respond normally to external stimuli. Simple partial seizures can evolve into complex partial seizures, the first signs of this being a change in perception and reaction pattern (ILAE 1981).
In simple partial seizures as a rule, the abnormal electrical activity only involves one hemisphere, whereas complex partial seizures often affect both hemispheres. Spreading of the abnormal electrical activity involves structures of the limbic system. A complex partial seizure can evolve from a simple partial seizure or occur as a seizure where consciousness is impaired from the onset.
Whether it is possible from the symptomatology alone (as described by the owner and/or documented on video), to distinguish between simple and complex partial seizures in cats and dogs, is debatable and should be a topic for discussion in veterinary neurology.
Partial seizures with secondary generalization: secondary generalization of a partial seizure happens when partial seizure activity does not remain focal, but projects rapidly to subcortical structures to involve the entire brain. Symptomatology is initially characterized by the function of the anatomical site of the seizure focus, then is rapidly (within seconds to minutes) followed by convulsions as seizure activity spreads from the focus to involve the entire brain. Partial seizures with secondary generalization appear to be the seizure type most commonly observed in dogs (Heynold et al., 1997, Podell 1995, Berendt and Gram 1999, Berendt et al., 2001). In many patients, the partial seizure onset is very subtle and is followed by a rapid secondary generalization, which can make it difficult to detect the partial onset, as acknowledged already by Holliday in 1980.
Aura is the synonym for a simple partial seizure. In humans, by tradition the term aura has been used about the phenomenology of the simple partial seizure acting as a signal/warning sign of the forthcoming seizure development (in cases of simple partial seizures evolving into complex partial seizures or secondary generalization with convulsions).
A variety of symptoms of partial and generalized seizures have been reported in humans and dogs (Panayiotopoulos 1988, Majkowsky 1991, Bell 1997, So 1997, Dreifuss 1998, Cromwell-Davis 1989, Dodman et al., 1992, March PA 1998, Berendt and Gram 1999, Berendt et al., 1999).
Work-up of patients suspected of epilepsy
The primary question when presented with a canine or feline seizure patient is if the event is of an epileptic nature. Many systemic disorders of organic, metabolic, endocrine, toxic, or psychogenic (behavioural) nature can appear clinically as imitators of epilepsy (Shell 1993b, Fisher 1994). Therefore, the examination of any patient presented with a history of seizures should as a minimum include a full physical and neurological examination, haematological and biochemical screening and urine analysis.
In order to confirm a suspected diagnosis of epilepsy and to classify epileptic seizures in dogs and cats the following diagnostic methods can be applied with the specific aim to uncover seizure aetiology, seizure origin (detect the seizure focus), and seizure development.
1. Neurological examination.
2. Questionnaire on seizure description.
3. Video documentation.
6. Cerebrospinal fluid (CSF) examination.
Neurological deficits/symptomatology can reflect cerebral lesions. Based upon the symptomatology identified, the lesion can be localised to a specific part of the brain leading to a neuro-anatomical diagnosis.
The questionnaire is a systematic tool in collecting and recording detailed anamnestic information on seizure symptomatology. Given to the owners, the questionnaire ensures that details that might otherwise be missed, especially with respect to detecting a partial seizure onset, are recorded. The questionnaire should be given as an oral interview. The patient history should focus on the previous medical history, including clues of a possible birth trauma and information with regard to earlier occurrence of head trauma or febrile disorders affecting the brain; seizure onset and frequency; and a careful description of seizure development as observed by the owner.
Videotaped seizure episodes should be used to document the nature of the seizures and to detect subtle signs of a partial seizure onset, which might otherwise be missed by the owner. Owners should be urged to videotape suspected seizure episodes at home (home video). Hospitalized animals should be videotaped during seizure episodes, if possible. Since it is extremely infrequent that veterinarians have the opportunity to observe seizures in the canine and feline epilepsy patient, video registration of seizures represents an excellent supplement to the seizure description given by the owner.
The source of the EEG is electrical potentials generated by cortical neurons. In the surface EEG, only activity from the surface areas that are anatomically accessible, is recorded. Therefore an abnormal EEG can support the diagnosis of epilepsy whereas a normal EEG does not exclude this diagnosis (Holliday et al., 1970, Berendt et al., 1999). The EEG is used to confirm the clinical suspicion of epilepsy and discriminate between partial and generalized epileptic discharges. Also, the EEG can be helpful in identifying a suspected seizure focus.
Computer-assisted tomography/magnetic resonance scanning (CT-/MR-scanning)
CT-scanning/MR-scanning of the brain are highly beneficial in the diagnostic work-up of animals suspected of an intracranial lesion as the cause of epilepsy. On CT-scans and MR-scans of the head, it is possible to visualize the brain and to differentiate between grey and white matter structures, the ventricular system and bony tissue. CT-scans may be used to identify gross structural brain lesions in patients experiencing seizures, while MR-scanning provides the clinician with a more detailed view of the brain structures. Compared with CT, with the MR technique, it has been possible to identify more delicate lesions in the brain, e.g., hippocampal atrophy and sclerosis, as well as focal cortical developmental disorders associated with epilepsy in humans and animals (Kuzniecky and Jackson 1995). In cases, where brain scanning identifies an intracranial lesion as the probable cause of seizures, the dog/cat should be classified as having symptomatic epilepsy.
Cerebrospinal fluid (CSF) examination
CSF pathology reflects lesions in the central nervous system. Therefore, CSF examination is an important aid in diagnosing conditions leading to symptomatic epilepsy, e.g., granulomatous meningoencephalitis (GME) or inflammatory lesions.
“Despite the wide-ranging advances of sophisticated technological methods used in the diagnostic work-up of patients with epilepsy, accuracy of observation still remains the basis for any clinical endeavour.” This statement was made by the human epileptologist Dreifuss (1997) and should be recognized as a golden rule when working with feline and canine epilepsy patients as well.
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