J . small Anim. Pract. (1 973) 14,28 1-289.

Epilepsy in the dog-a comparative approach

JOHN B A R K E R WelIcome Laboratory for Comparative Neurology, Department of Veterinary Clinical Studies,

School of Veterinary Medicine, Madingley Road, Cambridge

A B S T R A C T

A review of the current theories of the physiopathogenesis of the epilepsies is presented ; emphasis is placed on the value of a more basic approach to the naturally-occuring seizure disorders of the dog, from both a clinical and electroencephalographic viewpoint. The comparative and veterinary rewards of such an approach are stressed.

I N T R O D U C T I O N

Epilepsy may be defined as a paroxysmal and excessive neuronal discharge in the brain (Cunningham, 1971), the clinical expression of which is described as a ‘seizure’, a ‘convulsion’ or a ‘fit’. The site of origin and propagation of the dis- charge is of critical importance in determining its clinical manifestation, and an understanding of its basic mechanisms is essential in adopting a rational approach to diagnosis and treatment.

Clinically, epilepsy has an incidence of about 0.5% in the human population (Williams, 1969); a corresponding figure for the canine population is not avail- able, but seizure disorders formed 1 % of cases in one survey (Cunningham, 1971), and clinical experience indicates the relatively high frequency of the syndrome in the dog as opposed to other domestic species.

The veterinary literature shows a strong bias towards listing of the aetiologies and clinical signs with little emphasis on the underlying physiopathogenesis. Gastaut et al. (1958) describe canine epilepsy as ‘poorly classified’ and deplore the numerous accounts of its ‘protean clinical manifestations’, while the electro- encephalographic and anatomical aspects are largely ignored. Certainly, the tendency to classify epilepsy in the dog into myriad subtypes, based on the clinical signs and causes, has led to confusion in the mind of the practitioner. The following account of current theories in epileptology is greatly simplified, in the hope that this may enhance its value to the clinician.

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T H E P H Y S I O P A T H O G E N E S I S OF E P I L E P S Y

Two major forms are recognized on clinical EEG and pathological grounds. These are (a) Generalized, and (b) Partial epilepsies (Gastaut & Fischer-Williams, 1959) (Table 1).

Table 1 . Table to illustrate basic differences between generalized and par- tial epilepsy on clinical, EEG, and pathological grounds.

Generalized Partial

Sudden onset of unconsciousness, tonic/clonic seizure.

EEG abnormality bilaterally symmetrical, generalized. Usually no pathological lesion.

Gradual onset of localizing signs, (focal motor signs, ‘aura’ behaviour changes.) EEG abnormality focal.

Frequently well-defined intra-cranial pathological lesions.

(a) Generalized The generalized epilepsies comprise 5 % of the total incidence of convulsive dis-

orders in man (Bicard, Gastaut & Roger, 1955), and in this species the clinical signs fall into two groups, ‘Grand mal’ and ‘Petit mal’. A ‘Grand mal’ seizure is the classical epileptiform fit. Its onset is abrupt, the patient becomes suddenly unconscious with no prodromal signs, and enters a phase of bilaterally symmetrical extensor spasm (the tonic phase), with apnoea and cyanosis. Autonomic symptoms, including urination and defaecation, commonly occur during this period. Due to fatigue of the discharging neurons, which rapidly exhaust their available energy reserves, as well as oxygen and glucose (Passonneau, 1969), and possibly due to a more active inhibition by other centres (Gastaut & Fischer- Williams, 1959), the tonic seizure is followed rapidly by alternating extensor spasms and flaccidity (clonus), which passes into a flaccid coma. During this phase, respiration is re-established, and the patient sleeps. Unless status epilepticus exists, a confused recovery of consciousness occurs often with amaurosis and poly- phagia (Pryse-Phillips, 1969). With repeated attacks the post-ictal confusion increases, and becomes more prolonged.

Abnormal EEG activity is similarly sudden in onset, and consists of the develop- ment of spikes of increasing amplitude (‘recruitment’), which are generalized, and bilaterally symmetrical over the whole cortex. During the tonic phase, these are maintained, but are replaced by alternating periods of spiking and isoelec- tricity (lack of electrical activity) corresponding to the clonic ‘jerk‘ and relaxation, and finally give way to total lack of cortical activity during the post-ictal coma.

‘Petit mal’, however, falls into two clinical types-‘absences’ of several seconds

E P I L E P S Y I N T H E D O G 283

duration, and myoclonic jerking of limbs. The EEG activity during the seizure is frequently the classic ‘spike and wave’ much referred to in the veterinary literature. There is little evidence, however, that any analogue of ‘petit mal’ occurs spon- taneously in the dog.

The site of origin of seizure discharges in the generalized epilepsies is the subject of much contention, and hence research. Again, great simplification is adopted in discussing this point because it allows clarification of the ciinical situation. The ‘centrencephalic’ theory postulates that the discharge arises in the diencephalon, possibly in the thalamic reticular formation. The expression of this activity is immediate disruption of conduction, producing a functional severence of the midbrain. The rostra1 transmission of the discharge via the thalamus and the diffuse cortical projection system, produces the abnormal activity seen in the EEG as recruitment and spiking, and its caudal spread, via the reticulospinal and vestibulospinal tracts, gives rise to the tonic phase, closely resembling classical decerebrate rigidity (Gastaut & Fischer-Williams, 1959) (Figs 1 and 2).

The aetiology of the generalized epilepsies falls into two groups. The majority are of metabolic origin. An alteration in the ‘milieu interieur’ of the reticular formation lowers the discharge threshold of its intimately interconnected neuron population. In this ideal substrate, a spontaneous discharge is rapidly disseminated and transmitted elsewhere in the brain. Because of the role of the reticular formation in arousal reactions to sound, light and touch, stimuli will trigger discharges, and hence seizures ; such patients are frequently described as being ‘hyperaesthetic’ to the stimuli. In the metabolic group, the causes include hypoxia, hypocalcaemia, hypoglycaemia, uraemia, hepatic failure, the effects of convulsant drugs, and various toxins, including organochlorides, organophosphates and strychnine (Gastaut et al., 1969).

The remainder of the generalized epilepsies in man are genetically determined

EEG Trace - -Reticulospinol -

Reticular

I1 formation

A Skele to l muscle

Fig. 1. Diagram showing onset of generalized seizure discharge in the ‘centrencephalon’ Note EEG recruitment.

284 J O H N BARKER

,,,,,, ,.,,...,.I..,,.i..I.I...I . . . ,I. , 3 > ! A ? . ., 1 , , , 1 I I I, ., , , , , , , . I , ,I, , , .: .: . : ’

Fig. 2. Diagram showing projection of discharge rostally to the cortex and caudally via vestibulospinal and reticulospinal tracts to extensor muscles. EEG shows generalized

spiking.

and form the group previously designated as ‘idiopathic’, a term still in common parlance in the canine literature. The genetic basis takes three forms: -

Seizures may occur as part of the symptomatology of certain syndromes, including hereditary metabolic diseases, disturbances of chromosome formula and congenital neurectoderm defects. A simple convulsive predisposition expressed as a low seizure threshold may, under the influence of an intercurrent activation, be it metabolic, sensory or pathological, appear as overt seizure activity. Such a predisposition is distributed in a population in a like manner to other polymeric factors, i.e. some individuals convulse readily with minimal stimulation, most convulse if sufficiently activated, and a few never convulse under physiological conditions. Those in the low threshold group, if never challenged, do not show spontaneous attacks; the required challenge, however, may be so minor as to escape detection. A true genetic epileptic predisposition, with a specific gene for generalized seizures has been demonstrated in man. I t appears to have a dominant mode of inheritance, with very weak penetrance (Radermecker & Dumon, 1969).

(b) Partial Ninety-five per cent of human epilepsies come into this category (Bicard,

Gastaut & Roger, 1955). No reliable data exist for the canine incidence. The symptomatology of the partial epilepsies is complex, representing a number

of somatomotor, sensory (‘aura’), autonomic and behavioural manifestations. Attempts to correlate the clinical signs with the supposed site of the seizure discharge-the concept of representation-can be misleading (Gastaut & Fischer- Williams, 1959), but nonetheless of value to the clinician. Thus a focus in the

E P I L E P S Y I N T H E D O G 285

somatomotor cortex gives rise to contralateral motor signs (a ‘Jacksonian convul- sion’) , and a focus in the temporal lobe produces a ‘psychomotor attack‘-a breaking- off of normal and appropriate behaviour and its replacement by abnormal or inappropriate actions (Driver, 197 1). Psychomotor epilepsy is of major importance in man, the temporal lobe having a low seizure threshold, and often, in cases of intra-cranial lesions, producing symptoms when not itself directly involved. Discharges in the sensory cortex give rise to subjective sensations, known as ‘auras’ (meaning ‘a cool breeze’).

Fig. 3. Diagram showing seizure discharge in partial epilepsy (in the somatomotor cortex). Projection in this case is via the corticospinal tract to the contralateral limb musculature.

Note focal nature of the EEG discharge.

Electroencephalography in the partial epilepsies frequently allows the locali- zation of a focus. Spike activity may be observed between seizures, either spon- taneously in the conscious patient, or in response to activation techniques employ- ing natural or drug-induced sleep, photic stimulation, overbreathing or drugs. Direct localization of pyriform cortex (temporal lobe) phenomena in the dog is difficult: in man, where surgical removal of an epileptogenic focus is indicated, sphenoidal needle electrodes are introduced under the zygoma to lie directly beneath the temporal lobe and thus record its activity. The induction of clinical seizures using convulsant drugs allows the observation of the objective form of the attack, as well as recording of its onset and spread over the cortex.

Partial epilepsies originate at a focus or series of foci in cortical or sub-cortical grey matter. However they tend to spread to adjacent areas (Ward, 1966), or, by inter-hemisphere pathways, produce ‘mirror foci’ in the opposite cortex, or, by projection down to the diencephalon, induce secondary discharges in the ‘centrencephalic’ structures and thus in susceptible individuals, precipitate a generalized seizure (Figs 3 and 4). This last mechanism is of major significance, since it leads to much confusion among clinicians: a partial attack may become

D

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, Induced cent rencephalic'

discharge

Fig. 4. Diagram to illustrate secondary generalization of partial epilepsy. EEG shows replacement of focal abnormality by generalized spiking.

generalized so rapidly that its true nature is obscured, and the seizure may then be classified as primary generalized epilepsy.

Partial epilepsies, unlike the generalized group, frequently arise from well- defined pathological process within the cranium. In man, a large number of causes are known; in the dog, trauma, cerebral neoplasia, abscesses, cerebrovascular accidents, hydrocephalus and, most significantly, encephalitis have all been described as causing 'fits' (Anderson & Olsen, 1959; Croft, 1965; Gastaut et al. 1958; Hoerlein, 1971 ; McGrath, 1960; Oliver & Hoerlein, 1965; Palmer, 1972; Redding, 1969).

E P I L E P S Y I N T H E D O G

An attempt has been made to describe the underlying basic mechanisms of the epilepsies, derived from their clinical expression in man and from animal experi- mentation in various species, including the dog, in simple terms. Application of these principles to canine spontaneous seizure disorders should enable clarification of a confused clinical situation, avoiding the pitfalls of emphasis on the taxonomy of symptoms and causes.

Generalized epilepsr In the published investigations using clinical EEG and anatomical approaches to

assess spontaneous seizures of no obvious aetiology-the so-called 'idiopathic' group-no evidence of a 'primary generalized epilepsy of non-metabolic origin has arisen, and no genetically derived 'epileptic predisposition', parallel to that of man, has been defined. I t is obvious, however, that breed tendencies to con- vulsive episodes do occur. The Alsatian, the Beagle, the Cocker Spaniel, the Dachshund, the Keeshond, the Miniature Poodle and the Tervuen Shepherd Dog are all breeds said to suffer from a 'hereditary epilepsy' (Croft, 1968; Holliday,

E P I L E P S Y I N T H E DOG 287

Fig. 5. Onset of spontaneous seizure in 2-year-old Alsatian bitch. Animal shows anxiety with masticatory movements and ptyalism. This attack became rapidly generalized and

tonic/clonic in form.

Cunningham & Gutnick, 1970; Lawler, 1971; Redman & Weir, 1969; Van der Velden, 1968). There has been very little detailed analysis of the mode of inheri- tance of this predisposition.

Descriptions of the seizures said to typify ‘hereditary epilepsy’ often include prodromal signs such as behaviour changes and focal motor activity more con- sistent with partial epilepsy than with the sudden onset to be expected in a gener- alized attack (Fig. 5). Furthermore, an elevation of the seizure threshold by inadequate anticonvulsant therapy in some cases of apparently generalized attacks exposes signs more compatible with a diagnosis of partial epilepsy, secondarily generalized, than with a primary generalized form.

The high incidence of interictal spiking, often lateralized or localized, reported in the ‘hereditary epilepsy’ group of dogs is further evidence against a ‘centrece- phalic’ origin for the seizure discharges. Holliday, Cunningham & Gutnick (1970) observed focal origin of ictal discharge in dogs with generalized clinical seizures, and failed to establish the existence of a spontaneous generalized epilepsy in the seventy dogs studied. Obviously, such a form may occur, but possibly at a much lower frequency than now supposed.

If one attempts to draw a parallel between the clinical situation in ‘hereditary epilepsy’ in the dog and epilepsy in man, the closest correlation exists with partial epilepsy with rapid generalization in individuals having a genetically determined

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‘convulsive predisposition’. In other words, the role of hereditary is to supply a suitable substrate for acquired factors to act, not in itself to provide the activation.

Metabolic origin for generalized epilepsies requires little discussion here. I t is of interest, however, that disturbances of the internal environment are usually extreme before they give rise to clinical seizures. To appreciate this point one has only to consider the degree of uraemia attained before ‘uraemic fits’ appear in the dog in renal failure, or the profound depression of serum calcium in the bitch with eclampsia.

Partial epilepsy As in man, it is becoming increasingly obvious that the partial epilepsies are of

major importance and, even more significantly, that psychomotor epilepsy has a high incidence. In an important study of naturally-occurring epilepsy in the dog, Gastaut et al. (1958) described psychomotor seizures in eleven of nineteen animals. Clinical signs reported include anxiety, fear, masticatory movements and auto- matism. At post-mortem examination, the pyriform-insulo-orbital complex was found to show a predilection for lesions. In a follow-up study, the feeding of agenized flour to experimental dogs produced psychomotor symptoms and lesions were again maximal in the pyriform cortex (Gastaut, Toga & Naquet, 1958). For more general details of the causes of partial epilepsy in the dog the reader is again referred to the papers of Croft (1965), Hoerlein (1971), Palmer (1972) and Redding (1969). These list the various aetiologies and discuss their relative significance.

R E F E R E N C E S

ANDERSON, B. & OLSSEN, S.E. (1959) Acta. Vet. Scanda. 1,98. BICARD, N., GASTAUT, Y . & ROGER, J. (1955) Epilepsia 4,73. CUNNINGHAM, J.G. (1971) 3. A m . Vet. M e d . Ass. 158,589. CROFT, P.G. (1965) Vet. Rec. 77,438. CROFT, P.G. (1968) Vet. Rec. 82, 712. DRIVER, M.V. (197 1) Seminars in Electroencephalography, p. 45. Proc. tY Journal Electrophysiol.

GASTAUT, H., BERARD-BADIER, M., DANESPEN, M., & VAN BOGAERT, L. (1958) Temporal Lobe

GASTAUT, H., ROHMER, F., COSSETTE, A. & KURTZ, D. (1969) n2e Physiopathogenesis of the Epi-

GASTAUT, H. & FISCHER-WILLIAMS, M. (1959) Handbook of Physiology (Ed. by J. Field), Sect. 1. 1,

GASTAUT, H., TOGA, M. & NAQUET, R. (1958) Temporal Lobe Ep i l epy (Ed. by M. Baldwin and

HOLLIDAY, T.A., CUNNINGHAM, J.G. & GUTNICK, M.J. (1970) Epilepsia, 11,281. HOERIEIN, B.F. (1971) Canine Neurology, p. 489. W. B. Saunders, Philadelphia. LAWLER, D.C. (1971) N.Z. v e t . 3 . 19,53. MCGRATH, J.T. (1960) Neurological Examination ofthe Dog, p. 100. H. Kimpton, London. OLIVER, J.E. & HOERLEIN, B.F. (1965) J . Am. Vet. Med . Ass. 146, 1126.

Technol. Assoc. 17, (2) & (4).

Epilepy (Ed. by M. Baldwin & P. Bailey), p. 243. C. C. Thomas, Springfield, Ill.

lepsies (Ed. by H. Gastaut), p. 5. c. c. Thomas, Springfield, Ill.

p. 329. Williams and Wilkins. Baltimore.

P. Bailey), p. 268. C. C. Thomas, Springfield, 111.

EPILEPSY IN T H E D O G 289

PALMER, A.C. (1972) Vet. Rec. 90, 167. PARSONNEAU, J.V. (1969) Basic Mechanisms ofthe Epilepsies (Ed. by H. H. Jasper, A. A. Ward and A. Pope), p. 98. Little, Brown and Co. Boston.

PRYSE-PHILLIPS, W. (1969) Epilepsy, p. 17. J. Wright. Bristol. RADERMECKER, J.F.H. & DUMON, J.E.V. (1969) The Physiopathogenesis of the Epilepsies (Ed. by

Gastaut), p. 31. C. C. Thomas, Springfield 111. REDDING, R.W. (1969) Animal Hosp. 5,79, REDMAN, H.C. & WEIR, J.E. (1969) Am. 3. Vet. Res. 30,2075. VAN DER VELDEN, N.A. (1968) 3. small Anim. Pract. 9, 63. WARD, A.A. (1966) Gomparatiue and Gellular Pathophysiology of Epilepg (Ed. by Z. Servit), p. 171.

WILLIAMS, D. (1969) Epilepsy (By W. Pryse-Phillips), p. vii. J. Wright, Bristol. Excerpta Medica Foundation.

R6sumC. On a present6 une revue des thCories courantes de la physiopathogenbe des Cpilepsies. On a fait ressortir la valeur d’une approche plus fondamentale concernant les troubles d’attaque brusque se produisant naturellement chez le chien d’un point de vue A la fois clinique et Clectro- encephalographique. On a soulignC les rCcompenses comparatives et vCtCrinaires d’une telle approche.

Zusammenfassung. Eine nochmalige Ubersicht der zur Zeit herrschenden Theorie von der Physiopathogenese uber Epilepsien wird vorgelegt ; nachdrucklich betont man den Wert von einer mehr fundamentalen Stellungsnahme zu den spontanen Epilepsieanfall-Storngen des Hundes, von klinischer wie elektroenzephalographischer Hinsicht aus. Man betont die relativen und veterinaren Belohnungen von solch einer Annaherung des Problems.