Seizures
Seizure Causes

Seizures
Teri Dickinson, DVM
With special thanks for editorial assistance from Patricia J. Luttgen, DVM, MS, diplomate ACVIM (neurology), Lakewood CO and Grace Robinson, DVM, Dallas, TX

DEFINITION OF TERMS

A seizure has been defined as "a transitory disturbance of brain function"⁽¹⁾ which results in alterations to behavior and activity caused by abnormal brain function. The terms convulsion, fit and ictus⁽²⁾ are synonymous with the term seizure. A generalized seizure has been defined as "a period of generalized muscle activity accompanied by loss of consciousness."⁽³⁾

Epilepsy³ refers to recurrent seizures arising from a nonprogressive intracranial (located within the skull) disorder. Note that the term nonprogressive means that the cause is nonprogressive, not the severity or frequency of the seizures themselves.

Epilepsy is of acquired or idiopathic origin. Acquired or secondary epilepsy is that in which a previously active brain disorder has left the brain in a seizure prone state. An example might be a dog that is hit by a car and suffers head trauma, but survives. Idiopathic epilepsy is also known as inherited, congenital or primary epilepsy and involves recurrent seizures for which no cause can be identified.⁽⁴⁾

WHAT HAPPENS DURING A SEIZURE?

What happens during a seizure is complex, and not totally understood.⁽⁵⁾ In the field of human medicine much research has been devoted to how a seizure actually occurs but many questions remain to be answered.

For our purposes, a simple explanation will suffice. Neurons (nerve cells) in the brain transmit and process information through the creation and conduction of small electrical currents. Normal function of a neuron is associated with a different electrical charge inside the cell than outside. This difference is known as the membrane potential (MP). It reflects the different charges found inside the cell membrane versus outside. Under certain circumstances, this difference is turned into an actual electrical charge, which is passed on to neighboring cells. The neuron is said to have "fired."

Neurons also create special substances, neurotransmitters, which when released, act on the membranes of nearby cells. Neurotransmitters may act to excite or inhibit nearby cells. Normal transmission of information requires a finely tuned combination of excitement and inhibition. A seizure reflects the results of too much excitation, too little inhibition or neurons that are too sensitive to the neurotransmitters.

During a seizure, certain cells (a seizure focus) begin to fire repeatedly and spread this behavior to other cells. A normal brain responds with enough inhibitory neurotransmitters to stop the spread. If a group of neurons "runs away," firing repeatedly and the brain cannot inhibit them, a seizure results. Seizures are often self-limiting as the renegade neurons exhaust themselves and stop firing. The period after the seizure may reflect lower than normal activity among the neurons. How and why the "renegade" neurons cause a seizure is still a matter of much investigation.

PARTS OF A SEIZURE

A seizure consists of three parts, the aura, the ictus and the postictus. The aura signals the beginning of the seizure. It is characterized by behavioral changes such as whining, restlessness, hiding or apprehension. During this stage, abnormal electrical discharges are taking place among the neurons.

The ictus is the seizure stage and is characterized by all the signs associated with the seizure: unconsciousness, muscle activity, salivation, etc. Neurons are firing rapidly and are unresponsive to inhibitory substances.

The postictal phase occurs immediately after the seizure and may last a few minutes to several days. It may be characterized by confusion, wandering, blindness or unresponsiveness. The neurons are exhausted and unable to respond.

TYPES OF SEIZURES

Seizures can be divided into types, based on the signs seen during the seizure and changes to the EEG (a reading of the electrical currents in the brain). Most work on classifying seizures has been done in humans and may not always apply accurately to dogs, but at least two types of seizures are documented in dogs: partial (also known as focal) and generalized.⁽⁶⁾

Partial seizures have signs and EEG evidence that the seizure originates from one area (focus) of the brain. A partial seizure may progress and become a generalized seizure, or may be limited to a specific abnormality such as repetitive motions of a single limb or facial twitches. Partial seizures are commonly associated with acquired causes and brain tumors.

Generalized seizures are also called grand mal, major motor (affecting movement) or tonic-clonic⁽⁷⁾ and are characterized by signs and EEG abnormalities that are widespread from the very beginning of the attack. Generalized seizures are usually bilateral (affect both sides), symmetrical, include loss of consciousness, generalized motor dysfunction and sometimes urination and defecation. Idiopathic epilepsy is usually evidenced as generalized seizures.

DETERMINING THE CAUSE OF SEIZURES

In attempting to find the cause of seizures, it is important to remember that seizures are not a disease, but merely a symptom of a disease process. A process of elimination or "rule outs" is used to determine the cause.

The normal brain is capable of seizing in response to a variety of stimuli; therefore, the causes of seizures are many. Causes of seizures can be divided into two major categories, extracranial and intracranial.³ Extracranial causes are those that arise outside the nervous system, (i.e., exposure to toxins). Intracranial causes arise within the nervous system (i.e., brain tumors).

Each of these categories can be subdivided. Extracranial causes can be divided into external or those that originate outside the body (i.e., toxins) and internal or those that originate inside the body (i.e., liver disease). Intracranial diseases can be divided into those that are progressive or nonprogressive. Progressive disorders involve more and more brain tissue over time (i.e., tumors). Nonprogressive diseases do not involve additional brain tissue, although the severity of the seizures may increase over time. Epilepsy, both acquired and idiopathic, is an example of a nonprogressive, intracranial cause of seizures.

Determining the cause of seizures is a process of ruling out possible causes and begins with the veterinarian obtaining an accurate history, conducting a physical exam that includes a thorough neurologic (nervous system) examination, and running basic laboratory tests. A complete blood count, urinalysis and serum chemistries to check for kidney and liver function, hypoglycemia, hypothyroidism, etc. are routinely performed. Any abnormal test results will be followed by more specific tests. Acquired (secondary) epilepsy is usually diagnosed by taking a thorough history, especially regarding trauma (hit by car), anoxia (lack of oxygen due to near drowning, some type of entanglement, etc.) or other such incidents. If the history and subsequent testing fail to reveal abnormalities, an extracranial cause can usually be ruled out.

If an intracranial cause is suspected, more specific tests will be conducted. These may include skull x-rays, spinal fluid analysis, EEG's or possibly CT⁽⁸⁾ or MRI⁽⁹⁾ scans of the head. Economics and availability of some tests (EEG, CT or MRI) may limit diagnostic options.

If the specific testing for intracranial causes fails to identify abnormalities, the remaining choice is nonprogressive intracranial disease. For the most part, nonprogressive intracranial disease is classified as idiopathic or inherited epilepsy.

Dogs affected with idiopathic epilepsy are usually healthy and completely normal between seizures with no abnormal test results (even EEG)⁽¹⁰⁾ between seizures. Onset of seizures usually occurs between six months and five years of age, although seizures may not be recognized until the animal is older. In some individuals seizures may be triggered by some stimulus: fatigue, stress, fear, etc. In others, onset of seizures seems completely random. Epileptic⁽¹¹⁾ is the term used to describe individuals afflicted with epilepsy.

It has not been determined if idiopathic epilepsy is an inherited disease in all breeds of dogs. Despite the relatively high incidence of canine epilepsy, very little active research is being conducted in dogs.⁽¹²⁾

A review of the literature indicates that inheritance has been proven or is strongly suspected in the following breeds; Beagles,⁽¹³⁾ German Shepherds (Alsatians-England)⁽¹⁴⁾, Belgian Tervurens,⁽¹⁵⁾ Keeshonden,⁽¹⁶⁾ Dachshunds⁽¹⁷⁾ and Horak's laboratory dogs (Czechoslovakia).⁽¹⁸⁾ Many breeds are also reported to have a higher than average incidence of affected individuals, which may also point to a genetic component. Among these are Poodles, Cocker Spaniels, and Irish Setters.⁽¹⁹⁾ The incidence of affected individuals in various dog populations is reported to be between 0.5% and 5.7%^10,(20). No reports appear in which idiopathic epilepsy is proven not to be an inherited disease.

Three selective breeding studies of dogs produced incidences of 38%,⁽²¹⁾ 66%⁽²²⁾ and 100%¹⁵ epileptic offspring when both sire and dam were epileptic. Another study documents an incidence of 63%⁽²³⁾ epileptic offspring produced from an accidental breeding of two related, epileptic individuals. Two of these studies^15,19 also noted a very early onset (6-8 weeks of age) of seizures in these litters.

Pedigree analysis in several above mentioned breeds demonstrates a familial (occurring in more members of a family than expected by chance) pattern of inheritance. Studies of humans, mice, rats and rabbits leave little doubt that epilepsy in these species is inherited. Mice are common animal models for epilepsy in humans, and work is under way identifying the specific genes that cause the epilepsy.⁽²⁴⁾

Cunningham and Farnbach,¹⁸ in a study supported in part by the Irish Setter Club of America, reached the following conclusions:

"Until the genetic mechanisms involved are more clearly understood, it seems prudent for veterinarians to advise owners of epileptic dogs that:

1) The idiopathic form of canine epilepsy may have a major genetic component.

2) It generally is impossible, without considerable test breedings, to determine the degree of involvement of either the sire or the dam in producing epileptic offspring.

3) It is unwise to breed an epileptic dog or to repeat the breeding that produced it, and it is probably unwise to breed its litter mates."

TREATMENT OF SEIZURES

Treatment of seizures varies widely according to the cause. External extracranial causes such as environmental toxins (lead, insecticides, etc.) require removal of the offending substance from the animal's environment. In addition, specific treatments may be required to counteract the effects of the toxins and anticonvulsants (drugs used to control or prevent seizures) may be required to control the seizures.

Internal extracranial diseases require identifying the disease process and providing the specific treatment. These disease processes include fungal infections, kidney or liver disease, hypothyroidism, viral infections (i.e., distemper or rabies), and hypoglycemia.

Intracranial diseases include tumors, congenital defects (i.e., hydrocephalus) and infarctions (loss of blood supply to an area). Therapy includes specific treatment of the primary disease (if possible) and anticonvulsants as needed to control seizures.

Anticonvulsants are usually the only treatments given for idiopathic epilepsy. Not all affected individuals require drug therapy. The decision to treat epileptics is usually based on several factors: frequency and severity of seizures, likelihood of owner compliance with a treatment regime, and known side effects of anticonvulsants. Despite their frightening appearance, infrequent grand mal seizures of 1-3 minutes duration with no abnormalities remaining after the seizure are generally not dangerous to the patient.

In treating seizures, the goal is to keep seizures to a minimum, while avoiding serious side effects. All anticonvulsants have some undesirable side effects and require regular monitoring of the patient. LeCouteur and Child³ recommend anticonvulsant therapy for dogs known to have one or more seizures per month, unless animals have clusters of seizures or episodes of status epilepticus (rapidly repeating seizures with no period of consciousness between them). These animals should be treated regardless of the length of the interval between seizures. Status epilepticus is a medical emergency and requires immediate treatment.

Skerrit² states that 60-70% of all treated cases have a reasonable measure of control with proper, monitored, anticonvulsant therapy. A variety of drugs are used to treat seizures. At present, phenobarbital is considered the drug of choice. Additional drugs may be added to the treatment protocol if the level of control is not satisfactory.

Bibliography

1. DeLahunta, A: Veterinary Neuroanatomy and Clinical Neurology. WB Saunders Co., Philadelphia, 1977.

2. Skerritt, G: Canine Epilepsy. Canine Practice. Bailliere Tindall, London, 1991.

3. LeCouteur RA, et al: Clinical Management of Epilepsy in Dogs and Cats. Problems in Veterinary Medicine. 1:4, 578-595, 1989.

4. Oliver, JE et al: Handbook of Veterinary Neurology. 2nd Edition. WB Saunders, Co., Philadelphia, 1993.

5. Fenner, WR et al: Mechanisms of Seizure Disorders. Problems in Veterinary Medicine. 1:4, 501-515 1989.

6. Kay, W: What is Epilepsy? Problems in Veterinary Medicine. 1:4 495-500, 1989.

7. alternate muscle contraction and relaxation

8. computerized tomography, a specialized three dimensional form of X-ray, also known as a CAT scan

9. magnetic resonance image, a type of brain scan

10. Klemm, WR: Electroencephalography in the Diagnosis of Epilepsy. Problems in Veterinary Medicine. 1:4 535-555, 1989.

11. Dorland's Illustrated Medical Dictionary, 25th Ed. WB Saunders Co., Philadelphia, 1974.

12. Indrierei, RJ (Editor): Problems in Veterinary Medicine 1:4 preface, 1989.

13. Biefelt, MS et al: Sire- and Sex-Related Differences in Rates of Epileptiform Seizures in a Purebred Beagle Colony. American Journal of Veterinary Research. 32:12 2039-2048, 1971.

14. Falco, MJ et al: The Genetics of Epilepsy in the British Alsatian. Journal Small Animal Practice 1974;15:685-692.

15. Van der Nelden, NA: Fits in Tervuren Shepherd Dogs: A presumed Hereditary Trait. Journal of Small Animal Practice 1968,9:63.

16. Wallace, ME: Keeshonds: a Genetic Study of Epilepsy and EEG Readings. Journal Small Animal Practice 1975;16:1-10.

17. Holliday TA et al: Comparative Clinical and Electroencephalographic studies of Canine Epilepsy. Epilepsia 1970;11:281-92.

18. Martinek Z, Horak F: Development of so-called "Genuine" Epileptic Seizures in Dogs During Emotional Excitement. Physiol Bohemoslov 1970;19:185-95.

19. Oliver JE: Seizure Disorders in Companion Animals. The Compendium on Continuing Education II:1 77-85, 1980.

20. Koestner A, Rehfeld CE: Idiopathic Epilepsy in a Beagle Colony. Argonne National Laboratory Biological and Medical Research Division Annual Report, 1968:178-9.

21. Cunningham JG, Farnbach GC: Inheritance and Idiopathic Canine Epilepsy. Journal of the American Animal Hospital Association. 1988;24:421-24.

22. Edmonds HL et al: Anticonvulsant Properties of Ropizine in Epileptic and Nonepileptic Beagle Dogs. Epilepsia 1978;19:139-46.

23. Gerard VA, Cornack CN: Identifying the Cause of an Early Onset of Seizures in Puppies With Epileptic Parents. Veterinary Medicine 86:1060-61, 1991.

24. Rise ML et al: Genes of Epilepsy Mapped in the Mouse. Science 253:669-73, 1991.

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Seizure Causes
Teri Dickinson, DVM

In trying to determine the incidences of the various causes of seizures in dogs, researchers are often hampered by several things. One, most research is done in large referral veterinary hospitals, and those hospitals tend only to see the more difficult cases, which have been referred by general practitioners. Two, the dogs may have received various treatments prior to the referral, which might change results of tests run by the researchers. As a result, the incidence of the various causes of seizures in the general dog population has been difficult, if not impossible to determine.

In an effort to generate some valid data about the causes of seizures, the Veterinary College at the Ohio State University devised a new study. In cooperation with local general practitioners, they began to have seizuring dogs referred after the first visit to the local vet, and before any treatment had been initiated. In this manner, they saw all types of seizure cases, not just the difficult referrals. They also gained the ability to do diagnostic testing on the dogs prior to any treatment being started, and they were able to run a well standardized set of tests on all the dogs in the study.

The results of this study were recently published in the veterinary literature as Seizure classification in dogs from a non-referral based population, written by Michael Podell, MSc, DVM; William R. Fenner, DVM; and Jean D. Powers, PhD, in the Journal of the American Veterinary Medical Association, Vol 206, No 11, June 1, 1995. The following is an excerpt of pertinent points which might be of interest to IG owners.

A total of 50 previously healthy dogs who had suffered one or more seizures were entered in to the study. A series of diagnostic tests were performed in an attempt to classify the seizures into one of three categories:

• Primary Epileptic Seizures-those without identifiable cause (idiopathic)
• Secondary Epileptic Seizures-those with an identifiable abnormality within the head (intracranial cause)
• Reactive Epileptic Seizures-those due to metabolic disease or exposure to toxins (extracranial cause)

Each dog underwent standard blood and urine tests to check the function of liver, kidneys, thyroid, etc. Dogs which had abnormal liver function tests underwent liver biopsies to help determine the cause of the liver problem. All dogs had EEG's (brain wave recordings) and CSF (spinal fluid taps) performed. Any dog that did not have an identifiable metabolic cause for the seizures also underwent an MRI (magnetic resonance imaging) scan. MRI is similar in nature to an x-ray, but reveals much more information. Unfortunately, MRI can only be performed at large research institutions, due to the extremely high cost of the equipment.

Based on the owner's history, the seizures were classified as general (generalized motor activity) or partial (isolated motor activity with or without loss of consciousness). Notes were also made about how many seizures the dog had suffered, age at onset, interval between seizures, etc.

On the basis of all this information, the dogs were placed in one of the three classes mentioned above. Even with the intensive diagnostic work-up provided, 22 dogs (44%) were classified as primary (no identifiable cause). 23 (46%) had secondary epilepsy (intracranial cause) and only 5 (10%) had reactive (extracranial) seizures.

Causes of reactive (extracranial) seizures were identified as hepatic (liver) disease, hypothyroidism, and an overdose of orally administered thyroid hormone. Causes of secondary (intracranial) seizures were identified as cerebral developmental anomaly (one or more congenital brain defects) 52%, neoplasia (tumor) 22%, inflammatory process (canine distemper virus or some other infection) 17%, trauma 4%, and cerebral vascular accident, CVA, (stroke) 4%. The most common developmental abnormality was hydrocephalus, which is commonly known as water on the brain. In this condition, fluid does not drain properly and builds up in the brain, causing pressure, which in turn destroys brain cells.

In dogs less than one year old at the first observed seizure, 60% had secondary seizures, usually due to developmental anomalies. In general, one would expect a dog with a developmental anomaly to begin to seize at an early age, since the condition is present at birth. 30% of the dogs who began to seize at less than one year were diagnosed as primary epileptics (no cause could be determined).

Of the dogs greater than five years of age at the time of first seizure, 63% had secondary epilepsy, often caused by neoplasia, inflammatory processes or CVA. In this age group, 25% were diagnosed as primary epileptics.

Of the dogs that were between one and five years of age at the time of first seizures, 63% were diagnosed as having primary epilepsy. There was a greater statistical chance of primary epilepsy if the interval between the first and second seizures was greater than four weeks, (in dogs that had experienced more than one seizure), whereas seizures that occurred more frequently tended to be more indicative of other causes.

One interesting finding in the one to five year old group is that through the use of MRI, five dogs in this group were diagnosed as hydrocephalic. This is contrary to popular belief that dogs with hydrocephalus usually begin to seize at less than a year. Without the availability of the MRI, these dogs would (probably) have been assumed to have primary epilepsy. Nonetheless, even with MRI, CSF, etc. being performed, in dogs of this age range, a cause for the seizures could be established in only about 35% of the dogs.

In summary, dogs that begin to seize at less than one year of age should be suspected of developmental problems or primary epilepsy. Dogs that begin to seize after five years of age should be carefully examined for intracranial neoplasms, CVA, etc. Otherwise healthy dogs who begin to seize at one to five years of age are highly likely to be primary epileptics, particularly if the seizures occur four or more weeks apart. Seizures that occur more than once a month, may be indicative of a developmental, metabolic or infectious process. Neither sex of the dog, nor its neutering status, was found to be significant in predicting the cause of the seizures.

For more information about seizures in dogs, refer to the referenced article Seizures in Dogs Italian Greyhound Vol XXXVI, 4, p 56-61.

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