Newsletter: Volume 8, Issue 2 December 2004

I received information about a potential study to be done into the immunopathology of Familial Shar-Pei Fever/Amyloidosis in the Shar-Pei. I’m giving the Shar-Pei fancy in this area a heads up as I will be relying on you and your dogs to help with blood samples. Samples would be collected from the following groups of dogs: 1. Adult Shar-Pei dogs with an FSF history but no current symptoms. 2. Healthy adult Shar-Pei dogs with no history of FSF that have not had recent vaccinations or any clinical signs of infectious disease within the previous month. Approximately 20 mls of peripheral blood would be drawn in EDTA (anticoagulant) and an additional 5 mls drawn for serum. Clinical histories, including history of FSF, infectious disease, vaccination and current medication, as well as pedigree information if available, will also be provided with these samples. Acute phase cytokines IL-1b, TNFa, IL-6 and IL-10, and the acute phase proteins C-reactive protein and serum amyloid A will be measured. The goals of the study will be to develop a specific biological test for identifying individuals susceptible to FSF and to aid in the diagnosis of FSF. A second goal will be to study the immune system function of Shar-Pei dogs. This will better characterize immunodeficiency disorders in the breed. Studies such as this are very important and necessary to try to understand the mechanism of Familial Shar-Pei Fever. Hopefully the information generated will help in the development of a test to screen breeding stock for FSF and thus breed away from it. I will be contacting owners of dogs who fit the criteria in the new future providing the project gets the necessary funding. I know the CSPCA Charitable Trust will definitely provide funding if asked.

Seizures (Epilepsy)

Epilepsy is a disorder of the brain characterized by recurring seizures. Seizures, fits and convulsions are synonyms which are used interchangeably to describe the manifestations of abnormal brain activity, usually involving a generalized motor component. A convulsion is used to describe seizures with a generalized motor component. Seizures can be confused with fainting episodes (syncope); narcolepsy which is a disorder characterized by sudden recurring attacks of sleep, collapsing episodes, activated sleep in young dogs, acute vestibular syndrome in older dogs (“stroke”), etc. A seizure is really abnormal electrical activity in one area of the brain (a focus) which can affect adjacent areas and generalize to the entire brain.

A seizure actually consists of several components. The aura is a period of time just before the seizure in which altered behavior may occur. During this time the animal may know a seizure is about to occur and may hide, appear very nervous, seeking out the owner or become “clingy”. The actual seizure is called the ictus and this time period may vary from 1-2 minutes to several minutes. In thepostictal period following a seizure there can be several minutes of disorientation, lack of recognition of the owner, trouble with balance and walking, etc. The owner should be very careful during the seizure and immediately following as the dog may not be in full control of their facilities. It is not necessary for the owner to put something in the dog’s mouth to prevent them from biting their tongue, in fact handling the mouth is not recommended. It is important to prevent the dog from injuring itself falling down stairs, running into walls, getting caught under furniture and the like. I usually recommend covering the dog with a blanket or comforter. It’s also a wise thing to cut down on stimulation during the seizure by turning down the lights, turning the volume down on the TV or radio and keeping other people out of the room (primarily children). Also be aware that many dogs lose bowel and bladder control during a seizure.

Seizures can be classified into three basic types: generalized, partial and partial with secondary generalization. Severe generalized seizures with a total loss of consciousness are classified as grand mal seizures in humans. This type of seizure probably does not occur in animals. Generalized seizures usually indicate diffuse cerebral cortex involvement and are often associated with metabolic disturbances, toxicities, nutritional disturbances and true or inherited epilepsy. In dogs this type of seizure is characterized by a tonic phase in which the muscles become very rigid and a clonic phase in which jerking of the limbs, neck, face and jaw muscles may occur. There usually is excessive salivation and as the animal relaxes they may also urinate and defecate. Most generalized seizures last about 30-90 seconds. During the recovery period the dog may be exhausted and want to sleep or be anxious pacing and appearing disoriented. The first seizure often occurs between 1 and 7 years of age. The highest prevalence is in the 1-5 years of age range. There is no correlation between severity and etiology or the cause of the seizure.

Partial seizures are associated with a focus of brain damage (gross or microscopic changes in the forebrain) due to infection, metabolic or toxic insult (reactive epileptic seizures), trauma or neoplasia. Symptoms are unilateral muscle twitching (focal motor seizure), bizarre or aggressive behavior, chewing, lip smacking, excessive swallowing, running, confusion, psychomotor seizure, “fly biting”, “star gazing”, hallucinations (temporal/occipital lobe), tail chasing, self mutilation and even chronic episodic vomiting and diarrhea (limbic system/hypothalamus). Partial seizures may spread to other parts of the brain resulting in a generalized seizure (partial seizure with secondary generalization). It is very easy to overlook the partial part of the seizure but with careful observation the partial seizure may be identified and this helps to determine the type of seizure and the underlying disease process. Another classification of seizures is based on clinical signs with primary generalized epilepsy used for generalized seizures in which no cause can be determined and secondary epilepsy for those cases where an underlying organic cause can be found. Primary epilepsy is a genetic disease and inherited in some breeds. I can’t say it’s inherited in the Shar-Pei but I have seen lines of Shar-Pei with a seizure tendency. I have seen hydrocephalus (water on the brain) in a 6 month-old Shar-Pei with seizures and cases where I suspected birth anoxia (low or no oxygen) in pups from difficult whelping. Causes of secondary epilepsy are many and I’ve listed some below:

1. Scar tissue in the brain caused by trauma (seizures can occur up to 6 months to 2 years following a head injury), hypoxia (low oxygen), infectious diseases.
2. Electrolyte abnormalities involving sodium, potassium, chloride, and calcium which affect the electrical activity of the brain.
3. Congenital defects such as hydrocephalus, liver shunts, etc.
4. Liver disease in which by-products of protein metabolism, especially ammonia, build up in the blood and affect the brain.
5. The brain preferentially uses glucose as an energy source and any change in blood glucose levels can lead to seizures.
6. Toxicities such as salt intoxication, lead toxicity, heavy metal poisoning, strychnine toxicity (mole, gopher and rodent baits), arsenic, caffeine, cyanide, cocaine, ethylene glycol (antifreeze), heroin, insulin, nicotine, sodium fluoroacetate (compound 1080/1081 a rodenticide), phosphorus, vitamin D, metaldehyde (snail baits), chocolate toxicity, rodenticide toxicity, etc.
7. Potential immune-mediated diseases such as granulomatous meningoencephalitis, old-dog encephalitis, and others.
8. Viral diseases such as rabies, canine distemper, West Nile virus, others.
9. Protozoan diseases such as toxoplasmosis, Neospora caninum,
10. Parasitism such as aberrant migration of roundworms or heartworm, or an aberrant (abnormal) host such as cysticercosis involving the larval forms of tapeworms (hydatid cyst disease in humans).
11. Fungal diseases such as cryptococcosis, and blastomycosis.
12. Immune-mediated diseases such as granulomatous meningoencephalitis (GME) Vascular diseases (stroke) such as thromboembolism (blood clots) atherosclerosis, hemorrhage secondary to hypertension.

In humans four subdivisions of epilepsy are recognized based on clinical signs and EEG findings:

1. Grand mal – generalized seizures with subgroups: generalized, focal (localized) and Jacksonian.
2. Petit mal —
3. Psychomotor – may have clinical signs such as behavioral changes, running, fear, aggression, “fly biting”, “star gazing”, etc.
4. Autonomic – signs may include excessive salivation, diarrhea, vomiting and abdominal discomfort.

This classification is not used in animals for the most part although some of these seizure types may occur in animals and are not recognized or diagnosed.

Generally after an initial physical examination blood work is submitted to the laboratory to get a handle on reactive epileptic seizures. The basic blood chemistry screen evaluates liver and kidney function, blood sugar, electrolyte levels, serum protein levels, and a complete blood count. Additional blood tests are required to evaluate liver function tests such as bile acids and blood ammonia levels, serum antibody levels for various infectious diseases, and blood lead levels to evaluate lead toxicity. Additional diagnostic procedures include electroencephalography (EEG) in which the electrical activity of the brain is evaluated, magnetic resonance imaging (MRI), CT scan (computerized tomography), cerebrospinal fluid tap with analysis and dye studies of the brain to evaluate the blood supply to the brain.

When to begin anticonvulsant therapy depends on your veterinarian. A few seizures a year or mild seizures may have little long-term effect on the animal and anticonvulsant therapy might not be indicated. Severe generalized seizures, cluster seizures or very frequent seizures, or owners who are upset about the seizures anticonvulsant therapy should be considered. The goal of anticonvulsant therapy is to reduce the frequency and severity of seizures and not to necessarily eliminate them. The seizures are only controlled and not cured. Therapy more often depends on owner compliance and the realization that success varies with each animal. The length, severity, time of the seizure and possible triggers of the seizures should be logged.

Initial anticonvulsant therapy begins with phenobarbital orally. Potential adverse effects include transient lethargy, and behavior changes; more persistent problems such as polyuria, polydipsia, polyphagia, weight gain and excessive sedation; and severe effects with liver toxicity. Another drug often used early on is potassium bromide. It may take up to 4 months to range therapeutic levels and so is often started with phenobarbital or is used when phenobarbital is not as effective or liver toxicity is a problem. Side effects include lethargy, polydipsia, polyuria, pancreatitis, stupor and ataxia. As the dosage range is quite wide for both these drugs and they are often dosed to effect these drugs have therapeutic blood levels which can be monitored via blood testing.

Two serious complications of epilepsy are status epilepticus and severe cluster seizures. Status epilepticus is the condition of rapidly recurring seizures with incomplete recovery between the seizures. This can result in the death of the patient because of brain swelling caused by hypoxia and hyperthermia caused by the excessive muscle activity. Animals with status epilepticus may develop permanent brain damage due to brain hypoxia making them refractory to anticonvulsant therapy or predisposing them to future episodes of status epilepticus. Permanent neurologic signs such as blindness and mental retardation as evidenced by change in behavior, loss of house breaking, etc. may result. Status epilepticus is a medical emergency and your dog should be seen by a veterinarian immediately. Treatment involves support with IV fluids, and use of injectable anticonvulsant medications to control the seizures. Treatment for brain swelling may also be necessary. Cluster seizures are individual seizures that occur close together with short recovery periods between the seizures. These animals are at increased risk for status epilepticus.

Seizure dogs can be successfully managed but therapy requires attention to detail, a fairly structured routine and regular therapeutic drug monitoring by your veterinarian.