N.B. - These findings are not yet written in stone. Since the study is ongoing, these statistics may change as more input is acquired. All statements should be read with the mental preface “at present “ or “so far.“
1.) Several owners and breeders, not all of whom have entered this study, have mentioned that they felt that the seizures affecting some animals of their knowledge were caused by difficulties during the pregnancy or the dam’s whelping process. There were not enough entries to pursue this. It would be interesting to see how many of such cases are perceived to exist. The problem of seizures in the Irish Wolfhound has become noticable primarily during the last fifteen years. The first reported “producer” was born in 1962 and the first reported Irish Wolfhound affected with seizures was whelped in 1968. The majority of animals affected with seizures have been born since 1986, so far peaking in the years 1989 through 1997 (Graphs 1a, 1b, 1c)
1.) Today’s Irish
Wolfhounds are the direct descendants of the few hounds used in the nineteenth
century. Therefore, despite different breeding programs world wide, all
Irish Wolfhounds are related and the information derived from this study
applies to the entire breed community. It is through the international cooperation
of many owners and breeders who submitted information that a mode of inheritance
has been determined. Risk analysis for seizures in the IW, as well as for
PRA & PCD, is now available to breeders as a tool for decision making in
their breeding programs. 2.) The ratio of
affected males (90) to females ( 56) is 1: 0.62. There were 4 litters with
4 affected animals each. Two of these litters had a gender split of 2 males
and 2 females. The remaining two of these litters had a gender split of
1 male and 3 females. In addition, there were 7 litters with 3 affected
animals per litter and 22 litters with 2 affected animals each litter. The
gender split in these last 2 groups was not consistent.3.) The ages of
onset for most of the bitches are between 6 months of age and three years
of age. Some of the females were reported to experience first seizures at
or near the time that they came into season (see #14). The ages of onset
for the majority of the males are between 8 months and 4.75 years of age.
There were 10 animals (6 males & 4 bitches) with the onset age of over 5
years of age. (Graph 2)4.) The majority
of animals in this study ( 136 ) experienced recurring grand mal (1) seizures
of undetermined origin lasting 30 seconds to 4 minutes each in duration,
not including the incidences of cluster seizures. The remaining animals
experienced petit mal (2) episodes, mild generalized seizures (6) with 2
of this group advancing to grand mal seizures and two occurrences of
the “fly biting” type of seizure. Most seizure episodes (38.4%) usually
occurred during REM sleep regardless of time of day. The duration of the
seizures often changed and the episodes could be experienced at anytime,
even while walking. The condition of 29 animals advanced to include cluster (3)
seizures. 5.) Longevity after
onset of seizures is almost equal in males ( 27.14 months) and females (
27.96 months), with an average period of survival after onset of 26.74 months,
regardless of treatment protocol. The average age at death is 57.91 months
( 4.83 years), about 1.5 years earlier than the average age of death within
the general population (6.47 years as reported in Longevity and Morbidity
in the Irish Wolfhound in the United States – 1966 to 1986 by Gretchen Bernardi).
Of the animals that have died, 60.32% of the deaths were seizure-related.
Longevity for seizure related deaths are 1) 18.18 months for uncontrolled
seizures 2) 21.25 months where there is damage from phenobarbital and 3)
22.0 months for those who died during a seizure. Cancer and heart disease
followed as the most frequent causes of death. Most of the animals ( 102
of 126) were euthanized. (Graph 3 and
4a &
4b)6.) The overall
inbreeding coefficients (4) for the animals entered into the study average
15.63%, calculated at the recommended 10 generations. These coefficients
range from 0.00000% to 35.15%. Remember, an inbreeding coefficient as low
as 2% in 10 generations, when viewed in the form of a 6-generation pedigree,
will appear as an outcross. In other words, the sire and the dam will have
absolutely no common ancestors within the 6 generations. There is no correlation
between age of onset and inbreeding coefficient. 7.) Irish Wolfhounds
being treated with the conventional therapies of phenobarbital,potassium
bromide (KBr), Clorazepate,Dilantin and Diazepam used alone or in combination.
Gabapentins (Neurontin) were used experimentally with 3 animals. Two animals
were treated with a combination of conventional and alternative therapies.
Four individuals are being treated with homeopathic therapy only. There
was no difference between the use of conventional and alternative therapies
in treating the severity or frequency of seizures. 8.) Food as a cause
of seizures – The foods consumed by the dogs entered in the study were as
varied as the ownership of the animals. There were no reports of seizures
due to reactions to food ingredients.9.) Heartworm as
a cause of seizures - Most were on heartworm medication. The types of heartworm
preventives were varied. No tests connected with this study were done on
any of the entrants to determine toxicity levels. In the article by Dr.
Thomas reprinted in the Maintenance section, he mentions that Ivermectin
can “increase seizure activity” in an animal already afflicted with a seizure
condition. 10.) Housing as
a cause of seizures - Most were house dogs. Some were strictly kennel animals. 11.) Several hounds
had some form of cardiac condition. There is no way to tell in general if
or how that condition was related to the seizure disorder. One affected
male has been verified to have developed atrial fibrillation as a direct
result of his seizures. 12.) None of the
Irish Wolfhounds entered in the study had seizures caused by thyroid dysfunction.
Several, however, tested as mildly hypothyroid. This in itself is not unusual
for the breed. According to the clinical experience of Dr. Dayrell-Hart
during her tenure as a practicing neurologist at the University of Pennsylvania,
blood work on animals with seizures allegedly caused by severe hypothyroidism
show very high levels of cholesterol. Phenobarbital can lower the T4 readings
and may not reflect the actual T4 levels in the blood. Therefore, further
testing should be done to determine the true T4 levels before adjusting
thyroid medication. This information was confirmed to me by Dr Alevley,
veterinary neurologist, and Dr Feldman, veterinary endocronologist from
the University of California Davis during a telephone conversation. 13.) There is
no known single physiological mechanism that has been identified as cause
for the seizures in the animals entered in this study. No neurological or
neuropharmacological experiments were done on any of these animals. Of the
necropsies known to have been done, no pathology was found to explain a
cause for the seizure condition. Three necropsies showed hepatic damage
that might be due to drugs used in the maintenance protocol. 14.) Although
the hormone surges associated with estrus are known to have the potential
to trigger seizures, only 5 of the 56 female entries had onset of seizures
near their first estrus. Two additional entries reported one seizure of
sevearal during their lifetimes close to their 4th and 5th seasons respectively. 15.) There are
no reports or direct evidence of malignant hyperthermia as a cause for seizures
for the entries in this study. Things That Have Been Observed
1.) Behavior of Affected Animals -a. Many of the affected
animals have been described as shy, aloof, reticent, standoffish, withdrawn.
It is not known with certainty whether or not these character traits are
coincidental or signals of the disorder.b. Several entries showed
temperament changes after the onset of seizures. The most common behaviors
observed included photophobia, fear of loud noises, great agitation when
faced with changes and physical and/or social withdrawal from both humans
and other animals. These traits cannot be linked to the drugs taken to control
the seizures as these changes were observed in these animals whether or
not they were on a treatment protocol. Some of the behavioral changes may
be due to the damage done to the animal’s brain cells during a seizure.
None of the entries has been reported to exhibit continuing or escalating
violent behavior after onset of seizures, as has been reported in observations
of other breeds.c. The following are behaviors observed in animals who later became affected with seizures and in animals that, in the owner’s or breeder’s personal opinion, might be producers. Presence of any one or more of these traits does not necessarily indicate the presence of a potential seizure condition. These observations, combined with the breeders’ knowledge of their bloodline, may help determine which puppies the breeder wishes to watch closely or to test once the DNA work has been done. There is no scientific corroboration for these observations.i. Teeth chatteringii. Sticking entire head
in the bucket when drinkingiii. Sound sensitivityiv. Shyness of doors or
other barriersv. Exaggerated flight
distance. Will not approach.vi.Touch sensitive or
shy to an approaching perceived threat. Once on a lead will sometimes be
all right.vii. Spacey, non-responsiveThe following articles by Dr. Margret Casal describe the search for genetic markers. This study is at a very exciting point in the search for the marker for seizures in the Irish Wolfhound. Mode of inheritance has been determined, link analysis is progressing and several genome scans have been returned for the laborious analyzation stage. It is only through the cooperation of the participants of this study that this much progress has been possible.
Processing Blood for DNA Samples
Understanding Genes and Junk DNA
The Search for the Epilepsy Gene
(2) The mild form of generalized seizure involves little or no paddling of the legs and usually no loss of consciousness.
(3) Cluster seizures are multiple seizures occurring within a short period of time with very brief periods of consciousness in between.
(4) The inbreeding coefficient is the total percentage of identical gene contributions from All ancestors common to both parents, not just one ancestor in particular.
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