ARTICLE
Auteur(s) : Roberto
Poma1, Ayako Ochi2, Miguel A
Cortez2
1Dept. of Clinical Studies, Ontario Veterinary
College, University of Guelph
2Division of Neurology, Department
of Paediatrics, Hospital for Sick Children, University
of Toronto, Canada
Article reçu le 29 Octobre 2009, accepté le 19 Avril 2010
Epilepsy is the most common neurological disorder in dogs, with
an incidence that ranges from 0.5% to 5.7% (Chandler, 2006). The
current classification of canine seizures is mainly based on
seizure phenotypes, the majority of which are motor activities,
either focal or generalized (Berendt and Gram, 1999). There are
only a few epileptic syndromes described in canine epilepsy (Lohi
et al., 2005; Morita et al., 2002, Srenk and Jaggy,
1996). In this study, we report the first case of canine absence
epilepsy with myoclonias which presents similar clinical and EEG
characteristics to those reported in childhood absence epilepsy
(Sadleir et al., 2009).
Case study
An eight-month-old male intact Chihuahua dog was admitted for
evaluation of recurrent episodes of suspected focal seizures. The
dog had a four-month history of recurrent episodes of head and nose
twitching associated with intermittent hind limb jerking and
suspected staring for a duration of a few seconds. Although the
duration of these episodes remained unchanged the frequency
continued to increase to three or four episodes witnessed in a day.
There were no other abnormalities reported in his medical and
physical history. At the time of admission, the completed blood
count and a serum biochemistry profile were normal. On neurological
examination, no significant findings were observed. Brain MRI was
normal. Five-hour long-term video-EEG monitoring documented
multiple clinical events.
At four months of age, the dog owner observed intermittent head
and nose twitching along with occasional hind limb jerking
especially when the dog was lying down in a quiet state
(see video sequence 1). At that time, baseline metabolic
investigations were normal and no treatment was administered by the
referring veterinarian.
Multiple daily staring episodes with cessation of motor activity
continued to be noticed along with intermittent head and/or nose
twitching. A few seconds after each episode, the dog was
reported to be quieter than usual and slower to respond to
commands. Hind limb jerking episodes were occasionally seen and
often in association with the facial twitching.
Upon admission to our canine epilepsy monitoring unit (Ontario
Veterinary College, University of Guelph), the dog was sedated with
intravenous propofol to set up a standardized montage with nine
subdermal wiring electrodes located as follows: two frontal (F3,
F4), one central (Cz), two occipital (O1, O2), two temporal (T3,
T4) a ground and a reference. The reference was located 2 cm
rostral to the Fz electrode. All electrodes were secured with a
bandage and the dog was placed in a crate for long-term video-EEG
monitoring, performed with a digital Stellate Harmonie EEG system
using a referential montage.
Video-EEG documented multiple staring episodes either alone or
in association with head and/or nose myoclonic jerks (see video
sequence 2A and B). There were no episodes of hind limbs jerking
during this five-hour video-EEG session. The ictal EEG showed
generalised bilaterally synchronous 4 Hz spike-and-wave
complexes with rhythmic twitching of the head and/or nose, time
locked to the abnormal EEG frequency (figure 1). No photic
stimulation or hyperventilation tests were performed. Immediately
afterwards, treatment with phenobarbital 7.5 mg bd (6 mg/kg/day)
was initiated. Five months later, a significant decrease in the
number of episodes was reported and a follow-up five-hour long-term
video-EEG recording did not detect any clinical or EEG
abnormalities.
Discussion
Our clinical and EEG findings described in this case report appear
to be similar to human absence seizures with myoclonic features
(Hirsch et al., 2008; Tassinari, 2008). Absence seizures are
clinically described as a transient cessation of activity with
staring, unresponsiveness and “blanking out” episodes. Our canine
patient displayed similar features appearing somehow “disconnected”
and transiently impaired in his behavioural attitude. Other
clinical features usually reported in human patients with myoclonic
features include motor activity characterized by bilateral
myoclonic jerks mainly involving the muscles of the shoulders,
arms, and legs but also facial muscles more evident around the chin
and the mouth. In this case, the patient presented with a history
of intermittent hind limb jerks, transient impairment of
consciousness and motor manifestations characterized by
head twitching along with nose twitching, both rhythmically
correlated with the 4 Hz generalized spike-and-wave complexes,
indicative of epilepsy with myoclonic absences. The jerking hind
limb reported by the owner was not captured during the baseline and
follow-up long-term video-EEG recordings, although several episodes
were videotaped by the owner suggesting an abrupt, bilateral and
synchronous myoclonic jerk involving both hind limbs and occurring
at the same time as the head and nose twitching. These hind
limb jerks resembled those observed in human patients with
myoclonic absence epilepsy, a rare form of generalized
cryptogenic/symptomatic epilepsy where severe bilateral rhythmic
clonic jerks occur during an absence episode. The ictal EEG pattern
recorded in our canine patient showed multiple runs of generalised
bilaterally synchronous 4 Hz spike-wave complexes that
correlated with head and/or nose twitching as documented in the
video-EEG sequence.
Our patient responded partially to phenobarbital treatment
exhibiting an overall decrease of myoclonic events. Human typical
absences tend to respond well to sodium valproate and ethosuximide
at high doses. In individual cases, good seizure control was
achieved by using a combination of phenobarbitone, valproic acid
and benzodiazepines (Tassinari, 2008). Unfortunately, the use of
sodium valproate for dogs is not appropriate since its
pharmacokinetic profile reveals a very short half-life, precluding
the possibility to maintain a therapeutic concentration over
the long term. The use of ethosuximide in dogs with seizure
activity is so far unreported, and we reason that this could be an
ideal treatment for future similar cases. We believe that the
partial response to phenobarbital treatment in our case included
spontaneous remission of the myoclonic absences, as observed in
certain types of typical absences in humans. Since our patient is
currently on a decreasing course of phenobarbitone, further
considerations regarding efficacy of long-term response to
treatment versus spontaneous improvement will be made according to
his clinical neurological status and presence of eventual
relapses.
Human absence seizures with and without myoclonic features are
epileptic seizures manifested by impairment of consciousness during
the occurrence of high amplitude 2.5- to 4-Hz generalised
spike-and-slow-wave discharges. An absence seizure without
myoclonic features is clinically described as the transient
cessation of activity with staring, unresponsiveness and “blanking
out” episodes. Absence seizures with myoclonia are characterized by
motor activity including bilateral myoclonic jerks mainly involving
the muscles of the shoulders, arms, and legs but also facial
muscles, more evident around the chin and the mouth. Human
epileptic syndromes with absence seizures that display
electro-clinical manifestations similar to those observed in our
patient include childhood absence epilepsy (CAE) and juvenile
absence epilepsy (JAE). Children with CAE are usually aged 4-8
years old while JAE is more commonly seen around puberty
(10-12 years).
Clinically, CAE is characterized by very frequent absences (from
several to many per day) and generalised tonic-clonic seizures
during adolescence, while JAE has a much lower frequency of
seizures with similar phenomenology. First-line drugs for CAE are
ethosuximide, sodium valproate and lamotrigine, alone or in
combination. The majority of patients have a good response to
treatment, and in some cases, absence seizures may remit or, more
rarely, persist as the only seizure type. Patients with JAE are
usually treated with similar medications to those with CAE. The
response to treatment is good overall, especially when absence
seizures are the only manifested seizure type. A less
favourable response to treatment, however, is noted when
generalised tonic-clonic seizures are associated with absence
seizures (Hirsch et al., 2008).
The absence seizure phenotype is observed in mice, rats, dogs
and primates and each species presents similar seizure
characteristics including staring spells, blanking out,
unresponsiveness, stiffening and myoclonic jerks (Snead, 1995;
Cortez and Snead, 2006; Chandler, 2006). Currently, only a few
epileptic syndromes have been described in canine epilepsy (Lohi
et al., 2005; Morita et al., 2002; Srenk and Jaggy,
1996). Lohi and colleagues (Lohi et al., 2005) discovered a
mutation in the Epm2b gene as the cause of Lafora disease in
miniature wire-haired dachshunds. The genetic predisposition in our
canine patient is unknown, however, this case report suggests the
potential existence of a breed-related canine epileptic syndrome,
of pure-breed long hair Chihuahuas with seizure onset at four
months of age.
The adult stage of a dog is usually reached at around one year
of age. If we consider the most general assumption that one year of
life for a dog is equal to seven years of age for humans, we can
estimate that this dog started to have seizure episodes (noted by
the owner) at an equivalent human age of 3.5 years, comparable to
early onset childhood absence epilepsy. Since our patient is a pure
breed dog which was purchased from a selected breeder, further
investigations were made to retrieve information regarding
littermates and previous generations, however, there was no
significant evidence of similar neurological features. This lack of
findings for sibling or littermates may reflect a polygenic
inheritance of idiopathic generalised epilepsy. Based on the pure
breed nature of our patient, it is possible that only a few members
of the family would be affected. On the other hand, the lack of
evidence within a selected breed is not a surprising finding in
veterinary medicine since scientific collaboration with the vast
majority of breeders is often precluded by personal and financial
reasons. Since the owner of our dog owned one of the patient's
littermates, long-term video-EEG recording was performed with the
aim of discovering similar neurological and EEG features, however,
no abnormalities were detected by neurological examination or
during a three-hour video-EEG recording. Based on these
considerations, more work is warranted to identify patients with
similar phenotypes that may lead to the determination of a
breed-related syndrome in long hair Chihuahuas and characterize a
consistent clinical pattern that may correlate with a specific
human epileptic syndrome.
The adjuvant of long-term video-EEG monitoring for the diagnosis
of canine seizures represents a significant step forward in the
evaluation of seizure phenomenology and seizure classification in
dogs (Berendt et al., 1999). In the past, the classification
of canine seizures was purely based on seizure phenotypes, of which
the majority were either focal or generalised motor activities. The
existence of other seizure types, without overt motor
manifestations such as sensory or autonomic seizures, has been
speculated in canine epilepsy, although never scientifically
demonstrated by video-EEG or ambulatory recordings (Berendt
et al., 1999).
We reason that without the video-EEG monitoring system in our
clinical veterinary centre, this type of seizure in our canine
patient could easily have been misdiagnosed. The bilaterally
synchronous 4 Hz spike-and-wave complexes formally excluded
the possibility of either simple partial or complex partial
seizures. This case illustrates a formal indication of video-EEG
monitoring for diagnosis of subtle myoclonic absences with perioral
myoclonia and head twitching in dogs.
To our knowledge, this is the first case report of canine
epilepsy with myoclonic absences. The clinical and EEG features
recorded for our patient may represent a basis for facilitating
comparative studies between different species with spontaneous and
naturally occurring epilepsies. Further diagnostic studies are
warranted to determine the existence of novel canine epilepsy
syndromes and possibly breed-related epileptic syndromes with
specific genetic mutations which may be shared by their human
counterpart.
Legends for video sequences
Acknowledgments
We thank Dr Fiona James and Jennifer Collins for patient management
and help providing long-term video-EEG recording.
Disclosure.
None of the authors has any conflict of interest to
disclose.
References
[Berendt and Gram, 1999] Berendt M, Gram L. Epilepsy and
seizure classification in 63 dogs: a reappraisal of veterinary
epilepsy terminology. J Vet Intern Med 1999; 13: 14-20.
[Berendt et al., 1999] Berendt M, Høgenhaven H,
Flagstad A, Dam M. Electroencephalography in dogs with
epilepsy: similarities between human and canine findings. Acta
Neurol Scand 1999; 99: 276-83.
[Chandler, 2006] Chandler K. Canine epilepsy: what can we
learn from human seizure disorders? Vet J 2006; 172: 207-17.
[Cortez and Snead, 2006] Cortez MA, Snead III OC.
Pharmacological models of generalized absence seizures in rodents.
In: Pitkanen A, Schwartzkroin PA, Moshe SL, eds.
Models of Seizure and Epilepsy. San Diego: Elsevier, 2006:
111-26.
[Hirsch et al., 2008] Hirsch E, Thomas P,
Panayiotopoulos CP. Childhood and Juvenile Absence Epilepsies.
In: Engel J, Pedley TA, eds. Epilepsy,
A Comprehensive Textbook. Lippincott and Williams &
Wilkins, 2008: 2397-411.
[Lohi et al., 2005] Lohi H, Young EJ,
Fitzmaurice SN, et al. Expanded repeat in canine
epilepsy. Science 2005; 307: 81.
[Morita et al., 2002] Morita T, Shimada A,
Takeuchi T, et al. Cliniconeuropathologic findings of
familial frontal lobe epilepsy in Shetland sheepdogs. Can J Vet Res
2002; 66: 35-41.
[Sadleir et al., 2009] Sadleir LG, Scheffer IE,
Smith S, Carstensen B, Farrell K, Connolly MB.
EEG features of absence epilepsy in idiopathic generalized
epilepsy: impact of syndrome, age and state. Epilepsia 2009; 50:
1572-8.
[Snead, 1995] Snead III OC. Basic mechanisms of
generalized absence seizures. Ann Neurol 1995; 37: 146-57.
[Srenk and Jaggy, 1996] Srenk P, Jaggy A. Interictal
electroencephalographic findings in a family of golden retrievers
with idiopathic epilepsy. J Small Anim Pract 1996; 37: 317-21.
[Tassinari, 2008] Tassinari CA. Epilepsy with myoclonic
absences. In: Engel J, Pedley TA, eds. Epilepsy,
A Comprehensive Textbook. Lippincott and Williams &
Wilkins, 2008: 2413-6.
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