This document provides an in-depth overview of epilepsy in dogs and cats. It defines seizures, describes different seizure types including focal and generalized seizures. It discusses causes of seizures including idiopathic epilepsy which has a genetic basis in some breeds, structural epilepsy caused by brain abnormalities, and reactive seizures triggered by systemic issues. The document outlines testing, treatment including common anti-seizure medications like phenobarbital, and conditions that can mimic seizures.

1. The shake down: An in
depth look at epilepsy
Chelsie Estey, MSc, DVM
Neurology/Neurosurgery service
Upstate Veterinary Specialties

2. Outline
 Seizure definition
 Types of seizures
 Causes
 Mimics
 Treatment
 Emergency management

3. Seizures
 Seizures are the most common neurologic problem
in small-animal medicine
 Incidence of idiopathic epilepsy is between 0.5% -
5%
 Some breeds have much higher incidence
 Treatment dependent on underlying cause

4. What causes a seizure?
 An epileptic seizure: clinical manifestation of
excessive and/or hypersynchronous electrical activity
in the cortex
 Altered excitability of a group of neurons can lead to
marked and prolonged depolarization
 Can involve neurons in a specific region of the brain
 focal seizure
 Entire cerebrum
 generalized seizure
http://vanat.cvm.umn.edu/brainAtlas/

6. Pathophysiology
 Inadequate neuronal inhibition—major inhibitory
NTs include GABA and glycine
 Excessive neuronal excitation—major excitatory NTs
include aspartate and glutamate
 A combination of 1 & 2
http://thebark.com/content/vet-advice-seizures-dogs-and-canine-epilepsy

7.  Resting membrane potential is normally set so
neurons are not constantly firing
 Close enough to threshold that they can discharge
 AP generation is essential to CNS function
 The control of resting potential is critical to prevent
excessive discharge associated with seizures
https://primalcanine.wordpress.com/tag/infographic/

8.  Normally a high [K+] inside a neuron and there is a
high EC [Na+]
 If the balance is upset (e.g. if K+ is elevated in the EC
space), this can lead to depolarization that promotes
abnormal activity

9. Primary generalized seizures
 The initial clinical signs reflect involvement of both
hemispheres
 Impairment of consciousness is common
 Motor manifestations are bilateral
 Generalized tonic-clonic seizures are the most
common
http://www.labrador-retriever-pet.com/seizures-in-dogs.html

10. Seizure classification
 Generalized tonic-clonic seizures
 The 1st part of the seizure = tonic phase
 sustained contraction of all muscles
 Loss of consciousness and falling
 Breathing
 irregular or absent, and cyanosis
 Salivation, urination, or defecation
 The tonic phase lasts for ~1 min and leads to clonic
phase
 paddling or rhythmic jerking of the limbs and chewing
movements
 The clonic phase is usually < 1-2 min
 Consciousness can be maintained

11. Generalized tonic-clonic
seizures

12. Seizure classification
 Tonic seizures
 Consists of generalized muscle rigidity w/o clonus
 Clonic seizures
 Paddling and jerking with no tonic component
 Atonic seizures
 Sudden, often brief losses of muscle tone
 May be a brief drop of the head, or sudden collapse

13. Seizure classification
 Myoclonic seizures
 Brief contractions that may be generalized or confined
to individual muscle groups
 Not all myoclonic jerks are seizures
 Absence seizures
 In people defined as abrupt, brief losses of
consciousness
 Not recognized in vet med
 Characterized by brief episodes of unresponsiveness,
sometimes w/ facial twitching & mild limb jerking

14. Types of seizures: focal
 Initial clinical signs indicate abnormal activity in
one region of a cerebral hemisphere
 Simple focal seizures do not impair consciousness
 When consciousness is impaired  classified as
complex focal
 Motor signs, autonomic signs, and behavior signs
are most common

15. Focal seizures
 Focal seizures with motor signs
 Rhythmic contractions of facial or masticatory
muscles, abnormal movements of one limb, and
turning the head to one side
 Focal seizures with autonomic signs
 Autonomic signs include hypersalivation, vomiting,
gagging, diarrhea, and apparent abdominal pain

16. Focal seizures
 Focal seizures with abnormal behaviour
 In people can cause sensory symptoms: e.g. abnormal
skin or vision sensations
 Seizures manifested as licking or chewing and “fly-
biting” may be similar
 Complex focal seizures may be manifested as impaired
consciousness and bizarre behaviour, e.g. aggression
or extreme, irrational fear
http://www.vetneurochesapeake.com/index.php?
page=questions-about-dog-seizures

17. Focal seizure

18. Focal seizure

19. Stages of a seizure
Prodrome
 A long-term indication of a forthcoming seizure
 May exhibit abnormal behaviour
 restlessness, clinginess, and vocalizing (hours to days
before a seizure)
 Not always seen

20. Aura
 The initial sensation of a seizure before observable signs
 Last seconds to minutes
 Initial abnormal electrical activity in the brain
 Hide, clinginess, agitation
 Difference between a prodrome and an aura is that
prodromes are longer and not associated with abnormal
EEG
 Auras are short and caused by abnormal EEG
www.canine-epilepsy.net

21. Ictus
 The seizure itself
Postictal stage
 Transient abnormalities in brain
function that are caused by the ictus
and appear when the ictus has ended
 Disorientation, restlessness, ataxia,
blindness, and deafness
 Often resolve after several mins, but
may last for days
http://blogs.biomedcentral.com/bmcseriesblog/2014/10/22/
bmc-veterinary-research-authors-discuss-how-poor-study-design-
inhibits-progress/

22. Reactive Seizures
 Reactive seizures are the reaction of a normal brain
to a systemic problem
 Metabolic
 Nutritional
 Toxic disorder

23. Handbook of Veterinary Neurology 5th Ed

24.  From: Veterinary Neuroanatomy and Clinical Neurology 3rd Ed

25. Structural Epilepsy
 Caused by a known and identifiable structural
forebrain disorder
 vascular, inflammatory, traumatic, anomalous/
developmental, neoplastic and degenerative diseases
 Reported prevalence of structural epilepsy in dogs
and cats varies
 25–38% in dogs
 34–87% in cats

26. Structural Epilepsy
Handbook of Veterinary Neurology 5th Ed

27.  From A Practical guide to canine and feline neurology 2nd Ed

29. Idiopathic epilepsy
 Recurrent seizures and no identifiable brain
abnormality
 May have a genetic basis
 Normal interictal exam
 Diagnosis of exclusion
 Signalment
 Onset: 1st seizure between 6 mos and 6 yrs
http://newsnetwork.mayoclinic.org/discussion/epilepsy-symptoms-
causes-complications-and-what-you-can-do/

30. Genetic basis in some breeds
 Prevalence of epilepsy in certain breeds of dog has
been documented to be much higher than the
estimated 0.5 to 6% in the general population
 Belgian shepherd Tervueren and Groenendael
variants: prevalence estimated in one study to be
9.5%, and as high as 33% in one extended Belgian
shepherd family (Berendt et al., 2008, 2009)
 Prevalence of 18.3% was documented in Irish
wolfhounds with IE
 Study of Petit Basset Griffon Vendeen dogs with IE
revealed a prevalence of 8.9% (Casal et al., 2006; Gullov et al.,
2011).

31.  From Canine and Feline epilepsy

32. Lifespan and epilepsy
 MST after the initial seizure is 2.07 yrs in Border
collies and 2.3 years in a population of different
purebred and mixed-breed dogs (Proschowsky et al., 2003;
Berendt et al., 2007; Hulsmeyer et al., 2010)
 The life expectancy for Irish wolfhounds is
shortened by ~2 yrs in IE dogs compared with
seizure-free relatives
 > 60% of the total number of deaths in the
population were related to epilepsy (Casal et al., 2006)

33. Lifespan and epilepsy
 Study of survival in Belgian shepherds with IE
showed that the lifespan of epileptic dogs was not
significantly shortened by the presence of epilepsy
 Epilepsy was the predominant cause of death in the
population (Gullov et al., 2012)

35. Feline seizures
 The prevalence of feline seizures has been reported
as 2.1-14%
http://pets.thenest.com/tremors-seizures-cats-8114.html

36. From Canine and Feline Epilepsy

37. From Canine and Feline Epilepsy

38. Disorders mistaken for
seizures
 Syncope is characterized by partial or complete
loss of consciousness, lack of violent motor
activity, short duration and lack of post-ictal signs
 Often associated with exercise and caused by
cardiac or respiratory disease

40. Disorders mistaken for
seizures
 Narcolepsy is usually manifested as episodes of
flaccid paralysis or loss of consciousness
precipitated by excitement such as feeding,
greeting, or play
http://www.tomopop.com/dog-narcolepsy-the-growing-epidemic-11787.phtml

41. Narcolepsy

42. Disorders mistaken for
seizures
 Myasthenia gravis can cause stiffness, tremor, or
weakness with normal consciousness
 Clinical signs of MG may be induced by exercise
 Some myopathies can cause similar clinical signs

43. Myasthenia gravis

44. Disorders mistaken for
seizures
 Peripheral vestibular dysfunction is characterized
by ataxia, head tilt, and abnormal nystagmus with
no impairment of consciousness.

45. Vestibular disease

46. Vestibular disease

47. Disorders mistaken for
seizures
 Episodes of encephalopathy can cause
disorientation, ataxia, blindness, and abnormal
behavior
 E.g Hepatic encephalopathy

48. Disorders mistaken for
seizures
 Normal or abnormal movements during sleep
consist of twitching, paddling, or vocalizing while
the patient is asleep
 Waking the animal can interrupt these, and there
are no postictal signs

49. Disorders mistaken for
seizures
 Behavior disorders, such as stereotypy, can cause
specific patterns of unusual behavior
 These episodes can usually be interrupted, and
there are no postictal signs.

50. Disorders mistaken for
seizures
 Pain, especially neck pain, can cause episodes of
muscle rigidity or stiffness and crying
 Consciousness is not impaired

51. Seizure Mimic

52. Seizure Mimic

53. Testing
 A CBC/chem to screen for metabolic causes of
seizures (e.g. hypoglycemia)
 Serum BAs are tested in young animals to identify
PSS
 Blood lead with hx of possible exposure
 Thyroid function is evaluated in adult dogs
 hypothyroidism may complicate seizures and
phenobarbital can affect thyroid testing

54. Testing
 MRI +/- CSF are indicated in dogs with:
 interictal neurologic deficits
 seizures refractory to therapy
 onset of seizures <1 year or >5 years of age
 any cat with seizures
 Patients with IE often have normal MRIs, transient MRI
brain lesions secondary to seizure activity are
occasionally seen
 These lesions tend to be hyperintense on T2, do not
distort surrounding brain parenchyma, and tend to occur
in several brain regions (e.g., pyriform, temporal, and
frontal lobes, and the hippocampus)

55. Therapy
 The goal of tx is to  the frequency and severity of
the seizures
 QOL (pet and family)
 Tx: seizures vs mimic
 Therapeutic trial: seizure vs movement disorder
www.pinterest.com

56. When to start therapy?
 ≥ 2 seizures in 2-3 mo
 SE or cluster seizures
 Post-ictal behaviour
 Intracranial dz, trauma

57. From: Canine and Feline epilepsy

58. Seizure Medications

59. From: Canine and Feline epilepsy

60. From: Canine and Feline epilepsy

61. MOA
From: Canine and Feline epilepsy

62. MOA
From: Canine and Feline epilepsy

63. v
 From Canine and Feline epilepsy

64. From: Canine and Feline epilepsy

65. From: Canine and Feline epilepsy

66. Phenobarbital
 The elimination t½ is 40-90 hr in the dog and
~40-50 hr in the cat after PO admin
 10-15 days needed to reach steady-state
 Potent inducer of hepatic microsomal enzyme
activity and can lead to accelerated administration
of itself as well as other hepatically metabolized
drugs.

67. Phenobarbital
 From Canine and Feline epilepsy

68. Phenobarbital
 The initial dose is 3-5 mg/kg orally q 12 hr in dogs
 Similar range in cats
 Lower initial dose of 2.5 mg/kg orally q 12 hr
http://www.actavis.com.mt/en/products/Phenobarbital+-+Actavis.htm

69. Phenobarbital
 Serum levels should be checked 2 wks after
initiating therapy or changing the dose
 The target range is 20-30 ug/ml
 There is no clinically significant impact of the
timing of blood collection (e.g trough versus peak
level) in most dogs

70. Zonisamide
 ZNS is metabolized primarily by hepatic
microsomal enzymes and the t½ of elimination in
dogs is ~ 15 h
 The elimination t½ of ZNS is shorter in patients
already receiving drugs that stimulate hepatic
microsomal enzymes (e.g. phenobarbital)
http://www.heartlandvetsupply.com/
p-4681-zonisamide-capsules.aspx

71. Zonisamide
 From Canine and Feline epilepsy

72. Zonisamide
 When used as add-on therapy for dogs already
receiving phenobarbital, the recommended dose
regimen is 10 mg/kg PO q12 hr
 Has been shown to maintain canine serum [ZNS]
within the therapeutic range when used as add-on
therapy
 For dogs not receiving phenobarbital, it is
recommended to start at 5 mg/kg PO q12 hr
 Check trough serum ZNS concentrations after ~2
wks

73. Bromide
 Administered as KBr or NaBr
 KBr is preferred when Na+ intake must be
restricted (for example, CHF)
 NaBr is preferred when K+ intake must be
restricted (for example, hypoadrenocorticism)
http://www.petdoctorsofamerica.com/
pharmacy/index.php/k-brovet-potassium-
bromide-rx-required.html

74. Bromide
 From Canine and Feline epilepsy

75. Bromide
 The elimination t½ is 24 d in dogs, 11 d in cats
 It takes ~ 80-120 days to reach steady-state
kinetics in dogs, 6 weeks in cats
 The initial maintenance dose for KBr is 20-35 mg/
kg, PO SID, or divided BID
 If NaBr is used, the dose should be decreased by
15% (i.e., 17-30 mg/kg) to account for the higher
bromide content of the Na salt

76. KBr Loading
 24-hour loading dose
 (1) A total dose of 400-600 mg/kg of KBr is
administered PO over 24 hours
 (2) This is divided into doses of 100 mg/kg (the lower
end of the range) q 6 hr, for a total of 4 doses
 (3) If the patient appears obtunded prior to a dose,
skip it and resume when the patient is alert again
 (4) After loading, begin the regular dose the next day
 (5) This schedule is used in patients that need
adequate seizure protection immediately
 (6) The patient should be hospitalized for this loading
procedure

77. KBr Loading
 5 d loading dose
 (1) Administer 450 mg/kg of potassium
bromide over 5 days
 (2) The daily loading dose (90 mg/kg) is added
to the maintenance daily dose (35 mg/kg) for a
total PO dose for each of the 5 days of 125 mg/
kg/day. This dose should be divided BID to
avoid GI irritation
 (3) On day 6, the maintenance dose is started

78. Bromide
 A serum bromide level is checked within 1 week
after loading or 3 months after starting a
maintenance dose
 Timing of sample collection is unimportant
because of the long half-life
 The target range is 1-3 mg/ml for patients taking
bromide alone
 1-2 mg/ml for those taking bromide and
phenobarbital

79. Bromide
 Bromide competes with chloride for renal
elimination
 High chloride intake increases bromide elimination,
which increases the dose requirement
 The chloride content of the diet should not be
drastically altered during treatment

80. Levetiracetam (Keppra)
 The t½ of elimination for levetiracetam in dogs is
~4 hours
 Drug is nearly 100% bioavailable following PO
dose
 ~70%-90% of the drug is eliminated unchanged
in the urine, the remainder being hydrolyzed in
the serum and other organs
 There is no hepatic metabolism of
levetiracetam, and it is very safe in dogs

81. Keppra
 From Canine and Feline epilepsy

82.  Administered IV, can be administered IM
 IV administration is good in ER situations
 20-30 mg/kg, PO q8 hours

83. Gabapentin
 Despite undergoing some hepatic metabolism in
dogs, there does not appear to be any appreciable
induction of hepatic microsomal enzymes in this
species
 The elimination t½ for gabapentin in dogs is 3-4
hours
http://www.gaba-supplement.com/

84. Gabapentin
 Initial dose regimen of 10 mg/kg body weight q 8 hr,
titrate
 Side effects appear to be uncommon and are
typically limited to mild sedation, pelvic limb ataxia,
and increased appetite with attendant weight gain

85. Pregabalin
 Canine dosage of 2-4 mg/kg body weight, q 8 hrs
 Dosing should start at the low end (2 mg/kg) and
be increased weekly, as needed, in order to avoid
obvious side effects (e.g., sedation, ataxia).
http://www.searchhomeremedy.com/
drugs-and-medications-to-treat-
fibromyalgia/

86. Gabapentin/Pregabalin
 From Canine and Feline epilepsy

87. Diazepam
 Benzodiazepines are believed to exert anticonvulsant
activity by enhancing GABA effects in the brain
 Benzodiazepines are metabolized primarily by the
liver
 The short t½ of diazepam in dogs (2-4 hours) and
development of tolerance limits the use of this drug
for maintenance therapy
 Diazepam is used in dogs and cats IV or rectally for
emergency treatment of seizures
 Fatal hepatic necrosis has been associated with oral
diazepam in cats

88. Diazepam
 0.5 mg/kg IV
 1.0 mg/kg if given rectally

89. Adjunctive AEDs
 When monotherapy fails
 Drug level
 Side effects
 Poor control
 Pulse therapy
 Cluster
 Prodrome
www.pinterest.com

90. Doses for dogs
 From Canine and Feline epilepsy

91. Doses for cats
From Canine and Feline epilepsy

92. Therapeutic Monitoring
 After starting treatment
 Dose change
 Loading dose
 Poor seizure control
 Dose-related toxicity occur, to determine if a
dose decrease is necessary
 Every 6-12 months to verify that changes in
pharmacokinetics or compliance have not
caused change in concentration

93. Seizure emergencies

94. Cluster Seizures
 Cluster seizures (serial seizures, acute repetitive
seizures)
 ≥ 2 seizures occurring over a brief period with normal
consciousness between events
 Occurrence of > 3 seizures in 24 hrs should be
considered an emergency
 May evolve into SE and should be treated
 Study of 407 dogs with IE found that 41% had CS
at least once during their seizure history (Monteiro et al.,
2012)
 A study in Border collies with confirmed IE revealed
that CS occurred in 94% of the cases and SE in
53% (Hulsmeyer et al., 2010)

95. Cluster seizures
 48% of Australian shepherd dogs diagnosed with IE
< 5 years of age had both CS and SE, 12% SE only
and 20% CS only (Weissl et al., 2012)
 One study with 125 cats having primary and
secondary causes of seizure activity found CS in
53% and 59% of cases, respectively (Pakozdy et al., 2010)

96. Status epilepticus
 Continuous seizure ≥ 5 minutes or ≥ 2 discrete
seizures w/o full recovery of consciousness
between
 Relatively frequent among dogs with IE, can
occur with seizure disorders of any etiology
 ~59% of dogs with epilepsy of any cause will
have one or more episodes of SE during their
life (Saito et al., 2001)
 Large breed dogs are at increased risk
 Status is a life-threatening emergency

97. Status epilepticus
 Seizure activity >30 minutes may cause systemic
dysfunction, including hypoxia, altered BP, and
hyperthermia and can lead to temporary or
permanent brain lesions
 The most common type of SE is generalized tonic-
clonic status
 With a prolonged seizure, the clinical manifestations
can eventually become subtle, with only altered
mentation and small twitching movements of the
face or limbs.
 “electromechanical disassociation” and should be
treated

98.  From Canine and Feline Epilepsy 2014

99. ER treatment of seizures
− O2
− Stat: BG, PCV/TS, lactate, platelet count,
BUN / crea, ECG, thoracic radiographs
− Obtain blood sample for CBC/chem, UA,
[AED], sampling for toxicology and
infectious disease titers
− IVF

100. ER treatment
− Administer dextrose-IV bolus (1 to 5ml 50%
dextrose) ONLY in documented hypoglycemia
− Hyperthermia should be rapidly corrected
− Acidosis does not usually necessitate treatment
− Marked metabolic acidosis often resolves w/
stabilization
− Respiratory acidosis needs immediate treatment

101. Treatment
 Initiate AED to stop all gross motor seizure activity
or to rapidly reach therapeutic serum levels in the
non seizuring dog
 Diazepam (DZ) IV bolus 0.5 mg/kg
 Wait 5 minutes for effect / repeat
 Rectal DZ: reserved for patients where IV access
cannot be obtained / out-of-hospital treatment
 TREAT EARLY
 Administer diazepam at 0.5-1.0 mg/kg, IV. Repeat for a
total of 3 doses as necessary to stop the seizure
 The duration of anti seizure effects is 30 min or less, so a
longer-lasting AED drug should also be given

102. From Canine and Feline epilepsy

103. Questions?