ISVMA 2017 November, 2017

Canine Seizure
Panel Members
Management:
Update on the ACVIM
and IVETF Consensus
Statements Dr. Michael Podell (Chair) Dr. Wolfgang Löscher Dr. Karen Muñana
Dr. Mette Berendt
Affiliate Professor, U of Chicago, Professor Professor Professor
Michael Podell MSc, DVM, Diplomate ACVIM (Neurology) Pritzker School of Medicine ; University of University of Hannover NC State University,
MedVet Chicago Chicago Veterinary Specialty Group, Copenhagen, Denmark Germany USA
mpodell@medvetforpets.com USA
773-281-7110 Dr. Ned Patterson Dr. Simon Platt Dr. Holger Volk
Associate Professor Professor Co-Chair
University of University of Professor
Minnesota, USA Georgia, USA The Royal
Veterinary College,
London, UK

Berendt et al. BMC Veterinary Research (2015) 11:182

International Veterinary Epilepsy Task Force International veterinary epilepsy task force consensus report on epilepsy definition, classification
and terminology in companion animals

Hülsmeyer et al. BMC Veterinary Research (2015) 11:175

International Veterinary Epilepsy Task Force’s current understanding of idiopathic
epilepsy of genetic or suspected genetic origin in purebred dogs

Rusbridge et al. BMC Veterinary Research (2015) 11:194

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI
protocol

De Risio et al. BMC Veterinary Research (2015) 11:148

The International Veterinary Epilepsy TaskForce (IVETF) is
formed by a mondial (among others Europe, United States
of America, Australia) group of (veterinary) scientists
interested and specialised in the field of epilepsy. Our
group consists of clinical veterinary neurologists,
neuropharmacologists, and veterinary neuropathologists
http://www.ivetf.org/
International veterinary epilepsy task force consensus proposal: diagnostic approach to epilepsy in dogs
Bhatti et al. BMC Veterinary Research (2015) 11:176
International Veterinary Epilepsy Task Force consensus proposal: medical treatment of
canine epilepsy in Europe
Potschka et al. BMC Veterinary Research (2015) 11:177
International veterinary epilepsy task force consensus proposal: outcome of therapeutic
interventions in canine and feline epilepsy

International Approach CON-SEN-SUS

▪ Standardization of terminology
ACVIM ▪ Latin from consentire (to allow)
▪ Provide foundation of scientific
evaluation and recommendation ▪ General agreement: unanimity
▪ Establish a framework for
▪ The judgment arrived at by most of those concerned
veterinary clinical and human ECVIM
▪ Group solidarity in sentiment and belief
translation studies AND IVETF
▪ Parallel work with International ECVN
Veterinary Epilepsy Task Force

Dr Michael Podell MedVet Chicago 1

ISVMA 2017
Our Approach
Problems
▪ Epilepsy is a heterogeneous disease
process
▪ Incomplete diagnostic capabilities
▪ Unpredictable clinical outcome
▪ Wide-variability in treatment
approaches
▪ Small database of strong evidence-
based clinical studies
▪ Use of antiepileptic drugs (AED)
established for people
METHODOLOGY
Published evidence in the peer-reviewed
literature
• Standard electronic databases
• Pub Med (www.ncbi.nlm.nih.gov/PubMed)
CAB Abstracts (www.cabdirect.org) and Web
of Science (http://wok.mimas.ac.uk) search
strategies included reference lists of
published papers and proceedings
• Studies were included following modified
criteria laid out in detail by Charalambous
et al. 2014
• Any peer-reviewed study without language
restrictions in which an antiepileptic drug
was used and in dogs with epilepsy
• Proceedings
• Annual Congresses of the European Society
and College of Veterinary Neurology and the
American College of Veterinary Internal
Medicine
When Should Treatment Be Started?
▪ Decision to treat is a reflection of the
treatment goals:
▪ Reduce or eliminate epileptic events
▪ Reduce seizure severity
▪ Avoid adverse effects
▪ Reduce seizure-related mortality and morbidity
▪ Risk factors for seizure recurrence are not
well-established for dogs
▪ Seizure density is considered a strong risk
factor for seizure recurrence
▪ Packer et al. Clinical risk factors associated with AED
responsiveness in canine epilepsy, 2014
http://journals.plos.org/plosone/
Dr Michael Podell MedVet Chicago
November, 2017
Guidelines for the Diagnosis and Treatment
of Canine Epilepsy
Objectives ▪ Seizure identification and diagnosis (not included in this paper)
▪ Decision making treatment strategies
▪ Present a working clinical consensus
statement for canine seizure 1. When should treatment be started?
management 2. Which drug should be used first?
▪ Focus on epilepsy of undetermined 3. How should AED monitoring be performed?
cause (idiopathic/genetic/primary)
4. What are the risks of treatment?
▪ Chronic treatment only
5. What is drug-resistance?
▪ Recommendations based on published 6. When and which second AED should be started?
reports and clinical expertise opinion
▪ Complimentary and alternative treatment strategies
▪ Establish a predetermined, concise and
logical sequential approach to seizure ▪ Guidelines to enhance patient response and quality of life
management
▪ Emergency treatment strategies (not included in this paper)
Level Of
Evidence
Type Of Evidence ≠Recommendation
Grade Of
I Appropriately designed, controlled trials
▪ Random sequence generation
Blinded, randomized clinical trials and
drug efficacy of ≥50% seizure reduction
A Cochrane Risk of ▪ Allocation concealment
for at least 6 months
High and likely to Bias Assessment ▪ Blinding of participants
IB Blinded, randomized clinical trials and be effective
drug efficacy of ≥50% seizure reduction
for at < 6 months
Tool ▪ Personnel and outcome assessors
II Case-control or cohort studies (N > 15) B
Moderate and ▪ Completeness of outcome data
Non-blinded, randomized, or non-blinded
and non-randomized clinical trials and/or likely to be
drug efficacy of ≥50% seizure reduction effective ▪ Selective reporting of outcome measures
for > 12 weeks
Case-control or cohort studies: (N< 15) ▪ Other sources of bias
III
C
Non-blinded and non-randomized clinical
trials with cohort size of less than 15 Low and may not Charalambous et al. Treatment in
and/or drug efficacy of ≥50% seizure be effective
reduction for < 12 weeks
canine epilepsy- a systematic
IV Expert opinion only without
D
review. BMC Veterinary Research,
documentation by case reports or series
2014
Not
recommended
Levels of evidence and grades of recommendation. Table adapted from the National
Institute for Health and Care Excellence (NICE) guidelines (Eccles & Mason 2001)
ACVIM Panel Recommendations:
▪ Guidelines for people to start AED: The Reasons to Start AED Therapy
▪ Diagnosis of current or previous defined
cerebral lesions or trauma ▪ Identifiable structural lesion present or prior history of brain disease or injury
▪ Presence of inter-ictal EEG epileptic ▪ Acute repetitive seizures / status epilepticus has occurred
discharges (up to 90 % recurrence rate)
▪ Ictal event > 5 minutes or
▪ History of marked post-ictal adverse effects
▪ 3 or more generalized seizures occur within a 24 hour period or
▪ First unprovoked, seizure for adult onset?
▪ 2 or more seizures without completely regaining consciousness between seizures
▪ Individual risk and quality of life assessment
▪ Recurrence risk 21-45% within first 2 years ▪ Two or more seizure events occur within a 6 month period
▪ Immediate treatment improves seizure free
prediction by 50% ▪ Prolonged, severe, or unusual post-ictal periods occur
American Academy of Neurology, ▪ IVETF : “The epileptic seizure frequency and/or duration is increasing and/or
Summary of Evidence – Based Guidelines, 2015 seizure severity is deteriorating over 3 inter-ictal periods”
2
ISVMA 2017 November, 2017

Which AED Should Be Used First? Phenobarbital Monotherapy Level Evidence= I

Grade of
Recommendation =
A
High
8 studies (n = 311)
Recommendation
Moderate
6 studies: Treatment Risk of Higher Risk of Bias
5 studies (n > 15) Duration of 5 to 32 Complications
months

Primidone Imepitoin
Potassium •Approved in US •Approved in 82% with > 50% 15% with no
Phenobarbital and Europe Europe Levetiracetam Zonisamide 3% with > 0 and < Low Risk of Moderate High Risk of
bromide seizure reduction improvement
50% seizure reduction Bias Risk of Bias Bias
(N=255) (N=47)
(N=9) •2 studies •1 study •4 studies

31% with seizure

free status (N=96)
Cochrane Risk of Bias Assessment (Charalambous et al, 2014)

Potassium Bromide Monotherapy Primidone Monotherapy Level Evidence= II

Grade of
Recommendation
Grade of =D
Level Evidence= I Recommendation =
B (n= 1) Not Recommended
6 studies (n = 103)
1 study RISK OF Moderate
Recommendation High Higher Treatment
BIAS Higher Risk of
Risk of
5 studies: Bias
Moderate Complications
Lower Risk of Bias 5 studies (n > 15) Duration of 6 to 35
Treatment Risk of
(n=1) months
Complications
N = 23 6 months duration
38% with > 50% 21% with no
41% with > 0 and <
seizure reduction improvement 50% seizure reduction
Low Risk of Moderate Risk High Risk of (N=39) (N=22) Low Risk Moderate High Risk of Bias
Bias of Bias Bias (N=42) Risk of Bias
•1 •0 •0 •0 studies •3 studies •3 studies
74% with > 50% 35% with seizure
16% with >0 and <
seizure reduction free status
50% seizure reduction
(N=36)

Cochrane Risk of Bias Assessment (Charalambous et al, 2014) Cochrane Risk of Bias Assessment (Charalambous et al, 2014)

Imepitoin Monotherapy Level Evidence = I

Grade of
Recommendation Levetiracetam Grade of
=A Level Evidence= IV Recommendation
High Monotherapy =C
4 studies (n = 205) Insufficient Data to
Recommendation
Recommend
Low Treatment
Low to Moderate Low Treatment
Risk of Unknown Risk of
4 studies: Complications
Risk of Bias No published reports evaluating the Risk of
2 studies (n > 15)
Duration of 5 to 8 months use of levetiracetam as first line Complications Bias
therapy in dogs with epilepsy
38% with > 50% 2 % with no 60% with > 0 and <
seizure reduction improvement 50% seizure
(N=78) reduction Low Risk Moderate Risk High Risk of Bias
(N=3) Low Risk of Moderate Risk High Risk of Bias of Bias
(N=123*) Bias of Bias
•0 studies •0 studies •0 studies
•2 studies •2 studies •0 studies

40% with seizure

free status (N=82)
* = Estimated
Cochrane Risk of Bias Assessment (Charalambous et al, 2014)
Cochrane Risk of Bias Assessment (Charalambous et al, 2014)

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ISVMA 2017 November, 2017

Grade of ACVIM Panel Monotherapy Recommendations:

Zonisamide Monotherapy Level Evidence= III Recommendation
=C DRUG LEVEL OF EVIDENCE GRADE OF
Insufficient Data to RECOMMENDATION
1 study (n = 10) Recommend
Low Treatment Phenobarbital I A
Higher Risk of
Risk of
Bias
Duration of 12 to 36 Complications
0 studies (n > 15)
months Bromide I B

60% with > 40% with no 0% with > 0 and Low Risk Moderate
Risk of Bias
High Risk of Bias Primidone II D
50% seizure improvement < 50% seizure
reduction (n=6) (N=4) reduction •0 studies •0 studies •1 study
Imepitoin I A
0 % with seizure
free status Levetiracetam IV C
Cochrane Risk of Bias Assessment (Charalambous et al, 2014)

Zonisamide III C

ACVIM Panel Grade of Recommendations How Should AED Monitoring Be Performed?

(Level of Evidence) for AED Monotherapy ▪ Objectives
▪ Determine effective drug levels after
initiation of successful therapy (as
appropriate )
▪ Determine if drug failure is due to:
A (HIGH) B (MODERATE) C (LOW) D (NO)
▪ Pharmacokinetic factors to focus on a change
in dose (metabolic tolerance) or
•Phenobarbital •Bromide (I) •Levetiracetam •Primidone (II)
▪ Pharmacodynamic factors to focus on a
(I) (IV) change of drugs (functional tolerance)
•Imepitoin (I) •Zonisamide ▪ Determine if treatment failure is due to
(III) poor compliance, an inadequate or a TOLERANCE
change in drug level DOSE
▪ Prevent toxic effects from occurring [SERUM]
▪ Aid with individualization of therapy TIME TIME
METABOLIC FUNCTIONAL

▪ Pharmacology

Drug Monitoring ▪ Elimination half-life of 24-40 hours

▪ Auto-induction of hepatic metabolism results in enhanced

 Reference range is established by clearance over 6 weeks
laboratory /clinical study for a
population
Phenobarbital ▪ High degree of drug-drug interactions due to hepatic
metabolism and higher protein binding
 Sub-therapeutic: Lower limit below which ▪ Panel recommendations
therapeutic response is unlikely
Evidence level: I ▪ Initial dose of 2.5 mg/kg q 12 hours
 Toxicity: Upper limit below which toxic ▪ Monitor levels at 2 and 6 weeks and every 6 months,
response is likely Grade of Recommendation ▪ 2 weeks after a dose change or with increase in seizure frequency
for Monitoring: A ▪ Monitor if signs of toxicity
 Therapeutic range is the range of drug
concentrations associated with best ▪ Patient therapeutic range of 15-35 ug/ml
achievable results in an individual ▪ Collect trough sample for dogs with recurrent seizures
6 weeks
 Initial Start •Steady clearance
 Target

2 weeks
•Steady state

Dr Michael Podell MedVet Chicago 4

ISVMA 2017
▪ Pharmacology
▪ Panel recommendations :
Potassium Bromide
Evidence level: I
Grade of Recommendation for
Monitoring: A
Imepitoin
Evidence level: I
Grade of Recommendation: C
Approved in Europe
Zonisamide
Evidence level: II
Grade of
Recommendation for
Monitoring: A
Dr Michael Podell MedVet Chicago
November, 2017
▪ Pharmacology
▪ Elimination half-life 15 -20 days
▪ Rapidly metabolized to its major active metabolite
▪ Renal elimination phenobarbital that is responsible for more than 85% of the
total anticonvulsant activity
▪ No protein binding
▪ Similar pharmacokinetic profile as phenobarbital
▪ Initial dose or 30 to 40 mg/kg /day (single or divided) Primidone ▪ Panel recommendations
▪ Monitor at 8 to 12 weeks after initiation and every 12
months ▪ Initial dose of 10 mg/kg q 12 hours
▪ 1 month after a dose change, or if increase in seizure frequency ▪ Monitor levels at 2 and 6 weeks and every 6 months,
▪ Monitor if signs of toxicity ▪ 2 weeks after a dose change or with increase in seizure
Evidence level: I frequency
▪ Patient therapeutic range is 1000 to 3000 ug/ml for
monotherapy and 800 to 2500 ug/ml for combined therapy Grade of Recommendation for ▪ Monitor if signs of toxicity
▪ Collect sample after 2 hours of dosing Monitoring: A ▪ Patient therapeutic range of 15-35 ug/ml
▪ Avoid peak concentration
▪ Collect trough sample for dogs with recurrent seizures
6 to 12 months 6 weeks
Start
•Cumulative effect Start •Steady clearance
2 months 2 weeks
•Steady state •Steady state
▪ Pharmacology ▪ Pharmacology
▪ Elimination half-life of approximately 2 hours ▪ Elimination half-life
▪ Monotherapy: 4-8 hours
▪ No known therapeutic concentration
▪ With phenobarbital = 2-4 hours
▪ Low inter-individual metabolism variability Levetiracetam ▪ Low hepatic metabolism
▪ Low drug-drug interaction
▪ No indication of drug-drug interaction
▪ Panel recommendations:
▪ Panel recommendation:
Evidence level: I ▪ Initial dose of 20 mg/kg q 8 hours
▪ Initial dose of 10-30 mg/kg q 12 hours ▪ Monitoring is not routinely recommended
Grade of Recommendation
▪ Drug monitoring is not recommended except in for Monitoring: C ▪ Monitoring may be indicated with concomitant
rare cases of concern for owner compliance phenobarbital treatment if satisfactory seizure
control is not achieved.
▪ Trough and Peak levels are most helpful
▪ Pharmacology
▪ Elimination half-life of 15-20 hours What Are The Risks Of Treatment?
▪ Hepatic metabolism but without hepatic autoinduction
▪ Increased clearance with concomitant phenobarbital use ▪ Type 1: Predictable and directly
▪ Weak carbonic anhydrase inhibitor related to pharmacological effects
in a dose dependent fashion
▪ Panel recommendations with the following criteria:
▪ Initial dose ▪ Type 2: Unpredictable EFFICACY
Therapeutic Index
▪ Monotherapy: 5 mg/kg q 12 hours (idiosyncratic) and may be life-
▪ With phenobarbital : 10 mg/kg q 12 hours threatening
▪ Monitor levels at 2 weeks and then every 6 months, TOXICITY
▪ 2 weeks after a dose change or with increase in seizure frequency ▪ Type 3: Cumulative effects with
▪ Collect trough time if used as monotherapy longer term therapy and may be
life-threatening
▪ Collect trough and peak (3 hours) if used with phenobarbital
▪ Patient therapeutic range of 10-40 ug/ml
▪ Type 4: Delayed consequences
(carcinogenic/teratogenic) and
Start 6-12 weeks life-threatening
2 weeks
5
ISVMA 2017 November, 2017

Type 1 Type 2 Type 3 Type 4

Phenobarbital Behavioural changes • Immune-mediated anemia, • Psychogenic polydipsia with associated Not reported
neutropenia or thrombocytopenia,
• Acute, idiosyncratic hepatotoxic
reactions
polyuria
• Elevation of the serum alkaline phosphatase
level
What is Drug-Resistant Epilepsy?
• Superficial necrolytic dermatitis in
dogs
• Factitious decrease in serum total and free
thyroxine (T4)
International League Against Epilepsy Task Force
• Drug-induced hepatotoxicity (>35 ug/ml) Kwan et al, Epilepsia 52:1069-1077, 2010
• Physical dependence and associated
withdrawal effects
Drug Treatment Success Drug-Resistant Epilepsy
Potassium Increased lethargy and • Pancreatitis and gastrointestinal • Polydipsia and polyphagia Not reported
bromide mild ataxia with intolerance • Pelvic limb ataxia and weakness
increasing serum • Idiosyncratic allergic bronchitis • Altered behaviour ▪ Seizure free duration at least 3 times ▪ Level 1
concentration • Panniculitis • Megaesophagus the longest seizure free period prior to
▪ Undetermined outcome
• Caution should be used when treating dogs onset of treatment
with underlying renal insufficiency ▪ Inadequate time or drug dose
Primidone Similar to Phenobarbital Similar to phenobarbital • Higher prevalence of hepatotoxicity than Not reported ▪ Minimum duration of 12 months ▪ Monotherapy failure
phenobarbital
Imepitoin • Somnolence/sedation Not reported None reported Imepitoin is not ▪ Continued seizure recurrence despite
• Polyphagia, polyuria genotoxic, appropriate drug selection, time of
and polydipsia teratogenic or treatment and serum concentration
• Hyperactivity immune toxic
• Ataxia ▪ Level 2
Levetiracetam Ataxia only parameter to Not reported Not reported Not reported
▪ Failure of adequate trials of 2 tolerated
differ from baseline
and appropriately chosen AEDs
Zonisamide Sedation, ataxia and • KCS • Lower total T4 levels Not reported
gastrointestinal upset • Polyarthropathy • Lower total C02
• Acute toxic hepatic necrosis
• Renal tubular acidosis

What Causes Drug-

Resistance? When Should a Second AED Be Started?
▪ Strict criteria for decision-making strategy
▪ Transporter hypothesis (1) on starting a second AED is lacking in ▪ Panel Recommendations:
▪ Reduced AED CSF concentration veterinary medicine
▪ Documentation of appropriate drug
▪ Target hypothesis (2) ▪ Risk factors associated with poorer and maximal level of first AED for a
seizure control include male dogs and minimum of 3 months
▪ Decrease AED action at receptor
prior cluster seizure activity
▪ > 50% increase in seizure frequency
▪ Network hypothesis (3) ▪ (Packer et al. 2014) over 3 months
▪ Altered connectivity
▪ Factors to consider ▪ New onset of status epilepticus
▪ Gene variant hypothesis ▪ Selection of an AED with a different ▪ New onset of cluster seizures
▪ Genetic protein alteration mechanism of action
▪ Minimizing drug-drug interactions, avoiding
▪ Presence of drug-toxicity
▪ Intrinsic severity hypothesis additive toxicity
▪ High seizure density and/or ▪ Determination of risk-benefit of
frequency correlated with poorer polypharmacy versus quality of life
prognosis

Kwan P et al. Drug-Resistant Epilepsy N Engl J Med 2011; 365:919-926

Phenobarbital: Level Evidence= IV

Grade of
Recommendation
Add-on Therapy =B
Moderate
▪ No reported studies evaluating Recommendation
phenobarbital as an add-on AED
Moderate
treatment were found Treatment Risk of Higher Risk of Bias
▪ Recommendation is based on Complications
knowledge of efficacy as
monotherapy treatment
Low Risk of Moderate Risk High Risk of
Bias of Bias Bias

•0 studies •0 studies •0 studies

Cochrane Risk of Bias Assessment (Charalambous et al, 2014)

Perucca et al Epil Beh, 2012

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ISVMA 2017 November, 2017

Potassium Bromide: Add-on Therapy Primidone: Grade of

Level Evidence= IV Recommendation
Level Evidence= II
Grade of
Recommendation =
Add-on Therapy =D
5 studies (n=232) B
All with phenobarbital or Not recommended
primidone as primary AED RISK OF Moderate
Recommendation High ▪ No reported studies evaluating
BIAS
phenobarbital as an add-on High Treatment
Moderate AED treatment were found Risk of Higher Risk of Bias
All studies >6
4 studies (N
months Treatment Risk of Higher Risk of Bias Complications
>15) Complications
duration
▪ Recommendation is based on
knowledge of efficacy as
49% with > 50% 6 % with no
seizure reduction improvement
46% with >0 and <
50% seizure
monotherapy treatment Low Risk of
Bias
Moderate Risk
of Bias
High Risk of
Bias
(N=114) (N=14) Low Risk of Moderate Risk High Risk of
reduction (N=118)* of Bias Bias
Bias •0 studies •0 studies •0 studies
•0 studies •2 studies •3 studies

6% seizure
free (N=10) * Estimated
Cochrane Risk of Bias Assessment (Charalambous et al, 2014) Cochrane Risk of Bias Assessment (Charalambous et al, 2014)

Imepitoin: Add-On Therapy Levetiracetam: Add-on Therapy Grade of

Grade of Level Evidence= IB Recommendation
Level Evidence= III Recommendation = =B
C (n= 1) 3 studies (n = 71)
Moderate
1 study Insufficient Data for
RISK OF Recommendation
Recommendation High
BIAS N= 1 > 6 months
2 studies (n > 15)
(Duration of 9-95 months )
Low Treatment
Low Treatment Risk of Low Risk of Bias
Higher Risk of Bias
N = 17 6 months duration Risk of Complications
(n=1)
Complications 48% with > 50% 49% with > 0 and <
3 % with no
seizure reduction 50% seizure
improvement (N=2)
(n=34) reduction

41% with >50% 35% with no 24% with >0 and Low Risk of Moderate Risk High Risk of
Low Risk Moderate Risk High Risk of Bias
seizure reduction improvement < 50% seizure Bias of Bias Bias of Bias
NOTE: 67% (6/9) increase
(N=7) (N=6) reduction (N=4) 7 % with seizure
frequency 4-8 months
•0 •0 •1 free status (N=5) •1 study •1 study •1 study
(Volk et al, 2008)

6% seizure free
(N=1) NOTE: No statistical difference
Cochrane Risk of Bias Assessment (Charalambous et al, 2014) from placebo (Munana, et al 2012) Cochrane Risk of Bias Assessment (Charalambous et al, 2014)

Grade of ACVIM Panel Add-on Therapy Recommendations:

Zonisamide: Add-on Therapy Level Evidence= III Recommendation
=B DRUG LEVEL OF EVIDENCE GRADE OF
RECOMMENDATION
Moderate
3 studies (n = 33) Recommendation Phenobarbital IV B
Low Treatment
Moderate Risk of
Risk of
3 studies > 6 months Bias
Complications Bromide II B
0 studies N > 15) (Duration of 4-18
months )
Primidone II D
64% with > 50% 27 % with no 9 %with > 0 and Low Risk Moderate High Risk of Bias
seizure reduction improvement < 50% seizure Risk of Bias
(n=21) (N=9) reduction (N=3) •0 studies •2 studies •1 study
Imepitoin III C

24 % with Levetiracetam IB B
seizure free
status (N=8) Cochrane Risk of Bias Assessment (Charalambous et al, 2014)
Zonisamide III B

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ISVMA 2017 November, 2017

•1 clinical study (N= 6) (III)

ACVIM Panel Grade of Recommendations Felbamate •6/6 with > 50% reduction for 6 months (CP seizures)

(Level of Evidence) for Add-On AED Therapy Additional AED •2 clinical studies N=25 (III)
•11/25 with > 50% reduction for 3 or 4 months
Information for Gabapentin

A (HIGH) B (MODERATE) C (LOW) D (NO) Use •1 clinical study (n =9) (III)

Pregabalin •7/9 with > 50% reduction for 3 months
•Levetiracetam •Imepitoin (III) •Primidone (II)
(IB)
•1 clinical study (n =10) (III)
•Bromide (II) Insufficient Data •5/10 dogs with > 50% reduction for 6-15 months
•Zonisamide Topiramate

(III) For Treatment

•Phenobarbital Recommendations •No clinical studies
Lacosamide
(IV)

Rufinamide •No clinical studies

Vagal Nerve • Placebo-controlled, cross-over study evaluating the

What Alternative Stimulation (VNS) use of VNS in 10 dogs with medically refractory
idiopathic epilepsy (Muñana et al, 2002)
Non-Pharmacological Vagal Nerve
Stimulation • Treatment and control periods were both 13 weeks
Treatments Are in duration
• No significant difference seizure frequency
Available? between groups over the total study time period
• Significant decrease in seizure frequency of 34%
Homeopathy Complimentary Diet was detected with VNS for the final 4 weeks of
and Alternative treatment
Medicine

Acupuncture

Courtesy of Dr. Munana

Diet
Acupuncture
Fatty acid (Gold Bead Homeopathy
Ketogenic (MCT)
supplementation
Hypoallergenic
Eastern Based
Implantation)
Alternative
Level of evidence: IB Level of evidence: IB Level of evidence: IV Therapy
Insufficient Data to Insufficient Data to Insufficient Data to Evidence level = III Evidence level = III
Recommend Recommend Recommend Insufficient Data for Insufficient Data for
Recommendation Recommendation

Randomized placebo cross-over for Single blinded randomized,

6 months (N=11) placebo cross over for 3 months
One retrospective non-controlled
•Patterson et al, 2005 (N=15)
study (abstract N =8) with report of Overall decrease in Belladonna +/-
•No difference in seizure control •Matthews et al 2012 improvement (Luján et al, 2004) mean seizure Cocculus 6C (N=10) for
•3 cases pancreatitis •No difference in seizure control frequency of 38.7% up to 8 months with
(N= 15 with 7 on AED) variable degree of
Randomized, blinded placebo control for for 15 weeks (Goiz- improvement (Varshney,
3 months (N=21) (Law et al. 2015) Marquez et al, 2009) 2007)
•7 with > 50% improvement

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ISVMA 2017 November, 2017

What Are The Guidelines for Success And Quality of Life Parameters?
What We Accomplished
Etiology
•Symptomatic Treatment ▪ Developed a working clinical consensus statement for canine seizure management
•Breed risks Tolerance
▪ Demonstrated that a collaborative international approach is achievable

▪ Established a predetermined, concise and logical sequential approach to seizure

Seizure severity Owner Considerations management
•Cluster •Restrictive lifestyle
•Prolonged post-ictal •Cost ▪ Established a framework for future veterinary clinical and translational epilepsy treatment
•Emotional stress studies
•Family stress
▪ Revealed a great need for controlled clinical trials
Efficacy
• Frequency
Quality Client Education International Veterinary League Against Epilepsy ?
• Nocturnal of Life and Support

Dr Michael Podell MedVet Chicago 9